Susan R. Hintz, M.D., M.S. Epi.

All Publications

• Factors Associated with Timeliness of Surgical Repair among Infants with Myelomeningocele: California Perinatal Quality Care Collaborative, 2006 to 2011. American journal of perinatology Kancherla, V., Ma, C., Grant, G., Lee, H. C., Shaw, G. M., Hintz, S. R., Carmichael, S. L. 2019

  Abstract

  OBJECTIVE: To examine factors associated with timely (0-2 days after birth) myelomeningocele surgical repair.STUDY DESIGN: We examined 2006 to 2011 births from the California Perinatal Quality Care Collaborative, linking to hospital discharge and vital records. Selected maternal, infant, and delivery hospital characteristics were evaluated to understand disparities in timely repair. Poisson regression was used to estimate adjusted risk ratios (aRRs) and 95% confidence intervals (CIs).RESULTS: Overall, 399 of the 450 (89%) infants had a timely repair and approximately 80% of them were delivered in level III/IV hospitals. Infants with hydrocephalus were significantly less likely to have a delayed myelomeningocele repair compared with those without (aRR=0.22; 95% CI=0.13, 0.39); infants whose medical care was paid by Medi-Cal or other nonprivate insurance were 2.2 times more likely to have a delayed repair compared with those covered by a private insurance (aRR=2.23; 95% CI=1.17, 4.27). Low birth weight was a significant predictor for delayed repair (aRR=2.06; 95% CI=1.10, 3.83).CONCLUSION: There was a significant disparity in myelomenigocele repair based on medical care payer. Families and hospitals should work together for timely repair in hospitals having specialized multidisciplinary teams. Findings from the study can be used to follow best clinical practices for myelomeningocele repair.

  View details for DOI 10.1055/s-0039-1693127

  View details for PubMedID 31307103

• Factors Associated with Successful First High-Risk Infant Clinic Visit for Very Low Birth Weight Infants in California JOURNAL OF PEDIATRICS Hintz, S. R., Gould, J. B., Bennett, M., Lu, T., Gray, E. E., Jocson, M. L., Fuller, M. G., Lee, H. C. 2019; 210: 91-+

  View details for DOI 10.1016/j.jpeds.2019.03.007

  View details for Web of Science ID 000472497600019

• Prenatally diagnosed omphalocele: characteristics associated with adverse neonatal outcomes. Journal of perinatology : official journal of the California Perinatal Association Chock, V. Y., Davis, A. S., Cho, S., Bax, C., Fluharty, E., Weigel, N., Homeyer, M., Hudgins, L., Jones, R., Rubesova, E., Sylvester, K. G., Blumenfeld, Y. J., Hintz, S. R. 2019

  Abstract

  OBJECTIVE: To characterize factors associated with adverse neonatal outcomes in prenatally diagnosed omphalocele cases.STUDY DESIGN: Prenatally diagnosed omphalocele cases at a single referral center from 1 January 2009 to 31 December 2017 were retrospectively reviewed. Clinical variables and antenatal imaging measurements were collected. Associations between prenatal and neonatal characteristics and the adverse outcome of death or prolonged length of stay (LOS) were analyzed.RESULTS: Out of 63 fetal cases, 33 were live-born, >50% had other anomalies, and neonatal mortality was 12%. Adverse outcomes were associated with neonatal variables, including lower median 1-min Apgar score, initial mechanical ventilation, and late-onset sepsis, but not approach toomphalocele closure. With multivariate analysis, death or prolonged LOS was associated only with low lung volumes by fetal MRI (OR 34 (3-422), p=0.006).CONCLUSION: Low lung volumes by fetal MRI were associated with death or prolonged LOS in neonates with prenatally diagnosed omphalocele and may guide clinicians with counseling families.

  View details for DOI 10.1038/s41372-019-0410-1

  View details for PubMedID 31227786

• Differences in patient characteristics and care practices between two trials of therapeutic hypothermia PEDIATRIC RESEARCH Bonifacio, S. L., McDonald, S. A., Chock, V. Y., Wusthoff, C. J., Hintz, S. R., Laptook, A. R., Shankara, S., Van Meurs, K. P. 2019; 85 (7): 1008?15

  View details for DOI 10.1038/s41390-019-0371-2

  View details for Web of Science ID 000468524800020

• Factors Associated with First-Year Mortality in Infants with Myelomeningocele Kancherla, Ma, C., Grant, G., Lee, H. C., Hintz, S. R., Carmichael, S. L. WILEY. 2019: 528

  View details for Web of Science ID 000468051600147

• Outcomes of Extremely Preterm Infants With Birth Weight Less Than 400 g JAMA PEDIATRICS Brumbaugh, J. E., Hansen, N. I., Bell, E. F., Sridhar, A., Carlo, W. A., Hintz, S. R., Vohr, B. R., Colaizy, T. T., Duncan, A. F., Wyckoff, M. H., Baack, M. L., Rysavy, M. A., DeMauro, S. B., Stoll, B. J., Das, A., Higgins, R. D., Polin, R. A., Caplan, M. S., Laptook, A. R., Keszler, M., Hensman, A. M., Alksninis, B., Burke, R. T., Caskey, M., Hoffman, L., Johnson, K., Keszler, M., Leach, T. M., McGowan, E. C., Stephens, B. E., Basso, K., Vieira, E., Little, E., St Pierre, L., Watson, V. E., Walsh, M. C., Hibbs, A., Newman, N. S., Wilson-Costello, D. E., Skier, B. S., Bhola, M., Yalcinkaya, G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Scott, A., Parimi, P. S., Gaetano, L., Poindexter, B. B., Schibler, K., Kallapur, S. G., Yolton, K., Alexander, B., Gratton, T. L., Grisby, C., Kirker, K., Jackson, L. D., Steichen, J. J., Wuertz, S., Cotten, C., Goldberg, R. N., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Finkle, J., Fisher, K. A., Grimes, S., Gustafson, K. E., Lohmeyer, M. B., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Kicklighter, S. D., Rhodes-Ryan, G., Archer, S., Carlton, D. P., Adams-Chapman, I., Hale, E. C., Loggins, Y., Bottcher, D., Carter, S. L., Kendrick-Allwood, S., LaRossa, M., Mackie, C., Seabrook, I., Smikie, G., Wineski, L., Sokol, G. M., Poindexter, B. B., Dusick, A. M., Hamer, F., Herron, D. E., Hines, A. C., Lytle, C., Miller, L. C., Minnich, H. M., Papile, L., Richard, L., Smiley, L., Wilson, L., Kennedy, K. A., Tyson, J. E., Arldt-McAlister, J., Burson, K., Dempsey, A. G., Eason, E., Evans, P. W., Garcia, C., Green, C., Hall, D., Harris, B., Jiminez, M., John, J., Jones, P. M., Lillie, M., Martin, K., Martin, S. C., McDavid, G. E., Rodgers, S., Siddiki, S., Sperry, D., Stephens, E. K., Tate, P., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Wallace, D., Gantz, M. G., Auman, J., Crawford, M., Gabrio, J., Newman, J. E., Huitema, C., Poole, W., Zaterka-Baxter, K. M., Frantz, I. D., Fiascone, J. M., McGowan, E. C., MacKinnon, B. L., Furey, A., Nylen, E., Church, P. T., Van Meurs, K. P., Stevenson, D. K., Adams, M. M., Ball, M., Bentley, B., Bruno, E., DeAnda, M., DeBattista, A. M., Huffman, L. C., Ismael, M., Kohn, J. G., Krueger, C., Palmquist, A., Proud, M. S., St John, N. H., Weiss, H., Ambalavanan, N., Peralta-Carcelen, M., Nelson, K. G., Bailey, K. J., Biasini, F. J., Chopko, S. A., Collins, M. V., Cosby, S. S., Johnston, K. C., Moses, M., Patterson, C. S., Phillips, V. A., Preskitt, J., Rector, R. V., Whitley, S., Devaskar, U., Gary, M., Purdy, I. B., Chanlaw, T., Geller, R., Widness, J. A., Acarregui, M. J., Ellsbury, D. L., Johnson, K. J., Walker, J. R., Goeke, C. A., Eastman, D. L., Campbell, D. B., Tud, T. L., Watterberg, K. L., Ohls, R. K., Lacy, C., Brown, S., Fuller, J., Hartenberger, C., Lowe, J. R., Thomson, R. A., Beauman, S., Hanson, M., Kuan, E., Schmidt, B., Kirpalani, H., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D. M., Bernbaum, J. C., Gerdes, M., Hurt, H., Snyder, J., D'Angio, C. T., Phelps, D. L., Guillet, R., Myers, G. J., Lakshminrusimha, S., Reynolds, A., Reubens, L. J., Burnell, E., Scorsone, A., Binion, K., Orme, C., Wadkins, H. M., Sacilowski, M. G., Jensen, R. L., Merzbach, J., Zorn, W., Farooq, O., Maffett, D., Williams, A., Hunn, J., Guilford, S., Yost, K., Rowan, M., Prinzing, D., Wynn, K., Bowman, M., Brion, L. P., Sanchez, P. J., Heyne, R. J., Vasil, D. M., Adams, S. S., Chen, L., De Leon, M. M., Eubanks, F., Guzman, A., Heyne, E. T., Lee, L. E., Leps, M. H., Madden, L. A., Miller, N. A., Morgan, J. S., Pavageau, L., Sepulveda, P., Boatman, C., Yoder, B. A., Baserga, M., Faix, R. G., Minton, S. D., Sheffield, M. J., Rau, C. A., Winter, S., Osborne, K. A., Spencer, C., Weaver-Lewis, K., Baker, S., Burnett, J., Steffen, M., Loertscher, M. C., Woodbury, K. D., Reich, B. A., Schaefer, S. T., Cole-Bledsoe, L., Elmont, J. O., Parry, D., Marchant, T., Christensen, S., Maxson, E., Davis, B., Shankaran, S., Sood, B. G., Pappas, A., Natarajan, G., Chawla, S., Bajaj, M., Bara, R., Childs, K., Panaitescu, B., Johnson, M. E., Goldston, L. A., Wiggins, S. A., Christensen, M. K., Carlson, M., Barks, J., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Natl Inst Child Hlth Human Dev 2019; 173 (5): 434?45

  View details for DOI 10.1001/jamapediatrics.2019.0180

  View details for Web of Science ID 000467505200011

• Home Oxygen and 2-Year Outcomes of Preterm Infants With Bronchopulmonary Dysplasia PEDIATRICS DeMauro, S. B., Jensen, E. A., Bann, C. M., Bell, E. F., Hibbs, A., Hintz, S. R., Lorch, S. A. 2019; 143 (5)

  View details for DOI 10.1542/peds.2018-2956

  View details for Web of Science ID 000474923900027

• Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth JOURNAL OF PEDIATRICS Rysavy, M. A., Bell, E. F., Iams, J. D., Carlo, W. A., Li, L., Mercer, B. M., Hintz, S. R., Stoll, B. J., Vohr, B. R., Shankaran, S., Walsh, M. C., Brumbaugh, J. E., Colaizy, T. T., Das, A., Higgins, R. D., Caplan, M. S., Polin, R. A., Laptook, A. R., Hensman, A. M., Oh, W., Keszler, M., Burke, R., Caskey, M., Johnson, K., Alksninis, B., Leach, T. M., Stephens, B. E., Watson, V. E., Ventura, S., Basso, K. M., Vieira, E., Halbrook, A., Fanaroff, A. A., Hibbs, A., Wilson-Costello, D. E., Newman, N. S., Siner, B. S., Bhola, M., Yalcinkaya, G., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Schibler, K., Donovan, E. F., Bridges, K., Alexander, B., Grisby, C., Hessling, J., Fischer, E. E., Jackson, L. D., Kirker, K., Mincey, H. L., Muthig, G., Gratton, T. L., Steichen, J. J., Yolton, K., Goldberg, R. N., Goldstein, R. F., Fisher, K. A., Auten, K. J., Foy, K. A., Grimes, S., Finkle, J., Gustafson, K. E., Lohmeyer, M. B., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Clark, C., Carlton, D. P., Hale, E. C., Adams-Chapman, I., LaRossa, M., Carter, S. L., Archer, S., Poindexter, B. B., Dusick, A. M., Cook, A. B., Herron, D. E., Hamer, F., Lytle, C., Miller, L. C., Minnich, H. M., Wilson, L., Nelin, L. D., Jadcherla, S. R., Luzader, P., Fortney, C. A., Besner, G. E., Parikh, N. A., Poole, W., Wallace, D., Newman, J. E., Auman, J., Crawford, M. M., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Adams, M. M., Ball, M., Palmquist, A. W., Proud, M. S., Bruno, E., DeAnda, M., DeBattista, A. M., Kohn, J. G., Krueger, C. E., Weiss, H. E., Frantz, I. D., Fiascone, J. M., MacKinnon, B. L., Nylen, E., Furey, A., McGowan, E. C., Sibley, C. E., Brussa, A. K., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Nelson, K. G., Patterson, C. S., Phillips, V. A., Whitley, S., Soong, A. D., Kiser, C., Smith, L., Kryzwanski, S., Rector, R., Ryan, S., Domnanovich, K., Rodrigues, L., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Finer, N. N., Vaucher, Y. E., Kaegi, D., Rasmussen, M. R., Arnell, K., Demetrio, C., Fuller, M. G., Henderson, C., Rich, W., West, R., Ellsbury, D. L., Widness, J. A., Johnson, K. J., Campbell, D. B., Walker, J. R., Eastman, D. L., Duara, S., Bauer, C. R., Everett-Thomas, R., Hiriart-Fajardo, S., Rigaud, A., Calejo, M., Eguaras, S., Berkowits, M., Garcia, A., Pierre, H., Stoerger, A., Watterberg, K. L., Ohls, R. K., Fuller, J. F., Lacy, C., Montman, R. A., Lowe, J. R., Duncan, A., Brown, S., Wussow, T., Hartenberger, C., Rohr, J., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Cucinotta, D., Phelps, D. L., Myers, G. J., Reubens, L. J., Burnell, E., Hust, D., Johnson, J., Jensen, R. L., Kushner, E., Merzbach, J., Yost, K., Zwetsch, L., Lakshminrusimha, S., Reynolds, A., Farooq, O., Williams, A., Kennedy, K. A., Alaniz, N., Burson, K., Evans, P. W., Green, C., Harris, B., Jiminez, M., Lis, A. E., Martin, S., McDavid, G. E., Morris, B. H., Poundstone, M., Robichaux, P., Siddiki, S., Simmons, M. C., Tate, P., Wright, S. L., Sanchez, P. J., Heyne, R. J., Salhab, W. A., Rosenfeld, C. R., Brion, L. P., Chen, L., Guzman, A., Leps, M. H., Miller, N. A., Vasil, D. M., Torres, L. E., Hensley, G., Adams, S. S., Madden, L. A., Heyne, E., Morgan, J. S., Boatman, C., Faix, R. G., Yoder, B. A., Bodnar, A., Osborne, K. A., Baker, S., Bird, K., Burnett, J., Jensen, J. J., Spencer, C., Steffen, M., Weaver-Lewis, K., Winter, S., Zanetti, K., O'Shea, T., Dillard, R. G., Washburn, L. K., Jackson, B. G., Peters, N., Chiu, K., Allred, D., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M., Hounshell, G., Pappas, A., Barks, J., Bara, R., Goldston, L. A., Johnson, M., Muran, G., Sumner, L., Sawaya, K., Weingarden, K., Christensen, M., Wiggins, S., Ehrenkranz, R. A., Jacobs, H., Butler, C. G., Cervone, P., Greisman, S., Konstantino, M., Poulsen, J., Taft, J., Williams, J., Romano, E., Eunice Kennedy Shriver Natl Inst C 2019; 208: 156-+

  View details for DOI 10.1016/j.jpeds.2018.12.063

  View details for Web of Science ID 000465236700029

• Home Oxygen and 2-Year Outcomes of Preterm Infants With Bronchopulmonary Dysplasia. Pediatrics DeMauro, S. B., Jensen, E. A., Bann, C. M., Bell, E. F., Hibbs, A. M., Hintz, S. R., Lorch, S. A. 2019

  Abstract

  OBJECTIVES: To compare medical and developmental outcomes over the first 2 years of life in extremely preterm infants with bronchopulmonary dysplasia (BPD) who were discharged on supplemental oxygen via nasal cannula with outcomes of infants with a similar severity of respiratory illness who were discharged breathing in room air.METHODS: We performed a propensity score-matched cohort study. Eligible infants were born at <27 weeks' gestation, were receiving supplemental oxygen or respiratory support at 36 weeks' postmenstrual age, and were assessed at 18 to 26 months' corrected age. Study outcomes included growth, resource use, and neurodevelopment between discharge and follow-up. Outcomes were compared by using multivariable models adjusted for center and age at follow-up.RESULTS: A total of 1039 infants discharged on supplemental oxygen were propensity score matched 1:1 to infants discharged breathing in room air. Infants on oxygen had a marginal improvement in weight z score (adjusted mean difference 0.11; 95% confidence interval [CI] 0.00 to 0.22), with a significantly improved weight-for-length z score (adjusted mean difference 0.13; 95% CI 0.06 to 0.20) at 22 to 26 months' corrected age. Infants on oxygen were more likely to be rehospitalized for respiratory illness (adjusted relative risk 1.33; 95% CI 1.16 to 1.53) and more likely to use respiratory medications and equipment. Rates of neurodevelopmental impairment were similar between the groups.CONCLUSIONS: In this matched cohort of infants with BPD, postdischarge oxygen was associated with marginally improved growth and increased resource use but no difference in neurodevelopmental outcomes. Ongoing and future trials are critical to assess the efficacy and safety of postdischarge supplemental oxygen for infants with BPD.

  View details for PubMedID 30975699

• Factors Associated with Successful First High-Risk Infant Clinic Visit for Very Low Birth Weight Infants in California. The Journal of pediatrics Hintz, S. R., Gould, J. B., Bennett, M. V., Lu, T., Gray, E. E., Jocson, M. A., Fuller, M. G., Lee, H. C. 2019

  Abstract

  OBJECTIVES: To determine rates of at least 1 high-risk infant follow-up (HRIF) visit by 12months corrected age, and factors associated with successful first visit among very low birth weight (VLBW) infants in a statewide population-based setting.STUDY DESIGN: We used the linked California Perinatal Quality of Care Collaborative and California Perinatal Quality of Care Collaborative-California Children's Services HRIF databases. Multivariable logistic regression examined independent associations of maternal, sociodemographic, neonatal clinical, and HRIF program factors with a successful first HRIF visit among VLBW infants born in 2010-2011.RESULTS: Among 6512 VLBW children referred to HRIF, 4938 (76%) attended a first visit. Higher odds for first HRIF visit attendance was associated with older maternal age (OR, 1.48; 95% CI, 1.27-1.72; 30-39 vs 20-29years), lower birth weight (OR, 2.11; 95% CI, 1.69-2.65; ?750g vs 1251-1499g), private insurance (OR, 1.65; 95% CI, 1.19-2.31), a history of severe intracranial hemorrhage (OR, 1.61; 95% CI, 1.12-2.30), 2 parents as primary caregivers (OR, 1.18, 95% CI 1.03-1.36), and higher HRIF program volume (OR, 2.62; 95% CI, 1.88-3.66; second vs lowest quartile); and lower odds with maternal race African American or black (OR, 0.65; 95% CI, 0.54-0.78), and greater distance to HRIF program (OR, 0.69; 95% CI, 0.57-0.83). Rates varied substantially across HRIF programs, which remained after risk adjustment.CONCLUSIONS: In a population-based California VLBW cohort, maternal, sociodemographic, and home- and program-level disparities were associated with HRIF non-attendance. These findings underscore the need to identify challenges in access and resource risk factors during hospitalization in the neonatal intensive care unit, provide enhanced education about the benefits of HRIF, and create comprehensive neonatal intensive care unit-to-home transition approaches.

  View details for PubMedID 30967249

• Stillbirth and Live Birth at Periviable Gestational Age: A Comparison of Prevalence and Risk Factors AMERICAN JOURNAL OF PERINATOLOGY Carmichael, S. L., Blumenfeld, Y. J., Mayo, J. A., Profit, J., Shaw, G. M., Hintz, S. R., Stevenson, D. K. 2019; 36 (5): 537?44

  View details for DOI 10.1055/s-0038-1670633

  View details for Web of Science ID 000463944600016

• Predicting Pathology From Imaging in Children Undergoing Resection of Congenital Lung Lesions Narayan, R. R., Abadilla, N., Greenberg, D. R., Sylvester, K. G., Hintz, S. R., Barth, R. A., Bruzoni, M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2019: 68?73

  View details for DOI 10.1016/j.jss.2018.10.042

  View details for Web of Science ID 000458498300010

• Outcomes of Extremely Preterm Infants With Birth Weight Less Than 400 g. JAMA pediatrics Brumbaugh, J. E., Hansen, N. I., Bell, E. F., Sridhar, A., Carlo, W. A., Hintz, S. R., Vohr, B. R., Colaizy, T. T., Duncan, A. F., Wyckoff, M. H., Baack, M. L., Rysavy, M. A., DeMauro, S. B., Stoll, B. J., Das, A., Higgins, R. D., National Institute of Child Health and Human Development Neonatal Research Network 2019

  Abstract

  Importance: Birth weight (BW) is an important predictor of mortality and morbidity. At extremely early gestational ages (GAs), BW may influence decisions regarding initiation of resuscitation.Objective: To characterize outcomes of liveborn infants with a BW less than 400 g.Design, Setting, and Participants: This retrospective multicenter cohort study analyzed extremely preterm infants born between January 2008 and December 2016 within the National Institute of Child Health and Human Development Neonatal Research Network. Infants with a BW less than 400 g and a GA of 22 to 26 weeks were included. Active treatment was defined as the provision of any potentially lifesaving intervention after birth. Survival was analyzed for the entire cohort; neurodevelopmental impairment (NDI) was examined for those born between January 2008 and December 2015 (birth years with outcomes available for analysis). Neurodevelopmental impairment at 18 to 26 months' corrected age (CA) was defined as a Bayley Scales of Infant and Toddler Development, Third Edition, cognitive composite score less than 85, a motor composite score less than 85, moderate or severe cerebral palsy, gross motor function classification system score of 2 or greater, bilateral blindness, and/or hearing impairment. Data were analyzed from September 2017 to October 2018.Exposures: Birth weight less than 400 g.Main Outcomes and Measures: The primary outcome was survival to discharge among infants who received active treatment. Analysis of follow-up data was limited to infants born from 2008 to 2015 to ensure children had reached assessment age. Within this cohort, neurodevelopmental outcomes were assessed for infants who survived to 18 to 26 months' CA and returned for a comprehensive visit.Results: Of the 205 included infants, 121 (59.0%) were female, 133 (64.9%) were singletons, and 178 (86.8%) were small for gestational age. Almost half (101 of 205 [49.3%]) received active treatment at birth. A total of 26 of 205 infants (12.7%; 95% CI, 8.5-18.9) overall survived to discharge, and 26 of 101 actively treated infants (25.7%; 95% CI, 17.6-35.4) survived to discharge. Within the subset of infants with a BW less than 400 g and a GA of 22 to 23 weeks, 6 of 36 actively treated infants (17%; 95% CI, 6-33) survived to discharge. Among infants born between 2008 and 2015, 23 of 90 actively treated infants (26%; 95% CI, 17-36) survived to discharge. Two infants died after discharge, and 2 were lost to follow-up. Thus, 19 of 90 actively treated infants (21%; 95% CI, 13-31) were evaluated at 18 to 26 months' CA. Moderate or severe NDI occurred in 14 of 19 infants (74%).Conclusions and Relevance: Infants born with a BW less than 400 g are at high risk of mortality and significant morbidity. Although 21% of infants survived to 18 to 26 months' CA with active treatment, NDI was common among survivors.

  View details for PubMedID 30907941

• Differences in patient characteristics and care practices between two trials of therapeutic hypothermia. Pediatric research Bonifacio, S. L., McDonald, S. A., Chock, V. Y., Wusthoff, C. J., Hintz, S. R., Laptook, A. R., Shankara, S., Van Meurs, K. P. 2019

  Abstract

  BACKGROUND: The Induced Hypothermia (IH) and Optimizing Cooling (OC) trials for hypoxic-ischemic encephalopathy (HIE) had similar inclusion criteria. The rate of death/moderate-severe disability differed for the subgroups treated with therapeutic hypothermia (TH) at 33.5°C for 72h (44% vs. 29%, unadjusted p=0.03). We aimed to evaluate differences in patient characteristics and care practices between the trials.METHODS: We compared pre/post-randomization characteristics and care practices between IH and OC.RESULTS: There were 208 patients in the IH trial, 102 cooled, and 364 in the OC trial, 95 cooled to 33.5°C for 72h. In OC, neonates were less ill, fewer had severe HIE, and the majority were cooled prior to randomization. Differences between IH and OC were observed in the adjusted difference in the lowest PCO2 (+3.08mmHg, p=0.005) and highest PO2 (-82.7mmHg, p<0.001). In OC, compared to IH, the adjusted relative risk (RR) of exposure to anticonvulsant prior to randomization was decreased (RR 0.58, (0.40-0.85), p=0.005) and there was increased risk of exposure during cooling to sedatives/analgesia (RR 1.86 (1.21-2.86), p=0.005).CONCLUSION: Despite similar inclusion criteria, there were differences in patient characteristics and care practices between trials. Change in care practices over time should be considered when planning future neuroprotective trials.

  View details for PubMedID 30862961

• Neuroimaging and Bayley-III correlates of early hand function in extremely preterm children JOURNAL OF PERINATOLOGY Duncan, A. F., Bann, C. M., Dempsey, A. G., Adams-Chapman, I., Heyne, R., Hintz, S. R., Eunice Kennedy Shriver Natl Inst C 2019; 39 (3): 488?96

  View details for DOI 10.1038/s41372-019-0314-0

  View details for Web of Science ID 000459549600020

• Discordance in Antenatal Corticosteroid Use and Resuscitation Following Extremely Preterm Birth. The Journal of pediatrics Rysavy, M. A., Bell, E. F., Iams, J. D., Carlo, W. A., Li, L., Mercer, B. M., Hintz, S. R., Stoll, B. J., Vohr, B. R., Shankaran, S., Walsh, M. C., Brumbaugh, J. E., Colaizy, T. T., Das, A., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 2019

  Abstract

  OBJECTIVE: To describe discordance in antenatal corticosteroid use and resuscitation following extremely preterm birth and its relationship with infant survival and neurodevelopment.STUDY DESIGN: A multicenter cohort study of 4858 infants 22-26weeks of gestation born 2006-2011 at 24 US hospitals participating in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network, with follow-up through 2013. Survival and neurodevelopmental outcomes were available at 18-22months of corrected age for 4576 (94.2%) infants. We described antenatal interventions, resuscitation, and infant outcomes. We modeled the effect on infant outcomes of each hospital increasing antenatal corticosteroid exposure for resuscitated infants born at 22-24weeks of gestation to rates observed at 25-26weeks of gestation.RESULTS: Discordant antenatal corticosteroid use and resuscitation, where one and not the other occurred, were more frequent for births at 22 and 23 but not 24weeks (rate ratio [95% CI] at 22weeks: 1.7 [1.3-2.2]; 23weeks: 2.6 [2.2-3.2]; 24weeks: 1.0 [0.8-1.2]) when compared with 25-26weeks. Among infants resuscitated at 23weeks, adjusting each hospital's rate of antenatal corticosteroid use to the average at 25-26weeks (89.2%) was projected to increase infant survival by 7.1% (95% CI 5.4-8.8%) and survival without severe impairment by 6.4% (95% CI 4.7-8.1%). No significant change in outcomes was projected for infants resuscitated at 22weeks, where few (n=22) resuscitated infants received antenatal corticosteroids.CONCLUSIONS: Infants born at 23weeks were more frequently resuscitated without antenatal corticosteroids than other extremely preterm infants. When resuscitation is intended, consistent provision of antenatal corticosteroids may increase infant survival and survival without impairment.TRIAL REGISTRATION: ClinicalTrials.govNCT00063063 (Generic Database) and NCT00009633 (Follow-Up Study).

  View details for PubMedID 30738658

• Neurodevelopmental outcomes among extremely premature infants with linear growth restriction JOURNAL OF PERINATOLOGY Meyers, J. M., Tan, S., Bell, E. F., Duncan, A. F., Guillet, R., Stoll, B. J., D'Angio, C. T., Caplan, M. S., Laptook, A. R., Keszler, M., Vohr, B. R., Hensman, A. M., Vieira, E., Little, E., Alksninis, B., Keszler, M., Knoll, A. M., Leach, T. M., McGowan, E. C., Watson, V. E., Walsh, M. C., Fanaroff, A. A., Hibbs, A., Newman, N. S., Payne, A. H., Wilson-Costello, D. E., Siner, B. S., Bhola, M., Yalcinkaya, G., Friedman, H. G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Poindexter, B. B., Schibler, K., Alexander, B., Grisby, C., Gratton, T. L., Jackson, L., Kirker, K., Muthig, G., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Fisher, K. A., Finkle, J., Gustafson, K. E., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Carlton, D. P., Hale, E. C., Adams-Chapman, H., Loggins, Y., Carter, S. L., LaRossa, M., Wineski, L. C., Bottcher, D., Mackie, C., Higgins, R. D., Archer, S., Sokol, G. M., Papile, L., Harmon, H. M., Hines, A. C., Wilson, L., Herron, D. E., Gunn, S., Smiley, L., Kennedy, K. A., Tyson, J. E., Allain, E., Arldt-McAlister, J., Dempsey, A. G., Garcia, C., John, J., Jones, P. M., Lillie, L. M., Martin, K., Martin, S. C., McDavid, G. E., Rodgers, S., Siddiki, S., Sperry, D., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Fortney, C. A., Luzader, P., Besner, G. E., Parikh, N. A., Das, A., Wallace, D., Newman, J. E., Auman, J., Crawford, M., Gabrio, J., Gantz, M. G., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Hintz, S. R., Ball, M., Proud, M. S., Bentley, B., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R., Weiss, H. E., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Colaizy, T. T., Brumbaugh, J. E., Ellsbury, D. L., Johnson, K. J., Walker, J. R., Campbell, D. B., Eastman, D. L., Watterberg, K. L., Lowe, J. R., Fuller, J. F., Ohls, R. K., Lacy, C., Duncan, A. F., Dupont, T., Kuan, E., Beauman, S., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Bernbaum, J. C., Gerdes, M., Hurt, H., Cook, N., Cucinotta, D. M., Lakshminrusimha, S., Reynolds, A., Jensen, R. L., Merzbach, J., Myers, G. J., Williams, A., Yost, K., Zorn, W., Wynn, K., Maffett, D., Prinzing, D., Hunn, J., Guilford, S., Osman, F., Rowan, M., Sacilowski, M. G., Wadkins, H. M., Bowman, M., Fallone, C., Binion, K., Orme, C., Scorsone, A., Andrews-Hartley, M., Wyckoff, M. H., Brion, L. P., Vasil, D. M., Chen, L., Heyne, R. J., Adams, S. S., Heyne, E., Guzman, A., Lee, L. E., Boatman, C., Shankaran, S., Pappas, A., Natarajan, G., Chawla, S., Bajaj, M., February, M., Agarwal, P., Childs, K., Woldt, E., Bara, R., Goldston, L. A., Barks, J., Christensen, M., Wiggins, S., White, D., Eunice Kennedy Shriver Natl Inst 2019; 39 (2): 193?202

  Abstract

  To compare neurodevelopmental outcomes in linear growth-restricted (LGR) infants born <29 weeks with and without weight gain out of proportion to linear growth.We compared 2-year neurodevelopmental outcomes between infants with and without LGR and between LGR infants with and without weight gain out of proportion to linear growth. The outcomes were Bayley-III cognitive, motor, and language scores, cerebral palsy, Gross Motor Function Classification System (GMFCS) level???2, and neurodevelopmental impairment.In total, 1227 infants were analyzed. LGR infants were smaller and less mature at birth, had higher BMI, and had lower Bayley-III language scores (82.3 vs. 85.0, p?

  View details for PubMedID 30353080

• Neuroimaging and Bayley-III correlates of early hand function in extremely preterm children. Journal of perinatology : official journal of the California Perinatal Association Duncan, A. F., Bann, C. M., Dempsey, A. G., Adams-Chapman, I., Heyne, R., Hintz, S. R., Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network 2019

  Abstract

  OBJECTIVE(S): Investigate associations between 18 and 22-month corrected age hand function, adverse findings on serial cranial ultrasound (CUS) and near-term brain MRI (ntMRI), and Bayley-III scores in extremely preterm (EPT) toddlers.STUDY DESIGN: Cohort analysis of Neonatal Research Network SUPPORT NEURO data. Associations between brain abnormalities, hand function, and Bayley-III scores were examined using chi-square and generalized linear mixed effect model analyses.RESULTS: A total of 433 children were included. Sixteen percent had hand function deficits; these were associated with late CUS (p<0.001) abnormalities, white matter abnormality (WMA) on ntMRI (p<0.001), and Bayley-III scores. Six percent had CP. Fourteen percent of children without and 50% of those with CP had hand function abnormalities.CONCLUSIONS: Late CUS findings and severity of WMA were significantly associated with hand function deficits. Hand function deficits were nearly three times more common than CP and may be a useful marker of early brain insult and predictor of preterm birth effects on development.

  View details for PubMedID 30692613

• Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm JOURNAL OF PEDIATRICS Duncan, A. F., Bann, C. M., Dempsey, A., Peralta-Carcelen, M., Hintz, S., Eunice Kennedy Shriver Natl Inst C 2019; 204: 148-+

  View details for DOI 10.1016/j.jpeds.2018.08.059

  View details for Web of Science ID 000453785200028

• Behavioral problems are associated with cognitive and language scores in toddlers born extremely preterm EARLY HUMAN DEVELOPMENT Lowe, J. R., Fuller, J. F., Do, B. T., Vohr, B. R., Das, A., Hintz, S. R., Watterberg, K. L., Higgins, R. D., Caplan, M. S., Laptook, A. R., Keszler, M., Hensman, A. M., Vieira, E., Little, E., Alksninis, B., Keszler, M., Knoll, A. M., Leach, T. M., McGowan, E. C., Watson, V. E., Walsh, M. C., Hibbs, A., Newman, N. S., Payne, A. H., Wilson-Costello, D. E., Siner, B. S., Bhola, M., Ross, E., Taylor, H., Yalcinkaya, G., Truog, W. E., Pallotto, E. K., Kilbride, H. W., Gauldin, C., Holmes, A., Johnson, K., Knutson, A., Poindexter, B. B., Schibler, K., Merhar, S., Grisby, C., Gratton, T. L., Tepe, S., Yolton, K., Goldberg, R. N., Cotten, C., Goldstein, R. F., Malcolm, W. F., Ashley, P. L., Fisher, K. A., Finkle, J., Gustafson, K. E., Laughon, M. M., Bose, C. L., Bernhardt, J., Bose, G., Wereszczak, J., Carlton, D. P., Hale, E. C., Adams-Chapman, I., Loggins, Y., Carter, S. L., LaRossa, M., Wineski, L. C., Bottcher, D., Mackie, C., Archer, S., Sokol, G. M., Poindexter, B. B., Papile, L., Harmon, H. M., Hines, A. C., Wilson, L., Herron, D. E., Gunn, S., Smiley, L., Kennedy, K. A., Tyson, J. E., Allain, E., Arldt-McAlister, J., Dempsey, A. G., Duncan, A. F., Garcia, C., Eason, E., John, J., Jones, P. M., Lillie, M., Martin, K., Martin, S. C., McDavid, G. E., McKee, S., Rodgers, S., Sperry, D., Wright, S. L., Sanchez, P. J., Nelin, L. D., Jadcherla, S. R., Fortney, C. A., Luzader, P., Besner, G. E., Parikh, N. A., Wallace, D., Newman, J. E., Auman, J., Crawford, M., Gabrio, J., Gantz, M. G., Huitema, C., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Ball, M., Proud, M. S., Bentley, B., DeAnda, M., DeBattista, A. M., Earhart, B., Huffman, L. C., Krueger, C. E., Lucash, R., Weiss, H. E., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M., Cosby, S. S., Biasini, F. J., Johnston, K. C., Patterson, C. S., Phillips, V. A., Whitley, S., Devaskar, U., Garg, M., Purdy, I. B., Chanlaw, T., Geller, R., Bell, E. F., Colaizy, T. T., Brumbaugh, J. E., Ellsbury, D. L., Johnson, K. J., Walker, J. R., Campbell, D. B., Eastman, D. L., Tud, T. L., Ohis, R. K., Lacy, C., Duncan, A. F., Dupont, T., Kuan, E., Beauman, S., Hanson, M., Schmidt, B., Kirpalani, H., DeMauro, S. B., Chaudhary, A. S., Abbasi, S., Mancini, T., Bernbaum, J. C., Gerdes, M., Hurt, H., Cook, N., Cucinotta, D. M., D'Angio, C. T., Lakshminrusintha, S., Guillet, R., Reynolds, A., Jensen, R. L., Merzbach, J., Myers, G. J., Williams, A., Yost, K., Zorn, W., Wynn, K., Maffett, D., Prinzing, D., Hunn, J., Guilford, S., Farooq, O., Rowan, M., Sacilowski, M. G., Wadkins, H. M., Bowman, M., Fallone, C., Binion, K., Orme, C., Scorsone, A., Andrews-Hartley, M., Wyckoff, M. H., Sanchez, P. J., Brion, L. P., Vasil, D. M., Chen, L., Heyne, R. J., Adams, S. S., Heyne, E., Guzman, A., Lee, L. E., Boatman, C., Shankaran, S., Pappas, A., Natarajan, G., Chawla, S., Bajaj, M., February, M., Agarwal, P., Childs, K., Woldt, E., Bara, R., Goldston, L. A., Barks, J., Christensen, M., Wiggins, S., White, D., Eunice Kennedy Shriver Natl Inst, Human Dev Neonatal Res Network 2019; 128: 48?54

  View details for DOI 10.1016/j.earlhumdev.2018.11.007

  View details for Web of Science ID 000458094300008

• Neurodevelopmental Outcomes of Preterm Infants With Retinopathy of Prematurity by Treatment. Pediatrics Natarajan, G., Shankaran, S., Nolen, T. L., Sridhar, A., Kennedy, K. A., Hintz, S. R., Phelps, D. L., DeMauro, S. B., Carlo, W. A., Gantz, M. G., Das, A., Greenberg, R. G., Younge, N. E., Bliss, J. M., Seabrook, R., Sánchez, P. J., Wyckoff, M. H., Bell, E. F., Vohr, B. R., Higgins, R. D. 2019

  Abstract

  Among extremely preterm infants, we evaluated whether bevacizumab therapy compared with surgery for retinopathy of prematurity (ROP) is associated with adverse outcomes in early childhood.This study was a retrospective analysis of prospectively collected data on preterm (22-26 + 6/7 weeks' gestational age) infants admitted to the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network centers who received bevacizumab or surgery exclusively for ROP. The primary outcome was death or severe neurodevelopmental impairment (NDI) at 18 to 26 months' corrected age (Bayley Scales of Infant and Toddler Development, Third Edition cognitive or motor composite score <70, Gross Motor Functional Classification Scale level ?2, bilateral blindness or hearing impairment).The cohort (N = 405; 214 [53%] boys; median [interquartile range] gestational age: 24.6 [23.9-25.3] weeks) included 181 (45%) infants who received bevacizumab and 224 (55%) who underwent ROP surgery. Infants treated with bevacizumab had a lower median (interquartile range) birth weight (640 [541-709] vs 660 [572.5-750] g; P = .02) and longer durations of conventional ventilation (35 [21-58] vs 33 [18-49] days; P = .04) and supplemental oxygen (112 [94-120] vs 105 [84.5-120] days; P = .01). Death or severe NDI (adjusted odds ratio [aOR] 1.42; 95% confidence interval [CI] 0.94 to 2.14) and severe NDI (aOR 1.14; 95% CI 0.76 to 1.70) did not differ between groups. Odds of death (aOR 2.54 [95% CI 1.42 to 4.55]; P = .002), a cognitive score <85 (aOR 1.78 [95% CI 1.09 to 2.91]; P = .02), and a Gross Motor Functional Classification Scale level ?2 (aOR 1.73 [95% CI 1.04 to 2.88]; P = .04) were significantly higher with bevacizumab therapy.In this multicenter cohort of preterm infants, ROP treatment modality was not associated with differences in death or NDI, but the bevacizumab group had higher mortality and poor cognitive outcomes in early childhood. These data reveal the need for a rigorous appraisal of ROP therapy.

  View details for DOI 10.1542/peds.2018-3537

  View details for PubMedID 31337693

• Individualized Growth Assessment in pregnancies complicated by fetal gastroschisis Sherwin, E. B., Deter, R. L., Lee, W., El-Sayed, Y. Y., Girsen, A. I., Datoc, I. A., Hintz, S. R., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2019: S140?S141

  View details for DOI 10.1016/j.ajog.2018.11.214

  View details for Web of Science ID 000454249400194

• Congenital diaphragmatic hernia-associated neonatal morbidity and mortality based on TOTAL trial severity designation Boissiere, J. C., Anderson, J. N., Girsen, A. I., Hintz, S. R., El-Sayed, Y. Y., Van Meurs, K. P., Sylvester, K. G., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2019: S667?S668

  View details for DOI 10.1016/j.ajog.2018.11.1064

  View details for Web of Science ID 000454249403200

• Obstetric and neonatal outcomes in pregnancies complicated by fetal lung masses: does final histology matter? Anderson, J. N., Girsen, A. I., Hintz, S. R., El-Sayed, Y. Y., Davis, A. S., Barth, R. A., Halabi, S., Sylvester, K. G., Bruzoni, M., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2019: S151

  View details for DOI 10.1016/j.ajog.2018.11.230

  View details for Web of Science ID 000454249400210

• IMPACT OF CARDIAC ALGORITHM ON CYTOGENETIC TESTING Floyd, B. J., Hintz, S. R., Suarez, C. J., Cherry, A., Yu, L., Benitz, W., Priest, J. R., Wright, G. E., Bhombal, S., Davis, A., Chock, V. Y., Weigel, N., Kobayashi, D., Fluharty, B., Stevenson, D. BMJ PUBLISHING GROUP. 2019: 207

  View details for DOI 10.1136/jim-2018-000939.327

  View details for Web of Science ID 000457712500337

• Adrenal function links to early postnatal growth and blood pressure at age 6 in children born extremely preterm. Pediatric research Watterberg, K. L., Hintz, S. R., Do, B., Vohr, B. R., Lowe, J., Newman, J. E., Wallace, D., Lacy, C. B., Davis, E. P., Granger, D. A., Shankaran, S., Payne, A., Higgins, R. D., SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 2018

  Abstract

  BACKGROUND: Low birth weight in term-born individuals correlates with adverse cardiometabolic outcomes; excess glucocorticoid exposure has been linked to these relationships. We hypothesized that cortisol and adrenal androgens would correlate inversely with birthweight and directly with markers of cardiometabolic risk in school-aged children born extremely preterm; further, preterm-born would have increased cortisol and adrenal androgens compared to term-born children.METHODS: Saliva samples were obtained at age 6 from 219 preterm-born children followed since birth and 40 term-born children and analyzed for dehydroepiandrosterone (DHEA) and cortisol. Cortisol was also measured at home (awakening, 30' later, evening).RESULTS: For preterm-born children, cortisol and DHEA correlated inversely with weight and length Z-scores at 36 weeks PMA and positively with systolic BP. DHEA was higher in preterm-born than term-born children (boys p<0.01; girls p=0.04). Cortisol was similar between preterm-born and term-born at study visit; however, preterm-born children showed a blunted morning cortisol. In term-born children, DHEA correlated with BMI (p=0.04), subscapular, and abdominal skinfold thicknesses (both p<0.01).CONCLUSION: Cortisol and DHEA correlated inversely with early postnatal growth and directly with systolic BP in extremely preterm-born children, suggesting perinatal programming. Blunted morning cortisol may reflect NICU stress, as seen after other adverse childhood experiences (ACEs).

  View details for PubMedID 30631138

• Predicting Pathology From Imaging in Children Undergoing Resection of Congenital Lung Lesions. The Journal of surgical research Narayan, R. R., Abadilla, N., Greenberg, D. R., Sylvester, K. G., Hintz, S. R., Barth, R. A., Bruzoni, M. 2018; 236: 68?73

  Abstract

  BACKGROUND: Prenatal magnetic resonance imaging (MRI) is increasingly obtained to define congenital lung lesions (CLL) for surgical management. Postnatal, preoperative computed tomography (CT) provides further clarity at the cost of radiation. Depending on the lesion identified, the indication for resection remains controversial. We investigated the differences in detail found on prenatal MRI and postnatal CT compared with final pathology to determine their utility in preoperative decision-making.MATERIALS AND METHODS: All children undergoing resection of CLLs at a single institution between July 2009 and February 2018 were retrospectively identified. Their imaging, operative, and pathology reports were compared. All imaging studies were examined by pediatric radiologists with experience in prenatal CLL diagnosis.RESULTS: Fifty-five patients underwent CLL resection during the study period with 31 undergoing prenatal MRI, 45 postnatal CT, and 22 both. Resection was performed before 6 mo of age in 62% of patients. In the cohort undergoing both imaging studies, pathologic CLL diagnosis correlated with prenatal MRI and CT in 82% and 100% of patients, respectively (P=0.13). Eight patients had systemic feeding vessels, of which 38% were identified on MRI, and 88% on CT (P=0.13). Both studies had a specificity of 100% for detecting systemic feeding vessels.CONCLUSIONS: For children where prenatal MRI detected a systemic feeding vessel, CT was redundant for preoperative planning but had greater sensitivity. Ultimately, the CLL type predicted from postnatal CT was not significantly different from that predicted by prenatal MRI; however, both imaging modalities had some level of discrepancy with pathology.

  View details for PubMedID 30694781

• Behavioral problems are associated with cognitive and language scores in toddlers born extremely preterm. Early human development Lowe, J. R., Fuller, J. F., Do, B. T., Vohr, B. R., Das, A., Hintz, S. R., Watterberg, K. L., Higgins, R. D., Eunice Kennedy Shriver National Institute of Child Health, Human Development Neonatal Research Network 2018; 128: 48?54

  Abstract

  OBJECTIVE: To evaluate the relationship of parent-reported child behaviors on the Child Behavior Checklist (CBCL) to cognition, language, and motor skills on the Bayley Scales of Infant and Toddler Development - III (Bayley-III) in toddlers born extremely preterm.STUDY DESIGN: Toddlers born extremely preterm (gestational ages 22 0/7 to 26 6/7?weeks) were tested at 22-26?months corrected age with Bayley-III while parents completed the CBCL. Socio-demographic variables and medical history were recorded. Linear regression models were used to assess the relationship of Bayley-III cognitive, motor, and language scores with CBCL scores, adjusting for medical and socio-demographic factors.RESULTS: Internalizing, affective, and pervasive development problem behavior scores on the CBCL correlated significantly with lower Bayley-III cognitive, language, and motor scores on unadjusted and adjusted analyses. Although externalizing and anxiety problems were significantly associated with cognitive and language scores on unadjusted analysis, the relationships were not significant after adjusting for socio-economic factors. CBCL scores were similar for boys and girls, with the exception of the pervasive developmental problem scale; boys had significantly more problems than girls (p?=?0.02).CONCLUSIONS: This study showed that parent reported behavior problems were related to lower cognitive, language, and motor development in toddlers born extremely preterm. Early findings of behavioral problems in toddlers born extremely premature may help identify children at greater risk for later learning difficulties. Adding a measure of behavior to the evaluation of these children may help better understand factors that can contribute to delays, especially in cognition and language.

  View details for PubMedID 30522091

• Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly JOURNAL OF PERINATOLOGY Katz, J. A., Chock, V. Y., Davis, A. S., Blumenfeld, Y. J., Hahn, J. S., Barnes, P., Barth, R. A., Rubesova, E., Hintz, S. R. 2018; 38 (11): 1444?52

  View details for DOI 10.1038/s41372-018-0208-6

  View details for Web of Science ID 000449174800002

• Behavioral Deficits at 18-22 Months of Age Are Associated with Early Cerebellar Injury and Cognitive and Language Performance in Children Born Extremely Preterm. The Journal of pediatrics Duncan, A. F., Bann, C. M., Dempsey, A., Peralta-Carcelen, M., Hintz, S., Eunice Kennedy Shriver National Institute of Child Health and Development Neonatal Research Network, Jobe, A. H., Caplan, M. S., Laptook, A. R., Vohr, B. R., Oh, W., Hensman, A. M., Alksninis, B., Andrews, D., Angela, K., Barnett, S., Cashore, B., Caskey, M., Francis, K., Gingras, D., Johnson, K., Leach, T. M., Stephens, B. E., Watson, V. E., Walsh, M. C., Fanaroff, A. A., Newman, N. S., Wilson-Costello, D. E., Siner, B. S., Zadell, A., DiFiore, J., Bhola, M., Friedman, H. G., Yalcinkaya, G., Bulas, D., Goldberg, R. N., Cotten, C. M., Goldstein, R. F., Ashley, P., Auten, K. J., Fisher, K. A., Foy, K. A., Freedman, S. F., Gustafson, K. E., Lohmeyer, M. B., Malcolm, W. F., Wallace, D. K., Carlton, D. P., Stoll, B. J., Adams-Chapman, I., Buchter, S., Piazza, A. J., Carter, S., Fritz, S., Hale, E. C., Hutchinson, A. K., LaRossa, M. M., Higgins, R. D., Archer, S. W., Sokol, G. M., Poindexter, B. B., Dusick, A. M., Lemons, J. A., Wilson, L. D., Hamer, F., Cook, A. B., Herron, D. E., Lytle, C., Minnich, H. M., Berberich, M. A., Blaisdell, C. J., Gail, D. B., Kiley, J. P., Das, A., Gantz, M. G., Newman, J. E., Cheng, H., Hastings, B. K., McClure, E. M., Auman, J. O., Huitema, C. P., Poole, W. K., Pickett, J. W., Wallace, D., Wrage, L. A., Zaterka-Baxter, K. M., Van Meurs, K. P., Stevenson, D. K., Ball, M. B., Barnes, P. D., Bentley, B., Bruno, E. F., DeAnda, M. E., DeBattista, A. M., Kohn, J. G., Proud, M. S., Pyle, R. P., Weiss, H. E., Frantz, I. D., Fiascone, J. M., McGowan, E. C., Furey, A., MacKinnon, B. L., Nylen, E., Brussa, A., Sibley, C., Carlo, W. A., Ambalavanan, N., Collins, M. V., Cosby, S. S., Phillips, V. A., Bailey, K. J., Biasini, F. J., Hopkins, M., Johnston, K. C., Nelson, K. G., Patterson, C. S., Rector, R. V., Rodriguez, L., Soong, A., Whitley, S., York, S., Finer, N. N., Rasmussen, M. R., Wozniak, P. R., Vaucher, Y. E., Rich, W., Arnell, K., Barbieri-Welge, R., Ben-Tall, A., Bridge, R., Demetrio, C., Fuller, M. G., Ito, E., Lukasik, M., Pontillo, D., Posin, D., Runyan, C., Wilkes, J., Zlotnik, P., Bell, E. F., Widness, J. A., Acarregui, M. J., Klein, J. M., Colaizy, T. T., Johnson, K. J., Eastman, D. L., Duara, S., Bauer, C. R., Everett-Thomas, R., Calejo, M., Diaz, A. N., Frade Eguaras, S. M., Garcia, A., Hamlin-Smith, K., Berkowits, M. H., Hiriart-Fajardo, S., Mathews, E. O., Pierre, H., Riguard, A., Stroerger, A., Watterberg, K. L., Ohls, R. K., Fuller, J., Rohr, J., Lacy, C. B., Lowe, J., Montman, R., Brown, S., Laroia, N., Phelps, D. L., Myers, G. J., Markowitz, G. D., Reubens, L. J., Hust, D., Augostino, L., Johnson, J. B., Burnell, E., Gelbard, H., Jensen, R. L., Kushner, E., Merzbach, J., Mink, J., Torres, C., Wang, D., Yost, K., Sanchez, P. J., Rosenfeld, C. R., Salhab, W. A., Heyne, R. J., Adams, S. S., Allen, J., Grau, L., Guzman, A., Hensley, G., Heyne, E. T., Hickman, J. F., Leps, M. H., Madden, L. A., Martin, M., Miller, N. A., Morgan, J. S., Solis, A., Torres, L. E., Boatman, C. T., Vasil, D. M., Kennedy, K. A., Tyson, J. E., Evans, P. W., Akpa, E. G., Alaniz, N. I., Harris, B. F., Green, C., Jiminez, M., Lis, A. E., Martin, S., McDavid, G. E., Morris, B. H., Poundstone, M. L., Reddoch, S., Siddiki, S., Pierce Tate, P. L., Wright, S. L., Yoder, B. A., Faix, R. G., Baker, S., Bird, K., Bullwinkle, A. E., Burnett, J., Cole, L., Osborne, K. A., Spencer, C., Steele, R. E., Steffen, M., Weaver-Lewis, K., O'Shea, T. M., Dillard, R. G., Washburn, L. K., Peters, N. J., Jackson, B. G., Chiu, K., Allred, D. E., Goldstein, D. J., Halfond, R., Peterson, C., Waldrep, E. L., Welch, C. D., Morris, M. W., Hounshell, G. W., Shankaran, S., Sood, B. G., Slovis, T. L., Pappas, A., Bara, R., Billian, E., Goldston, L. A., Johnson, M. 2018

  Abstract

  OBJECTIVE: To investigate associations in toddlers born extremely preterm (<28weeks) between neonatal neuroimaging and 18- to 22-month developmental and behavioral outcomes.STUDY DESIGN: Cohort analysis from the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Surfactant Positive Airway Pressure and Pulse Oximetry Trial Neuroimaging and Neurodevelopmental Outcomes Study of infants born extremely preterm. Subjects underwent cranial ultrasonography and near-term magnetic resonance imaging (MRI). At 18-22 months of corrected age, the assessment included the Brief Infant Toddler Social Emotional Assessment (BITSEA) Problem and Competence Scale scores and the Bayley Scales of Infant Development, Third Edition (Bayley-III). The BITSEA Problem Scale assesses dysregulation; the Competence Scale assesses social-emotional competence. We examined associations of Problem and Competence scores and positive screen rates with cranial ultrasonography and near-term MRI. Mean BITSEA and Bayley-III scores were compared using ANOVA and positive screen rates with the chi2 test. We computed correlations between BITSEA and Bayley-III scores.RESULTS: Of the 397 children, positive BITSEA screens were found in 34% for the Problem score and 26% for the Competence score. Presence of lesions on near-term MRI that included cerebellar lesions were significantly associated with lower BITSEA Competence but not with Problem scores; Competence scores were inversely related to the presence/significance of lesions. Positive screens on Competence scores and on both Competence and Problem scores were significantly associated with Bayley-III cognitive and language scores <85 (P<.001).CONCLUSIONS: Social-emotional competence contributes to deficits in cognitive and language development. Presence of injury on near-term MRI that includes cerebellar lesions is associated with later social-emotional competence and may be a useful predictor to guide early assessment and intervention.TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063 and NCT00233324.

  View details for PubMedID 30292492

• Prolonged respiratory support of any type impacts outcomes of extremely low birth weight infants PEDIATRIC PULMONOLOGY Zhang, H., Dysart, K., Kendrick, D. E., Li, L., Das, A., Hintz, S. R., Vohr, B. R., Stoll, B. J., Higgins, R. D., Nelin, L., Carlton, D. P., Walsh, M. C., Kirpalani, H., Eunice Kennedy Shriver Natl Inst 2018; 53 (10): 1447?55

  Abstract

  This study tested the hypothesis that longer duration of any type of respiratory support is associated with an increased rate of death or neurodevelopmental impairment (NDI) at 18-22 months.Retrospective cohort study using the Generic Database of NICHD Neonatal Research Network from 2006 to 2010. Infants were born at <27 weeks gestational age with birth weights of 401-1000?g. Respiratory support received during initial hospitalization from birth was characterized as follows: no support, only invasive support, only non-invasive support or mixed invasive, and non-invasive support. The primary outcome was death after 24?h of life or NDI at 18-22 months corrected age.In a cohort of 3651 infants, 1494 (40.9%) died or had NDI. Cumulative respiratory support of any type beyond 60 days was associated with the likelihood of death or NDI. Infants who only received invasive support had the highest rate (89.1%), followed by those received mixed support (26.1%). Infants who received only non-invasive support had the lowest rate (7.7%). When compared to the only non-invasive support group, both invasive [OR 62.7 (95%CI 25.7, 152.6)] and mixed [OR 6.1 (95%CI 2.6, 14.4)] support groups were significantly more likely to die or have NDI.Prolonged respiratory support, whether invasive or non-invasive, is associated with increased odds of a poor outcome. The proportion of infants with a poor outcome increased in a dose dependent manner by two factors: the cumulative duration of respiratory support beyond 60 days, and the extent to which invasive support is provided.

  View details for PubMedID 30062831

• Stillbirth and Live Birth at Periviable Gestational Age: A Comparison of Prevalence and Risk Factors. American journal of perinatology Carmichael, S. L., Blumenfeld, Y. J., Mayo, J. A., Profit, J., Shaw, G. M., Hintz, S. R., Stevenson, D. K. 2018

  Abstract

  OBJECTIVE: We compared the prevalence of and risk factors for stillbirth and live birth at periviable gestational age (20-25 weeks).STUDY DESIGN: This is a cohort study of 2.5 million singleton births in California from 2007 to 2011. We estimated racial-ethnic prevalence ratios and used multivariable logistic regression for risk factor comparisons.RESULTS: In this study, 42% of deliveries at 20 to 25 weeks' gestation were stillbirths, and 22% were live births who died within 24 hours. The prevalence of delivery at periviable gestation was 3.4 per 1,000 deliveries among whites, 10.9 for blacks, 3.5 for Asians, and 4.4 for Hispanics. Nonwhite race-ethnicity, lower education, uninsured status, being U.S. born, older age, obesity, smoking, pre-pregnancy hypertension, nulliparity, interpregnancy interval, and prior preterm birth or stillbirth were all associated with increased risk of both stillbirth and live birth at 20 to 25 weeks' gestation, compared with delivery of a live birth at 37 to 41 weeks.CONCLUSION: Inclusion of stillbirths and live births in studies of deliveries at periviable gestations is important.

  View details for PubMedID 30208499

• Extreme Preterm Infant Rates of Overweight and Obesity at School Age in the SUPPORT Neuroimaging and Neurodevelopmental Outcomes Cohort. The Journal of pediatrics Vohr, B. R., Heyne, R., Bann, C. M., Das, A., Higgins, R. D., Hintz, S. R., Eunice Kennedy Shriver National Institute of Child Health, a. D., Jobe, A. H., Caplan, M. S., Polin, R. A., Laptook, A. R., Hensman, A. M., McGowan, E. C., Vieira, E., Little, E., Johnson, K., Alksninis, B., Keszler, M. L., Knoll, A. M., Leach, T. M., Watson, V. E., Walsh, M. C., Fanaroff, A. A., Wilson-Costello, D. E., Payne, A., Newman, N. S., Taylor, H. G., Siner, B. S., Zadell, A., DiFiore, J., Bhola, M., Friedman, H. G., Yalcinkaya, G., Bulas, D., Goldberg, R. N., Cotten, C. M., Goldstein, R. F., Gustafson, K. E., Ashley, P., Auten, K. J., Fisher, K. A., Foy, K. A., Freedman, S. F., Lohmeyer, M. B., Malcolm, W. F., Wallace, D. K., Carlton, D. P., Stoll, B. J., Adams-Chapman, I., Buchter, S., Piazza, A. J., Carter, Fritz, S., Hale, E. C., Hutchinson, A. K., LaRossa, M. M., Loggins, Y., Bottcher, D., Archer, S. W., Poindexter, B. B., Sokol, G. M., Harmon, H. M., Papile, L., Hines, A. C., Wilson, L. D., Herron, D. E., Smiley, L., Kennedy, K. A., Tyson, J. E., Duncan, A. F., Dempsey, A. G., John, J., Jones, P. M., Lillie, M. L., Siddiki, S., Sperry, D. K., Berberich, M. A., Blaisdell, C. J., Gail, D. B., Kiley, J. P., Wallace, D., Gantz, M. G., Newman, J. E., Auman, J. O., Hammond, J. A., Poole, W. K., Van Meurs, K. P., Stevenson, D. K., DeAnda, M. E., Ball, M. B., Goodlin, G. T., Frantz, I. D., Fiascone, J. M., McGowan, E. C., Furey, A., MacKinnon, B. L., Nylen, E., Brussa, A., Sibley, C., Carlo, W. A., Ambalavanan, N., Peralta-Carcelen, M., Collins, M. V., Cosby, S. S., Phillips, V. A., Bailey, K. J., Biasini, F. J., Hopkins, M., Johnston, K. C., Nelson, K. G., Patterson, C. S., Rector, R. V., Rodriguez, L., Soong, A., Whitley, S., York, S., Guest, K., Smith, L. A., Finer, N. N., Garey, D., Rasmussen, M. R., Wozniak, P. R., Vaucher, Y. E., Fuller, M. G., Akshoomoff, N., Rich, W., Arnell, K., Bridge, R., Bell, E. F., Colaizy, T. T., Widness, J. A., Klein, J. M., Johnson, K. J., Acarregui, M. J., Eastman, D. L., Wilgenbusch, T. L., Watterberg, K. L., Ohls, R. K., Fuller, J., Lowe, J., Rohr, J., Lacy, C. B., Montman, R., Brown, S., Sanchez, P. J., Rosenfeld, C. R., Salhab, W. A., Brion, L., Adams, S. S., Allen, J., Grau, L., Guzman, A., Hensley, G., Heyne, E. T., Hickman, J. F., Leps, M. H., Madden, L. A., Martin, M., Miller, N. A., Morgan, J. S., Solis, A., Lee, L. E., Boatman, C. T., Vasil, D. M., Yoder, B. A., Faix, R. G., Winter, S., Baker, S., Osborne, K. A., Rau, C. A., Cunningham, S., Ford, A., Shankaran, S., Pappas, A., Sood, B. G., Bara, R., Slovis, T. L., Billian, E., Goldston, L. A., Johnson, M. 2018; 200: 132

  Abstract

  OBJECTIVE: To identify rates of overweight (body mass index [BMI] ?85th percentile) and obesity (BMI ?95th percentile) at 6-7 years of age and associated risk factors among extremely preterm infants born at<28 weeks of gestation.STUDY DESIGN: Anthropometrics, blood pressure, and active and sedentary activity levels were prospectively assessed. Three groups were compared, those with a BMI ?85th percentile (overweight or obese for age, height, and sex) and ?95th percentile (obese) vs <85th percentile. Multiple regression analyses estimated the relative risks of BMI ?85th percentile and ?95th percentile associated with perinatal and early childhood factors.RESULTS: Of 388 children, 22% had a BMI of ?85th percentile and 10% were obese. Children with obesity and overweight compared with normal weight children had higher body fat (subscapular skinfold and triceps skinfold >85th percentile), central fat (waist circumference >90th percentile), spent more time in sedentary activity (20.5 vs 18.2 vs 16.7 hours/week), and had either systolic and/or diastolic hypertension (24% vs 26% vs 14%), respectively. Postdischarge weight gain velocities from 36 weeks postmenstrual age to 18 months, and 18 months to 6-7 years were independently associated with a BMI of ?85th percentile, whereas weight gain velocity from 18 months to 6-7 years was associated with obesity.CONCLUSIONS: One in 5 former extremely preterm infants is overweight or obese and has central obesity at early school age. Postdischarge weight gain velocities were associated with overweight and obesity. These findings suggest the obesity epidemic is spreading to the most extremely preterm infants.TRIAL REGISTRATION: ClinicalTrials.gov: NCT00063063 and NCT0000.

  View details for PubMedID 29793869

• Extreme Preterm Infant Rates of Overweight and Obesity at School Age in the SUPPORT Neuroimaging and Neurodevelopmental Outcomes Cohort JOURNAL OF PEDIATRICS Vohr, B. R., Heyne, R., Bann, C. M., Das, A., Higgins, R. D., Hintz, S. R., Eunice Kennedy Shriver Natl Inst, Dev Neonatal Res Network 2018; 200: 132-+

  View details for DOI 10.1016/j.jpeds.2018.04.073

  View details for Web of Science ID 000442390400024

• Utility of prenatal MRI in the evaluation and management of fetal ventriculomegaly. Journal of perinatology : official journal of the California Perinatal Association Katz, J. A., Chock, V. Y., Davis, A. S., Blumenfeld, Y. J., Hahn, J. S., Barnes, P., Barth, R. A., Rubesova, E., Hintz, S. R. 2018

  Abstract

  OBJECTIVE: Fetal ventriculomegaly may occur in isolation or as part of a broader syndrome. We aimed to determine the added value of magnetic resonance imaging (MRI) for informing the pre-natal and postnatal care of pregnancies complicated by ventriculomegaly (VM).STUDY DESIGN: Retrospective analysis of all cases of prenatally diagnosed VM referred to the fetal center at Lucile Packard Children's Hospital Stanford 1/1/2009-6/1/2014 were reviewed. Ultrasound (US) and MRI findings were reviewed, and the added yield of MRI evaluated.RESULTS: A total of 91 cases of fetal VM were identified and 74 (81%) underwent MRI. In 62/74 (84%) cases, additional CNS or non-CNS findings, not seen on US, were discovered on MRI, of which 58 were CNS-related. Forty-six (62%) of the additional findings were considered clinically relevant, of which 45 were CNS-related.CONCLUSION: Fetal MRI identifies additional, clinically relevant CNS and non-CNS findings in a majority of cases of VM following initial US.

  View details for PubMedID 30158676

• High Blood Pressure at Early School Age Among Extreme Preterms PEDIATRICS Vohr, B. R., Heyne, R., Bann, C., Das, A., Higgins, R. D., Hintz, S. R., Eunice Kennedy Shriver Natl Inst 2018; 142 (2)

  Abstract

  Former preterm infants are at increased risk of hypertension with increasing age. Our objective was to identify rates of high blood pressure (BP) (?90th percentile) and hypertension (BP ?95th percentile) and associated risk factors among extreme preterm (EPT) infants at 6 to 7 years of age.Assessment included BP and anthropometrics. Comparisons were made by BP ?90th versus <90th percentile. Regressions were run to identify relative risk (RR) of factors associated with BP ?90th percentile.Among 379 EPT infants, 20.6% had systolic high BP, 10.8% systolic hypertension, 21.4% diastolic high BP, and 11.4% diastolic hypertension. Children with systolic high BP had higher rates of BMI, triceps skinfolds >85th percentile, and waist circumference >90th percentile. In regression analyses, weight gain velocity from 18 months to school age (RR = 1.36), and maternal gestational diabetes (MGD) (RR = 2.04) predicted systolic and either systolic and/or diastolic high BP (RR = 1.27 and RR = 1.67). Among children with BMI <85th percentile, 17% had systolic and 19% had diastolic high BP. Regression analysis for normal weight children indicated public insurance (RR = 2.46) and MGD (RR = 2.16) predicted systolic high BP, and MGD (RR = 2.08) predicted either systolic or diastolic high BP.Both overweight and normal weight EPT children are at risk for high BP and hypertension. Public insurance, MGD, and weight gain velocity are risk factors. Findings of high BP among EPT children at early school age are worrisome and indicate a need for close follow-up.

  View details for PubMedID 30054344

• Association between sedation-analgesia and neurodevelopment outcomes in neonatal hypoxic-ischemic encephalopathy JOURNAL OF PERINATOLOGY Natarajan, G., Shankaran, S., Laptook, A. R., McDonald, S. A., Pappas, A., Hintz, S. R., Das, A., NICHD Neonatal Res Network NRN Who 2018; 38 (8): 1060?67

  Abstract

  To evaluate the association between sedation-analgesia (SA) during initial 72?h and death/disability at 18 months of age in neonatal hypoxic-ischemic encephalopathy (HIE).This was a secondary analysis of the NICHD therapeutic hypothermia (TH) randomized controlled trial in moderate or severe HIE. Receipt of SA and anticonvulsant medications at five time points were considered: prior to and at baseline, 24, 48, and 72?h of TH or normothermia. Disability was defined as mental developmental index <85, cerebral palsy, blindness, hearing impairment, or Gross Motor Function Classification System 2-5.Of the 208 RCT participants, 38 (18%) infants had no exposure to SA or anticonvulsants at any of the five time points, 20 (10%) received SA agents only, 81 (39%) received anticonvulsants only, and 69 (33%) received both SA and anticonvulsants. SA category drugs were not administered in 57% of infants while 18% received SA at ?3 time points; 72% infants received anticonvulsants during 72?h of intervention. At 18 months of age, disability among survivors and death/disability was more frequent in the groups receiving anticonvulsants, with (48 and 65%) or without (37 and 58%) SA, compared to groups with no exposure (14 and 34%) or SA (13 and 32%) alone. Severe HIE (aOR 3.60; 1.59-8.13), anticonvulsant receipt (aOR 2.48; 1.05-5.88), and mechanical ventilation (aOR 7.36; 3.15-17.20) were independently associated with 18-month death/disability, whereas TH (aOR 0.28; 0.13-0.60) was protective. SA exposure showed no association with outcome.The risk benefits of SA in HIE need further investigation.

  View details for PubMedID 29795315

  View details for PubMedCentralID PMC6092226

• Preterm Neuroimaging and School-Age Cognitive Outcomes PEDIATRICS Hintz, S. R., Vohr, B. R., Bann, C. M., Taylor, H., Das, A., Gustafson, K. E., Yolton, K., Watson, V. E., Lowe, J., DeAnda, M., Ball, M., Finer, N. N., Van Meurs, K. P., Shankaran, S., Pappas, A., Barnes, P. D., Bulas, D., Newman, J. E., Wilson-Costello, D. E., Heyne, R. J., Harmon, H. M., Peralta-Carcelen, M., Adams-Chapman, I., Duncan, A., Fuller, J., Vaucher, Y. E., Colaizy, T. T., Winter, S., McGowan, E. C., Goldstein, R. F., Higgins, R. D., SUPPORT Study Grp Eunice Kennedy S 2018; 142 (1)

  View details for DOI 10.1542/peds.2017-4058

  View details for Web of Science ID 000437262600023

• Preterm Neuroimaging and School-Age Cognitive Outcomes. Pediatrics Hintz, S. R., Vohr, B. R., Bann, C. M., Taylor, H. G., Das, A., Gustafson, K. E., Yolton, K., Watson, V. E., Lowe, J., DeAnda, M. E., Ball, M. B., Finer, N. N., Van Meurs, K. P., Shankaran, S., Pappas, A., Barnes, P. D., Bulas, D., Newman, J. E., Wilson-Costello, D. E., Heyne, R. J., Harmon, H. M., Peralta-Carcelen, M., Adams-Chapman, I., Duncan, A. F., Fuller, J., Vaucher, Y. E., Colaizy, T. T., Winter, S., McGowan, E. C., Goldstein, R. F., Higgins, R. D., SUPPORT study group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network 2018

  Abstract

  BACKGROUND AND OBJECTIVES: Children born extremely preterm are at risk for cognitive difficulties and disability. The relative prognostic value of neonatal brain MRI and cranial ultrasound (CUS) for school-age outcomes remains unclear. Our objectives were to relate near-term conventional brain MRI and early and late CUS to cognitive impairment and disability at 6 to 7 years among children born extremely preterm and assess prognostic value.METHODS: A prospective study of adverse early and late CUS and near-term conventional MRI findings to predict outcomes at 6 to 7 years including a full-scale IQ (FSIQ) <70 and disability (FSIQ <70, moderate-to-severe cerebral palsy, or severe vision or hearing impairment) in a subgroup of Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial enrollees. Stepwise logistic regression evaluated associations of neuroimaging with outcomes, adjusting for perinatal-neonatal factors.RESULTS: A total of 386 children had follow-up. In unadjusted analyses, severity of white matter abnormality and cerebellar lesions on MRI and adverse CUS findings were associated with outcomes. In full regression models, both adverse late CUS findings (odds ratio [OR] 27.9; 95% confidence interval [CI] 6.0-129) and significant cerebellar lesions on MRI (OR 2.71; 95% CI 1.1-6.7) remained associated with disability, but only adverse late CUS findings (OR 20.1; 95% CI 3.6-111) were associated with FSIQ <70. Predictive accuracy of stepwise models was not substantially improved with the addition of neuroimaging.CONCLUSIONS: Severe but rare adverse late CUS findings were most strongly associated with cognitive impairment and disability at school age, and significant cerebellar lesions on MRI were associated with disability. Near-term conventional MRI did not substantively enhance prediction of severe early school-age outcomes.

  View details for PubMedID 29945955

• 17q12 DELETION: A COMMON CAUSE OF KIDNEY AND URINARY TRACT ABNORMALITIES IDENTIFIED PRENATALLY? Hudgins, L., Richardson, A., Homeyer, M., Grimm, P., Blumenfeld, Y., Hintz, S. WILEY. 2018: 1499?1500

  View details for Web of Science ID 000434040600101

• Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease JOURNAL OF PERINATOLOGY Balasundaram, M., Chock, V. Y., Wu, H., Blumenfeld, Y. J., Hintz, S. R. 2018; 38 (6): 658?64

  View details for DOI 10.1038/s41372-018-0093-z

  View details for Web of Science ID 000437240700009

• A Population-Based Analysis of Factors Associated with Timeliness of Surgical Repair among Infants with Myelomeningocele Kancherla, Ma, C., Grant, G., Shaw, G. M., Hintz, S. R., Carmichael, S. L. WILEY. 2018: 804

  View details for Web of Science ID 000433565700166

• An Investigation of Racial-Ethnic Disparities in Location of Delivery, Hospital Transfer, and Survival Among Infants with Congenital Diaphragmatic Hernia Carmichael, S. L., Ma, C., Shaw, G. M., Sylvester, K. G., Hintz, S. R. WILEY. 2018: 801

  View details for Web of Science ID 000433565700161

• Neurodevelopmental Impairment Among Extremely Preterm Infants in the Neonatal Research Network PEDIATRICS Adams-Chapman, I., Heyne, R. J., DeMauro, S. B., Duncan, A. F., Hintz, S. R., Pappas, A., Vohr, B. R., McDonald, S. A., Das, A., Newman, J. E., Higgins, R. D., Follow-Up Study Eunice Kennedy Shr, Human Development Neonatal Res Net 2018; 141 (5)

  Abstract

  Evaluate the spectrum of neurodevelopmental outcome in a contemporary cohort of extremely preterm infants. We hypothesize that the rate of severe neurodevelopmental impairment (NDI) decreases over time.Retrospective analysis of neurodevelopmental outcome of preterm infants ?27 weeks' gestational age (GA) from a Neonatal Research Network center that completed neurodevelopmental follow-up assessments between April 1, 2011, and January 1, 2015. The Bayley Scales of Infant Development-III (BSID III) and a standardized neurosensory examination were performed between 18 and 26 months' adjusted age. Outcome measures were neurologic examination diagnoses, BSID III cognitive and motor scores, sensory impairment, and the composite outcome of NDI, based on the BSID III cognitive score (analyzed by using a cutoff of <85 or <70), BSID III motor score of <70, moderate or severe cerebral palsy (CP), bilateral blindness, and hearing impairment.Two thousand one hundred and thirteen infants with a mean GA of 25.0 ± 1.0 weeks and mean birth weight of 760 ± 154 g were evaluated. The 11% lost to follow-up were less likely to have private insurance, late-onset sepsis, or severe intraventricular hemorrhage. Neurologic examination results were normal in 59%, suspect abnormal in 19%, and definitely abnormal in 22%. Severe CP decreased 43% whereas mild CP increased 13% during the study. The rate of moderate to severe NDI decreased from 21% to 16% when using the BSID III cognitive cutoff of <70 (P = .07) or from 34% to 31% when using the BSID III cognitive cutoff of <85 (P = .67).Extremely preterm children are at risk for NDI. Over time, the rate of moderate to severe NDI did not differ, but the rates of severe CP decreased, and mild CP increased.

  View details for PubMedID 29666163

  View details for PubMedCentralID PMC5914487

• Outcome of Preterm Infants with Transient Cystic Periventricular Leukomalacia on Serial Cranial Imaging Up to Term Equivalent Age JOURNAL OF PEDIATRICS Sarkar, S., Shankaran, S., Barks, J., Do, B. T., Laptook, A. R., Das, A., Ambalavanan, N., Van Meurs, K. P., Bell, E. F., Sanchez, P. J., Hintz, S. R., Wyckoff, M. H., Stoll, B. J., Carlo, W. A., Eunice Kennedy Shriver Natl Inst C 2018; 195: 59-+

  Abstract

  To determine the outcome of preterm infants whose cystic periventricular leukomalacia "disappeared" on serial screening cranial imaging studies.Infants ?26 weeks of gestation born between 2002 and 2012 who had cranial imaging studies at least twice, the most abnormal study at <28 days of age and another closest to 36 weeks, were reviewed. The outcome of late death (after 36 weeks postmenstrual age) or neurodevelopmental impairment (NDI) in surviving infants at 18-26 months corrected age was compared between the infants with no cystic periventricular leukomalacia on both studies and cystic periventricular leukomalacia that disappeared (cystic periventricular leukomalacia at <28 days but not at 36 weeks), persisted (cystic periventricular leukomalacia on both studies), or appeared late (cystic periventricular leukomalacia only at 36 weeks). Predictors of NDI were evaluated by logistic regression.Of 7063 eligible infants, 433 (6.1%) had cystic periventricular leukomalacia. Among the 433 infants with cystic periventricular leukomalacia, cystic periventricular leukomalacia disappeared in 76 (18%), persisted in 87 (20%), and 270 (62%) had late cystic periventricular leukomalacia. Loss to follow-up ranged between 3% and 13%. Death or NDI was more common in infants with disappeared cystic periventricular leukomalacia compared with those with no cystic periventricular leukomalacia (38 of 72 [53%] vs 1776 of 6376 [28%]; OR [95% CI] 2.8 [1.8-4.6]). Disappeared, persistent, and late cystic periventricular leukomalacia were all also independently associated with NDI (OR 1.17, 1.21, and 1.16, respectively).Infants with "disappeared" cystic periventricular leukomalacia are at increased risk of adverse outcome similar to infants with persistent or late cystic periventricular leukomalacia.

  View details for PubMedID 29398046

• Predictors of poor neonatal outcomes in prenatally diagnosed multicystic dysplastic kidney disease. Journal of perinatology : official journal of the California Perinatal Association Balasundaram, M., Chock, V. Y., Wu, H. Y., Blumenfeld, Y. J., Hintz, S. R. 2018

  Abstract

  OBJECTIVE: Multicystic dysplastic kidney (MCDK) is one of the most common anomalies detected by prenatal ultrasound. Our objective was to identify factors associated with severe adverse neonatal outcomes of prenatally diagnosed MCDK STUDY DESIGN: A retrospective review of prenatally diagnosed MCDK (1 January 2009 to 30 December 2014) from a single academic center was conducted. The primary outcome was death or need for dialysis among live-born infants. Associations between prenatal characteristics and outcome were analyzed by Fisher's exact test and Mann-Whitney test.RESULTS: A total of 53 cases of prenatally suspected MCDK were included, of which 46 cases were live-born and confirmed postnatally (38 survivors, 8 non-survivors). Prenatally diagnosed extrarenal anomalies, bilateral MCDK, contralateral renal anomalies, and anhydramnios were significantly associated with death or need for dialysis (all p<0.0001).CONCLUSIONS: Prenatally identified findings are associated with adverse neonatal outcome, and can guide counseling and management planning. In the absence of significant associated findings, prenatally diagnosed unilateral MCDK has a benign neonatal course.

  View details for PubMedID 29572458

• Noninvasive Prenatal Diagnosis of Single-Gene Disorders by Use of Droplet Digital PCR CLINICAL CHEMISTRY Camunas-Soler, J., Lee, H., Hudgins, L., Hintz, S. R., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2018; 64 (2): 336?45

  View details for DOI 10.1373/clinchem.2017.278101

  View details for Web of Science ID 000424396200017

• Imaging before 24 weeks gestation can predict neonatal respiratory morbidity in pregnancies complicated by fetal lung masses Sherwin, K., Girsen, A. I., Halabi, S. S., Spiegel, A. M., Lee, C. J., Hintz, S. R., El-Sayed, Y. Y., Barth, R. A., Blumenfeld, Y. J. MOSBY-ELSEVIER. 2018: S287?S288

  View details for Web of Science ID 000422946900478

• PRENATALLY IDENTIFIED KIDNEY AND URINARY TRACT ABNORMALITIES IN 17Q12 DELETION Bodle, E. E., Richardson, A., Homeyer, M., Hintz, S. R., Grimm, P. C., Blumenfeld, Y., Mcdougall, C., Zackai, E., Hudgins, L. BMJ PUBLISHING GROUP. 2018: 141?42

  View details for DOI 10.1136/jim-2017-000663.181

  View details for Web of Science ID 000432007400193

• Neurodevelopmental and Behavioral Outcomes in Extremely Premature Neonates With Ventriculomegaly in the Absence of Periventricular-Intraventricular Hemorrhage JAMA PEDIATRICS Pappas, A., Adams-Chapman, I., Shankaran, S., McDonald, S. A., Stoll, B. J., Laptook, A. R., Carlo, W. A., Van Meurs, K. P., Hintz, S. R., Carlson, M. D., Brumbaugh, J. E., Walsh, M. C., Wyckoff, M. H., Das, A., Higgins, R. D., Eunice Kennedy Shriver Nat 2018; 172 (1): 32?42

  View details for DOI 10.1001/jamapediatrics.2017.3545

  View details for Web of Science ID 000419144300013

• Noninvasive Prenatal Diagnosis of Single-Gene Disorders by Use of Droplet Digital PCR. Clinical chemistry Camunas-Soler, J., Lee, H., Hudgins, L., Hintz, S. R., Blumenfeld, Y. J., El-Sayed, Y. Y., Quake, S. R. 2018; 64 (2): 336?45

  Abstract

  Prenatal diagnosis in pregnancies at risk of single-gene disorders is currently performed using invasive methods such as chorionic villus sampling and amniocentesis. This is in contrast with screening for common aneuploidies, for which noninvasive methods with a single maternal blood sample have become standard clinical practice.We developed a protocol for noninvasive prenatal diagnosis of inherited single-gene disorders using droplet digital PCR from circulating cell-free DNA (cfDNA) in maternal plasma. First, the amount of cfDNA and fetal fraction is determined using a panel of TaqMan assays targeting high-variability single-nucleotide polymorphisms. Second, the ratio of healthy and diseased alleles in maternal plasma is quantified using TaqMan assays targeting the mutations carried by the parents. Two validation approaches of the mutation assay are presented.We collected blood samples from 9 pregnancies at risk for different single-gene disorders, including common conditions and rare metabolic disorders. We measured cases at risk of hemophilia, ornithine transcarbamylase deficiency, cystic fibrosis, ?-thalassemia, mevalonate kinase deficiency, acetylcholine receptor deficiency, and DFNB1 nonsyndromic hearing loss. We correctly differentiated affected and unaffected pregnancies (2 affected, 7 unaffected), confirmed by neonatal testing. We successfully measured an affected pregnancy as early as week 11 and with a fetal fraction as low as 3.7% (0.3).Our method detects single-nucleotide mutations of autosomal recessive diseases as early as the first trimester of pregnancy. This is of importance for metabolic disorders in which early diagnosis can affect management of the disease and reduce complications and anxiety related to invasive testing.

  View details for PubMedID 29097507

• Neurodevelopmental and Behavioral Outcomes in Extremely Premature Neonates With Ventriculomegaly in the Absence of Periventricular-Intraventricular Hemorrhage. JAMA pediatrics Pappas, A., Adams-Chapman, I., Shankaran, S., McDonald, S. A., Stoll, B. J., Laptook, A. R., Carlo, W. A., Van Meurs, K. P., Hintz, S. R., Carlson, M. D., Brumbaugh, J. E., Walsh, M. C., Wyckoff, M. H., Das, A., Higgins, R. D. 2018; 172 (1): 32?42

  Abstract

  Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood.To characterize the outcomes of extremely preterm neonates younger than 27 weeks' gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks' postmenstrual age.This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks' gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks' postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017.The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes.Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ.Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.

  View details for PubMedID 29181530

• Programmatic and Administrative Barriers to High-Risk Infant Follow-Up Care. American journal of perinatology Tang, B. G., Lee, H. C., Gray, E. E., Gould, J. B., Hintz, S. R. 2018; 35 (10): 940?45

  Abstract

  ?This article characterizes programmatic features of a population-based network of high-risk infant follow-up programs and identifies potential challenges associated with attendance from the providers' perspective.?A web-based survey of high-risk infant follow-up program directors, coordinators, and providers of a statewide high-risk infant follow-up system. Frequencies and percentages were used to describe the survey responses.?Of the 68 high-risk infant follow-up programs in California, 56 (82%) responded to the survey. The first visit no-show rate between 10 and 30% was estimated by 44% of programs with higher no-show rates for subsequent visits. Common strategies to remind families of appointments were phone calls and mailings. Most programs (54%) did not have a strategy to help families who lived distant to the high-risk infant follow-up clinic.?High-risk infant follow-up programs may lack resources and effective strategies to enhance follow-up, particularly for those living at a distance.

  View details for PubMedID 29439282

• Prenatal treatment of ornithine transcarbamylase deficiency. Molecular genetics and metabolism Wilnai, Y., Blumenfeld, Y. J., Cusmano, K., Hintz, S. R., Alcorn, D., Benitz, W. E., Berquist, W. E., Bernstein, J. A., Castillo, R. O., Concepcion, W., Cowan, T. M., Cox, K. L., Lyell, D. J., Esquivel, C. O., Homeyer, M., Hudgins, L., Hurwitz, M., Palma, J. P., Schelley, S., Akula, V. P., Summar, M. L., Enns, G. M. 2018

  Abstract

  Patients with neonatal urea cycle defects (UCDs) typically experience severe hyperammonemia during the first days of life, which results in serious neurological injury or death. Long-term prognosis despite optimal pharmacological and dietary therapy is still poor. The combination of intravenous sodium phenylacetate and sodium benzoate (Ammonul®) can eliminate nitrogen waste independent of the urea cycle. We report attempts to improve outcomes for males with severe ornithine transcarbamylase deficiency (OTCD), a severe X-linked condition, via prenatal intravenous administration of Ammonul and arginine to heterozygous carrier females of OTCD during labor.Two heterozygote OTCD mothers carrying male fetuses with a prenatal diagnosis of OTCD received intravenous Ammonul, arginine and dextrose-containing fluids shortly before birth. Maintenance Ammonul and arginine infusions and high-caloric enteral nutrition were started immediately after birth. Ammonul metabolites were measured in umbilical cord blood and the blood of the newborn immediately after delivery. Serial ammonia and biochemical analyses were performed following delivery.Therapeutic concentrations of Ammonul metabolites were detected in umbilical cord and neonatal blood samples. Plasma ammonia and glutamine levels in the postnatal period were within the normal range. Peak ammonia levels in the first 24-48h were 53mcmol/l and 62mcmol/l respectively. The boys did not experience neurological sequelae secondary to hyperammonemia and received liver transplantation at ages 3months and 5months. The patients show normal development at ages 7 and 3years.Prenatal treatment of mothers who harbor severe OTCD mutations and carry affected male fetuses with intravenous Ammonul and arginine, followed by immediate institution of maintenance infusions after delivery, results in therapeutic levels of benzoate and phenylacetate in the newborn at delivery and, in conjunction with high-caloric enteral nutrition, prevents acute hyperammonemia and neurological decompensation. Following initial medical management, early liver transplantation may improve developmental outcome.

  View details for PubMedID 29396029

• Survival and Neurodevelopmental Outcomes Among Periviable Infants OBSTETRICAL & GYNECOLOGICAL SURVEY Younge, N., Goldstein, R. F., Bann, C. M., Hintz, S. R., Patel, R. M., Smith, P., Bell, E. F., Rysavy, M. A., Duncan, A. F., Vohr, B. R., Das, A., Goldberg, R. N., Higgins, R. D., Cotten, C., Eunice Kennedy Shriver Natl Inst 2017; 72 (7): 401?3

  View details for DOI 10.1097/OGX.0000000000000453

  View details for Web of Science ID 000405330200003

• EXPANDING THE FRAME - OUTCOMES FOLLOWING EXTREMELY PREMATURE BIRTH BEYOND NEURODEVELOPMENTAL IMPAIRMENT Rysavy, M. A., Colaizy, T. T., Bann, C. M., Hintz, S. R., DeMauro, S. B., Duncan, A. F., Vohr, B. R., Peralta-Carcelen, M., Bell, E. F., NICHD Neonatal Research Network WILEY. 2017: 8?9

  View details for Web of Science ID 000405213500008

• Sutureless vs Sutured Gastroschisis Closure: A Prospective Randomized Controlled Trial. Journal of the American College of Surgeons Bruzoni, M., Jaramillo, J. D., Dunlap, J. L., Abrajano, C., Stack, S. W., Hintz, S. R., Hernandez-Boussard, T., Dutta, S. 2017; 224 (6): 1091-1096 e1

  Abstract

  Sutureless gastroschisis repair involves covering the abdominal wall defect with the umbilical cord or a synthetic dressing to allow closure by secondary intention. No randomized studies have described the outcomes of this technique. Our objective was to prospectively compare short-term outcomes of sutureless vs sutured closure in a randomized fashion.We recruited patients who presented with gastroschisis between 2009 and 2014 and were randomized into either sutureless or sutured treatment groups. Patients with complicated gastroschisis (stricture, perforation, and ischemia) were excluded. Predefined ventilation, feeding, and dressing change protocols were instituted. Primary outcomes were time to extubation and time to full feeds. Secondary outcomes included time to discharge and rate of complications. Data were analyzed using Fisher's exact or t-tests using a p value ? 0.05. Factors associated with increased time to discharge were estimated using multivariate analyses.Thirty-nine patients were enrolled, 19 to sutureless and 20 to sutured repair. There was no statistical difference in time to extubation (sutureless 1.89 vs sutured 3.15 days; p = 0.061). The sutureless group had a significant increase in mean time to full feeds (45.1 vs 27.8 days; p = 0.031) and mean time to discharge (49.3 vs 31.4 days; p = 0.016). Complication rates were similar in both groups. Multivariate regression modeling showed that an increase in time to discharge was independently associated with sutureless repair, feeding complications, and sepsis.Sutureless repair of uncomplicated gastroschisis can be performed safely, however, it is associated with a significant increase in time to full feeds and time to discharge.

  View details for DOI 10.1016/j.jamcollsurg.2017.02.014

  View details for PubMedID 28279777

• Association between small-for-gestational age and neurocognitive impairment at two years of corrected age among infants born at preterm gestational ages: a cohort study. Journal of perinatology Girsen, A. I., Do, S. C., El-Sayed, Y. Y., Hintz, S. R., Blumenfeld, Y. J. 2017

  Abstract

  To investigate the association between small-for-gestational age (SGA) and neurocognitive impairment at 2 years of corrected age among infants born at preterm gestational ages.A secondary analysis of a prospectively conducted NICHD/Maternal-Fetal Medicine Units BEAM trial. Non-anomalous pregnancies delivered before 37 weeks of gestation were included in the analysis. Neurocognitive outcomes at 2 years of corrected age were compared between infants who were SGA (<10% for gestational age) and those appropriately grown (AGA). The primary outcome was a severe or moderate neurocognitive impairment at 2 years of corrected age among survivors, defined as either mental (MDI) or psychomotor (PDI) developmental index score <70 for severe and <85 for moderate impairment.Of 2299 preterm neonates 67 (3%) were SGA. SGA infants were more often twin pregnancies (31% vs 17%, P=0.003) and delivered more often by cesarean section (63% vs 40%, P<0.001) at similar gestational ages (30.0±2.6 vs 29.5±2.8 weeks, P=0.11). At 2 years of corrected age, SGA and AGA survivors had similar rates of neurocognitive impairment (MDI <70: 18% vs 18%, P=1.0; MDI <85: 44% vs 46%, P=0.96; PDI <70: 20% vs 15%, P=0.51; PDI <85: 40% vs 34%, P=0.48).In this cohort, SGA at preterm gestational ages was associated with similar rates of neurocognitive impairment at two years of corrected age among surviving infants.Journal of Perinatology advance online publication, 27 April 2017; doi:10.1038/jp.2017.58.

  View details for DOI 10.1038/jp.2017.58

  View details for PubMedID 28448062

• Utility of third trimester sonographic measurements for predicting SGA in cases of fetal gastroschisis. Journal of perinatology Blumenfeld, Y. J., Do, S., Girsen, A. I., DAVIS, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Shamshirsaz, A. A., Lee, H. C. 2017

  Abstract

  To assess the accuracy of different sonographic estimated fetal weight (EFW) cutoffs, and combinations of EFW and biometric measurements for predicting small for gestational age (SGA) in fetal gastroschisis.Gastroschisis cases from two centers were included. The sensitivity, specificity, positive and negative predictive values (PPV and NPV) were calculated for different EFW cutoffs, as well as EFW and biometric measurement combinations.Seventy gastroschisis cases were analyzed. An EFW<10% had 94% sensitivity, 43% specificity, 33% PPV and 96% NPV for SGA at delivery. Using an EFW cutoff of <5% improved the specificity to 63% and PPV to 41%, but decreased the sensitivity to 88%. Combining an abdominal circumference (AC) or femur length (FL) z-score less than -2 with the total EFW improved the specificity and PPV but decreased the sensitivity.A combination of a small AC or FL along with EFW increases the specificity and PPV, but decreases the sensitivity of predicting SGA.Journal of Perinatology advance online publication, 26 January 2017; doi:10.1038/jp.2016.275.

  View details for DOI 10.1038/jp.2016.275

  View details for PubMedID 28125100

• Prediction of neonatal respiratory distress in pregnancies complicated by fetal lung masses. Prenatal diagnosis Girsen, A. I., Hintz, S. R., Sammour, R., Naqvi, A., El-Sayed, Y. Y., Sherwin, K., Davis, A. S., Chock, V. Y., Barth, R. A., Rubesova, E., Sylvester, K. G., Chitkara, R., Blumenfeld, Y. J. 2017

  Abstract

  The objective of this article is to evaluate the utility of fetal lung mass imaging for predicting neonatal respiratory distress.Pregnancies with fetal lung masses between 2009 and 2014 at a single center were analyzed. Neonatal respiratory distress was defined as intubation and mechanical ventilation at birth, surgery before discharge, or extracorporeal membrane oxygenation (ECMO). The predictive utility of the initial as well as maximal lung mass volume and congenital pulmonary airway malformation volume ratio by ultrasound (US) and magnetic resonance imaging (MRI) was analyzed.Forty-seven fetal lung mass cases were included; of those, eight (17%) had respiratory distress. The initial US was performed at similar gestational ages in pregnancies with and without respiratory distress (26.4 ± 5.6 vs 22.3 ± 3 weeks, p = 0.09); however, those with respiratory distress had higher congenital volume ratio at that time (1.0 vs 0.3, p = 0.01). The strongest predictors of respiratory distress were maximal volume >24.0 cm(3) by MRI (100% sensitivity, 91% specificity, 60% positive predictive value, and 100% negative predictive value) and maximal volume >34.0 cm(3) by US (100% sensitivity, 85% specificity, 54% positive predictive value, and 100% negative predictive value).Ultrasound and MRI parameters can predict neonatal respiratory distress, even when obtained before 24 weeks. Third trimester parameters demonstrated the best positive predictive value. © 2017 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.5002

  View details for PubMedID 28061000

• Acute Perinatal Sentinel Events, Neonatal Brain Injury Pattern, and Outcome of Infants Undergoing a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy JOURNAL OF PEDIATRICS Shankaran, S., Laptook, A. R., McDonald, S. A., Hintz, S. R., Barnes, P. D., Das, A., Higgins, R. D. 2017; 180: 275-?

  Abstract

  Infants with perinatal sentinel events in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Hypothermia for Encephalopathy Trial had more basal ganglia and thalamus lesions on brain magnetic resonance imaging but similar neurodevelopmental outcomes at 18 months of age than infants without perinatal sentinel events. Outcomes correlated with the neonatal magnetic resonance imaging findings.ClinicalTrials.gov: NCT00005772.

  View details for DOI 10.1016/j.jpeds.2016.09.026

  View details for Web of Science ID 000390028100054

  View details for PubMedCentralID PMC5183477

• PRETERM BIRTH AFTER TREATMENT OF MATERNAL METASTATIC MELANOMA WITH IMMUNOTHERAPEUTICS Niemi, A., Foeller, M. E., Yeaton-Massey, A., Fan, A. C., Winn, V. D., Hintz, S. R. BMJ PUBLISHING GROUP. 2017: 289

  View details for DOI 10.1136/jim-2016-000365.448

  View details for Web of Science ID 000433055100441

• Practices surrounding pulmonary hypertension and bronchopulmonary dysplasia amongst neonatologists caring for premature infants. Journal of perinatology : official journal of the California Perinatal Association Altit, G., Lee, H. C., Hintz, S., Tacy, T. A., Feinstein, J. A., Bhombal, S. 2017

  Abstract

  Pulmonary hypertension (PH) is associated with bronchopulmonary dysplasia (BPD). Screening strategies, a thorough investigation of co-morbidities, and multidisciplinary involvement prior to anti-PH medications have been advocated by recent guidelines. We sought to evaluate current practices of neonatologists caring for premature infants with PH.Electronic survey of American Academy of Pediatrics neonatology members.Among 306 neonatologist respondents, 38% had an institutional screening protocol for patients with BPD; 83% screened at 36 weeks for premature neonates on oxygen/mechanical ventilation. In those practicing more than 5 years, 54% noted increasing numbers of premature infants diagnosed with PH. Evaluation for PH in BPD patients included evaluations for micro-aspiration (41%), airways anomalies (29%), and catheterization (10%). Some degree of acquired pulmonary vein stenosis was encountered in 47%. A majority (90%) utilized anti-PH medications during the neonatal hospitalization.Screening for PH in BPD, and subsequent evaluation and management is highly variable.

  View details for PubMedID 29234146

• Predicting severe pulmonary hypoplasia in lower urinary tract obstruction using fetal lung area Ruano, R., Dunn, T. N., Blumenfeld, Y. J., de la Penha, M. M., Koh, C. J., Angelo, J., Grimm, P., Hintz, S. R., Roth, D. R., Welty, S., Braun, M. C., Belfort, M. A. MOSBY-ELSEVIER. 2017: S102

  View details for Web of Science ID 000414256401103

• Survival and Neurodevelopmental Outcomes among Periviable Infants. New England journal of medicine Younge, N., Goldstein, R. F., Bann, C. M., Hintz, S. R., Patel, R. M., Smith, P. B., Bell, E. F., Rysavy, M. A., Duncan, A. F., Vohr, B. R., Das, A., Goldberg, R. N., Higgins, R. D., Cotten, C. M. 2017; 376 (7): 617-628

  Abstract

  Data reported during the past 5 years indicate that rates of survival have increased among infants born at the borderline of viability, but less is known about how increased rates of survival among these infants relate to early childhood neurodevelopmental outcomes.We compared survival and neurodevelopmental outcomes among infants born at 22 to 24 weeks of gestation, as assessed at 18 to 22 months of corrected age, across three consecutive birth-year epochs (2000-2003 [epoch 1], 2004-2007 [epoch 2], and 2008-2011 [epoch 3]). The infants were born at 11 centers that participated in the National Institute of Child Health and Human Development Neonatal Research Network. The primary outcome measure was a three-level outcome - survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, or death. After accounting for differences in infant characteristics, including birth center, we used multinomial generalized logit models to compare the relative risk of survival without neurodevelopmental impairment, survival with neurodevelopmental impairment, and death.Data on the primary outcome were available for 4274 of 4458 infants (96%) born at the 11 centers. The percentage of infants who survived increased from 30% (424 of 1391 infants) in epoch 1 to 36% (487 of 1348 infants) in epoch 3 (P<0.001). The percentage of infants who survived without neurodevelopmental impairment increased from 16% (217 of 1391) in epoch 1 to 20% (276 of 1348) in epoch 3 (P=0.001), whereas the percentage of infants who survived with neurodevelopmental impairment did not change significantly (15% [207 of 1391] in epoch 1 and 16% [211 of 1348] in epoch 3, P=0.29). After adjustment for changes in the baseline characteristics of the infants over time, both the rate of survival with neurodevelopmental impairment (as compared with death) and the rate of survival without neurodevelopmental impairment (as compared with death) increased over time (adjusted relative risks, 1.27 [95% confidence interval {CI}, 1.01 to 1.59] and 1.59 [95% CI, 1.28 to 1.99], respectively).The rate of survival without neurodevelopmental impairment increased between 2000 and 2011 in this large cohort of periviable infants. (Funded by the National Institutes of Health and others; ClinicalTrials.gov numbers, NCT00063063 and NCT00009633 .).

  View details for DOI 10.1056/NEJMoa1605566

  View details for PubMedID 28199816

• Defining outcomes for high-risk infants: Problems and possibilities SEMINARS IN PERINATOLOGY Hintz, S. R., Hess, R. L. 2016; 40 (8): 495?96

  View details for PubMedID 27842712

• Acute Perinatal Sentinel Events, Neonatal Brain Injury Pattern, and Outcome of Infants Undergoing a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. journal of pediatrics Shankaran, S., Laptook, A. R., McDonald, S. A., Hintz, S. R., Barnes, P. D., Das, A., Higgins, R. D. 2016

  Abstract

  Infants with perinatal sentinel events in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network Hypothermia for Encephalopathy Trial had more basal ganglia and thalamus lesions on brain magnetic resonance imaging but similar neurodevelopmental outcomes at 18 months of age than infants without perinatal sentinel events. Outcomes correlated with the neonatal magnetic resonance imaging findings.ClinicalTrials.gov: NCT00005772.

  View details for DOI 10.1016/j.jpeds.2016.09.026

  View details for PubMedID 27776752

  View details for PubMedCentralID PMC5183477

• Changing definitions of long-term follow-up: Should "long term" be even longer? Seminars in perinatology Hintz, S. R., Newman, J. E., Vohr, B. R. 2016; 40 (6): 398-409

  Abstract

  There have been amazing changes in outcomes of preterm (PT) infants in the past decades. Whereas early studies reported only survival rates, Dr. Julius Hess published the first outcome study of PT infants in Chicago in 1953. Dr. Lubchenco then published the 10-year follow-up of premature infants born in 1947-1953 and identified a 68% handicap rate. As a result of these early studies, the importance of evaluating NICU graduates both for surveillance and as an outcome of trials was recognized. During the 1970s, there was a gradual expansion in the number of follow-up programs in the United States (US) with an increasing number of follow-up studies published. In the 1980s, the importance of multicenter clinical research networks was recognized and the NICHD Neonatal Research Network (NRN) was initiated in 1986. Follow-up protocols, definitions, and outcomes have evolved over the last 30 years and will be reviewed with a focus on NICHD NRN studies.

  View details for DOI 10.1053/j.semperi.2016.05.011

  View details for PubMedID 27417651

• Sutureless vs Sutured Gastroschisis Closure: A Prospective Randomized Controlled Trial Bruzoni, M., Jaramillo, J. D., Abrajano, C., Hintz, S. R., Hernandez-Boussard, T., Dutta, S. ELSEVIER SCIENCE INC. 2016: S91

  View details for DOI 10.1016/j.jamcollsurg.2016.06.181

  View details for Web of Science ID 000393077500152

• Growth Outcomes of Preterm Infants Exposed to Different Oxygen Saturation Target Ranges from Birth. journal of pediatrics Navarrete, C. T., Wrage, L. A., Carlo, W. A., Walsh, M. C., Rich, W., Gantz, M. G., Das, A., Schibler, K., Newman, N. S., Piazza, A. J., Poindexter, B. B., Shankaran, S., Sánchez, P. J., Morris, B. H., Frantz, I. D., Van Meurs, K. P., Cotten, C. M., Ehrenkranz, R. A., Bell, E. F., Watterberg, K. L., Higgins, R. D., Duara, S. 2016; 176: 62-68 e4

  Abstract

  To test whether infants randomized to a lower oxygen saturation (peripheral capillary oxygen saturation [SpO2]) target range while on supplemental oxygen from birth will have better growth velocity from birth to 36 weeks postmenstrual age (PMA) and less growth failure at 36 weeks PMA and 18-22 months corrected age.We evaluated a subgroup of 810 preterm infants from the Surfactant, Positive Pressure, and Oxygenation Randomized Trial, randomized at birth to lower (85%-89%, n = 402, PMA 26 ± 1 weeks, birth weight 839 ± 186 g) or higher (91%-95%, n = 408, PMA 26 ± 1 weeks, birth weight 840 ± 191 g) SpO2 target ranges. Anthropometric measures were obtained at birth, postnatal days 7, 14, 21, and 28; then at 32 and 36 weeks PMA; and 18-22 months corrected age. Growth velocities were estimated with the exponential method and analyzed with linear mixed models. Poor growth outcome, defined as weight <10th percentile at 36 weeks PMA and 18-22 months corrected age, was compared across the 2 treatment groups by the use of robust Poisson regression.Growth outcomes including growth at 36 weeks PMA and 18-22 months corrected age, as well as growth velocity were similar in the lower and higher SpO2 target groups.Targeting different oxygen saturation ranges between 85% and 95% from birth did not impact growth velocity or reduce growth failure in preterm infants.

  View details for DOI 10.1016/j.jpeds.2016.05.070

  View details for PubMedID 27344218

• HDlive imaging of a giant omphalocele. Ultrasound in obstetrics & gynecology Blumenfeld, Y. J., E Milan, K., Rubesova, E., Sylvester, K. G., DAVIS, A. S., Chock, V. Y., Hintz, S. R. 2016; 48 (3): 407-408

  View details for DOI 10.1002/uog.15993

  View details for PubMedID 27299988

• Prenatally Diagnosed Cases of Binder Phenotype Complicated by Respiratory Distress in the Immediate Postnatal Period. Journal of ultrasound in medicine Blumenfeld, Y. J., Davis, A. S., Hintz, S. R., Milan, K., Messner, A. H., Barth, R. A., Hudgins, L., Chueh, J., Homeyer, M., Bernstein, J. A., Enns, G., Atwal, P., Manning, M. 2016; 35 (6): 1353-1358

  Abstract

  Binder phenotype, or maxillonasal dysostosis, is a distinctive pattern of facial development characterized by a short nose with a flat nasal bridge, an acute nasolabial angle, a short columella, a convex upper lip, and class III malocclusion. We report 3 cases of prenatally diagnosed Binder phenotype associated with perinatal respiratory impairment.

  View details for DOI 10.7863/ultra.15.02050

  View details for PubMedID 27162279

• Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis JOURNAL OF MATERNAL-FETAL & NEONATAL MEDICINE Girsen, A. I., Wallenstein, M. B., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Druzin, M. L., Oshiro, B. T., Blumenfeld, Y. J. 2016; 29 (15): 2499-2503

  View details for DOI 10.3109/14767058.2015.1090971

  View details for Web of Science ID 000374775200021

  View details for PubMedID 26445130

• Neonatal Biomarkers of Inflammation: Correlates of Early Neurodevelopment and Gait in Very-Low-Birth-Weight Preterm Children. American journal of perinatology Rose, J., Vassar, R., Cahill-Rowley, K., Hintz, S. R., Stevenson, D. K. 2016; 33 (1): 71?78

  Abstract

  Neonatal biomarkers of inflammation were examined in relation to early neurodevelopment and gait in very-low-birth-weight (VLBW) preterm children. We hypothesized that preterm infants exposed to higher levels of neonatal inflammation would demonstrate lower scores on Bayley Scales of Infant Toddler Development, 3rd ed. (BSID-III) and slower gait velocity at 18 to 22 months adjusted age.A total of 102 VLBW preterm infants (birthweight [BW]???1,500?g, gestational age [GA]???32 weeks) admitted to neonatal intensive care unit [NICU] were recruited. Neonatal risk factors examined were GA at birth, BW, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and serum C-reactive protein (CRP), albumin, and total bilirubin over first 2 postnatal weeks. At 18 to 22 months, neurodevelopment was assessed with BSID-III and gait was assessed with an instrumented mat.Children with neonatal CRP???0.20 mg/dL (n?=?52) versus < 0.20 mg/dL (n?=?37) had significantly lower BSID-III composite cognitive (92.0?±?13.1 vs. 100.1?±?9.6, p?=?0.002), language (83.9?±?16.0 vs. 95.8?±?14.2, p?

  View details for PubMedID 26212060

• Early Conventional MRI for Prediction of Neurodevelopmental Impairment in Extremely-Low-Birth-Weight Infants NEONATOLOGY Slaughter, L. A., Bonfante-Mejia, E., Hintz, S. R., Dvorchik, I., Parikh, N. A. 2016; 110 (1): 47-54

  Abstract

  Extremely-low-birth-weight (ELBW; ?1,000 g) infants are at high risk for neurodevelopmental impairments. Conventional brain MRI at term-equivalent age is increasingly used for prediction of outcomes. However, optimal prediction models remain to be determined, especially for cognitive outcomes.The aim was to evaluate the accuracy of a data-driven MRI scoring system to predict neurodevelopmental impairments.122 ELBW infants had a brain MRI performed at term-equivalent age. Conventional MRI findings were scored with a standardized algorithm and tested using a multivariable regression model to predict neurodevelopmental impairment, defined as one or more of the following at 18-24 months' corrected age: cerebral palsy, bilateral blindness, bilateral deafness requiring amplification, and/or cognitive/language delay. Results were compared with a commonly cited scoring system.In multivariable analyses, only moderate-to-severe gyral maturational delay was a significant predictor of overall neurodevelopmental impairment (OR: 12.6, 95% CI: 2.6, 62.0; p < 0.001). Moderate-to-severe gyral maturational delay also predicted cognitive delay, cognitive delay/death, and neurodevelopmental impairment/death. Diffuse cystic abnormality was a significant predictor of cerebral palsy (OR: 33.6, 95% CI: 4.9, 229.7; p < 0.001). These predictors exhibited high specificity (range: 94-99%) but low sensitivity (30-67%) for the above outcomes. White or gray matter scores, determined using a commonly cited scoring system, did not show significant association with neurodevelopmental impairment.In our cohort, conventional MRI at term-equivalent age exhibited high specificity in predicting neurodevelopmental outcomes. However, sensitivity was suboptimal, suggesting additional clinical factors and biomarkers are needed to enable accurate prognostication.

  View details for DOI 10.1159/000444179

  View details for PubMedID 27050735

• Neonatal Biomarkers of Inflammation: Correlates of Early Neurodevelopment and Gait in Very-Low-Birth-Weight Preterm Children AMERICAN JOURNAL OF PERINATOLOGY Rose, J., Vassar, R., Cahill-Rowley, K., Hintz, S. R., Stevenson, D. K. 2016; 33 (1): 71-78

  Abstract

  Neonatal biomarkers of inflammation were examined in relation to early neurodevelopment and gait in very-low-birth-weight (VLBW) preterm children. We hypothesized that preterm infants exposed to higher levels of neonatal inflammation would demonstrate lower scores on Bayley Scales of Infant Toddler Development, 3rd ed. (BSID-III) and slower gait velocity at 18 to 22 months adjusted age.A total of 102 VLBW preterm infants (birthweight [BW]???1,500?g, gestational age [GA]???32 weeks) admitted to neonatal intensive care unit [NICU] were recruited. Neonatal risk factors examined were GA at birth, BW, bronchopulmonary dysplasia, necrotizing enterocolitis, retinopathy of prematurity, sepsis, and serum C-reactive protein (CRP), albumin, and total bilirubin over first 2 postnatal weeks. At 18 to 22 months, neurodevelopment was assessed with BSID-III and gait was assessed with an instrumented mat.Children with neonatal CRP???0.20 mg/dL (n?=?52) versus < 0.20 mg/dL (n?=?37) had significantly lower BSID-III composite cognitive (92.0?±?13.1 vs. 100.1?±?9.6, p?=?0.002), language (83.9?±?16.0 vs. 95.8?±?14.2, p?

  View details for DOI 10.1055/s-0035-1557106

  View details for Web of Science ID 000367556500010

• Early neurodevelopmental outcomes of extremely preterm infants. Seminars in perinatology Rogers, E. E., Hintz, S. R. 2016; 40 (8): 497?509

  Abstract

  Infants born at extreme preterm gestation are at risk for both death and disability. Although rates of survival have improved for this population, and some evidence suggests a trend toward decreased neuromotor impairment over the past decades, a significant improvement in overall early neurodevelopmental outcome has not yet been realized. This review will examine the rates and types of neurodevelopmental impairment seen after extremely preterm birth, including neurosensory, motor, cognitive, and behavioral outcomes. We focus on early outcomes in the first 18-36 months of life, as the majority of large neonatal studies examining neurodevelopmental outcomes stop at this age. However, this early age is clearly just a first glimpse into lifetime outcomes; the neurodevelopmental effects of extreme prematurity may last through school age, adolescence, and beyond. Importantly, prematurity appears to be an independent risk factor for adverse development, but this population demonstrates considerable variability in the types and severity of impairments. Understanding both the nature and prevalence of neurodevelopmental impairment among extremely preterm infants is important because it can lead to targeted interventions that in turn may lead to improved outcomes.

  View details for PubMedID 27865437

• Effect of antepartum meconium staining on perinatal and neonatal outcomes among pregnancies with gastroschisis. journal of maternal-fetal & neonatal medicine Girsen, A. I., Wallenstein, M. B., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Druzin, M. L., Oshiro, B. T., Blumenfeld, Y. J. 2016; 29 (15): 2500-2504

  Abstract

  To investigate the association between meconium staining and perinatal and neonatal outcomes in pregnancies with gastroschisis.Retrospective analysis of infants with prenatally diagnosed gastroschisis born in two academic medical centers between 2008 and 2013. Neonatal outcomes of deliveries with and without meconium staining were compared. Primary outcome was defined as any of the following: neonatal sepsis, prolonged mechanical ventilation, bowel atresia or death. Secondary outcomes were preterm delivery, preterm-premature rupture of membranes (PPROM) and prolonged hospital length of stay.One hundred and eight infants with gastroschisis were included of which 56 (52%) had meconium staining at delivery. Infants with meconium staining had a lower gestational age at delivery (36.3 (±1.4) versus 37.0 (±1.2) weeks, p?=?0.007), and a higher rate of PPROM (25% versus 8%, p?=?0.03) than infants without meconium. Meconium staining was not significantly associated with the primary composite outcome or with any of its components. After adjustments, meconium staining remained significantly associated with preterm delivery at?<36 weeks [odds ratio OR?=?4.0, 95% confidence intervals (CI): 1.5-11.4] and PPROM (OR?=?3.8, 95%CI: 1.2-14.5).Among infants with gastroschisis, meconium staining was associated with prematurity and PPROM. No significant increase in other adverse neonatal outcomes was seen among infants with meconium staining, suggesting a limited prognostic value of this finding.

  View details for DOI 10.3109/14767058.2015.1090971

  View details for PubMedID 26445130

• Neonatal brain microstructure correlates of neurodevelopment and gait in preterm children 18-22 mo of age: an MRI and DTI study PEDIATRIC RESEARCH Rose, J., Cahill-Rowley, K., Vassar, R., Yeom, K. W., Stecher, X., Stevenson, D. K., Hintz, S. R., Barnea-Goraly, N. 2015; 78 (6): 700-708

  Abstract

  Near-term brain structure was examined in preterm infants in relation to neurodevelopment. We hypothesized that near-term macrostructural brain abnormalities identified using conventional magnetic resonance imaging (MRI), and white matter (WM) microstructure detected using diffusion tensor imaging (DTI), would correlate with lower cognitive and motor development and slower, less-stable gait at 18-22 mo of age.One hundred and two very-low-birth-weight preterm infants (?1,500?g birth weight; ?32?wk gestational age) were recruited prior to routine near-term brain MRI at 36.6?±?1.8?wk postmenstrual age. Cerebellar and WM macrostructure was assessed on conventional structural MRI. DTI was obtained in 66 out of 102 and WM microstructure was assessed using fractional anisotropy and mean diffusivity (MD) in six subcortical brain regions defined by DiffeoMap neonatal atlas. Neurodevelopment was assessed with Bayley-Scales-of-Infant-Toddler-Development, 3rd-Edition (BSID-III); gait was assessed using an instrumented mat.Neonates with cerebellar abnormalities identified using MRI demonstrated lower mean BSID-III cognitive composite scores (89.0?±?10.1 vs. 97.8?±?12.4; P = 0.002) at 18-22 mo. Neonates with higher DTI-derived left posterior limb of internal capsule (PLIC) MD demonstrated lower cognitive and motor composite scores (r = -0.368; P = 0.004; r = -0.354; P = 0.006) at 18-22 mo; neonates with higher genu MD demonstrated slower gait velocity (r = -0.374; P = 0.007). Multivariate linear regression significantly predicted cognitive (adjusted r(2) = 0.247; P = 0.002) and motor score (adjusted r(2) = 0.131; P = 0.017).Near-term cerebellar macrostructure and PLIC and genu microstructure were predictive of early neurodevelopment and gait.

  View details for DOI 10.1038/pr.2015.157

  View details for PubMedID 26322412

• Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy JOURNAL OF PEDIATRICS Shankaran, S., McDonald, S. A., Laptook, A. R., Hintz, S. R., Barnes, P. D., Das, A., Pappas, A., Higgins, R. D. 2015; 167 (5): 987-?

  View details for DOI 10.1016/j.jpeds.2015.08.013

  View details for Web of Science ID 000363550300009

• Prenatal hydrops foetalis associated with infantile free sialic acid storage disease. Journal of obstetrics and gynaecology Chock, V. Y., MILAN, K. E., Folkins, A. K., Hazard, F. K., Bernstein, J. A., Hintz, S. R. 2015; 35 (8): 850-852

  View details for DOI 10.3109/01443615.2015.1017558

  View details for PubMedID 26076308

• Fetofetal Transfusion Syndrome in Monochorionic-Triamniotic Triplets Treated with Fetoscopic Laser Ablation: Report of Two Cases and A Systematic Review. AJP reports Blumenfeld, Y. J., Shamshirsaz, A. A., Belfort, M. A., Hintz, S. R., Moaddab, A., Ness, A., Chueh, J., El-Sayed, Y. Y., Ruano, R. 2015; 5 (2): e153-60

  Abstract

  Objective?This study aims to determine the clinical outcomes of monochorionic-triamniotic (MT) pregnancies complicated by severe fetofetal transfusion undergoing laser photocoagulation. Study Design?We report two cases of MT triplets complicated by fetofetal transfusion syndrome (FFTS) and a systematic review classifying cases into different subtypes: MT with two donors and one recipient, MT with one donor and two recipients, MT with one donor, one recipient, and one unaffected triplet. The number of neonatal survivors was analyzed based on this classification as well as Quintero staging. Results?A total of 26 cases of MT triples complicated by FFTS were analyzed. In 56% of the cases, the FFTS involved all three triplets, 50% of whom had an additional donor and 50% an additional recipient. Among the 24 cases that survived beyond 1?week after the procedure, the average gestational age of delivery was 29.6 weeks, and the average interval from procedure to delivery was 10.1 weeks. The overall neonatal survival rate was 71.7%, with demises occurring equally between donor and recipient triplets. Overall neonatal survival including survival of at least two fetuses occurred with equal frequency between the different groups. Conclusion?Significant neonatal survival can be achieved in most cases of MT triplets with FFTS.

  View details for DOI 10.1055/s-0035-1552931

  View details for PubMedID 26495175

  View details for PubMedCentralID PMC4603872

• Between-Hospital Variation in Treatment and Outcomes in Extremely Preterm Infants OBSTETRICAL & GYNECOLOGICAL SURVEY Rysavy, M. A., Li, L., Bell, E. F., Das, A., Hintz, S. R., Stoll, B. J., Vohr, B. R., Carlo, W. A., Shankaran, S., Walsh, M. C., Tyson, J. E., Cotten, C., Smith, P., Murray, J. C., Colaizy, T. T., Brumbaugh, J. E., Higgins, R. D., Eunice Kennedy Shriver Natl Inst C 2015; 70 (9): 549?51

  View details for DOI 10.1097/01.ogx.0000471596.46762.bf

  View details for Web of Science ID 000361749900003

• Cognitive Outcomes After Neonatal Encephalopathy OBSTETRICAL & GYNECOLOGICAL SURVEY Pappas, A., Shankaran, S., McDonald, S. A., Vohr, B. R., Hintz, S. R., Ehrenkranz, R. A., Tyson, J. E., Yolton, K., Das, A., Bara, R., Hammond, J., Higgins, R. D., Eunice Kennedy Shriver NICHD Neona 2015; 70 (8): 487?88

  View details for DOI 10.1097/OGX.0000000000000232

  View details for Web of Science ID 000360143200005

• Do currently recommended Bayley-III cutoffs overestimate motor impairment in infants born < 27 weeks gestation? JOURNAL OF PERINATOLOGY Duncan, A. F., Bann, C., BOATMAN, C., Hintz, S. R., Vaucher, Y. E., Vohr, B. R., Yolton, K., Heyne, R. J. 2015; 35 (7): 516-521

  Abstract

  To determine whether a Bayley-III motor composite score of 85 may overestimate moderate-severe motor impairment by analyzing Bayley-III motor components and developing cut-point scores for each.Retrospective study of 1183 children born <27 weeks gestation at NICHD Neonatal Research Network centers and evaluated at 18-22 months corrected age. Gross Motor Function Classification System determined gross motor impairment. Statistical analyses included linear and logistic regression and sensitivity/specificity.Bayley-III motor composite scores were strong indicators of gross/fine motor impairment. A motor composite cut-point of 73 markedly improved the specificity for identifying gross and/or fine motor impairment (94% compared with a specificity of 76% for the proposed new cut-point of 85). A Fine Motor Scaled Score <3 differentiated mild from moderate-severe fine motor impairment.This study indicates that a Bayley-III motor composite score of 85 may overestimate impairment. Further studies are needed employing term controls and longer follow-up.

  View details for DOI 10.1038/jp.2014.243

  View details for Web of Science ID 000357059200012

  View details for PubMedID 25634519

  View details for PubMedCentralID PMC4531094

• Between-Hospital Variation in Treatment and Outcomes in Extremely Preterm Infants NEW ENGLAND JOURNAL OF MEDICINE Rysavy, M. A., Li, L., Bell, E. F., Das, A., Hintz, S. R., Stoll, B. J., Vohr, B. R., Carlo, W. A., Shankaran, S., Walsh, M. C., Tyson, J. E., Cotten, C. M., Smith, P. B., Murray, J. C., Colaizy, T. T., Brumbaugh, J. E., Higgins, R. D. 2015; 372 (19): 1801-1811

  Abstract

  Between-hospital variation in outcomes among extremely preterm infants is largely unexplained and may reflect differences in hospital practices regarding the initiation of active lifesaving treatment as compared with comfort care after birth.We studied infants born between April 2006 and March 2011 at 24 hospitals included in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Data were collected for 4987 infants born before 27 weeks of gestation without congenital anomalies. Active treatment was defined as any potentially lifesaving intervention administered after birth. Survival and neurodevelopmental impairment at 18 to 22 months of corrected age were assessed in 4704 children (94.3%).Overall rates of active treatment ranged from 22.1% (interquartile range [IQR], 7.7 to 100) among infants born at 22 weeks of gestation to 99.8% (IQR, 100 to 100) among those born at 26 weeks of gestation. Overall rates of survival and survival without severe impairment ranged from 5.1% (IQR, 0 to 10.6) and 3.4% (IQR, 0 to 6.9), respectively, among children born at 22 weeks of gestation to 81.4% (IQR, 78.2 to 84.0) and 75.6% (IQR, 69.5 to 80.0), respectively, among those born at 26 weeks of gestation. Hospital rates of active treatment accounted for 78% and 75% of the between-hospital variation in survival and survival without severe impairment, respectively, among children born at 22 or 23 weeks of gestation, and accounted for 22% and 16%, respectively, among those born at 24 weeks of gestation, but the rates did not account for any of the variation in outcomes among those born at 25 or 26 weeks of gestation.Differences in hospital practices regarding the initiation of active treatment in infants born at 22, 23, or 24 weeks of gestation explain some of the between-hospital variation in survival and survival without impairment among such patients. (Funded by the National Institutes of Health.).

  View details for DOI 10.1056/NEJMoa1410689

  View details for PubMedID 25946279

• Serial aEEG recordings in a cohort of extremely preterm infants: feasibility and safety JOURNAL OF PERINATOLOGY Davis, A. S., Gantz, M. G., Do, B., Shankaran, S., Hamrick, S. E., Kennedy, K. A., TYSON, J. E., Chalak, L. F., Laptook, A. R., Goldstein, R. F., Hintz, S. R., Das, A., Higgins, R. D., Ball, M. B., HALE, E. C., Van Meurs, K. P. 2015; 35 (5): 373-378

  Abstract

  Objective:Amplitude-integrated electroencephalography (aEEG) monitoring is increasing in the neonatal population, but the safety and feasibility of performing aEEG in extremely preterm infants have not been systematically evaluated.Study Design:Inborn infants 23(0/7) to 28(6/7) weeks gestation or birth weight 401 to 1000?g were eligible. Serial, 6-h aEEG recordings were obtained from first week of life until 36 weeks postmenstrual age. Adverse events were documented, and surveys evaluated the impact of the aEEGs on routine care. Success of performing aEEGs according to protocol and aEEG quality were assessed.Result:A total of 102 infants were enrolled, with 755 recordings performed. 83% of recordings were performed according to schedule, and 96% were without adverse event. Bedside nurses reported no interference with routine care for 89% of recordings. 92% of recordings had acceptable signal quality.Conclusion:Serial aEEG monitoring is safe in preterm infants, with few adverse events and general acceptance by nursing staff.Journal of Perinatology advance online publication, 4 December 2014; doi:10.1038/jp.2014.217.

  View details for DOI 10.1038/jp.2014.217

  View details for PubMedID 25474559

• Peripartum and neonatal outcomes of small- for- gestational- age infants with gastroschisis PRENATAL DIAGNOSIS Girsen, A. I., Do, S., Davis, A. S., Hintz, S. R., Desai, A. K., Mansour, T., Merritt, T. A., Oshiro, B. T., El-Sayed, Y. Y., Blumenfeld, Y. J. 2015; 35 (5): 477-482

  Abstract

  Neonates with gastroschisis are often small-for-gestational-age (SGA) based on population nomograms. Our objective was to evaluate the effect of SGA on perinatal and neonatal outcomes in cases of gastroschisis.Retrospective study of neonates with prenatally diagnosed gastroschisis from two academic centers between 2008-13. Perinatal and neonatal outcomes of neonates with SGA at birth were compared with appropriate for gestational age (AGA) neonates. The primary composite outcome was defined as any of: neonatal sepsis, short bowel syndrome at discharge, prolonged mechanical ventilation (upper quartile for the cohort), bowel atresia, or death.We identified 112 cases of gastroschisis, 25 of whom (22%) were SGA at birth. There were no differences in adverse peripartum outcomes between SGA and AGA infants. No difference was found in the primary composite neonatal outcome (52% vs. 36%, p=0.21), but SGA infants were more likely to have prolonged mechanical ventilation (44% vs. 22%, p=0.04) and prolonged LOS (52% vs. 22%, p=0.007). After adjusting for GA at delivery, SGA remained associated with prolonged LOS (OR=4.3, CI:1.6 - 11.8).Among infants with gastroschisis, SGA at birth is associated with a 4-fold increase in odds for prolonged LOS, independent of GA. © 2015 John Wiley & Sons, Ltd.

  View details for DOI 10.1002/pd.4562

  View details for Web of Science ID 000353987100011

  View details for PubMedID 25613462

• Cognitive Outcomes After Neonatal Encephalopathy PEDIATRICS Pappas, A., Shankaran, S., McDonald, S. A., Vohr, B. R., Hintz, S. R., Ehrenkranz, R. A., Tyson, J. E., Yolton, K., Das, A., Bara, R., Hammond, J., Higgins, R. D. 2015; 135 (3): E624-E634

  Abstract

  To describe the spectrum of cognitive outcomes of children with and without cerebral palsy (CP) after neonatal encephalopathy, evaluate the prognostic value of early developmental testing and report on school services and additional therapies.The participants of this study are the school-aged survivors of the National Institute of Child Health and Human Development Neonatal Research Network randomized controlled trial of whole-body hypothermia. Children underwent neurologic examinations and neurodevelopmental and cognitive testing with the Bayley Scales of Infant Development-II at 18 to 22 months and the Wechsler intelligence scales and the Neuropsychological Assessment-Developmental Neuropsychological Assessment at 6 to 7 years. Parents were interviewed about functional status and receipt of school and support services. We explored predictors of cognitive outcome by using multiple regression models.Subnormal IQ scores were identified in more than a quarter of the children: 96% of survivors with CP had an IQ <70, 9% of children without CP had an IQ <70, and 31% had an IQ of 70 to 84. Children with a mental developmental index <70 at 18 months had, on average, an adjusted IQ at 6 to 7 years that was 42 points lower than that of those with a mental developmental index >84 (95% confidence interval, -49.3 to -35.0; P < .001). Twenty percent of children with normal IQ and 28% of those with IQ scores of 70 to 84 received special educational support services or were held back ?1 grade level.Cognitive impairment remains an important concern for all children with neonatal encephalopathy.

  View details for DOI 10.1542/peds.2014-1566

  View details for PubMedID 25713280

• Cesarean Sections Increase the Risk of Sepsis in Neonates With Gastroschisis. Desai, A. K., Mansour, T., Billings, T. L., Merritt, T. A., Girsen, A., Judy, A., Davis, A. S., Hintz, S., Blumenfeld, Y., Oshiro, B. T. SAGE PUBLICATIONS INC. 2015: 339A

  View details for Web of Science ID 000351407202491

• Referral of Very Low Birth Weight Infants to High-Risk Follow-Up at Neonatal Intensive Care Unit Discharge Varies Widely across California. journal of pediatrics Hintz, S. R., Gould, J. B., Bennett, M. V., Gray, E. E., Kagawa, K. J., Schulman, J., Murphy, B., Villarin-Duenas, G., Lee, H. C. 2015; 166 (2): 289-295

  Abstract

  To determine rates and factors associated with referral to the California Children's Services high-risk infant follow-up (HRIF) program among very low birth weight (BW) infants in the California Perinatal Quality of Care Collaborative.Using multivariable logistic regression, we examined independent associations of demographic and clinical variables, neonatal intensive care unit (NICU) volume and level, and California region with HRIF referral.In 2010-2011, 8071 very low BW infants were discharged home; 6424 (80%) were referred to HRIF. Higher odds for HRIF referral were associated with lower BW (OR 1.9, 95% CI 1.5-2.4; ? 750 g vs 1251-1499 g), higher NICU volume (OR 1.6, 1.2-2.1; highest vs lowest quartile), and California Children's Services Regional level (OR 3.1, 2.3-4.3, vs intermediate); and lower odds with small for gestational age (OR 0.79, 0.68-0.92), and maternal race African American (OR 0.58, 0.47-0.71) and Hispanic (OR 0.65, 0.55-0.76) vs white. There was wide variability in referral among regions (8%-98%) and NICUs (<5%-100%), which remained after risk adjustment.There are considerable disparities in HRIF referral, some of which may indicate regional and individual NICU resource challenges and barriers. Understanding demographic and clinical factors associated with failure to refer present opportunities for targeted quality improvement initiatives.

  View details for DOI 10.1016/j.jpeds.2014.10.038

  View details for PubMedID 25454311

• Neuroimaging and neurodevelopmental outcome in extremely preterm infants. Pediatrics Hintz, S. R., Barnes, P. D., Bulas, D., Slovis, T. L., Finer, N. N., Wrage, L. A., Das, A., Tyson, J. E., Stevenson, D. K., Carlo, W. A., Walsh, M. C., Laptook, A. R., Yoder, B. A., Van Meurs, K. P., Faix, R. G., Rich, W., Newman, N. S., Cheng, H., Heyne, R. J., Vohr, B. R., Acarregui, M. J., Vaucher, Y. E., Pappas, A., Peralta-Carcelen, M., Wilson-Costello, D. E., Evans, P. W., Goldstein, R. F., Myers, G. J., Poindexter, B. B., McGowan, E. C., Adams-Chapman, I., Fuller, J., Higgins, R. D. 2015; 135 (1): e32-42

  Abstract

  Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age.Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants <28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score <70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors.Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes.Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging.

  View details for DOI 10.1542/peds.2014-0898

  View details for PubMedID 25554820

• CVR at the time of mid-trimester diagnosis of congenital lung lesions as a predictor of adverse neonatal outcomes Sammour, R., Hintz, S., Davis, A., Riley, K., Barth, R., Rubesova, E., Sylvester, K., Girsen, A., Blumenfeld, Y. MOSBY-ELSEVIER. 2015: S197

  View details for DOI 10.1016/j.ajog.2014.10.423

  View details for Web of Science ID 000361140900373

• Neuroimaging and neurodevelopmental outcome in extremely preterm infants. Pediatrics Hintz, S. R., Barnes, P. D., Bulas, D., Slovis, T. L., Finer, N. N., Wrage, L. A., Das, A., Tyson, J. E., Stevenson, D. K., Carlo, W. A., Walsh, M. C., Laptook, A. R., Yoder, B. A., Van Meurs, K. P., Faix, R. G., Rich, W., Newman, N. S., Cheng, H., Heyne, R. J., Vohr, B. R., Acarregui, M. J., Vaucher, Y. E., Pappas, A., Peralta-Carcelen, M., Wilson-Costello, D. E., Evans, P. W., Goldstein, R. F., Myers, G. J., Poindexter, B. B., McGowan, E. C., Adams-Chapman, I., Fuller, J., Higgins, R. D. 2015; 135 (1): e32-42

  View details for DOI 10.1542/peds.2014-0898

  View details for PubMedID 25554820

• Neonatal Magnetic Resonance Imaging Pattern of Brain Injury as a Biomarker of Childhood Outcomes following a Trial of Hypothermia for Neonatal Hypoxic-Ischemic Encephalopathy. The Journal of pediatrics Shankaran, S., McDonald, S. A., Laptook, A. R., Hintz, S. R., Barnes, P. D., Das, A., Pappas, A., Higgins, R. D. 2015; 167 (5): 987?93.e3

  Abstract

  To examine the ability of magnetic resonance imaging (MRI) patterns of neonatal brain injury defined by the National Institute of Child Health and Human Development Neonatal Research Network to predict death or IQ at 6-7 years of age following hypothermia for neonatal encephalopathy.Out of 208 participants, 124 had MRI and primary outcome (death or IQ <70) data. The relationship between injury pattern and outcome was assessed.Death or IQ <70 occurred in 4 of 50 (8%) of children with pattern 0 (normal MRI), 1 of 6 (17%) with 1A (minimal cerebral lesions), 1 of 4 (25%) with 1B (extensive cerebral lesions), 3 of 8 (38%) with 2A (basal ganglia thalamic, anterior or posterior limb of internal capsule, or watershed infarction), 32 of 49 (65%) with 2B (2A with cerebral lesions), and 7 of 7 (100%) with pattern 3 (hemispheric devastation), P < .001; this association was also seen within hypothermia and control subgroups. IQ was 90 ± 13 among the 46 children with a normal MRI and 69 ± 25 among the 50 children with an abnormal MRI. In childhood, for a normal outcome, a normal neonatal MRI had a sensitivity of 61%, specificity of 92%, a positive predictive value of 92%, and a negative predictive value of 59%; for death or IQ <70, the 2B and 3 pattern combined had a sensitivity of 81%, specificity of 78%, positive predictive value of 70%, and a negative predictive value of 87%.The Neonatal Research Network MRI pattern of neonatal brain injury is a biomarker of neurodevelopmental outcome at 6-7 years of age.ClinicalTrials.gov: NCT00005772.

  View details for PubMedID 26387012

• In memoriam: Raymond L. Hintz, MD (1939- 2014). Pediatric endocrinology reviews : PER Hintz, S. R. 2014; 12 (2): 198-199

  View details for PubMedID 25581984

• In Memoriam: Raymond L. Hintz, MD (1939-2014) PEDIATRIC ENDOCRINOLOGY REVIEWS PER Hintz, S. R. 2014; 12 (2): 198?99

  View details for Web of Science ID 000209572300005

• Functional status at 18 months of age as a predictor of childhood disability after neonatal hypoxic-ischemic encephalopathy DEVELOPMENTAL MEDICINE AND CHILD NEUROLOGY Natarajan, G., Shankaran, S., Pappas, A., Bann, C., Tyson, J. E., McDonald, S., Das, A., Hintz, S., Vohr, B., Higgins, R. 2014; 56 (11): 1052-1058

  Abstract

  In children with neonatal hypoxic-ischemic encephalopathy (HIE), we examined the association between 18-month functional status by parental report and disability at 6-7 years.Prospective observational study involving participants in the NICHD randomized controlled trial of hypothermia for HIE. Parent questionnaires-Functional Status-II (FS-II), Impact on Family (IOF) and Family Resource Scale (FRS) at 18 months were correlated with 6- to 7-year developmental assessments. Disability at 6-7 years was defined as IQ < 70, gross motor functional classification scale level III-V, bilateral blindness, deafness, or epilepsy.Rates of severe HIE (32 vs. 15%), public insurance (73% vs. 47%) and IOF scales were higher and mean (SD) FS-II independence (I) {54 (SD 35) vs. 98 (SD 8)} and general health (GH) {87 (SD 14) vs. 98 (SD 6)} scores were significantly lower in children with disability (n=37) at 6-7 years, compared to those (n=74) without disability. FS-II I scores were significantly associated with disability (OR 0.92; 95% CI 0.87-0.97; p=0.003). On path analysis, severe HIE, greater IOF and public insurance were associated with poorer 18-month FS-II I scores, which, in turn, were associated with disability at 6 to 7 years.Poor independent functioning by parental report at 18 months in children with HIE was associated with childhood disability.

  View details for DOI 10.1111/dmcn.12512

  View details for Web of Science ID 000343803100012

  View details for PubMedCentralID PMC4324462

• Functional status at 18 months of age as a predictor of childhood disability after neonatal hypoxic-ischemic encephalopathy. Developmental medicine and child neurology Natarajan, G., Shankaran, S., Pappas, A., Bann, C., Tyson, J. E., McDonald, S., Das, A., Hintz, S., Vohr, B., Higgins, R. 2014; 56 (11): 1052-1058

  Abstract

  In children with neonatal hypoxic-ischemic encephalopathy (HIE), we examined the association between 18-month functional status by parental report and disability at 6-7 years.Prospective observational study involving participants in the NICHD randomized controlled trial of hypothermia for HIE. Parent questionnaires-Functional Status-II (FS-II), Impact on Family (IOF) and Family Resource Scale (FRS) at 18 months were correlated with 6- to 7-year developmental assessments. Disability at 6-7 years was defined as IQ < 70, gross motor functional classification scale level III-V, bilateral blindness, deafness, or epilepsy.Rates of severe HIE (32 vs. 15%), public insurance (73% vs. 47%) and IOF scales were higher and mean (SD) FS-II independence (I) {54 (SD 35) vs. 98 (SD 8)} and general health (GH) {87 (SD 14) vs. 98 (SD 6)} scores were significantly lower in children with disability (n=37) at 6-7 years, compared to those (n=74) without disability. FS-II I scores were significantly associated with disability (OR 0.92; 95% CI 0.87-0.97; p=0.003). On path analysis, severe HIE, greater IOF and public insurance were associated with poorer 18-month FS-II I scores, which, in turn, were associated with disability at 6 to 7 years.Poor independent functioning by parental report at 18 months in children with HIE was associated with childhood disability.

  View details for DOI 10.1111/dmcn.12512

  View details for PubMedID 24957482

• Perinatal features of the RASopathies: Noonan syndrome, cardiofaciocutaneous syndrome and Costello syndrome. American journal of medical genetics. Part A Myers, A., Bernstein, J. A., Brennan, M., Curry, C., Esplin, E. D., Fisher, J., Homeyer, M., Manning, M. A., Muller, E. A., Niemi, A., Seaver, L. H., Hintz, S. R., Hudgins, L. 2014; 164A (11): 2814-2821

  Abstract

  The RASopathies are a family of developmental disorders caused by heritable defects of the RAS/MAPK signaling pathway. While the postnatal presentation of this group of disorders is well known, the prenatal and neonatal findings are less widely recognized. We report on the perinatal presentation of 10 patients with Noonan syndrome (NS), nine with Cardiofaciocutaneous syndrome (CFCS) and three with Costello syndrome (CS), in conjunction with the results of a comprehensive literature review. The majority of perinatal findings in NS, CS, and CFCS are shared: polyhydramnios; prematurity; lymphatic dysplasia; macrosomia; relative macrocephaly; respiratory distress; hypotonia, as well as cardiac and renal anomalies. In contrast, fetal arrhythmia and neonatal hypoglycemia are relatively specific to CS. NS, CS, and CFCS should all be considered as a possible diagnosis in pregnancies with a normal karyotype and ultrasound findings of a RASopathy. Recognition of the common perinatal findings of these disorders should facilitate both their prenatal and neonatal diagnosis. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.a.36737

  View details for PubMedID 25250515

• Perinatal Features of the RASopathies: Noonan Syndrome, Cardiofaciocutaneous Syndrome and Costello Syndrome AMERICAN JOURNAL OF MEDICAL GENETICS PART A Myers, A., Bernstein, J. A., Brennan, M., Curry, C., Esplin, E. D., Fisher, J., Homeyer, M., Manning, M. A., Muller, E. A., Niemi, A., Seaver, L. H., Hintz, S. R., Hudgins, L. 2014; 164A (11): 2814-2821

  Abstract

  The RASopathies are a family of developmental disorders caused by heritable defects of the RAS/MAPK signaling pathway. While the postnatal presentation of this group of disorders is well known, the prenatal and neonatal findings are less widely recognized. We report on the perinatal presentation of 10 patients with Noonan syndrome (NS), nine with Cardiofaciocutaneous syndrome (CFCS) and three with Costello syndrome (CS), in conjunction with the results of a comprehensive literature review. The majority of perinatal findings in NS, CS, and CFCS are shared: polyhydramnios; prematurity; lymphatic dysplasia; macrosomia; relative macrocephaly; respiratory distress; hypotonia, as well as cardiac and renal anomalies. In contrast, fetal arrhythmia and neonatal hypoglycemia are relatively specific to CS. NS, CS, and CFCS should all be considered as a possible diagnosis in pregnancies with a normal karyotype and ultrasound findings of a RASopathy. Recognition of the common perinatal findings of these disorders should facilitate both their prenatal and neonatal diagnosis. © 2014 Wiley Periodicals, Inc.

  View details for DOI 10.1002/ajmg.a.36737

  View details for Web of Science ID 000344187200019

• Hypothermia Therapy for Neonatal Hypoxic Ischemic Encephalopathy in the State of California. journal of pediatrics Kracer, B., Hintz, S. R., Van Meurs, K. P., Lee, H. C. 2014; 165 (2): 267-273

  Abstract

  To characterize the implementation of hypothermia for neonatal hypoxic ischemic encephalopathy (HIE) in a population-based cohort.Using the California Perinatal Quality Care Collaborative and California Perinatal Transport System linked 2010-2012 datasets, we categorized infants ?36 weeks' gestation with HIE as receiving hypothermia or normothermia. Sociodemographic and clinical factors were compared, and multivariable logistic regression was used to determine factors associated with hypothermia therapy.There were 238 reported encephalopathy cases in 2010, 280 in 2011, and 311 in 2012. Hypothermia therapy use in newborns with HIE increased from 59% to 73% across the study period, mainly occurring in newborns with mild or moderate encephalopathy. A total of 36 centers provided hypothermia and cared for 94% of infants, with the remaining 6% being cared for at one of 25 other centers. Of the centers providing hypothermia, 12 centers performed hypothermia therapy to more than 20 patients during the 3-year study period, and 24 centers cared for <20 patients receiving hypothermia. In-hospital mortality was 13%, which primarily was associated with the severity of encephalopathy.Our findings highlight an opportunity to explore practice-site variation and to develop quality improvement interventions to assure consistent evidence-based care of term infants with HIE and appropriate application of hypothermia therapy for eligible newborns.

  View details for DOI 10.1016/j.jpeds.2014.04.052

  View details for PubMedID 24929331

  View details for PubMedCentralID PMC4111956

• Fetal centers and the role of the neonatologist in complex fetal care. American journal of perinatology Davis, A. S., Chock, V. Y., Hintz, S. R. 2014; 31 (7): 549-556

  Abstract

  As prenatal imaging and genetic diagnostic techniques developed, clinicians knew earlier and with greater accuracy of the extent and severity of fetal anomalies. This, coupled with an acute awareness of high rates of death or devastating neonatal morbidities in some cases, drove efforts to create innovative fetal interventions. However, with advances in neonatal quaternary care, infants with even the most complex congenital anomalies now have a substantially greater chance of survival. But many still require highly coordinated intensive care from the moment of delivery, have lengthy and complicated hospitalizations, and need ongoing complex care and services. Therefore, a new vision of complex fetal medicine must evolve, actively integrating robust multidisciplinary involvement in collaborative counseling, planning, and management. The clinical arc visualized for complex fetal patients should shift toward a comprehensive continuum of care concept-extending from fetal life, through neonatal intensive care, to childhood. The neonatologist plays a critical role in bridging this trajectory, coordinating complex processes to a smooth delivery and neonatal plan, counseling and preparing expectant mothers, and integrating many components of subspecialty input for families and other fetal team members. Neonatologists' engagement and perspective can substantively inform the clinical and strategic direction for fetal centers.

  View details for DOI 10.1055/s-0034-1371709

  View details for PubMedID 24705973

• Respiratory Outcomes of the Surfactant Positive Pressure and Oximetry Randomized Trial (SUPPORT). journal of pediatrics Stevens, T. P., Finer, N. N., Carlo, W. A., Szilagyi, P. G., Phelps, D. L., Walsh, M. C., Gantz, M. G., Laptook, A. R., Yoder, B. A., Faix, R. G., Newman, J. E., Das, A., Do, B. T., Schibler, K., Rich, W., Newman, N. S., Ehrenkranz, R. A., Peralta-Carcelen, M., Vohr, B. R., Wilson-Costello, D. E., Yolton, K., Heyne, R. J., Evans, P. W., Vaucher, Y. E., Adams-Chapman, I., McGowan, E. C., Bodnar, A., Pappas, A., Hintz, S. R., Acarregui, M. J., Fuller, J., Goldstein, R. F., Bauer, C. R., O'Shea, T. M., Myers, G. J., Higgins, R. D. 2014; 165 (2): 240-249 e4

  Abstract

  To explore the early childhood pulmonary outcomes of infants who participated in the National Institute of Child Health and Human Development's Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial (SUPPORT), using a factorial design that randomized extremely preterm infants to lower vs higher oxygen saturation targets and delivery room continuous positive airway pressure (CPAP) vs intubation/surfactant.The Breathing Outcomes Study, a prospective secondary study to the Surfactant Positive Airway Pressure and Pulse Oximetry Randomized Trial, assessed respiratory morbidity at 6-month intervals from hospital discharge to 18-22 months corrected age (CA). Two prespecified primary outcomes-wheezing more than twice per week during the worst 2-week period and cough longer than 3 days without a cold-were compared for each randomized intervention.One or more interviews were completed for 918 of the 922 eligible infants. The incidences of wheezing and cough were 47.9% and 31.0%, respectively, and did not differ between the study arms of either randomized intervention. Infants randomized to lower vs higher oxygen saturation targets had a similar risk of death or respiratory morbidity (except for croup and treatment with oxygen or diuretics at home). Infants randomized to CPAP vs intubation/surfactant had fewer episodes of wheezing without a cold (28.9% vs 36.5%; P < .05), respiratory illnesses diagnosed by a doctor (47.7% vs 55.2%; P < .05), and physician or emergency room visits for breathing problems (68.0% vs 72.9%; P < .05) by 18-22 months CA.Treatment with early CPAP rather than intubation/surfactant is associated with less respiratory morbidity by 18-22 months CA. Longitudinal assessment of pulmonary morbidity is necessary to fully evaluate the potential benefits of respiratory interventions for neonates.

  View details for DOI 10.1016/j.jpeds.2014.02.054

  View details for PubMedID 24725582

• Surgery and neurodevelopmental outcome of very low-birth-weight infants. JAMA pediatrics Morriss, F. H., Saha, S., Bell, E. F., Colaizy, T. T., Stoll, B. J., Hintz, S. R., Shankaran, S., Vohr, B. R., Hamrick, S. E., Pappas, A., Jones, P. M., Carlo, W. A., Laptook, A. R., Van Meurs, K. P., Sánchez, P. J., Hale, E. C., Newman, N. S., Das, A., Higgins, R. D. 2014; 168 (8): 746-754

  Abstract

  Reduced death and neurodevelopmental impairment among infants is a goal of perinatal medicine.To assess the association between surgery during the initial hospitalization and death or neurodevelopmental impairment of very low-birth-weight infants.A retrospective cohort analysis was conducted of patients enrolled in the National Institute of Child Health and Human Development Neonatal Research Network Generic Database from 1998 through 2009 and evaluated at 18 to 22 months' corrected age. Twenty-two academic neonatal intensive care units participated. Inclusion criteria were birth weight 401 to 1500 g, survival to 12 hours, and availability for follow-up. A total of 12 111 infants were included in analyses.Surgical procedures; surgery also was classified by expected anesthesia type as major (general anesthesia) or minor (nongeneral anesthesia).Multivariable logistic regression analyses planned a priori were performed for the primary outcome of death or neurodevelopmental impairment and for the secondary outcome of neurodevelopmental impairment among survivors. Multivariable linear regression analyses were performed as planned for the adjusted mean scores of the Mental Developmental Index and Psychomotor Developmental Index of the Bayley Scales of Infant Development, Second Edition, for patients born before 2006.A total of 2186 infants underwent major surgery, 784 had minor surgery, and 9141 infants did not undergo surgery. The risk-adjusted odds ratio of death or neurodevelopmental impairment for all surgery patients compared with those who had no surgery was 1.29 (95% CI, 1.08-1.55). For patients who had major surgery compared with those who had no surgery, the risk-adjusted odds ratio of death or neurodevelopmental impairment was 1.52 (95% CI, 1.24-1.87). Patients classified as having minor surgery had no increased adjusted risk. Among survivors who had major surgery compared with those who had no surgery, the adjusted risk of neurodevelopmental impairment was greater and the adjusted mean Bayley scores were lower.Major surgery in very low-birth-weight infants is independently associated with a greater than 50% increased risk of death or neurodevelopmental impairment and of neurodevelopmental impairment at 18 to 22 months' corrected age. The role of general anesthesia is implicated but remains unproven.

  View details for DOI 10.1001/jamapediatrics.2014.307

  View details for PubMedID 24934607

• Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia GENETICS IN MEDICINE Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

  View details for DOI 10.1038/gim.2013.194

  View details for Web of Science ID 000338601400012

• Fetal Diagnosis and Interventions AMERICAN JOURNAL OF PERINATOLOGY Moise, K. J., Hintz, S. R. 2014; 31 (7): 547

  View details for PubMedID 24915554

• Noninvasive prenatal diagnosis in a fetus at risk for methylmalonic acidemia. Genetics in medicine Gu, W., Koh, W., Blumenfeld, Y. J., El-Sayed, Y. Y., Hudgins, L., Hintz, S. R., Quake, S. R. 2014; 16 (7): 564-567

  Abstract

  Purpose:Prenatal diagnosis of fetal Mendelian disorders can benefit from noninvasive approaches using fetal cell-free DNA in maternal plasma. Detecting metabolic disorders before birth can result in immediate treatment postpartum in order to optimize outcome.Methods:We developed a mathematical model and an experimental methodology to analyze the case of a fetus with a 25% risk of inheriting two known mutations in MUT that cause methylmalonic acidemia. To accomplish this, we measured allelic counts at the mutation sites and the fetal fraction from high minor-allele-frequency single-nucleotide polymorphism positions.Results:By counting linked alleles, the test was able to distinguish 11 positive markers from the negative controls and thereby determine whether or not the mutations carried by the parents were inherited by the fetus. For a homozygous fetus, the Z-score of the mutation site was 5.97, whereas the median Z-score of all the linked alleles was 4.56 when all negative (heterozygous) controls had a Z-score <2.5.Conclusion:The application of this methodology for diagnosing methylmalonic acidemia shows that this is a cost-effective and noninvasive approach to diagnosing known mutations related to Mendelian disorders in the fetus.Genet Med advance online publication 9 January 2014Genetics in Medicine (2014); doi:10.1038/gim.2013.194.

  View details for DOI 10.1038/gim.2013.194

  View details for PubMedID 24406457

• Developmental outcomes of very preterm infants with tracheostomies. journal of pediatrics DeMauro, S. B., D'Agostino, J. A., Bann, C., Bernbaum, J., Gerdes, M., Bell, E. F., Carlo, W. A., D'Angio, C. T., Das, A., Higgins, R., Hintz, S. R., Laptook, A. R., Natarajan, G., Nelin, L., Poindexter, B. B., Sanchez, P. J., Shankaran, S., Stoll, B. J., Truog, W., Van Meurs, K. P., Vohr, B., Walsh, M. C., Kirpalani, H. 2014; 164 (6): 1303-1310 e2

  View details for DOI 10.1016/j.jpeds.2013.12.014

  View details for PubMedID 24472229

• Early working memory as a racially and ethnically neutral measure of outcome in extremely preterm children at 18-22 months (vol 89, pg 1055, 2013) EARLY HUMAN DEVELOPMENT Lowe, J. R., Duncan, A., Bann, C. M., Fuller, J., Hintz, S. R., Das, A., Higgins, R. D., Watterberg, K. L., Eunice Kennedy Shriver Natl Inst C 2014; 90 (6): 319

  View details for DOI 10.1016/j.earlhumdev.2014.03.004

  View details for Web of Science ID 000336714600009

• Outcomes of extremely preterm infants following severe intracranial hemorrhage. Journal of perinatology DAVIS, A. S., Hintz, S. R., Goldstein, R. F., Ambalavanan, N., Bann, C. M., Stoll, B. J., Bell, E. F., Shankaran, S., Laptook, A. R., Walsh, M. C., HALE, E. C., Newman, N. S., Das, A., Higgins, R. D. 2014; 34 (3): 203-208

  Abstract

  Objective:Severe intracranial hemorrhage (ICH) is an important prognostic variable in extremely preterm (EPT) infants. We examined imaging and clinical variables that predict outcomes in EPT infants with severe ICH.Study design:Retrospective analysis of 353 EPT infants with severe ICH. Outcomes were compared by examining: (i) unilateral vs bilateral ICH; and (ii) presence vs absence of hemorrhagic parenchymal infarction (HPI). Regression analyses identified variables associated with death or neurodevelopmental impairment (NDI).Result:Bilateral ICH and HPI had higher rates of adverse outcomes and were independently associated with death/NDI. HPI was the most important variable for infants of lower birth weight, and bilateral ICH for larger infants. For infants surviving to 36 weeks, shunt placement was most associated with death/NDI.Conclusion:Bilateral ICH and the presence of HPI in EPT infants with severe ICH are associated with death/NDI, though the importance depends on birth weight and survival to 36 weeks.

  View details for DOI 10.1038/jp.2013.162

  View details for PubMedID 24370654

• PRENATAL TREATMENT OF ORNITHINE TRANSCARBAMYLASE DEFICIENCY Wilnai, Y., Alcorn, D., Benitz, W., Berquist, W., Bernstein, J., Blumenfeld, Y. J., Castillo, R., Concepcion, W., Cowan, T., Cox, K. L., Cusmano, K., Deirdre, L., Esquival, C., Hintz, S. R., Homeyer, M., Hudgins, L., Palma, J., Summar, M. L., Schelley, S., Vishnu, P., Enns, G. M. ACADEMIC PRESS INC ELSEVIER SCIENCE. 2014: 248

  View details for Web of Science ID 000332500200048

• Neurodevelopmental outcomes of extremely low birth weight infants with spontaneous intestinal perforation or surgical necrotizing enterocolitis JOURNAL OF PERINATOLOGY Wadhawan, R., Oh, W., Hintz, S. R., Blakely, M. L., Das, A., Bell, E. F., Saha, S., Laptook, A. R., Shankaran, S., Stoll, B. J., Walsh, M. C., Higgins, R. D. 2014; 34 (1): 64-70

  Abstract

  To determine if extremely low birth weight infants with surgical necrotizing enterocolitis have a higher risk of death or neurodevelopmental impairment and neurodevelopmental impairment among survivors (secondary outcome) at 18-22 months corrected age compared with infants with spontaneous intestinal perforation and infants without necrotizing enterocolitis or spontaneous intestinal perforation.Retrospective analysis of the Neonatal Research Network very low birth weight registry, evaluating extremely low birth weight infants born between 2000 and 2005. The study infants were designated into three groups: (1) spontaneous intestinal perforation without necrotizing enterocolitis; (2) surgical necrotizing enterocolitis (Bell's stage III); and (3) neither spontaneous intestinal perforation nor necrotizing enterocolitis. Multivariate logistic regression analysis was performed to evaluate the association between the clinical group and death or neurodevelopmental impairment, controlling for multiple confounding factors including center.Infants with surgical necrotizing enterocolitis had the highest rate of death before hospital discharge (53.5%) and death or neurodevelopmental impairment (82.3%) compared with infants in the spontaneous intestinal perforation group (39.1 and 79.3%) and no necrotizing enterocolitis/no spontaneous intestinal perforation group (22.1 and 53.3%; P<0.001). Similar results were observed for neurodevelopmental impairment among survivors. On logistic regression analysis, both spontaneous intestinal perforation and surgical necrotizing enterocolitis were associated with increased risk of death or neurodevelopmental impairment (adjusted odds ratio 2.21, 95% confidence interval (CI): 1.5, 3.2 and adjusted OR 2.11, 95% CI: 1.5, 2.9, respectively) and neurodevelopmental impairment among survivors (adjusted OR 2.17, 95% CI: 1.4, 3.2 and adjusted OR 1.70, 95% CI: 1.2, 2.4, respectively).Spontaneous intestinal perforation and surgical necrotizing enterocolitis are associated with a similar increase in the risk of death or neurodevelopmental impairment and neurodevelopmental impairment among extremely low birth weight survivors at 18-22 months corrected age.

  View details for DOI 10.1038/jp.2013.128

  View details for PubMedID 24135709

• LONGITUDINAL PLASMA ENDOTHELIN-1 LEVELS IN PREMATURE INFANTS WITH AND WITHOUT BRONCHOPULMONARY DYSPLASIA Johnson, C., Chitkara, R., McCarthy, E., Fineman, J. R., Sun, C., Kim, L., Hintz, S. R., Van Meurs, K. P., Punn, R., Milla, C. E., Feinstein, J. A. LIPPINCOTT WILLIAMS & WILKINS. 2014: 179?80

  View details for Web of Science ID 000336284900134

• Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants. NeuroImage. Clinical Rose, J., Vassar, R., Cahill-Rowley, K., Stecher Guzman, X., Hintz, S. R., Stevenson, D. K., Barnea-Goraly, N. 2014; 5: 169-177

  Abstract

  Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ? 1500 g, gestational age (GA) ? 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

  View details for DOI 10.1016/j.nicl.2014.05.013

  View details for PubMedID 25068107

• Early working memory as a racially and ethnically neutral measure of outcome in extremely preterm children at 18-22months. Early human development Lowe, J. R., Duncan, A. F., Bann, C. M., Fuller, J., Hintz, S. R., Das, A., Higgins, R. D., Watterberg, K. L. 2013; 89 (12): 1055-1061

  Abstract

  Difficulties with executive function have been found in preterm children, resulting in difficulties with learning and school performance.This study evaluated the relationship of early working memory as measured by object permanence items to the cognitive and language scores on the Bayley Scales-III in a cohort of children born extremely preterm.Logistic regression models were conducted to compare object permanence scores derived from the Bayley Scales-III by race/ethnicity and maternal education, controlling for medical covariates.Extremely preterm toddlers (526), who were part of a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network's multi-center study, were evaluated at 18-22 months corrected age.Object permanence scores derived from the Bayley Developmental Scales were compared by race/ethnicity and maternal education, controlling for medical covariates.There were no significant differences in object permanence mastery and scores among the treatment groups after controlling for medical and social variables, including maternal education and race/ethnicity. Males and children with intraventricular hemorrhage, retinopathy of prematurity, and bronchopulmonary dysplasia were less likely to demonstrate object permanence mastery and had lower object permanence scores. Children who attained object permanence mastery had significantly higher Bayley Scales-III cognitive and language scores after controlling for medical and socio-economic factors.Our measure of object permanence is free of influence from race, ethnic and socio-economic factors. Adding this simple task to current clinical practice could help detect early executive function difficulties in young children.

  View details for DOI 10.1016/j.earlhumdev.2013.08.009

  View details for PubMedID 23993309

  View details for PubMedCentralID PMC3830714

• Apgar scores at 10 min and outcomes at 6-7 years following hypoxic-ischaemic encephalopathy ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION Natarajan, G., Shankaran, S., Laptook, A. R., Pappas, A., Bann, C. M., McDonald, S. A., Das, A., Higgins, R. D., Hintz, S. R., Vohr, B. R. 2013; 98 (6): F473-F479

  Abstract

  To determine the association between 10 min Apgar scores and 6-7-year outcomes in children with perinatal hypoxic-ischaemic encephalopathy (HIE) enrolled in the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) whole body cooling randomised controlled trial (RCT).Evaluations at 6-7 years included the Wechsler Preschool and Primary Scale of Intelligence III or Wechsler Intelligence Scale for Children IV and Gross Motor Functional Classification Scale. Primary outcome was death/moderate or severe disability. Logistic regression was used to examine the association between 10 min Apgar scores and outcomes after adjusting for birth weight, gestational age, gender, outborn status, hypothermia treatment and centre.In the study cohort (n=174), 64/85 (75%) of those with 10 min Apgar score of 0-3 had death/disability compared with 40/89 (45%) of those with scores >3. Each point increase in 10 min Apgar scores was associated with a significantly lower adjusted risk of death/disability, death, death/IQ <70, death/cerebral palsy (CP) and disability, IQ<70 and CP among survivors (all p<0.05). Among the 24 children with a 10 min Apgar score of 0, five (20.8%) survived without disability. The risk-adjusted probabilities of death/disability were significantly lower in cooled infants with Apgar scores of 0-3; there was no significant interaction between cooling and Apgar scores (p=0.26).Among children with perinatal HIE enrolled in the NICHD cooling RCT, 10 min Apgar scores were significantly associated with school-age outcomes. A fifth of infants with 10 min Apgar score of 0 survived without disability to school age, suggesting the need for caution in limiting resuscitation to a specified duration.

  View details for DOI 10.1136/archdischild-2013-303692

  View details for Web of Science ID 000325556000003

  View details for PubMedID 23896791

• Apgar scores at 10 min and outcomes at 6-7 years following hypoxic-ischaemic encephalopathy. Archives of disease in childhood. Fetal and neonatal edition Natarajan, G., Shankaran, S., Laptook, A. R., Pappas, A., Bann, C. M., McDonald, S. A., Das, A., Higgins, R. D., Hintz, S. R., Vohr, B. R. 2013; 98 (6): F473-9

  Abstract

  To determine the association between 10 min Apgar scores and 6-7-year outcomes in children with perinatal hypoxic-ischaemic encephalopathy (HIE) enrolled in the National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) whole body cooling randomised controlled trial (RCT).Evaluations at 6-7 years included the Wechsler Preschool and Primary Scale of Intelligence III or Wechsler Intelligence Scale for Children IV and Gross Motor Functional Classification Scale. Primary outcome was death/moderate or severe disability. Logistic regression was used to examine the association between 10 min Apgar scores and outcomes after adjusting for birth weight, gestational age, gender, outborn status, hypothermia treatment and centre.In the study cohort (n=174), 64/85 (75%) of those with 10 min Apgar score of 0-3 had death/disability compared with 40/89 (45%) of those with scores >3. Each point increase in 10 min Apgar scores was associated with a significantly lower adjusted risk of death/disability, death, death/IQ <70, death/cerebral palsy (CP) and disability, IQ<70 and CP among survivors (all p<0.05). Among the 24 children with a 10 min Apgar score of 0, five (20.8%) survived without disability. The risk-adjusted probabilities of death/disability were significantly lower in cooled infants with Apgar scores of 0-3; there was no significant interaction between cooling and Apgar scores (p=0.26).Among children with perinatal HIE enrolled in the NICHD cooling RCT, 10 min Apgar scores were significantly associated with school-age outcomes. A fifth of infants with 10 min Apgar score of 0 survived without disability to school age, suggesting the need for caution in limiting resuscitation to a specified duration.

  View details for DOI 10.1136/archdischild-2013-303692

  View details for PubMedID 23896791

• Neurodevelopmental outcome of extremely low birth weight infants with Candida infection. journal of pediatrics Adams-Chapman, I., Bann, C. M., Das, A., Goldberg, R. N., Stoll, B. J., Walsh, M. C., Sánchez, P. J., Higgins, R. D., Shankaran, S., Watterberg, K. L., Duara, S., Miller, N. A., Heyne, R. J., Peralta-Carcelen, M., Goldstein, R. F., Steichen, J. J., Bauer, C. R., Hintz, S. R., Evans, P. W., Acarregui, M. J., Myers, G. J., Vohr, B. R., Wilson-Costello, D. E., Pappas, A., Vaucher, Y. E., Ehrenkranz, R. A., McGowan, E. C., Dillard, R. G., Fuller, J., Benjamin, D. K. 2013; 163 (4): 961-7 e3

  Abstract

  OBJECTIVE: Candida remains an important cause of late-onset infection in preterm infants. Mortality and neurodevelopmental outcome of extremely low birth weight (ELBW) infants enrolled in the Candida study were evaluated based on infection status. STUDY DESIGN: ELBW infants born at Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers between March 2004 and July 2007 who were screened for suspected sepsis were eligible for inclusion in the Candida study. Primary outcome data for neurodevelopmental impairment (NDI) or death were available for 1317 of the 1515 infants (87%) enrolled in the Candida study. The Bayley Scales of Infant Development-II or -III was administered at 18 months' adjusted age. A secondary comparison was performed with 864 infants enrolled in the NRN Generic Database during the same cohort who were never screened for sepsis and therefore not eligible for the Candida study. RESULTS: Among ELBW infants enrolled in the Candida study, 31% with Candida and 31% with late-onset non-Candida sepsis had NDI at 18 months. Infants with Candida sepsis and/or meningitis had an increased risk of death and were more likely to have the composite outcome of death and/or NDI compared with uninfected infants in adjusted analysis. Compared with infants in the NRN registry never screened for sepsis, overall risk for death were similar but those with Candida infection were more likely to have NDI (OR 1.83, 95% CI 1.01-3.33, P = .047). CONCLUSIONS: In this cohort of ELBW infants, those with infection and/or meningitis were at increased risk for death and/or NDI. This risk was highest among those with Candida sepsis and/or meningitis.

  View details for DOI 10.1016/j.jpeds.2013.04.034

  View details for PubMedID 23726546

• Cerebral palsy and growth failure at 6 to 7 years. Pediatrics Vohr, B. R., Stephens, B. E., McDonald, S. A., Ehrenkranz, R. A., Laptook, A. R., Pappas, A., Hintz, S. R., Shankaran, S., Higgins, R. D., Das, A. 2013; 132 (4): e905-14

  Abstract

  To evaluate the association between severity of cerebral palsy (CP) and growth to 6 to 7 years of age among children with moderate to severe (Mod/Sev) hypoxic ischemic encephalopathy (HIE). It was hypothesized that children with Mod/Sev CP would have poorer growth, lower cognitive scores, and increased rehospitalization rates compared with children with no CP (No CP).Among 115 of 122 surviving children followed in the hypothermia trial for neonatal HIE, growth parameters and neurodevelopmental status at 18 to 22 months and 6 to 7 years were available. Group comparisons (Mod/Sev CP and No CP) with unadjusted and adjusted analyses for growth <10th percentile and z scores by using Fisher's exact tests and regression modeling were conducted.Children with Mod/Sev CP had high rates of slow growth and cognitive and motor impairment and rehospitalizations at 18 to 22 months and 6 to 7 years. At 6 to 7 years of age, children with Mod/Sev CP had increased rates of growth parameters <10th percentile compared with those with No CP (weight, 57% vs 3%; height, 70% vs 2%; and head circumference, 82% vs 13%; P < .0001). Increasing severity of slow growth was associated with increasing age (P < .04 for weight, P < .001 for length, and P < .0001 for head circumference). Gastrostomy feeds were associated with better growth.Term children with HIE who develop Mod/Sev CP have high and increasing rates of growth <10th percentile by 6 to 7 years of age. These findings support the need for close medical and nutrition management of children with HIE who develop CP.

  View details for DOI 10.1542/peds.2012-3915

  View details for PubMedID 24019415

• Cerebral Palsy and Growth Failure at 6 to 7 Years PEDIATRICS Vohr, B. R., Stephens, B. E., McDonald, S. A., Ehrenkranz, R. A., Laptook, A. R., Pappas, A., Hintz, S. R., Shankaran, S., Higgins, R. D., Das, A. 2013; 132 (4): E905-E914

  View details for DOI 10.1542/peds.2012-3915

  View details for Web of Science ID 000325095400012

  View details for PubMedID 24019415

• Ten-year review of major birth defects in VLBW infants. Pediatrics Adams-Chapman, I., Hansen, N. I., Shankaran, S., Bell, E. F., Boghossian, N. S., Murray, J. C., Laptook, A. R., Walsh, M. C., Carlo, W. A., Sánchez, P. J., Van Meurs, K. P., Das, A., Hale, E. C., Newman, N. S., Ball, M. B., Higgins, R. D., Stoll, B. J. 2013; 132 (1): 49-61

  Abstract

  OBJECTIVE:Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care.METHODS:Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics.RESULTS:A BD was present in 1776 (4.8%) of the 37?262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41-3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001).CONCLUSIONS:Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.

  View details for DOI 10.1542/peds.2012-3111

  View details for PubMedID 23733791

• Neurodevelopmental outcomes of extremely low-gestational-age neonates with low-grade periventricular-intraventricular hemorrhage. JAMA pediatrics Payne, A. H., Hintz, S. R., Hibbs, A. M., Walsh, M. C., Vohr, B. R., Bann, C. M., Wilson-Costello, D. E. 2013; 167 (5): 451-459

  Abstract

  Low-grade periventricular-intraventricular hemorrhage is a common neurologic morbidity among extremely low-gestational-age neonates, yet the outcomes associated with this morbidity are not fully understood. In a contemporary multicenter cohort, we evaluated the impact of such hemorrhages on early (18-22 month) neurodevelopmental outcomes of extremely premature infants.To compare neurodevelopmental outcomes at 18 to 22 months' corrected age for extremely low-gestational-age infants with low-grade (grade 1 or 2) periventricular-intraventricular hemorrhage with those of infants with either no hemorrhage or severe (grade 3 or 4) hemorrhage demonstrated on cranial ultrasonography.Longitudinal observational study.Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.A total of 1472 infants born at less than 27 weeks' gestational age between January 1, 2006, and December 31, 2008, with ultrasonography results within the first 28 days of life and surviving to 18 to 22 months with complete follow-up assessments were eligible.Low-grade periventricular-intraventricular hemorrhage.Outcomes included cerebral palsy; gross motor functional limitation; cognitive and language scores according to the Bayley Scales of Infant Development, 3rd Edition; and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences.Low-grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared with infants without hemorrhage. Compared with low-grade hemorrhage, severe hemorrhage was associated with decreased adjusted continuous cognitive (?, -3.91 [95% CI, -6.41 to -1.42]) and language (?, -3.19 [-6.19 to -0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (odds ratio [OR], 1.46 [0.74 to 2.88]) and mild language impairment (OR, 1.35 [0.88 to 2.06]).At 18 to 22 months, the neurodevelopmental outcomes of extremely low-gestational-age infants with low-grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. Additional study at school age and beyond would be informative.

  View details for DOI 10.1001/jamapediatrics.2013.866

  View details for PubMedID 23460139

• HYPOXIC ISCHEMIC ENCEPHALOPATHY IN THE COOLING ERA: SHORT TERM OUTCOMES IN THE STATE OF CALIFORNIA Western Regional Meeting of the American-Federation-for-Medical-Research Kracer, B., Hintz, S. R., Van Meurs, K. P., Lee, H. C. LIPPINCOTT WILLIAMS & WILKINS. 2013: 166?66

  View details for Web of Science ID 000312657900204

• Conservatively Managed Fetal Goiter: An Alternative to in utero Therapy. Fetal diagnosis and therapy Blumenfeld, Y. J., Davis, A., Milan, K., Chueh, J., Hudgins, L., Barth, R. A., Hintz, S. R. 2013; 34 (3): 184-187

  Abstract

  Fetal goiter may arise from a variety of etiologies including iodine deficiency, overtreatment of maternal Graves' disease, inappropriate maternal thyroid replacement and, rarely, congenital hypothyroidism. Fetal goiter is often associated with a retroflexed neck and polyhydramnios, raising concerns regarding airway obstruction in such cases. Prior reports have advocated for cordocentesis and intra-amniotic thyroid hormone therapy in order to confirm the diagnosis of fetal thyroid dysfunction, reduce the size of the fetal goiter, reduce polyhydramnios, aid with the assistance of maternal thyroid hormone therapy and reduce fetal malpresentation. We report two cases of conservatively managed fetal goiter, one resulting in a vaginal delivery, and no evidence of postnatal respiratory distress despite the presence of polyhydramnios and a retroflexed neck on prenatal ultrasound. © 2013 S. Karger AG, Basel.

  View details for DOI 10.1159/000353387

  View details for PubMedID 23920148

• Neurodevelopmental Outcomes in the Early CPAP and Pulse Oximetry Trial NEW ENGLAND JOURNAL OF MEDICINE Vaucher, Y. E., Peralta-Carcelen, M., Finer, N. N., Carlo, W. A., Gantz, M. G., Walsh, M. C., Laptook, A. R., Yoder, B. A., Faix, R. G., Das, A., Schibler, K., Rich, W., Newman, N. S., Vohr, B. R., Yolton, K., Heyne, R. J., Wilson-Costello, D. E., Evans, P. W., Goldstein, R. F., Acarregui, M. J., Adams-Chapman, I., Pappas, A., Hintz, S. R., Poindexter, B., Dusick, A. M., McGowan, E. C., Ehrenkranz, R. A., Bodnar, A., Bauer, C. R., Fuller, J., O'Shea, T. M., Myers, G. J., Higgins, R. D. 2012; 367 (26): 2495-2504

  Abstract

  Previous results from our trial of early treatment with continuous positive airway pressure (CPAP) versus early surfactant treatment in infants showed no significant difference in the outcome of death or bronchopulmonary dysplasia. A lower (vs. higher) target range of oxygen saturation was associated with a lower rate of severe retinopathy but higher mortality. We now report longer-term results from our prespecified hypotheses.Using a 2-by-2 factorial design, we randomly assigned infants born between 24 weeks 0 days and 27 weeks 6 days of gestation to early CPAP with a limited ventilation strategy or early surfactant administration and to lower or higher target ranges of oxygen saturation (85 to 89% or 91 to 95%). The primary composite outcome for the longer-term analysis was death before assessment at 18 to 22 months or neurodevelopmental impairment at 18 to 22 months of corrected age.The primary outcome was determined for 1234 of 1316 enrolled infants (93.8%); 990 of the 1058 surviving infants (93.6%) were evaluated at 18 to 22 months of corrected age. Death or neurodevelopmental impairment occurred in 27.9% of the infants in the CPAP group (173 of 621 infants), versus 29.9% of those in the surfactant group (183 of 613) (relative risk, 0.93; 95% confidence interval [CI], 0.78 to 1.10; P=0.38), and in 30.2% of the infants in the lower-oxygen-saturation group (185 of 612), versus 27.5% of those in the higher-oxygen-saturation group (171 of 622) (relative risk, 1.12; 95% CI, 0.94 to 1.32; P=0.21). Mortality was increased with the lower-oxygen-saturation target (22.1%, vs. 18.2% with the higher-oxygen-saturation target; relative risk, 1.25; 95% CI, 1.00 to 1.55; P=0.046).We found no significant differences in the composite outcome of death or neurodevelopmental impairment among extremely premature infants randomly assigned to early CPAP or early surfactant administration and to a lower or higher target range of oxygen saturation. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Heart, Lung, and Blood Institute; SUPPORT ClinicalTrials.gov number, NCT00233324.).

  View details for DOI 10.1056/NEJMoa1208506

  View details for Web of Science ID 000312714200007

  View details for PubMedID 23268664

• Infants with Prenatally Diagnosed Anomalies Special Approaches to Preparation and Resuscitation CLINICS IN PERINATOLOGY Colby, C. E., Carey, W. A., Blumenfeld, Y. J., Hintz, S. R. 2012; 39 (4): 871-887

  Abstract

  When a fetal anomaly is suspected, a multidisciplinary approach to diagnosis, counseling, pregnancy management, surveillance, delivery planning, and neonatal care is critical to creating a comprehensive management plan. This article provides a basic framework for integrating prenatal diagnostic and maternal-fetal care considerations, delivery planning, special resuscitation needs, and immediate and later neonatal care and evaluation into developing a thoughtful management plan for infants with prenatally diagnosed complex anomalies including congenital heart disease, intrathoracic masses, fetal airway obstruction, neural tube defects, abdominal wall defects, and skeletal dysplasia.

  View details for DOI 10.1016/j.clp.2012.09.012

  View details for Web of Science ID 000312623900011

  View details for PubMedID 23164184

• Brain injury following trial of hypothermia for neonatal hypoxic-ischaemic encephalopathy ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION Shankaran, S., Barnes, P. D., Hintz, S. R., Laptook, A. R., Zaterka-Baxter, K. M., McDonald, S. A., Ehrenkranz, R. A., Walsh, M. C., Tyson, J. E., Donovan, E. F., Goldberg, R. N., Bara, R., Das, A., Finer, N. N., Sanchez, P. J., Poindexter, B. B., Van Meurs, K. P., Carlo, W. A., Stoll, B. J., Duara, S., Guillet, R., Higgins, R. D. 2012; 97 (6): F398-F404

  Abstract

  The objective of our study was to examine the relationship between brain injury and outcome following neonatal hypoxic-ischaemic encephalopathy treated with hypothermia.Neonatal MRI scans were evaluated in the National Institute of Child Health and Human Development (NICHD) randomised controlled trial of whole-body hypothermia and each infant was categorised based upon the pattern of brain injury on the MRI findings. Brain injury patterns were assessed as a marker of death or disability at 18-22 months of age.Scans were obtained on 136 of 208 trial participants (65%); 73 in the hypothermia and 63 in the control group. Normal scans were noted in 38 of 73 infants (52%) in the hypothermia group and 22 of 63 infants (35%) in the control group. Infants in the hypothermia group had fewer areas of infarction (12%) compared to infants in the control group (22%). Fifty-one of the 136 infants died or had moderate or severe disability at 18 months. The brain injury pattern correlated with outcome of death or disability and with disability among survivors. Each point increase in the severity of the pattern of brain injury was independently associated with a twofold increase in the odds of death or disability.Fewer areas of infarction and a trend towards more normal scans were noted in brain MRI following whole-body hypothermia. Presence of the NICHD pattern of brain injury is a marker of death or moderate or severe disability at 18-22 months following hypothermia for neonatal encephalopathy.

  View details for DOI 10.1136/archdischild-2011-301524

  View details for Web of Science ID 000311022800003

  View details for PubMedID 23080477

• Screening for Autism Spectrum Disorders in Extremely Preterm Infants JOURNAL OF DEVELOPMENTAL AND BEHAVIORAL PEDIATRICS Stephens, B. E., Bann, C. M., Watson, V. E., Sheinkopf, S. J., Peralta-Carcelen, M., Bodnar, A., Yolton, K., Goldstein, R. F., Dusick, A. M., Wilson-Costello, D. E., Acarregui, M. J., Pappas, A., Adams-Chapman, I., McGowan, E. C., Heyne, R. J., Hintz, S. R., Ehrenkranz, R. A., Fuller, J., Das, A., Higgins, R. D., Vohr, B. R. 2012; 33 (7): 535-541

  Abstract

  Extremely preterm (EP) infants screen positive for autism spectrum disorders (ASD) at high rates. However, it is not clear whether this is because of high rates of ASD in EPs or to high rates of false-positive screens for ASD in children with a high rate of underlying neurodevelopmental impairments. Combining a parent questionnaire designed to distinguish developmental delay from ASD with direct observation of infant behavior may more accurately screen for ASD in EPs.To determine rates of positive screen for ASD at 18 to 22 months(m) in EPs using 3 screens; to determine factors associated with a positive screen.Five hundred fifty-four infants born <27 weeks were screened at 18 to 22 m using the Pervasive Developmental Disorders Screening test, second edition Stage 2, and the response to name and response to joint attention items from the Autism Diagnostic Observation Schedule. Infants with severe cerebral palsy, deafness, and blindness were excluded. Associations between positive screen and neonatal/ infant characteristics were determined.Of 554 infants, 113 (20%) had ? 1 positive screen. 10% had a positive Pervasive Developmental Disorders Screening test, second edition, 6% response to name, 9% response to joint attention; in only 1 % all 3 screens were positive. Positive screen was associated with male gender, more hospital days, white race, lower maternal education, abnormal behavioral scores, and cognitive/ language delay.The use of 3 screens for ASD in EPs results in higher screen positive rates than use of 1 screen alone. Diagnostic confirmation is needed before true rates of ASD in EPs are known.

  View details for DOI 10.1097/DBP.0b013e31825fd0af

  View details for Web of Science ID 000308668400002

  View details for PubMedID 22926660

  View details for PubMedCentralID PMC3434239

• Are Outcomes of Extremely Preterm Infants Improving? Impact of Bayley Assessment on Outcomes JOURNAL OF PEDIATRICS Vohr, B. R., Stephens, B. E., Higgins, R. D., Bann, C. M., Hintz, S. R., Das, A., Newman, J. E., Peralta-Carcelen, M., Yolton, K., Dusick, A. M., Evans, P. W., Goldstein, R. F., Ehrenkranz, R. A., Pappas, A., Adams-Chapman, I., Wilson-Costello, D. E., Bauer, C. R., Bodnar, A., Heyne, R. J., Vaucher, Y. E., Dillard, R. G., Acarregui, M. J., McGowan, E. C., Myers, G. J., Fuller, J. 2012; 161 (2): 222-?

  Abstract

  To compare 18- to 22-month cognitive scores and neurodevelopmental impairment (NDI) in 2 time periods using the National Institute of Child Health and Human Development's Neonatal Research Network assessment of extremely low birth weight infants with the Bayley Scales of Infant Development, Second Edition (Bayley II) in 2006-2007 (period 1) and using the Bayley Scales of Infant and Toddler Development, Third Edition (Bayley III), with separate cognitive and language scores, in 2008-2011 (period 2).Scores were compared with bivariate analysis, and regression analyses were run to identify differences in NDI rates.Mean Bayley III cognitive scores were 11 points higher than mean Bayley II cognitive scores. The NDI rate was reduced by 70% (from 43% in period 1 to 13% in period 2; P < .0001). Multivariate analyses revealed that Bayley III contributed to a decreased risk of NDI by 5 definitions: cognitive score <70 and <85, cognitive or language score <70; cognitive or motor score <70, and cognitive, language, or motor score <70 (P < .001).Whether the Bayley III is overestimating cognitive performance or whether it is a more valid assessment of emerging cognitive skills than the Bayley II is uncertain. Because the Bayley III identifies significantly fewer children with disability, it is recommended that all extremely low birth weight infants be offered early intervention services at the time of discharge from the neonatal intensive care unit, and that Bayley scores be interpreted with caution.

  View details for DOI 10.1016/j.jpeds.2012.01.057

  View details for Web of Science ID 000306693800013

  View details for PubMedID 22421261

• Childhood Outcomes after Hypothermia for Neonatal Encephalopathy NEW ENGLAND JOURNAL OF MEDICINE Shankaran, S., Pappas, A., McDonald, S. A., Vohr, B. R., Hintz, S. R., Epi, M. S., Yolton, K., Gustafson, K. E., Leach, T. M., Green, C., Bara, R., Huitema, C. M., Ehrenkranz, R. A., Tyson, J. E., Das, A., Hammond, J., Peralta-Carcelen, M., Evans, P. W., Heyne, R. J., Wilson-Costello, D. E., Vaucher, Y. E., Bauer, C. R., Dusick, A. M., Adams-Chapman, I., Goldstein, R. F., Guillet, R., Papile, L., Higgins, R. D. 2012; 366 (22): 2085-2092

  Abstract

  We previously reported early results of a randomized trial of whole-body hypothermia for neonatal hypoxic-ischemic encephalopathy showing a significant reduction in the rate of death or moderate or severe disability at 18 to 22 months of age. Long-term outcomes are now available.In the original trial, we assigned infants with moderate or severe encephalopathy to usual care (the control group) or whole-body cooling to an esophageal temperature of 33.5°C for 72 hours, followed by slow rewarming (the hypothermia group). We evaluated cognitive, attention and executive, and visuospatial function; neurologic outcomes; and physical and psychosocial health among participants at 6 to 7 years of age. The primary outcome of the present analyses was death or an IQ score below 70.Of the 208 trial participants, primary outcome data were available for 190. Of the 97 children in the hypothermia group and the 93 children in the control group, death or an IQ score below 70 occurred in 46 (47%) and 58 (62%), respectively (P=0.06); death occurred in 27 (28%) and 41 (44%) (P=0.04); and death or severe disability occurred in 38 (41%) and 53 (60%) (P=0.03). Other outcome data were available for the 122 surviving children, 70 in the hypothermia group and 52 in the control group. Moderate or severe disability occurred in 24 of 69 children (35%) and 19 of 50 children (38%), respectively (P=0.87). Attention-executive dysfunction occurred in 4% and 13%, respectively, of children receiving hypothermia and those receiving usual care (P=0.19), and visuospatial dysfunction occurred in 4% and 3% (P=0.80).The rate of the combined end point of death or an IQ score of less than 70 at 6 to 7 years of age was lower among children undergoing whole-body hypothermia than among those undergoing usual care, but the differences were not significant. However, hypothermia resulted in lower death rates and did not increase rates of severe disability among survivors. (Funded by the National Institutes of Health and the Eunice Kennedy Shriver NICHD Neonatal Research Network; ClinicalTrials.gov number, NCT00005772.).

  View details for DOI 10.1056/NEJMoa1112066

  View details for Web of Science ID 000304613400008

  View details for PubMedID 22646631

  View details for PubMedCentralID PMC3459579

• Ventricular Access Devices Are Safe and Effective in the Treatment of Posthemorrhagic Ventricular Dilatation prior to Shunt Placement PEDIATRIC NEUROSURGERY Tian, A. G., Hintz, S. R., Cohen, R. S., Edwards, M. S. 2012; 48 (1): 13-20

  Abstract

  Intraventricular hemorrhage of prematurity (IVH) is a diagnosis that has become more frequent in recent years. Advances in medical care have led to survival of increasingly premature infants, as well as infants with more complex medical conditions. Treatment with a ventricular access device (VAD) was reported almost 3 decades ago; however, it is unclear how effective this treatment is in the current population of premature infants. At our institution (from 2004 to present), we treat posthemorrhagic hydrocephalus (PHH) with a VAD. In order to look at safety and efficacy, we retrospectively combed the medical records of premature children, admitted to Lucile Packard Children's Hospital from January 2005 to December 2009, and identified 310 premature children with IVH. Of these, 28 children required treatment for PHH with a VAD. There were no infections associated with placement of these devices and a very low rate of other complications, such as need for repositioning (7.41%) or replacement (3.75%). Our data show that treatment with a VAD is very safe, with few complications and can be used to treat PHH in this very complex infant population.

  View details for DOI 10.1159/000337876

  View details for PubMedID 22832699

• Newborn with prenatally diagnosed choroidal fissure cyst and panhypopituitarism and review of the literature. AJP reports Chitkara, R., Rajani, A., Bernstein, J., Shah, S., Hahn, J. S., Barnes, P., Hintz, S. R. 2011; 1 (2): 111-114

  Abstract

  Little has been reported on fetal diagnosis of choroidal fissure cysts and prediction of the clinical complications that can result. We describe the case of a near-term male infant with prenatally diagnosed choroidal fissure cyst and bilateral clubfeet. His prolonged course in the neonatal intensive care nursery was marked by severe panhypopituitarism, late-onset diabetes insipidus, placement of a cystoperitoneal shunt, and episodes of sepsis. Postnatal genetic evaluation also revealed an interstitial deletion involving most of band 10q26.12 and the proximal half of band 10q26.13. The patient had multiple readmissions for medical and surgical indications and died at 6 months of age. This case represents the severe end of the spectrum of medical complications for children with choroidal fissure cysts. It highlights not only the importance of comprehensive evaluation and multidisciplinary management and counseling in such cases, but also the need for heightened vigilance in these patients.

  View details for DOI 10.1055/s-0031-1293512

  View details for PubMedID 23705098

• Is phototherapy exposure associated with better or worse outcomes in 501-to 1000-g-birth-weight infants? ACTA PAEDIATRICA Hintz, S. R., Stevenson, D. K., Yao, Q., Wong, R. J., Das, A., Van Meurs, K. P., Morris, B. H., Tyson, J. E., Oh, W., Poole, W. K., Phelps, D. L., McDavid, G. E., Grisby, C., Higgins, R. D. 2011; 100 (7): 960-965

  Abstract

  ?To compare risk-adjusted outcomes at 18- to 22-month-corrected age for extremely low birth weight (ELBW) infants who never received phototherapy (NoPTx) to those who received any phototherapy (PTx) in the NICHD Neonatal Research Network randomized trial of Aggressive vs. Conservative Phototherapy.Outcomes at 18 to 22-month-corrected age included death, neurodevelopmental impairment (NDI) and Bayley Scales Mental Developmental Index (MDI). Regression models evaluated the independent association of PTx with adverse outcomes controlling for centre and other potentially confounding variables.Of 1972 infants, 216 were NoPTx and 1756 were PTx. For the entire 501- to 1000-g-BW cohort, PTx was not independently associated with death or NDI (OR 0.85, 95% CI: 0.60-1.20), death or adverse neurodevelopmental endpoints. However, among infants 501-750 g BW, the rate of significant developmental impairment with MDI?

  View details for DOI 10.1111/j.1651-2227.2011.02175.x

  View details for PubMedID 21272067

• Early-Childhood Neurodevelopmental Outcomes Are Not Improving for Infants Born at < 25 Weeks' Gestational Age EDITORIAL COMMENT OBSTETRICAL & GYNECOLOGICAL SURVEY Hintz, S. R., Kendrick, D. E., Wilson-Costello, D. E., Das, A., Bell, E. F., Vohr, B. R., Higgins, R. D. 2011; 66 (5): 273-275

  View details for DOI 10.1097/OGX.0b013e31822942fd

  View details for Web of Science ID 000293127200007

• Improved outcomes with a standardized feeding protocol for very low birth weight infants JOURNAL OF PERINATOLOGY McCallie, K. R., Lee, H. C., Mayer, O., Cohen, R. S., Hintz, S. R., Rhine, W. D. 2011; 31: S61-S67

  Abstract

  The objective of this study was to evaluate the impact of a standardized enteral feeding protocol for very low birth weight (VLBW) infants on nutritional, clinical and growth outcomes.Retrospective analysis of VLBW cohorts 9 months before and after initiation of a standardized feeding protocol consisting of 6-8 days of trophic feedings, followed by an increase of 20?ml/kg/day. The primary outcome was days to reach full enteral feeds defined as 160?ml/kg/day. Secondary outcomes included rates of necrotizing enterocolitis and culture-proven sepsis, days of parenteral nutrition and growth end points.Data were analyzed on 147 VLBW infants who received enteral feedings, 83 before ('Before') and 64 subsequent to ('After') feeding protocol initiation. Extremely low birth weight (ELBW) infants in the After group attained enteral volumes of 120?ml/kg/day (43.9 days Before vs 32.8 days After, P=0.02) and 160?ml/kg/day (48.5 days Before vs 35.8 days After, P=0.02) significantly faster and received significantly fewer days of parenteral nutrition (46.2 days Before vs 31.3 days After, P=0.01). Necrotizing enterocolitis decreased in the After group among VLBW (15/83, 18% Before vs 2/64, 3% After, P=0.005) and ELBW infants (11/31, 35% Before vs 2/26, 8% After, P=0.01). Late-onset sepsis decreased significantly in the After group (26/83, 31% Before vs 6/64, 9% After, P=0.001). Excluding those with weight <3rd percentile at birth, the proportion with weight <3rd percentile at discharge decreased significantly after protocol initiation (35% Before vs 17% After, P=0.03).These data suggest that implementation of a standardized feeding protocol for VLBW infants results in earlier successful enteral feeding without increased rates of major morbidities.

  View details for DOI 10.1038/jp.2010.185

  View details for Web of Science ID 000289236900010

  View details for PubMedID 21448207

• Early-Childhood Neurodevelopmental Outcomes Are Not Improving for Infants Born at < 25 Weeks' Gestational Age PEDIATRICS Hintz, S. R., Kendrick, D. E., Wilson-Costello, D. E., Das, A., Bell, E. F., Vohr, B. R., Higgins, R. D. 2011; 127 (1): 62-70

  Abstract

  We compared neurodevelopmental outcomes at 18 to 22 months' corrected age of infants born with extremely low birth weight at an estimated gestational age of <25 weeks during 2 periods: 1999-2001 (epoch 1) and 2002-2004 (epoch 2).We conducted a multicenter, retrospective analysis of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Perinatal and neonatal variables and outcomes were compared between epochs. Neurodevelopmental outcomes at 18 to 22 months' corrected age were evaluated with neurologic exams and Bayley Scales of Infant Development II. Logistic regression analyses determined the independent risk of epoch for adverse outcomes.Infant survival was similar between epochs (epoch 1, 35.4%, vs epoch 2, 32.3%; P = .09). A total of 411 of 452 surviving infants in epoch 1 and 405 of 438 surviving infants in epoch 2 were evaluated at 18 to 22 months' corrected age. Cesarean delivery (P = .03), surgery for patent ductus arteriosus (P = .004), and late sepsis (P = .01) were more common in epoch 2, but postnatal steroid use was dramatically reduced (63.5% vs 32.8%; P < .0001). Adverse outcomes at 18 to 22 months' corrected age were common in both epochs. Moderate-to-severe cerebral palsy was diagnosed in 11.1% of surviving infants in epoch 1 and 14.9% in epoch 2 (adjusted odds ratio [OR]: 1.52 [95% confidence interval (CI): 0.86-2.71]; P = .15), the Mental Developmental Index was <70 in 44.9% in epoch 1 and 51% in epoch 2 (OR: 1.30 [95% CI: 0.91-1.87]; P = .15), and neurodevelopmental impairment was diagnosed in 50.1% of surviving infants in epoch 1 and 58.7% in epoch 2 (OR: 1.4 [95% CI: 0.98-2.04]; P = .07).Early-childhood outcomes for infants born at <25 weeks' estimated gestational age were unchanged between the 2 periods.

  View details for DOI 10.1542/peds.2010-1150

  View details for PubMedID 21187312

• PRENATAL DIAGNOSIS OF AMYOPLASIA CONGENITA Muller, E., Enns, G., Hintz, S., Barth, R., Hudgins, L. LIPPINCOTT WILLIAMS & WILKINS. 2011: 165

  View details for Web of Science ID 000285542500292

• NEWBORN WITH CHOROIDAL FISSURE CYST AND PANHYPOPITUITARISM Western Regional Meeting of the American-Federation-for-Medical-Research Chitkara, R., Rajani, A., Bernstein, J., Hudgins, L., Shah, S., Hahn, J., Hintz, S. LIPPINCOTT WILLIAMS & WILKINS. 2011: 166?66

  View details for Web of Science ID 000285542500296

• Seizures in Extremely Low Birth Weight Infants Are Associated with Adverse Outcome JOURNAL OF PEDIATRICS Davis, A. S., Hintz, S. R., Van Meurs, K. P., Li, L., Das, A., Stoll, B. J., Walsh, M. C., Pappas, A., Bell, E. F., Laptook, A. R., Higgins, R. D. 2010; 157 (5): 720-U47

  Abstract

  To examine risk factors for neonatal clinical seizures and to determine the independent association with death or neurodevelopmental impairment (NDI) in extremely low birth weight (ELBW) infants.A total of 6499 ELBW infants (401-1000 g) surviving to 36 weeks postmenstrual age (PMA) were included in this retrospective study. Unadjusted comparisons were performed between infants with (n = 414) and without (n = 6085) clinical seizures during the initial hospitalization. Using multivariate logistic regression modeling, we examined the independent association of seizures with late death (after 36 weeks PMA) or NDI after controlling for multiple demographic, perinatal, and neonatal variables.Infants with clinical seizures had a greater proportion of neonatal morbidities associated with poor outcome, including severe intraventricular hemorrhage, sepsis, meningitis, and cystic periventricular leukomalacia (all P < .01). Survivors were more likely to have NDI or moderate-severe cerebral palsy at 18 to 22 months corrected age (both P < .01). After adjusting for multiple confounders, clinical seizures remained significantly associated with late death or NDI (odds ratio, 3.15; 95% CI, 2.37-4.19).ELBW infants with clinical seizures are at increased risk for adverse neurodevelopmental outcome, independent of multiple confounding factors.

  View details for DOI 10.1016/j.jpeds.2010.04.065

  View details for PubMedID 20542294

• Prediction of Death for Extremely Premature Infants in a Population-Based Cohort PEDIATRICS Lee, H. C., Green, C., Hintz, S. R., Tyson, J. E., Parikh, N. A., Langer, J., Gould, J. B. 2010; 126 (3): E644-E650

  Abstract

  Although gestational age (GA) is often used as the primary basis for counseling and decision-making for extremely premature infants, a study of tertiary care centers showed that additional factors could improve prediction of outcomes. Our objective was to determine how such a model could improve predictions for a population-based cohort.From 2005 to 2008, data were collected prospectively for the California Perinatal Quality Care Collaborative, which encompasses 90% of NICUs in California. For infants born at GAs of 22 to 25 weeks, we assessed the ability of the Eunice Kennedy Shriver National Institute of Child Health and Human Development 5-factor model to predict survival rates, compared with a model using GA alone.In the study cohort of 4527 infants, 3647 received intensive care. Survival rates were 53% for the whole cohort and 66% for infants who received intensive care. In multivariate analyses of data for infants who received intensive care, prenatal steroid exposure, female sex, singleton birth, and higher birth weight (per 100-g increment) were each associated with a reduction in the risk of death before discharge similar to that for a 1-week increase in GA. The multivariate model increased the ability to group infants in the highest and lowest risk categories (mortality rates of >80% and <20%, respectively).In a population-based cohort, the addition of prenatal steroid exposure, sex, singleton or multiple birth, and birth weight to GA allowed for improved prediction of rates of survival to discharge for extremely premature infants.

  View details for DOI 10.1542/peds.2010-0097

  View details for Web of Science ID 000281535700047

  View details for PubMedID 20713479

• A National Survey of Pediatric Residents and Delivery Room Training Experience JOURNAL OF PEDIATRICS Lee, H. C., Chitkara, R., Halamek, L. P., Hintz, S. R. 2010; 157 (1): 158-U211

  Abstract

  To investigate current delivery room training experience in US pediatric residency programs and the relationship between volume of delivery room training and confidence in neonatal resuscitation skills.Links to a web-based survey were sent to pediatric residency programs and distributed to residents. The survey concerned delivery room attendance during training and comfort level in leading neonatal resuscitation for various scenarios. Comfort level was rated on a 1 to 9 scale. Mixed models accounted for residency programs as random effects.For PL-3s, the mean number of deliveries attended was 60 (standard deviation, 43), ranging from 13 to 143 deliveries for individual residency programs. Residents' confidence level in leading neonatal resuscitation was higher when attending more deliveries, with 90.3% of those attending>48 deliveries having average score 5 or greater vs 51.5% of those attending<21 deliveries. Higher attendance also correlated with confidence in endotracheal intubation and umbilical line placement.Wide variability existed within and among residency programs in number of deliveries attended. Volume of experience correlated with confidence in leading neonatal resuscitation and related procedural skills.

  View details for DOI 10.1016/j.jpeds.2010.01.029

  View details for Web of Science ID 000278649200037

  View details for PubMedID 20304418

  View details for PubMedCentralID PMC2886184

• Aluminum Content of Parenteral Nutrition in Neonates: Measured Versus Calculated Levels JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Poole, R. L., Schiff, L., Hintz, S. R., Wong, A., Mackenzie, N., Kerner, J. A. 2010; 50 (2): 208-211

  Abstract

  Aluminum (Al) is associated with significant central nervous system toxicity and bone and liver damage. Because Al is a contaminant of parenteral nutrition (PN) components including calcium and phosphate additives, premature infants are at potentially high risk for toxicity. The US Food and Drug Administration (FDA) has mandated PN component product labeling and recommended maximum Al daily exposure limits. The objective of this article is to determine the actual Al content of neonatal PN solutions, compare these values to the calculated amounts from manufacturers' PN product labels, and ascertain whether the actual Al exposure exceeds the FDA recommended maximum of 5 microg . kg(-1) . day(-1).Samples from 40 neonatal patient PN solutions were selected for sampling and Al content determination. Samples were also taken from 16 manufacturer's component products used in PN formulation. All of the samples were sent to Mayo Laboratories for Al content measurement. The calculated Al concentrations in PN samples were determined from the manufacturer's labeled content.Both measured and calculated Al concentrations exceeded the FDA recommended safe limit of <5 microg . kg(-1) . day(-1). The actual measured Al content was significantly lower than the calculated Al content in both the patient PN solutions and the component product samples.Al exposure exceeded the FDA recommended maximum limit for all patient samples; however, the actual measured Al content of all the samples was significantly less than the calculated Al content based on manufacturer's labels. These findings suggest that manufacturers label their products with actual Al content at the time of product release rather than at time of expiration. Periodic monitoring of Al levels should be considered with prolonged PN therapy. Changes in manufacturing processes, including the use of better raw materials, are essential to reduce Al contamination to meet FDA mandates.

  View details for DOI 10.1097/MPG.0b013e3181aed70b

  View details for Web of Science ID 000273994000018

  View details for PubMedID 20038851

• Predicting Time to Hospital Discharge for Extremely Preterm Infants PEDIATRICS Hintz, S. R., Bann, C. M., Ambalavanan, N., Cotten, M., Das, A., Higgins, R. D. 2010; 125 (1): E146-E154

  Abstract

  As extremely preterm infant mortality rates have decreased, concerns regarding resource use have intensified. Accurate models for predicting time to hospital discharge could aid in resource planning, family counseling, and stimulate quality-improvement initiatives.To develop, validate, and compare several models for predicting the time to hospital discharge for infants <27 weeks' estimated gestational age, on the basis of time-dependent covariates as well as the presence of 5 key risk factors as predictors.We conducted a retrospective analysis of infants <27 weeks' estimated gestational age who were born between July 2002 and December 2005 and survived to discharge from a Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network site. Time to discharge was modeled as continuous (postmenstrual age at discharge) and categorical (early and late discharge) variables. Three linear and logistic regression models with time-dependent covariate inclusion were developed (perinatal factors only, perinatal + early-neonatal factors, and perinatal + early-neonatal + later factors). Models for early and late discharge that used the cumulative presence of 5 key risk factors as predictors were also evaluated. Predictive capabilities were compared by using the coefficient of determination (R(2)) for the linear models and the area under the curve (AUC) of the receiver operating characteristic curve for the logistic models.Data from 2254 infants were included. Prediction of postmenstrual age at discharge was poor. However, models that incorporated later clinical characteristics were more accurate in predicting early or late discharge (AUC: 0.76-0.83 [full models] vs 0.56-0.69 [perinatal factor models]). In simplified key-risk-factors models, the predicted probabilities for early and late discharge compared favorably with the observed rates. Furthermore, the AUC (0.75-0.77) was similar to those of the models that included the full factor set.Prediction of early or late discharge is poor if only perinatal factors are considered, but it improves substantially with knowledge of later-occurring morbidities. Predictive models that use a few key risk factors are comparable to the full models and may offer a clinically applicable strategy.

  View details for DOI 10.1542/peds.2009-0810

  View details for PubMedID 20008430

• OCULOCEREBROCUTANEOUS (DELLEMAN) SYNDROME: A NEW CASE WITH PRENATAL FINDINGS AND DIFFERENTIAL DIAGNOSIS Muller, E., Barnes, P., Montez, K., Hahn, J., Yang, J., Hintz, S., Penn, A., Enns, G. BMJ PUBLISHING GROUP. 2010: 183

  View details for Web of Science ID 000273638400291

• SEVERE HYPERAMMONEMIA AS INITIAL PRESENTATION IN PATIENTS WITH LONG CHAIN FATTY ACID OXIDATION DEFECTS - CONSIDERATIONS FOR INITIAL TREATMENT Niemi, A., Hintz, S., Enns, G. M. BMJ PUBLISHING GROUP. 2010: 123?24

  View details for Web of Science ID 000273638400091

• Medical Management of Extremely Low-Birth-Weight Infants in the First Week of Life: A Survey of Practices in the United States AMERICAN JOURNAL OF PERINATOLOGY Kiefer, A. S., Wickremasinghe, A. C., Johnson, J. N., Hartman, T. K., Hintz, S. R., Carey, W. A., Colby, C. E. 2009; 26 (6): 407-418

  Abstract

  We sought to determine the current practices of neonatologists in their management of extremely low-birth-weight (< 1000 g) infants. We directly mailed an anonymous survey to the medical directors of 809 neonatal intensive care units in the United States. More than one-third of those surveyed responded, with a substantial majority from intensive care (level III) nurseries or extracorporeal membrane oxygenation centers. Academic centers and private practice environments were both well represented. Some traditional practices have changed, such as beginning resuscitation with 40% rather than 100% oxygen. Many practices vary based on whether neonates are cared for in private versus academic centers, including initial resuscitation method, type of ventilation used, use of intraventricular hemorrhage prophylaxis, and routine antibiotic therapy. Parenteral nutrition composition and the use of inhaled nitric oxide differ based on the responding center's participation in clinical trials. The number of years in practice as a neonatologist does not affect practice decisions. Among all our findings, the prevalence of one potentially harmful practice, the continued use of dexamethasone for corticosteroid therapy, was particularly noteworthy. In conclusion, the strength of evidence does not always predict whether practices are adopted or abandoned. Further research is necessary to clarify the optimal management for this high-risk patient population.

  View details for DOI 10.1055/s-0029-1214235

  View details for Web of Science ID 000266332500002

  View details for PubMedID 19301226

• Inhaled Nitric Oxide for Preterm Premature Rupture of Membranes, Oligohydramnios, and Pulmonary Hypoplasia AMERICAN JOURNAL OF PERINATOLOGY Chock, V. Y., Van Meurs, K. P., Hintz, S. R., Ehrenkranz, R. A., Lemons, J. A., Kendrick, D. E., Stevenson, D. K. 2009; 26 (4): 317-322

  Abstract

  We sought to determine if inhaled nitric oxide (iNO) administered to preterm infants with premature rupture of membranes (PPROM), oligohydramnios, and pulmonary hypoplasia improved oxygenation, survival, or other clinical outcomes. Data were analyzed from infants with suspected pulmonary hypoplasia, oligohydramnios, and PPROM enrolled in the National Institute of Child Health and Development Neonatal Research Network Preemie Inhaled Nitric Oxide (PiNO) trial, where patients were randomized to receive placebo (oxygen) or iNO at 5 to 10 ppm. Outcome variables assessed were PaO (2) response, mortality, bronchopulmonary dysplasia (BPD), and severe intraventricular hemorrhage (IVH) or periventricular leukomalacia (PVL). Twelve of 449 infants in the PiNO trial met criteria. Six infants received iNO and six received placebo. The iNO group had a mean increase in PaO (2) of 39 +/- 50 mm Hg versus a mean decrease of 11 +/- 15 mm Hg in the control group. Mortality was 33% versus 67%, BPD (2/5) 40% versus (2/2) 100%, and severe IVH or PVL (1/5) 20% versus (1/2) 50% in the iNO and control groups, respectively. None of these changes were statistically significant. Review of a limited number of cases from a large multicenter trial suggests that iNO use in the setting of PPROM, oligohydramnios, and suspected pulmonary hypoplasia improves oxygenation and may decrease the rate of BPD and death without increasing severe IVH or PVL. However, the small sample size precludes definitive conclusions. Further studies are required to determine if iNO is of benefit in this specific patient population.

  View details for DOI 10.1055/s-0028-1104743

  View details for PubMedID 19067285

• Changes in Attendance at Deliveries by Pediatric Residents 2000 to 2005 AMERICAN JOURNAL OF PERINATOLOGY Lee, H. C., Rhee, C. J., Sectish, T. C., Hintz, S. R. 2009; 26 (2): 129-134

  Abstract

  We sought to determine if pediatric resident attendance at deliveries for newborn assessment and resuscitation had changed over the years at a training hospital. Data were abstracted from medical records of newborns discharged during the same 6-week periods for 5 consecutive academic years spanning a period before and after resident duty hour regulation changes were implemented. Names of personnel attending deliveries were noted in delivery records. The proportions of deliveries attended by any practitioner were compared by year, as well as the proportion of deliveries attended by practitioner type and training level. A total of 2666 delivery records were reviewed. The proportions of deliveries attended by any practitioner over the 5 years were similar, ranging from 43 to 49%. The proportion of deliveries attended by pediatric residents was highest at 51 to 57% from 2000 to 2002, declined to a low of 5% during 2002 to 2003, and rose to 20 to 23% during 2003 to 2005 ( P < 0.0001). The decrease in attendance by residents was compensated by an increase in attendance by hospitalists. At this training institution, pediatric resident attendance at deliveries declined substantially over recent years, likely due in part to resident duty hour regulations and increased use of hospitalists in roles previously held by residents.

  View details for DOI 10.1055/s-0028-1091395

  View details for Web of Science ID 000262934700006

  View details for PubMedID 18850515

• PEDIATRIC RESIDENT ATTENDANCE AT DELIVERIES Western Regional Meeting of the American-Federation-for-Medical-Research Chitkara, R., LEE, H., Hintz, S. LIPPINCOTT WILLIAMS & WILKINS. 2009: 238?38

  View details for Web of Science ID 000270092400511

• School Outcomes of Late Preterm Infants: Special Needs and Challenges for Infants Born at 32-to 36-Week Gestation OBSTETRICAL & GYNECOLOGICAL SURVEY Chyl, L. J., Lee, H. C., Hintz, S. R., Gould, J. B., Sutcliffe, T. L. 2008; 63 (11): 691?92

  View details for DOI 10.1097/01.ogx.0000334732.35212.87

  View details for Web of Science ID 000260854500007

• Aggressive vs. conservative phototherapy for infants with extremely low birth weight NEW ENGLAND JOURNAL OF MEDICINE Morris, B. H., Oh, W., Tyson, J. E., Stevenson, D. K., Phelps, D. L., O'Shea, T. M., McDavid, G. E., Perritt, R. L., Van Meurs, K. P., Vohr, B. R., Grisby, C., Yao, Q., Pedroza, C., Das, A., Poole, W. K., Carlo, W. A., Duara, S., Laptook, A. R., Salhab, W. A., Shankaran, S., Poindexter, B. B., Fanaroff, A. A., Walsh, M. C., Rasmussen, M. R., Stoll, B. J., Cotten, C. M., Donovan, E. F., Ehrenkranz, R. A., Guillet, R., Higgins, R. D. 2008; 359 (18): 1885-1896

  Abstract

  It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 micromol per liter], P<0.01) but not the rate of the primary outcome (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543.)

  View details for Web of Science ID 000260454500005

  View details for PubMedID 18971491

  View details for PubMedCentralID PMC2821221

• Community supports after surviving extremely low-birth-weight, extremely preterm birth - Special outpatient services in early childhood ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE Hintz, S. R., Kendrick, D. E., Vohr, B. R., Poole, W. K., Higgins, R. D. 2008; 162 (8): 748-755

  Abstract

  To determine special outpatient services (SOS) use, need, associated factors, and neurodevelopmental and functional outcomes among extremely preterm infants at 18 to 22 months' corrected age.Retrospective analysis.National Institute of Child Health and Human Development (NICHD) Neonatal Research Network.Infants younger than 28 weeks' gestational age who had been born weighing less than 1000 g at an NICHD Neonatal Research Network center from January 1, 1997, to December 31, 2000, and who were receiving follow-up at 18 to 22 months' corrected age.Questionnaires were administered at the 18- to 22-month follow-up visit regarding SOS use since hospital discharge and the current need for SOS (social work, visiting nurse, medical specialty, early intervention, speech and language services, occupational therapy and physical therapy, and neurodevelopmental and behavioral services).The use of and need for SOS were analyzed by gestational age. Logistic regression analysis identified factors independently associated with the use of more than 5 services and with the need for any services.Of 2315 infants, 54.7% used more than 3 SOS by 18 to 22 months, and 19.1% used 6 to 7 SOS. The need for any SOS was reported by approximately 37%. The following variables that were commonly associated with adverse neurodevelopmental outcomes were also associated with the use of more than 5 SOS: sepsis, birth weight, postnatal corticosteroid use, bronchopulmonary dysplasia, and cystic periventricular leukomalacia or grade 3 or 4 intraventricular hemorrhage. Male sex was associated with the need for any SOS. Although high SOS use was more likely among children with adverse neurodevelopmental outcomes, a reported need for SOS was common even among those with mild developmental impairment (39.7%) and mild cerebral palsy (42.2%).High SOS use is common, has identifiable neonatal risk factors, and is associated with neurodevelopmental impairment. Extremely preterm survivors have substantial need for community supports regardless of their impairment level. Efforts to improve comprehensive delivery of family-centered community-based services are urgently needed.

  View details for PubMedID 18678807

• School outcomes of late preterm infants: Special needs and challenges for infants born at 32 to 36 weeks gestation JOURNAL OF PEDIATRICS Chyi, L. J., Lee, H. C., Hintz, S. R., Gould, J. B., Sutcliffe, T. L. 2008; 153 (1): 25-31

  Abstract

  Because limited long-term outcome data exist for infants born at 32 to 36 weeks gestation, we compared school outcomes between 32- to 33-week moderate preterm (MP), 34-36 week late preterm (LP) and full-term (FT) infants.A total of 970 preterm infants and 13 671 FT control subjects were identified from the Early Childhood Longitudinal Study-Kindergarten Cohort. Test scores, teacher evaluations, and special education enrollment from kindergarten (K) to grade 5 were compared.LP infants had lower reading scores than FT infants in K to first grade (P < .05). Adjusted risk for poor reading and math scores remained elevated in first grade (P < .05). Teacher evaluations of math skills from K to first grade and reading skills from K to fifth grade were worse for LP infants (P < .05). Adjusted odds for below average skills remained higher for math in K and for reading at all grades (P < .05). Special education participation was higher for LP infants at early grades (odds ratio, 1.4-2.1). MP infants had lower test and teacher evaluation scores than FT infants and twice the risk for special education at all grade levels.Persistent teacher concerns through grade 5 and greater special education needs among MP and LP infants suggest a need to start follow-up, anticipatory guidance, and interventions for infants born at 32 to 36 weeks gestation.

  View details for DOI 10.1016/j.jpeds.2008.01.027

  View details for Web of Science ID 000257154800010

  View details for PubMedID 18571530

• Aluminum exposure from pediatric parenteral nutrition: Meeting the new FDA regulation JOURNAL OF PARENTERAL AND ENTERAL NUTRITION Poole, R. L., Hintz, S. R., Mackenzie, N. I., Kerner, J. A. 2008; 32 (3): 242-246

  Abstract

  Aluminum toxicity can cause serious central nervous system and bone toxicities. Aluminum is a contaminant of parenteral nutrition (PN) solution components. Premature neonates requiring high doses of calcium and phosphate to mineralize their bones, children with impaired renal function, and children on PN therapy for prolonged duration are at the highest risk. Effective in July 2004, the U.S. Food and Drug Administration (FDA) mandated labeling requirements for aluminum content in all PN solution components. To assess the aluminum exposure in neonatal and pediatric populations, this study aims to determine patients' daily aluminum load (mug/kg/d) delivered from PN solutions.The study included all inpatients who received PN during calendar year 2006 (13,384 PN patient days). The calculated parameters of mug/kg/d and mug/L of parentally administered aluminum were stratified according to patient age and weight. Aluminum content by product and manufacturer were tabulated.Forty-nine percent of the PN patient days were in patients weighing < 3 kg. These patients also received the largest amounts of aluminum (range, 30-60 mug/kg/d). Meeting the FDA regulation was possible only in patients weighing > 50 kg.Currently available parenteral products used to make PN solutions contain amounts of aluminum that make it impossible to meet the new FDA rule of <5 mug/kg/d of aluminum exposure. Manufacturers must identify, develop, and adopt new methods to reduce the aluminum contamination in their products. Health care professionals should calculate aluminum loads in patients and make informed decisions when choosing PN products.

  View details for DOI 10.1177/0148607108316187

  View details for Web of Science ID 000259016300003

  View details for PubMedID 18443135

• Neuroimaging and neurodevelopmental outcomes in preterm infants SEMINARS IN PERINATOLOGY Hintz, S. R., O'Shea, M. 2008; 32 (1): 11-19

  Abstract

  Imaging of the preterm infant brain has advanced dramatically beyond the earliest era of transillumination. Computed tomography (CT), a crucial innovation during the early 1970s, allowed noninvasive visualization of intracerebral lesions, particularly hemorrhage. The capability to document brain injury in the preterm infant led to better clarification of links to developmental outcomes. With the development of cranial ultrasound (CUS), and more recently, magnetic resonance imaging (MRI), CT is used rarely for imaging the brain of preterm infants. Despite extensive experience with neonatal neuroimaging, significant questions still remain. Substantial controversies exist pertaining to when and how neuroimaging should be performed and how images should be interpreted.

  View details for DOI 10.1053/j.semperi.2007.12.010

  View details for Web of Science ID 000253220800003

  View details for PubMedID 18249235

• Clinical data predict neurodevelopmental outcome better than head ultrasound in extremely low birth weight infants JOURNAL OF PEDIATRICS Broitman, E., Ambalavanan, N., Higgins, R. D., Vohr, B. R., Das, A., Bhaskar, B., Murray, K., Hintz, S. R., Carlo, W. A. 2007; 151 (5): 500-505

  Abstract

  To determine the relative contribution of clinical data versus head ultrasound scanning (HUS) in predicting neurodevelopmental impairment (NDI) in extremely low birth weight infants.A total of 2103 extremely low birth weight infants (<1000 g) admitted to a National Institute of Child Health and Human Development Neonatal Research Network center who underwent HUS within the first 28 days, a repeat one around 36 weeks' postmenstrual age, and neurodevelopmental assessment at 18 to 22 months corrected age were selected. Multivariate logistic regression models were developed with clinical or HUS variables. The primary outcome was the predictive abilities of the HUS performed before 28 days after birth and closer to 36 weeks postmenstrual age, either alone or in combination with "Early" and "Late" clinical variables.Models with clinical variables alone predicted NDI better than models with only HUS variables at both 28 days and 36 weeks (both P < .001), and the addition of the HUS data did not improve prediction. NDI was absent in 30% and 28% of the infants with grade IV intracranial hemorrhage or periventricular leukomalacia, respectively, but was present in 39% of the infants with a normal HUS result.Clinical models were better than HUS models in predicting neurodevelopment.

  View details for DOI 10.1016/j.jpeds.2007.04.013

  View details for Web of Science ID 000250815900013

  View details for PubMedID 17961693

  View details for PubMedCentralID PMC2879162

• Reply to McAdams and Milhoan JOURNAL OF PERINATOLOGY Lee, H. C., Silverman, N., Hintz, S. R. 2007; 27 (11): 735?36

  View details for DOI 10.1038/sj.jp.7211814

  View details for Web of Science ID 000250444500015

• Prenatal diagnosis of congenital diaphragmatic hernia: how should the babies be delivered? 53rd Annual International Congress of the British-Association-of-Paediatric-Surgeons Frenckner, B. P., Lally, P. A., Hintz, S. R., Lally, K. P. W B SAUNDERS CO-ELSEVIER INC. 2007: 1533?38

  Abstract

  Congenital diaphragmatic hernia (CDH) in many patients is diagnosed in utero. In these patients, the delivery can be planned as an elective cesarean, induced vaginal, or spontaneous vaginal delivery. The optimal method has yet to be determined. The aim of this study was to compare the outcome of patients with CDH delivered by different methods.The Congenital Diaphragmatic Hernia Study Group was formed in 1995 to compile data on liveborn babies with CDH. Beginning in 2001, data concerning delivery were collected. By October 2005, delivery data were available on 1039 term and near-term infants without cardiac malformations. Five hundred forty-eight had a prenatal diagnosis and complete data on delivery (194 delivered by elective cesarean delivery, 121 by induced vaginal delivery, and 233 by spontaneous vaginal delivery). Patients delivered by a nonelective cesarean delivery were assigned to the delivery group for which they were originally planned.The overall survival among the 548 patients was 69%. It was highest in patients delivered by cesarean delivery (71%) followed by those delivered through induced vaginal delivery (70%) and spontaneous vaginal delivery (67%). The difference was not statistically significant. Fifty-three percent of all patients survived without extracorporeal membrane oxygenation (ECMO). This was significantly higher after cesarean delivery (60%) than after induced vaginal delivery (49%) or spontaneous vaginal delivery (49%) (P < .05). At 30 days of age, 45% of the patients delivered by cesarean delivery had survived and were on room air. This was slightly lower after induced vaginal delivery (37%) or after spontaneous vaginal delivery (37%), although not statistically significant.Cesarean delivery was associated with a slightly better outcome in terms of a significantly higher survival without the use of extracorporeal membrane oxygenation, although there was no significant difference in total survival. Because this study was not randomized, it is not possible to determine if the elective cesarean delivery was the cause for the better outcome or if centers favoring elective cesarean delivery by protocol are more skillful in the management of patients with CDH. Mode of delivery for term and near-term infants with CDH deserves further prospective study.

  View details for DOI 10.1016/j.jpedsurg.2007.04.016

  View details for Web of Science ID 000249746100012

  View details for PubMedID 17848244

• Neurodevelopmental outcomes of premature infants with severe respiratory failure enrolled in a randomized controlled trial of inhaled nitric oxide JOURNAL OF PEDIATRICS Hintz, S. R., Van Meurs, K. P., Perritt, R., Poole, W. K., Das, A., Stevenson, D. K., Ehrenkranz, R. A., Lemons, J. A., Vohr, B. R., Heyne, R., Childers, D. O., Peralta-Carcelen, M., Dusick, A., Johnson, Y. R., Morris, B., Dillard, R., Vaucher, Y., Steichen, J., Adams-Chapman, I., Konduri, G., Myers, G. J., De Ungria, M., Tyson, J. E., Higgins, R. D. 2007; 151 (1): 16-22

  Abstract

  We hypothesized that inhaled nitric oxide (iNO) would not decrease death or neurodevelopmental impairment (NDI) in infants enrolled in the National Institute of Child Health and Human Development Preemie iNO Trial (PiNO) trial, nor improve neurodevelopmental outcomes in the follow-up group.Infants <34 weeks of age, weighing <1500 g, with severe respiratory failure were enrolled in the multicenter, randomized, controlled trial. NDI at 18 to 22 months corrected age was defined as: moderate to severe cerebral palsy (CP; Mental Developmental Index or Psychomotor score Developmental Index <70), blindness, or deafness.Of 420 patients enrolled, 109 who received iNO (52%) and 98 who received placebo (47%) died. The follow-up rate in survivors was 90%. iNO did not reduce death or NDI (78% versus 73%; relative risk [RR], 1.07; 95% CI, 0.95-1.19), or NDI or Mental Developmental Index <70 in the follow-up group. Moderate-severe CP was slightly higher with iNO (RR, 2.41; 95% CI, 1.01-5.75), as was death or CP in infants weighing <1000 g (RR, 1.22; 95% CI, 1.05-1.43).In this extremely ill cohort, iNO did not reduce death or NDI or improve neurodevelopmental outcomes. Routine iNO use in premature infants should be limited to research settings until further data are available.

  View details for DOI 10.1016/j.jpeds.2007.03.017

  View details for Web of Science ID 000247851900007

  View details for PubMedID 17586184

  View details for PubMedCentralID PMC2770191

• Inhaled nitric oxide in infants > 1500 g and < 34 weeks gestation with severe respiratory failure JOURNAL OF PERINATOLOGY Van Meurs, K. P., Hintz, S. R., Ehrenkranz, R. A., Lemons, J. A., Ball, M. B., Poole, W. K., Perritt, R., Das, A., Higgins, R. D., Stevenson, D. K. 2007; 27 (6): 347-352

  Abstract

  Inhaled nitric oxide (iNO) use in infants >1500 g, but <34 weeks gestation with severe respiratory failure will reduce the incidence of death and/or bronchopulmonary dysplasia (BPD).Infants born at <34 weeks gestation with a birth weight >1500 g with respiratory failure were randomly assigned to receive placebo or iNO.Twenty-nine infants were randomized. There were no differences in baseline characteristics, but the status at randomization showed a statistically significant difference in the use of high-frequency ventilation (P=0.03). After adjustment for oxygenation index entry strata, there was no difference in death and/or BPD (adjusted relative risk (RR) 0.80, 95% confidence interval (CI) 0.43 to 1.48; P=0.50), death (adjusted RR 1.26, 95% CI 0.47 to 3.41; P=0.65) or BPD (adjusted RR 0.40, 95% CI 0.47 to 3.41; P=0.21).Although sample size limits our ability to make definitive conclusions, this small pilot trial of iNO use in premature infants >1500 g and <34 weeks with severe respiratory failure suggests that iNO does not affect the rate of BPD and/or death.

  View details for DOI 10.1038/sj.jp.7211690

  View details for Web of Science ID 000246905800005

  View details for PubMedID 17443204

• Interobserver reliability and accuracy of cranial ultrasound scanning interpretation in premature infants JOURNAL OF PEDIATRICS Hintz, S. R., Slovis, T., Bulas, D., Van Meurs, K. P., Perritt, R., Stevenson, D. K., Poole, W. K., Das, A., Higgins, R. D. 2007; 150 (6): 592-596

  Abstract

  To assess interobserver reliability between 2 central readers of cranial ultrasound scanning (CUS) and accuracy of local, compared with central, interpretations.The study was a retrospective analysis of CUS data from the National Institute of Child Health and Human Development (NICHD) trial of inhaled nitric oxide for premature infants. Interobserver reliability of 2 central readers was assessed with kappa or weighted kappa. Accuracy of local, compared with central, interpretations was assessed by using sensitivity and specificity.CUS from 326 infants had both central reader and local interpretations. Central reader agreement for grade 3/4 intraventricular hemorrhage (IVH), grade 3/4 IVH or periventricular leukomalacia (PVL), grade of IVH, and degree of ventriculomegaly was very good (kappa = 0.84, 0.81, 0.79, and 0.75, respectively). Agreement was poor for lower grade IVH and for PVL alone. Local interpretations were highly accurate for grade 3/4 IVH or PVL (sensitivity, 87%-90%; specificity, 92%-93%), but sensitivity was poor-to-fair for grade 1/2 IVH (48%-68%) and PVL (20%-44%).Our findings demonstrate reliability and accuracy of highly unfavorable CUS findings, but suggest caution when interpreting mild to moderate IVH or white matter injury.

  View details for DOI 10.1016/j.jpeds.2007.02.012

  View details for PubMedID 17517240

• Diagnosis of patent ductus arteriosus by a neonatologist with a compact, portable ultrasound machine JOURNAL OF PERINATOLOGY Lee, H. C., Silverman, N., Hintz, S. R. 2007; 27 (5): 291-296

  Abstract

  To conduct a pilot study assessing a neonatologist's accuracy in diagnosing patent ductus arteriosus (PDA) using compact, portable ultrasound after limited training.Prospective study of premature infants scheduled for echocardiography for suspected PDA. A neonatologist with limited training performed study exams before scheduled exams. Sensitivity and specificity were calculated, compared to the scheduled echocardiogram interpreted by a cardiologist.There were 24 exams. Compared to the scheduled exam, the neonatologist's exam had sensitivity 69% (95% confidence interval (CI), 41 to 89%) and specificity 88% (95% CI, 47 to 99%). When a cardiologist interpreted the study exams, the sensitivity was 87% (95% CI, 60 to 98%) and specificity 71% (95% CI, 29 to 96%).A neonatologist with limited training was able to detect PDA with moderate success. A more rigorous training process or real-time transmission with cardiologist interpretation may substantially improve accuracy. Institutions with experienced technicians and on-site pediatric cardiologists may not gain from intensive training of neonatologists, but hospitals where diagnosis and treatment of PDA would be delayed may benefit from such processes.

  View details for DOI 10.1038/sj.jp.7211693

  View details for Web of Science ID 000246105400008

  View details for PubMedID 17363908

• Hypothermia for the treatment of neonatal ischemic encephalopathy: Is the genie out of the bottle? AMERICAN JOURNAL OF PERINATOLOGY Lang, T. R., Hartman, T. K., Hintz, S. R., Colby, C. E. 2007; 24 (1): 27-31

  Abstract

  Evidence suggests that hypothermia for hypoxic ischemic encephalopathy in the term neonate may decrease the risk of death or neurodevelopmental impairment. The objective of this study was to determine how hypothermia has been incorporated into practice. An anonymous survey was sent to medical directors of United States neonatal intensive care units (NICUs) in October 2005. We received completed surveys from 441 (54.5%) of 809 of NICUs. Only 6.4% of respondents used hypothermia. The most common method was total body cooling (64.3%) compared with head cooling (25%) or both (10.7%). At centers that did not offer hypothermia, 29% transferred infants to an institution that did. Centers that offered hypothermia were more likely at academic institutions (76.9%) compared with private practices (11.5%; p < 0.001). Hypothermia was more likely offered at institutions that offered extracorporeal membrane oxygenation (ECMO; 57%) than centers where ECMO was not offered (43%; p < 0.001). There has not been widespread use of hypothermia. There are a variety of protocols used. As results of further outcome studies become available, educational efforts and national practice guidelines will be essential.

  View details for DOI 10.1055/s-2006-958157

  View details for Web of Science ID 000245040700006

  View details for PubMedID 17195147

• The use of inhaled nitric oxide in the premature infant with respiratory distress syndrome. Minerva pediatrica Van Meurs, K., Hintz, S., Rhine, W., Benitz, W. 2006; 58 (5): 403-422

  Abstract

  The identification of the biologic properties of nitric oxide (NO) is one of the key scientific discoveries of the century, but its potential for treating human disease is yet to be fully realized. NO has a basic role in regulating vascular tone of the pulmonary circulation, and recent animal models have suggested a more wide reaching influence on perinatal lung development. In animal models, NO has effects on lung growth, angiogenesis, airway smooth muscle proliferation, vascular remodeling, surfactant function, inflammation, and pulmonary mechanics. However, despite extensive basic science investigation and completion of several large clinical trials, the role of NO in the treatment of the premature infant with respiratory distress syndrome remains unclear. One must conclude that the interaction of lung immaturity, ventilator and oxygen-induced lung injury, and NO biology in the premature newborn is incompletely understood. Clinical trial results of inhaled NO therapy in the premature infant are accumulating, but the results do not suggest a clear-cut advantage for the population at greatest risk for death and disability. Whether trial design, dose, duration of therapy, or other factors are responsible has not been determined. Further research is needed to answer these questions and more clearly define the population of premature infants who may derive benefit from this new therapy.

  View details for PubMedID 17008853

• Gender differences in neurodevelopmental outcomes among extremely preterm, extremely-low-birthweight infants ACTA PAEDIATRICA Hintz, S. R., Kendrick, D. E., Vohr, B. R., Poole, W. K., Higgins, R. D. 2006; 95 (10): 1239-1248

  Abstract

  To determine whether gender-specific responses to perinatal and neonatal events and exposures explain the male disadvantage in early childhood outcomes.Infants were in the National Institute of Child Health and Human Development (NICHD) Neonatal Research Network, born 1/1/1997-12/31/2000, <28 wk, with neurodevelopmental follow-up at 18-22 mo corrected age. We evaluated and compared univariate and multivariate associations of risk factors with neurodevelopmental outcomes for girls and boys. Neurodevelopmental impairment (NDI) was one or more of the following: moderate--severe cerebral palsy (CP), Bayley Mental (MDI) or Psychomotor (PDI) Development Indices <70, deafness or blindness.Boys (n=1216) were more likely than girls (n=1337) to have adverse outcomes (moderate--severe CP: 10.7% vs 7.3%; MDI < 70: 41.9% vs 27.1%; NDI: 48.1% vs 34.1%). Major risk factors were also more common in boys. Independent multivariate associations of risk factors with outcome differed by gender, but not consistently in favor of girls. In multivariate models including both girls and boys, male gender remained an independent risk factor for MDI < 70 (2.0, 95% CI 1.6-2.5) and NDI (1.8, 95% CI 1.5-2.2).Perinatal, neonatal and early childhood factors confer similar incremental risk or protection to boys and girls, but boys appear to have inherently greater baseline risk. Unmeasured biological variables likely contribute to the preterm male neurodevelopmental outcome disadvantage.

  View details for DOI 10.1080/08035250600599727

  View details for Web of Science ID 000240562000016

  View details for PubMedID 16982497

• Changes in neurodevelopmental outcomes at 18 to 22 months' corrected age among infants of less than 25 weeks' gestational age born in 1993-1999 PEDIATRICS Hintz, S. R., Kendrick, D. E., Vohr, B. R., Poole, W. K., Higgins, R. D. 2005; 115 (6): 1645-1651

  Abstract

  Increased survival rates for extremely preterm, extremely low birth weight infants during the postsurfactant era have been reported, but data on changes in neurosensory and developmental impairments are sparse.To compare neuromotor and neurodevelopmental outcomes at 18 to 22 months' corrected age for infants of <25 weeks' estimated gestational age (EGA) who were born in the 1990s.This was a multicenter, retrospective, comparative analysis of infants of <25 weeks' EGA, with birth weights of 501 to 1000 g, born between January 1993 and June 1996 (epoch I) or between July 1996 and December 1999 (epoch II), in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental assessments were performed at 18 to 22 months' corrected age. Logistic-regression models were constructed to evaluate the independent risk of cerebral palsy, Mental Development Index of <70, Psychomotor Development Index of <70, and neurodevelopmental impairment.A total of 366 patients in epoch I and 473 patients in epoch II were evaluated. Prenatal steroid use, cesarean section, surfactant treatment, bronchopulmonary dysplasia, and severe retinopathy of prematurity were more likely in epoch II, whereas Apgar scores of <5 at 5 minutes, patent ductus arteriosus, and severe intraventricular hemorrhage were more likely in epoch I. The prevalences of cerebral palsy, Psychomotor Development Index of <70, and neurodevelopmental impairment were similar between epochs. The prevalences of Mental Development Index of <70 were 40% for epoch I and 47% for epoch II. Regression analysis revealed that epoch II was an independent risk factor for Mental Developmental Index of <70 (epoch I versus II: odds ratio: 0.63; 95% confidence interval: 0.45-0.87) but not for other outcomes.Early childhood neurodevelopmental outcomes among infants of <25 weeks' EGA are not improving in the postsurfactant era, despite more aggressive perinatal and neonatal treatment. Later childhood follow-up assessment is needed to delineate trends in severe cognitive impairment in this extremely high-risk group.

  View details for DOI 10.1542/peds.2004-2215

  View details for Web of Science ID 000229504800025

  View details for PubMedID 15930228

• Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era ARCHIVES OF DISEASE IN CHILDHOOD Hintz, S. R., Poole, W. K., Wright, L. L., Fanaroff, A. A., Kendrick, D. E., Laptook, A. R., Goldberg, R., Duara, S., Stoll, B. J., Oh, W. 2005; 90 (2): F128-F133

  Abstract

  To compare mortality and death or major morbidity (DOMM) among infants <25 weeks estimated gestational age (EGA) born during two post-surfactant era time periods.Comparative cohort study of very low birthweight (501-1500 g) infants <25 weeks EGA in the NICHD Neonatal Research Network born during two post-surfactant era time periods (group I, 1991-1994, n=1408; group II, 1995-1998, n=1348). Perinatal and neonatal factors were compared, and group related mortality and DOMM risk were evaluated.Mortality was higher for group I (63.1% v 56.7%; p=0.0006). Antenatal steroids (ANS) and antenatal antibiotics (AABX), surfactant (p<0.0001), and bronchopulmonary dysplasia (p=0.0008) were more prevalent in group II. In a regression model that controlled for basic and delivery factors only, mortality risk was greater for group I than for group II (odds ratio (OR) 1.4, 95% confidence interval (CI) 1.2 to 1.7); the addition of AABX and surfactant, or ANS (OR 0.97, 95% CI 0.79 to 1.2) to the model appeared to account for this difference. There was no difference in DOMM (86.8% v 88.4%; p=0.2), but risk was lower for group I in regression models that included ANS (OR 0.70, 95% CI 0.52 to 0.94).Survival to discharge was more likely during the more recent period because of group differences in ANS, AABX, and surfactant. However, this treatment shift may reflect an overall more aggressive management approach. More consistent application of treatment has led to improving survival of <25 week EGA infants during the post-surfactant era, but possibly at the cost of greater risk of major in-hospital morbidities.

  View details for DOI 10.1136/adc.2003.046268

  View details for Web of Science ID 000227543700009

  View details for PubMedID 15724036

  View details for PubMedCentralID PMC1721837

• Changes in mortality and morbidities among infants born at less than 25 weeks during the post-surfactant era ARCHIVES OF DISEASE IN CHILDHOOD-FETAL AND NEONATAL EDITION Hintz, S. R., Poole, W. K., Wright, L. L., Fanaroff, A. A., Kendrick, D. E., Laptook, A. R., Goldberg, R., Duara, S., Stoll, B. J., Oh, W. 2005; 90 (2): 128-133

  View details for DOI 10.1136/adc.2003.046268

  View details for Web of Science ID 000230340700009

• Neurodevelopmental and growth outcomes of extremely low birth weight infants after necrotizing enterocolitis PEDIATRICS Hintz, S. R., Kendrick, D. E., Stoll, B. J., Vohr, B. R., Fanaroff, A. A., Donovan, E. F., Poole, W. K., Blakely, M. L., Wright, L., Higgins, R. 2005; 115 (3): 696-703

  Abstract

  Necrotizing enterocolitis (NEC) is a significant complication for the premature infant. However, subsequent neurodevelopmental and growth outcomes of extremely low birth weight (ELBW) infants with NEC have not been well described. We hypothesized that ELBW infants with surgically managed (SurgNEC) are at greater risk for poor neurodevelopmental and growth outcomes than infants with medically managed NEC (MedNEC) compared with infants without a history of NEC (NoNEC). The objective of this study was to compare growth, neurologic, and cognitive outcomes among ELBW survivors of SurgNEC and MedNEC with NoNEC at 18 to 22 months' corrected age.Multicenter, retrospective analysis was conducted of infants who were born between January 1, 1995, and December 31, 1998, and had a birth weight <1000 g in the National Institute of Child Health and Human Development Neonatal Research Network Registry. Neurodevelopment and growth were assessed at 18 to 22 months' postmenstrual age. chi2, t test, and logistic regression analyses were used.A total of 2948 infants were evaluated at 18 to 22 months, 124 of whom were SurgNEC and 121 of whom were MedNEC. Compared with NoNEC, both SurgNEC and MedNEC infants were of lower birth weight and had a greater incidence of late sepsis; SurgNEC but not MedNEC infants were more likely to have received a diagnosis of cystic periventricular leukomalacia and bronchopulmonary dysplasia and been treated with postnatal steroids. Weight, length, and head circumference <10 percentile at 18 to 22 months were significantly more likely among SurgNEC but not MedNEC compared with NoNEC infants. After correction for anthropometric measures at birth and adjusted age at follow-up, all growth parameters at 18 to 22 months for SurgNEC but not MedNEC infants were significantly less than for NoNEC infants. SurgNEC but not MedNEC was a significant independent risk factor for Mental Developmental Index <70 (odds ratio [OR]: 1.61; 95% confidence interval [CI]: 1.05-2.50), Psychomotor Developmental Index <70 (OR: 1.95; 95% CI: 1.25-3.04), and neurodevelopmental impairment (OR: 1.78; 95% CI: 1.17-2.73) compared with NoNEC.Among ELBW infants, SurgNEC is associated with significant growth delay and adverse neurodevelopmental outcomes at 18 to 22 months' corrected age compared with NoNEC. MedNEC does not seem to confer additional risk. SurgNEC is likely to be associated with greater severity of disease.

  View details for DOI 10.1542/peds.2004-0569

  View details for Web of Science ID 000227596900029

  View details for PubMedID 15741374

• Utilization and outcomes of neonatal cardiac extracorporeal life support: 1996-2000. Pediatric critical care medicine Hintz, S. R., Benitz, W. E., Colby, C. E., Sheehan, A. M., Rycus, P., Van Meurs, K. P. 2005; 6 (1): 33-38

  Abstract

  Extracorporeal life support for neonatal respiratory failure has decreased, but utilization and outcome of cardiac extracorporeal life support are not well characterized. Among neonates born 1996-2000, our objects were to evaluate changes in utilization and outcome of cardiac extracorporeal life support and characterize correlates of survival.Retrospective analysis of Extracorporeal Life Support Organization Registry data.Intensive care units participating in the ELSO registry.Patients placed on extracorporeal life support for center-specified "cardiac support" at 15 days was associated with improved survival among hypoplastic left heart syndrome patients (p = .03), and survivors had fewer mean extracorporeal life support hours (89.3 +/- 52.3 vs. 147.5 +/- 129.7, p = .015). Logistic regression showed that only greater number of hours on extracorporeal life support was independently associated with nonsurvival.Neonatal cardiac extracorporeal life support use increased substantially from 1996 to 2000, with survival to discharge or transfer in more than one third of patients. Hypoplastic left heart syndrome was not associated with nonsurvival. Fewer hours on extracorporeal life support, diagnoses of persistent pulmonary hypertension of the neonate and transposition of the great arteries, and extracorporeal life support at <3 days were associated with survival.

  View details for PubMedID 15636656

• Neurodevelopmental and growth impairment among extremely low-birth-weight infants with neonatal infection JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION Stoll, B. J., Hansen, N. I., Adams-Chapman, I., Fanaroff, A. A., Hintz, S. R., Vohr, B., Higgins, R. D. 2004; 292 (19): 2357-2365

  Abstract

  Neonatal infections are frequent complications of extremely low-birth-weight (ELBW) infants receiving intensive care.To determine if neonatal infections in ELBW infants are associated with increased risks of adverse neurodevelopmental and growth sequelae in early childhood.Infants weighing 401 to 1000 g at birth (born in 1993-2001) were enrolled in a prospectively collected very low-birth-weight registry at academic medical centers participating in the National Institute of Child Health and Human Development Neonatal Research Network. Neurodevelopmental and growth outcomes were assessed at a comprehensive follow-up visit at 18 to 22 months of corrected gestational age and compared by infection group. Eighty percent of survivors completed the follow-up visit and 6093 infants were studied. Registry data were used to classify infants by type of infection: uninfected (n = 2161), clinical infection alone (n = 1538), sepsis (n = 1922), sepsis and necrotizing enterocolitis (n = 279), or meningitis with or without sepsis (n = 193).Cognitive and neuromotor development, neurologic status, vision and hearing, and growth (weight, length, and head circumference) were assessed at follow-up.The majority of ELBW survivors (65%) had at least 1 infection during their hospitalization after birth. Compared with uninfected infants, those in each of the 4 infection groups were significantly more likely to have adverse neurodevelopmental outcomes at follow-up, including cerebral palsy (range of significant odds ratios [ORs], 1.4-1.7), low Bayley Scales of Infant Development II scores on the mental development index (ORs, 1.3-1.6) and psychomotor development index (ORs, 1.5-2.4), and vision impairment (ORs, 1.3-2.2). Infection in the neonatal period was also associated with impaired head growth, a known predictor of poor neurodevelopmental outcome.This large cohort study suggests that neonatal infections among ELBW infants are associated with poor neurodevelopmental and growth outcomes in early childhood. Additional studies are needed to elucidate the pathogenesis of brain injury in infants with infection so that novel interventions to improve these outcomes can be explored.

  View details for Web of Science ID 000225070100024

  View details for PubMedID 15547163

• Surfactant replacement therapy on ECMO does not improve outcome in neonates with congenital diaphragmatic hernia JOURNAL OF PEDIATRIC SURGERY Colby, C. E. 2004; 39 (11): 1632-1637

  Abstract

  Respiratory failure in neonates with congenital diaphragmatic hernia (CDH) may in part be caused by a primary or secondary surfactant deficiency. Knowledge of the optimal approach to surfactant replacement in neonates with CDH and respiratory failure is limited. The aim of this study was to determine if surfactant replacement on extracorporeal membrane oxygenation (ECMO) results in improved outcomes in neonates > or =35 weeks' gestation with unrepaired CDH.Using the CDH Study Group Registry, the authors identified 448 neonates with CDH who were > or =35 weeks' gestation, had no major anomalies, were treated with ECMO within the first 7 days of life, and underwent repair on or after ECMO therapy. Patients in 2 groups were compared: group 1 (- Surf, n = 334) consisted of patients who received no surfactant and group 2 (+ Surf, n = 114) consisted of patients who received at least 1 dose of surfactant while on ECMO. An analysis of all patients in both groups was performed. Additionally, subgroup analyses stratified by gestational age were performed for patients 351/7 to 366/7 weeks' gestation and for patients > or =37 weeks' gestation. Primary end-points for the study were survival and length of ECMO run. Secondary end-points were length of intubation, need for supplemental oxygen at 30 days of life, and at discharge to home. Demographic, clinical, and outcome variables were examined using Fisher's Exact tests for categorical variables and using unpaired t tests for continuous variables. Odds ratios were calculated for categorical end-point variables.Demographic and clinical variables were similar between groups. Analyses of aggregate data showed no significant differences between groups in length of ECMO run, survival, number of days intubated, and percent of patients requiring supplemental oxygen at 30 days or discharge. Subgroup stratification by gestational age did not show significant differences between groups in any of the outcome variables.The data from this study suggest that surfactant replacement on ECMO for neonates with congenital diaphragmatic hernia does not provide significant benefit in the infant's clinical course with respect to survival, length of ECMO course, length of intubation, or subsequent need for supplemental oxygen.

  View details for DOI 10.1016/j.pedsurg.2004.07.005

  View details for Web of Science ID 000225445100005

  View details for PubMedID 15547824

• Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants PEDIATRICS Mirmiran, M., Barnes, P. D., Keller, K., Constantinou, J. C., Fleisher, B. E., Hintz, S. R., Ariagno, R. L. 2004; 114 (4): 992-998

  Abstract

  To compare the value of serial cranial ultrasound (US) with a single magnetic resonance imaging (MRI) before discharge in very low birth weight preterm infants to predict cerebral palsy (CP).Infants who weighed <1250 g at birth and were <30 weeks' gestational age underwent conventional brain MRI at near term (36-40 weeks' postmenstrual age) using 1.5 Tesla MRI scanner. Sagittal and axial T1 and T2 fluid attenuated inversion recovery and gradient recalled echo images were obtained. Cranial US was also obtained at least twice during the first 2 weeks of life. MRI and US images were interpreted by 2 independent radiologists, who were masked to clinical outcome, and scored as follows: category 1, no abnormality; category 2, subependymal hemorrhage or mineralization; category 3, moderate to severe ventriculomegaly; category 4, focal parenchymal abnormality with or without ventriculomegaly. For the purpose of this study, 1 and 2 were categorized as "normal," and 3 and 4 were categorized as "abnormal." The infants were assessed at a mean age of 20 and 31 months using the Amiel-Tison standardized neurodevelopmental examination.The sensitivity and specificity of MRI for predicting CP were 71% and 91% at 20 month and 86% and 89% at 31 months, respectively. The sensitivity and specificity of US for predicting CP were 29% and 86% at 20 months and 43% and 82% at 31 months.As a predictor of outcome for CP, MRI at near-term in very low birth weight preterm neonates is superior to US. However, both US and MRI demonstrate high specificity.

  View details for DOI 10.1542/peds.2003-0772-L

  View details for Web of Science ID 000224242200034

  View details for PubMedID 15466096

• Low yield of ancillary diagnostic studies in neonates infected with Candida. Journal of perinatology Colby, C. E., Drohan, L., Benitz, W., Hintz, S. R. 2004; 24 (4): 241-246

  Abstract

  Fungal infection can be a significant complication for the critically ill neonate. However, the usefulness of extensive radiologic and ophthalmologic investigations in this population has not been thoroughly elucidated.To report the incidence of organ fungal involvement diagnosed by ancillary testing (echocardiogram, ophthalmologic examination, brain imaging, and renal ultrasound (RUS)) among neonatal intensive care unit (NICU) patients with Candida infection.This was a single center review of all NICU patients with Candida-positive cultures of blood, urine, peritoneal fluid, endotracheal tube aspirate, or cerebrospinal fluid from January 1, 1997 to June 1 2002. Data regarding the number of positive cultures, species isolated, and presence of specific risk factors and clinical symptoms were recorded for each case, as well as occurrence, timing and results of ancillary testing.In all, 66 patients had at least one positive culture for Candida. The majority (71%) were <1500 g at birth, and mean gestational age was 29.5+/-5.6 weeks. Echocardiograms were obtained in 54/66 (82%), and ophthalmology examinations were obtained in 36/66 (55%); none of these was consistent with fungal involvement. Brain imaging was performed in 50/66 (76%), only one of which was positive, in a patient with 16 positive blood cultures for Candida albicans. RUS were performed in 58/66 (88%) of patients, with concerning findings for fungal involvement in seven of the studies. RUS findings alone did not appear to consistently influence the length of therapy.Ancillary evaluations to investigate for fungal dissemination were undertaken frequently, but were of overall low yield. Although ancillary testing may be of limited additional value in centers with a low threshold for suspecting fungal infections and an aggressive approach to therapy, potentially important findings, which could impact management, may occur.

  View details for PubMedID 15014535

• Diffusion tensor MRI before discharge detects brain injury associated with later neurological abnormalities in VLBW preterm infants Mirmiran, M., Ariagno, R. L., Fleisher, B. E., Hintz, S., Barnes, P. D. INT PEDIATRIC RESEARCH FOUNDATION, INC. 2004: 582A

  View details for Web of Science ID 000220591103379

• Pulmonary glial heterotopia in a monoamniotic twin PEDIATRIC PULMONOLOGY Morgan, T., Anderson, J., Jorden, M., Keller, K., Robinson, T., Hintz, S. 2003; 36 (2): 162-166

  Abstract

  Brain heterotopia in the lungs is rare, but when it occurs in an otherwise healthy newborn, it presents a difficult diagnostic problem and uncertain pathophysiology. We report on a 2-week-old premature infant who presented with respiratory distress and widespread cystic lung changes identified by chest imaging studies. Autopsy demonstrated that the cyst walls were composed of well-differentiated neuroglial tissue, which was confirmed by immunohistochemistry. The cysts were partially lined by bronchial epithelium and contained keratinous debris. For the first time, we demonstrate that the debris stain for human chorionic gonadotropin, compatible with aspirated amnion. There were no other congenital abnormalities. Her monoamniotic twin was anencephalic and died at birth. Although the etiology of glial heterotopia in the lungs is unknown, the majority of cases are associated with anencephalic newborns. Some authors postulated that this heterotopia may therefore be a consequence of fetal aspiration of brain tissue. Other possibilities include glial predominant teratomas, hamartomatous malformations, and abnormal neural crest migration. Our review of the 21 cases reported over the past century suggests that in utero aspiration of glial cells, or abnormal neural crest migration, are the most likely explanations for this rare and fatal disease.

  View details for DOI 10.1002/ppul.10292

  View details for Web of Science ID 000184621100011

  View details for PubMedID 12833496

• Long-term neurodevelopmental outcome of extremely low birth weight (ELBW) infants after necrotizing enterocolitis Hintz, Kendrick, D. E., Stoll, B. J., Vohr, B. R., Fanaroff, A. A., Donovan, E. F., Poole, W. K., Blakely, M. L., Wright, L. L., NICHD Neonatal Res Network INT PEDIATRIC RESEARCH FOUNDATION, INC. 2003: 398A

  View details for Web of Science ID 000181897902250

• Bilateral cystic lung disease in a monoamnionic twin of an anencephalic: A case of glial heterotopia in the lungs. Western Regional Meeting of the American-Federation-for-Medical-Research Anderson, J. M., Adams, M. L., Morgan, T., Robinson, T., Enns, G. M., Keller, K. A., Sylvester, K. G., Hintz, S. R. LIPPINCOTT WILLIAMS & WILKINS. 2003: S119?S120

  View details for Web of Science ID 000180569600170

• Adrenocortical function and clinical outcome in extremely ill very low birthweight premature infants. Hintz, Benitz, W. E., Hintz, R. L. B C DECKER INC. 2003: S139?S140

  View details for Web of Science ID 000180569600286

• The jaundiced newborn. Understanding and managing transitional hyperbilirubinemia. Minerva pediatrica Stevenson, D. K., Wong, R. J., Hintz, S. R., Vreman, H. J. 2002; 54 (5): 373-382

  Abstract

  Neonatal jaundice is one of the most common conditions diagnosed by the pediatrician. This normally benign transitional phenomenon is a dynamic balance between the production and elimination of bilirubin. These processes can be exacerbated by a number of pathophysiologic conditions, which cause either an increase in bilirubin production rates, such as hemolysis, or a decrease in bilirubin elimination rates, such as bilirubin conjugation defects. The most dangerous circumstance for an infant is the combination of increased bilirubin production with impaired elimination. These infants are at considerable risk for developing excessive and potentially dangerous hyperbilirubinemia and subsequent kernicterus. Therefore, the importance of early recognition of the imbalance is paramount. In this review, we will discuss the various risk factors associated with hyperbilirubinemia and describe strategies for the diagnosis and management of transitional hyperbilirubinemia.

  View details for PubMedID 12244276

• Early neonatal diagnosis of long-chain 3-hydroxyacyl coenzyme A dehydrogenase and mitochondrial trifunctional protein deficiencies MOLECULAR GENETICS AND METABOLISM Hintz, S. R., Matern, D., Strauss, A., Bennett, M. J., Hoyme, H. E., Schelley, S., Kobori, J., Colby, C., Lehman, N. L., Enns, G. M. 2002; 75 (2): 120-127

  Abstract

  Tandem mass spectrometry (MS/MS) has been introduced in several newborn screening programs for the detection of a large number of inborn errors of metabolism, including fatty acid oxidation disorders (FAOD). Early identification and treatment of FAOD have the potential to improve outcome and may be life-saving in some cases; an estimated 5% of sudden infant deaths are attributable to undiagnosed disorders of fatty acid oxidation. We report very early neonatal presentations of long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) and mitochondrial trifunctional protein (TFP) deficiencies confirmed by molecular analysis. Both patients had cardiorespiratory collapse and hypoglycemia, without a history of maternal pregnancy complications. Retrospective MS/MS analysis of the original newborn screening blood spots revealed characteristic acylcarnitine profiles. These cases are among the earliest reported presentations of LCHAD and TFP deficiencies and further illustrate the potential of MS/MS as a valuable tool for newborn screening of FAOD. However, timely analysis and reporting of results to clinicians are essential, because these disorders can manifest in the first few days of life.

  View details for DOI 10.1006/mgme.2001.3282

  View details for PubMedID 11855930

• Understanding newborn jaundice. Journal of perinatology Stevenson, D. K., Dennery, P. A., Hintz, S. R. 2001; 21: S21-4

  View details for PubMedID 11803411

• Just when you thought it was safe... PEDIATRIC RESEARCH Hintz, S. R., Stevenson, D. K. 2001; 50 (6): 676-677

  View details for PubMedID 11726720

• Limb/pelvis hypoplasia/aplasia with skull defect (Schinzel phocomelia): Distinctive features and prenatal detection AMERICAN JOURNAL OF MEDICAL GENETICS Olney, R. S., Hoyme, H. E., Roche, F., Ferguson, K., Hintz, S., Madan, A. 2001; 103 (4): 295-301

  Abstract

  Schinzel phocomelia syndrome is characterized by limb/pelvis hypoplasia/aplasia: specifically, intercalary limb deficiencies and absent or hypoplastic pelvic bones. The phenotype is similar to that described in a related multiple malformation syndrome known as Al-Awadi/Raas-Rothschild syndrome. The additional important feature of large parietooccipital skull defects without meningocele, encephalocele, or other brain malformation has thus far been reported only in children with Schinzel phocomelia syndrome. We recently evaluated a boy affected with Schinzel phocomelia born to nonconsanguineous healthy parents of Mexican origin. A third-trimester fetal ultrasound scan showed severe limb deficiencies and an absent pelvis. The infant died shortly after birth. Dysmorphology examination, radiographs, and autopsy revealed quadrilateral intercalary limb deficiencies with preaxial toe polydactyly; an absent pelvis and a 7 x 3-cm skull defect; and extraskeletal anomalies including microtia, telecanthus, micropenis with cryptorchidism, renal cysts, stenosis of the colon, and a cleft alveolar ridge. A normal 46,XY karyotype was demonstrated, and autosomal recessive inheritance was presumed on the basis of previously reported families. This case report emphasizes the importance of recognizing severe pelvic and skull deficiencies (either post- or prenatally) in differentiating infants with Schinzel phocomelia from other multiple malformation syndromes that feature intercalary limb defects, including thalidomide embryopathy and Roberts-SC phocomelia.

  View details for Web of Science ID 000171752600006

  View details for PubMedID 11746009

• Serum bilirubin levels at 72 hours by selected characteristics in breastfed and formula-fed term infants delivered by cesarean section ACTA PAEDIATRICA Hintz, S. R., Gaylord, T. D., Oh, W., Fanaroff, A. A., Mele, L., Stevenson, D. K. 2001; 90 (7): 776-781

  Abstract

  The present multicenter study analysed the relative impact of maternal and infant factors on serum bilirubin levels at 72 +/- 12 h in exclusively breastfed vs formula-fed term infants. End-tidal carbon monoxide levels corrected for ambient air (ETCOc), an index of bilirubin production, were measured in exclusively breastfed (B = 66) or formula-fed (F = 210) term infants at 2-8 h of age. Inclusion criteria included cesarean section to ensure a 3 d hospitalization, birthweight > or = 2,500 g, gestational age >37 wk and absence of any illness. The ETCOc for B infants and F infants did not differ significantly (1.3 +/- 0.7 ppm vs 1.3 +/- 0.8 ppm). The serum bilirubin level at 72 +/- 12 h was significantly higher in B infants than in F infants (8.5 +/- 3.4mg dl(-1) vs 6.7 +/- 3.4mg dl(-1) p < 0.001), as was the percentage weight loss from birthweight. Serum bilirubin levels were significantly higher in infants who were male, who did not have meconium-stained amniotic fluid, and in those whose mothers were insulin-dependent diabetics or hypertensive. There was no difference between groups in the need for phototherapy or exchange transfusion.Although higher bilirubin levels were observed in group B at 72 +/- 12 h compared with group F, this finding was not of clinical or therapeutic consequence in this study. The lack of difference in ETCOc between the groups may be a factor of the timing of ETCOc measurement in this study, or may suggest that early increased bilirubin production is not a significant contributor to jaundice observed in exclusively breastfed infants. Key words: bilirubin, breastfeeding, jaundice

  View details for Web of Science ID 000170367700013

  View details for PubMedID 11519981

• Bedside functional imaging of the premature infant brain during passive motor activation JOURNAL OF PERINATAL MEDICINE Hintz, S. R., Benaron, D. A., Siegel, A. M., Zourabian, A., Stevenson, D. K., Boas, D. A. 2001; 29 (4): 335-343

  Abstract

  Changes in regional brain blood flow and hemoglobin oxygen saturation occur in the human cortex in response to neural activation. Traditional functional radiologic methods cannot provide continuous, portable measurements. Imaging methods, which use near-infrared light allow for non-invasive measurements by taking advantage of the fact that hemoglobin is a strong absorber at these wavelengths.To test the feasibility of a new optical functional imaging system in premature infants, and to obtain preliminary brain imaging of passive motor activation in this population.A new optical imaging system, the Diffuse Optical Tomography System (DOTS), was used to provide real-time, bedside assessments. Custom-made soft flexible fiberoptic probes were placed on two extremely ill, mechanically ventilated 24 week premature infants, and three healthier 32 week premature infants. Passive motor stimulation protocols were used during imaging.Specific movement of the arm resulted in reproducible focal, contralateral changes in cerebral absorption. The data suggest an overall increase in blood volume to the imaged area, as well as an increase in deoxyhemoglobin concentration. These findings in premature infants differ from those expected in adults.In the intensive care setting, continuous non-invasive optical functional imaging could be critically important and, with further study, may provide a bedside monitoring tool for prospectively identifying patients at high risk for brain injury.

  View details for PubMedID 11565203

• Decreased use of neonatal extracorporeal membrane oxygenation (ECMO): How new treatment modalities have affected ECMO utilization PEDIATRICS Hintz, S. R., Suttner, D. M., Sheehan, A. M., Rhine, W. D., Van Meurs, K. P. 2000; 106 (6): 1339-1343

  Abstract

  Over the last decade, several new therapies, including high-frequency oscillatory ventilation (HFOV), exogenous surfactant therapy, and inhaled nitric oxide (iNO), have become available for the treatment of neonatal hypoxemic respiratory failure. The purpose of this retrospective study was to ascertain to what extent these modalities have impacted the use of neonatal extracorporeal membrane oxygenation (ECMO) at our institution.Patients from 2 time periods were evaluated: May 1, 1993 to November 1, 1994 (group 1) and May 1, 1996 to November 1, 1997 (group 2). During the first time period (group 1), HFOV was not consistently used; beractant (Survanta) use for meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia was under investigation; and iNO was not yet available. During the second time period (group 2), HFOV and beractant treatment were considered to be standard therapies, and iNO was available to patients with oxygenation index (OI) >/=25 x 2 at least 30 minutes apart, or on compassionate use basis. Patients were included in the data collection if they met the following entry criteria: 1) OI >15 x 1 within the first 72 hours of admission; 2) EGA >/=35 weeks; 3) diagnosis of MAS, PPHN or sepsis/pneumonia; 4) <5 days of age on admission; and 5) no congenital heart disease, diaphragmatic hernia, or lethal congenital anomaly.Of the 49 patient in group 1, 21 (42.8%) required ECMO therapy. Of these ECMO patients, 14 (66.6%) had received diagnoses of MAS or PPHN. Only 3 of the patients that went on to ECMO received beractant before the initiation of bypass (14.3%). All ECMO patients in group 1 would have met criteria for iNO had it been available. Of all patients in group 1, 18 (36.7%) were treated with HFOV, and 13 (26.5%) received beractant. Of the 47 patients in group 2, only 13 (27.7%) required ECMO therapy (compared with group 1). Of these ECMO patients, only 5 (38.5%) had diagnoses of MAS or PPHN, with the majority of patients (61.5%) requiring ECMO for sepsis/pneumonia, with significant cardiovascular compromise. Only 5 of these ECMO patients, all outborn, did not receive iNO before cannulation because of the severity of their clinical status on admission. Of all patients in group 2, 41 (87.2%) were treated with HFOV (compared with group 1), 42 (89.3%) received beractant (compared with group 1), and 18 (44.7%) received iNO.The results indicate that ECMO was used less frequently when HFOV, beractant and iNO was more commonly used. The differences in treatment modalities used and subsequent use of ECMO were statistically significant. We speculate that, in this patient population, the diagnostic composition of neonatal ECMO patients has changed over time.

  View details for Web of Science ID 000165914800020

  View details for PubMedID 11099586

• Secondary infection presenting as recurrent pulmonary hypertension. Journal of perinatology Hintz, S. R., Benitz, W. E., Halamek, L. P., Van Meurs, K. P., Rhine, W. D. 2000; 20 (4): 262-264

  Abstract

  Primary infection in the neonate, especially group B streptococcal infection, has long been recognized as a cause of persistent pulmonary hypertension of the newborn (PPHN), sometimes requiring treatment with inhaled nitric oxide (iNO) and extracorporeal membrane oxygenation (ECMO). However, secondary nosocomial infections in the neonatal period have not been widely reported as a cause of severe recurrent pulmonary hypertension (PHTN). We now present two cases of secondary infection in the neonate leading to significant PHTN. In both cases, the infants presented with PPHN soon after birth, requiring transfer to a level 3 neonatal intensive care unit and treatment with high-frequency oscillatory ventilation and iNO. After successful resolution of the initial PPHN, including extubation to nasal cannula, both infants developed signs of severe recurrent PHTN, leading to reintubation, high-frequency oscillatory ventilation and iNO therapy, and consideration of ECMO. In both cases, blood cultures taken at the time of recurrence of PHTN returned positive, one for Staphylococcus epidermidis, the other for methicillin-resistant Staphylococcus aureus. These unusual cases present the possibility of severe recurrent PHTN requiring iNO or ECMO in the setting of secondary infection. We speculate that these infants, although extubated after their first episodes of PHTN, were at risk for recurrence of PHTN due to continued pulmonary vascular reactivity.

  View details for PubMedID 10879342

• Noninvasive functional imaging of human brain using light JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM Benaron, D. A., Hintz, S. R., Villringer, A., Boas, D., Kleinschmidt, A., Frahm, J., Hirth, C., Obrig, H., van Houten, J. C., Kermit, E. L., Cheong, W. F., Stevenson, D. K. 2000; 20 (3): 469-477

  Abstract

  Analysis of photon transit time for low-power light passing into the head, and through both skull and brain, of human subjects allowed for tomographic imaging of cerebral hemoglobin oxygenation based on photon diffusion theory. In healthy adults, imaging of changes in hemoglobin saturation during hand movement revealed focal, contralateral increases in motor cortex oxygenation with spatial agreement to activation maps determined by functional magnetic resonance imaging; in ill neonates, imaging of hemoglobin saturation revealed focal regions of low oxygenation after acute stroke, with spatial overlap to injury location determined by computed tomography scan. Because such slow optical changes occur over seconds and co-localize with magnetic resonance imaging vascular signals whereas fast activation-related optical changes occur over milliseconds and co-localize with EEG electrical signals, optical methods offer a single modality for exploring the spatio-temporal relationship between electrical and vascular responses in the brain in vivo, as well as for mapping cortical activation and oxygenation at the bedside in real-time for clinical monitoring.

  View details for PubMedID 10724111

• Neonatal cerebral oxygenation measurements and the effects of curvature on frequency domain multiple distance near infrared spectroscopy. Biomedical Topical Meeting Wallace, D. J., Barbieri, B., Hintz, S. R. OPTICAL SOC AMERICA. 2000: 88?90

  View details for Web of Science ID 000176203200024

• Alveolar capillary dysplasia: diagnostic potential for cardiac catheterization. Journal of perinatology Hintz, S. R., Vincent, J. A., Pitlick, P. T., Fineman, J. R., Steinhorn, R. H., Kim, G. E., Benitz, W. E. 1999; 19 (6): 441-446

  Abstract

  Alveolar capillary dysplasia is a rare cause of persistent pulmonary hypertension of the newborn. Infants with this condition die despite maximal medical intervention including inhaled nitric oxide therapy and extracorporeal membrane oxygenation. To date, diagnosis of this lethal condition was made by open lung biopsy or during postmortem examination. We examined the possibility that distinct cardiac catheterization findings could be used in the diagnosis of this lethal disorder.We present three infants with fatal persistent pulmonary hypertension of the newborn refractory to extracorporeal membrane oxygenation and inhaled nitric oxide therapy, two with postmortem autopsy confirmation of alveolar capillary dysplasia. Each infant underwent cardiac catheterization to complete the diagnostic evaluations.Significant right ventricular hypertension and normal pulmonary venous return were demonstrated, but a markedly diminished or absent capillary blush phase was noted in each infant. This finding is distinct from the normal capillary blush seen in infants with persistent pulmonary hypertension of the newborn of other etiologies.Cardiac catheterization may provide a useful alternative to tissue examination in the diagnosis of alveolar capillary dysplasia.

  View details for PubMedID 10685275

• Real-time functional imaging of the premature infant brain during passive motor activation Hintz, Benaron, D. A., Siegel, A. M., Stevenson, D. K., Boas, D. A. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1999: 343A

  View details for DOI 10.1203/00006450-199904020-02037

  View details for Web of Science ID 000079476702021

• Bedside imaging of intracranial hemorrhage in the neonate using light: Comparison with ultrasound, computed tomography, and magnetic resonance imaging PEDIATRIC RESEARCH Hintz, S. R., Cheong, W. F., van Houten, J. P., Stevenson, D. K., Benaron, D. A. 1999; 45 (1): 54-59

  Abstract

  Medical optical imaging (MOI) uses light emitted into opaque tissues to determine the interior structure. Previous reports detailed a portable time-of-flight and absorbance system emitting pulses of near infrared light into tissues and measuring the emerging light. Using this system, optical images of phantoms, whole rats, and pathologic neonatal brain specimens have been tomographically reconstructed. We have now modified the existing instrumentation into a clinically relevant headband-based system to be used for optical imaging of structure in the neonatal brain at the bedside. Eight medical optical imaging studies in the neonatal intensive care unit were performed in a blinded clinical comparison of optical images with ultrasound, computed tomography, and magnetic resonance imaging. Optical images were interpreted as correct in six of eight cases, with one error attributed to the age of the clot, and one small clot not seen. In addition, one disagreement with ultrasound, not reported as an error, was found to be the result of a mislabeled ultrasound report rather than because of an inaccurate optical scan. Optical scan correlated well with computed tomography and magnetic resonance imaging findings in one patient. We conclude that light-based imaging using a portable time-of-flight system is feasible and represents an important new noninvasive diagnostic technique, with potential for continuous monitoring of critically ill neonates at risk for intraventricular hemorrhage or stroke. Further studies are now underway to further investigate the functional imaging capabilities of this new diagnostic tool.

  View details for PubMedID 9890608

• Bedside functional imaging of the premature infant brain during passive motor activation Conference on Optical Tomography and Spectroscopy of Tissue III Hintz, S. R., Benaron, D. A., Siegel, A. M., Zourabian, A., Boas, D. A. SPIE-INT SOC OPTICAL ENGINEERING. 1999: 221?229

  View details for Web of Science ID 000082585500024

• Stationary headband for clinical time-of-flight optical imaging at the bedside PHOTOCHEMISTRY AND PHOTOBIOLOGY Hintz, S. R., Benaron, D. A., van Houten, J. P., Duckworth, J. L., Liu, F. W., Spilman, S. D., Stevenson, D. K., Cheong, W. F. 1998; 68 (3): 361-369

  Abstract

  Conventional brain-imaging modalities may be limited by high cost, difficulty of bedside use, noncontinuous operation, invasiveness or an inability to obtain measurements of tissue function, such as oxygenation during stroke. Our goal was to develop a bedside clinical device able to generate continuous, noninvasive, tomographic images of the brain using low-power nonionizing optical radiation. We modified an existing stage-based time-of-flight optical tomography system to allow imaging of patients under clinical conditions. First, a stationary head-band consisting of thin, flexible optical fibers was constructed. The headband was then calibrated and tested, including an assessment of fiber lengths, the existing system software was modified to collect headband data and to perform simultaneous collection of data and image reconstruction, and the existing hardware was modified to scan optically using this headband. The headband was tested on resin models and allowed for the generation of tomographic images in vitro; the headband was tested on critically ill infants and allowed for optical tomographic images of the neonatal brain to be obtained in vivo.

  View details for PubMedID 9747590

• Brain functional imaging using time-of-flight optical spectroscopy Conference on Photon Propagation in Tissues III Hintz, S. R., Benaron, D. A., Robbins, R., Duckworth, J. L., Murphy, A. L., Price, J. W., Liu, F. W., Stevenson, D. K., Cheong, W. F. SPIE - INT SOC OPTICAL ENGINEERING. 1998: 176?183

  View details for Web of Science ID 000072611700021

• Alveolar capillary dysplasia: Diagnostic potential for cardiac catheterization. Hintz, Vincent, J. A., Steinhorn, R. H., Benitz, W. E. SLACK INC. 1998: 132A

  View details for Web of Science ID 000071684700703

• Non-invasive optical monitoring of cerebral oxygenation. Hintz, Benaron, D. A., Duckworth, J. L., Rhine, W. D., Cheong, W. F., Robbins, R. C., Stevenson, D. K. SLACK INC. 1998: 96A

  View details for Web of Science ID 000071684700510

• Automated quantitation of tissue components using real-time spectroscopy Conference on Photon Propagation in Tissues III Benaron, D. A., Rubinski, B., Hintz, S. R., Duckworth, J. L., Murphy, A. L., Price, J. W., Liu, F. W., Otten, D. M., Stevenson, D. K., Cheong, W. F., Kermit, E. L. SPIE - INT SOC OPTICAL ENGINEERING. 1998: 500?511

  View details for Web of Science ID 000072611700060

• Calibration of time-of-flight optical spectroscopy Conference on Photon Propagation in Tissues III Duckworth, J. L., Benaron, D. A., Hintz, S. R., Liu, F. W., Stevenson, D. K., Cheong, W. F. SPIE - INT SOC OPTICAL ENGINEERING. 1998: 73?82

  View details for Web of Science ID 000072611700009

• Automated classification of tissue by type using real-time spectroscopy Conference on Optical Biopsies and Microscopic Techniques II Benaron, D. A., Cheong, W. F., Duckworth, J. L., Noles, K., Nezhat, C., Seidman, D., Hintz, S. R., Levinson, C. J., Murphy, A. L., Price, J. W., Liu, F. W., Stevenson, D. K., Kermit, E. L. SPIE - INT SOC OPTICAL ENGINEERING. 1997: 99?107

  View details for Web of Science ID 000071861300013

• MORTALITY OF METALLOPORPHYRIN-TREATED NEONATAL RATS AFTER LIGHT EXPOSURE DEVELOPMENTAL PHARMACOLOGY AND THERAPEUTICS Hintz, S. R., Vreman, H. J., Stevenson, D. K. 1990; 14 (3): 187-192

  Abstract

  Tin protoporphyrin (SnPP) has been used to suppress hyperbilirubinemia in human neonates through inhibition of heme oxygenase. Some of the subjects exhibited mild erythema upon receiving phototherapy. SnPP and three proposed alternatives, tin mesoporphyrin (SnMP), zinc protoporphyrin (ZnPP) and zinc mesoporphyrin (ZnMP) are potential photosensitizers. We therefore studied the phototoxic effects of these compounds in the neonatal rat model. Fed Wistar rats (24-36 h old) were injected intraperitoneally with up to 40 mumol SnPP/kg body weight, 30 mumol SnMP/kg body weight, 60 mumol ZnPP/kg body weight, or 45 mumol ZnMP/kg body weight. The animals were placed over cool white light (20 microW/cm2/nm) for 12 h. Light exposure resulted in SnPP dose-dependent mortality, and the LD50 was determined to be 11.7 mumol/kg body weight. No deaths were observed in pups treated with up to 20 mumol SnMP/kg; treatment with 30 mumol SnMP/kg resulted in a 40% mortality rate. No fatalities were observed among the light-exposed ZnPP- or ZnMP-treated pups. No deaths were observed among control pups treated with the highest metalloporphyrin doses and kept in the dark; similarly, no mortality was observed in untreated light-exposed control animals. We conclude that (1) SnPP and SnMP are potentially fatal phototoxic substances in the neonatal rat; (2) ZnPP and ZnMP may be safer drugs for neonatal rats receiving light exposure, and (3) further studies are needed to fully assess the photobiological hazards of metalloporphyrin administration to humans.

  View details for Web of Science ID A1990DG27100006

  View details for PubMedID 2364856

• DETERMINATION OF PLASMA ZINC PROTOPORPHYRIN LEVELS IN ADULT-RATS RODGERS, P. A., HINTZ, STEVENSON, D. K. SLACK INC. 1990: A168

  View details for Web of Science ID A1990CF63600970

• MORTALITY AFTER LIGHT EXPOSURE OF TIN PROTOPORPHYRIN-TREATED NEONATAL RATS HINTZ, VREMAN, H. J., STEVENSON, D. K. SLACK INC. 1989: A205

  View details for Web of Science ID A1989R585101200

• EFFECTS OF ORAL-ADMINISTRATION OF TIN AND ZINC PROTOPORPHYRIN ON NEONATAL AND ADULT-RAT TISSUE HEME OXYGENASE ACTIVITY JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Vreman, H. J., Hintz, S. R., Kim, C. B., Castillo, R. O., Stevenson, D. K. 1988; 7 (6): 902-906

  Abstract

  The purpose of this study was to investigate if oral metalloporphyrin treatment could suppress intestinal heme oxygenase (HO) activity and thus prevent HO-mediated heme degradation in this organ. Six hours after a single 40 mumol/kg oral dose of tin protoporphyrin (TP), zinc protoporphyrin (ZP), or heme to adult rats, no significant difference in the HO activity of the intestine was observed relative to control tissues. Moreover, the activity was not inhibited by in vitro exposure to 40 microM TP or ZP. Liver and spleen HO activity was also not significantly inhibited in vivo after oral administration of metalloporphyrins; however, in vitro exposure to TP or ZP decreased the HO activity of preparations from these organs significantly. Like adults, the intestinal HO activity of neonates was not inhibited effectively by oral administration of either metalloporphyrin. The results of subsequent in vitro exposure of control neonatal tissue preparations to ZP or TP was similar to those using adult tissue preparations. Even at 100 microM, only ZP seemed to have some in vitro inhibitory effect on the intestinal HO of suckling rats. We conclude that intestinal HO is less inhibitable by TP or ZP reaching the intestine via the stomach in concentrations at least 30-fold greater than those achieved after parenteral 40 mumol/kg doses, which cause significant hepatic and splenic HO inhibition. Intestinal absorption and enterohepatic circulation of heme, TP, and ZP do not seem to occur in amounts sufficient to consistently and significantly affect HO activity in liver or spleen.

  View details for Web of Science ID A1988Q638900019

  View details for PubMedID 3199276

• INVITRO CARBON-MONOXIDE PRODUCTION BY THE SMALL-INTESTINE OF SUCKLING AND ADULT WISTAR RATS - EFFECT OF PARENTERAL TIN-PROTOPORPHYRIN DEVELOPMENTAL PHARMACOLOGY AND THERAPEUTICS Kim, C. B., Hintz, S. R., Vreman, H. J., Stevenson, D. K. 1988; 11 (3): 166-172

  Abstract

  Single subcutaneous doses (25 mumol/kg body weight) of tin-protoporphyrin (TP), a potent competitive inhibitor or heme oxygenase (HO), were administered to both suckling and adult Wistar rats. The effect of TP on the carbon monoxide excretion rate (VeCO), an index of total bilirubin formation, and on in vitro carbon monoxide (CO) production by the small intestine were evaluated. Whereas the VeCO of the adult group was decreased (p less than 0.0005) after TP, that of the suckling rat was unchanged. Gradients of CO production along the small intestine were observed in sucklings as well as adults; however, these gradients were in opposite directions. Intestinal CO production was greatest in the adult duodenum, decreasing distally; conversely, the CO production was greatest in the suckling ileum, decreasing proximally. No significant difference in CO production between control and TP-treated adult intestinal mucosa was observed. In sucklings, a significant reduction of intestinal CO production in the TP-treated rats was detected in the duodenum only (p less than 0.05). The results suggest that suckling rats differ from adults in terms of the capacity to produce CO and the direction of the gradient of CO production along the intestine. We conclude that (1) TP may not substantially decrease the in vivo production of CO by the small intestine at a dose which inhibits hepatic and splenic heme oxygenase, and (2) because after a heme load, heme is excreted into the intestine after TP administration, heme-degrading, CO-producing processes in the intestine may contribute to an animal's VeCO under such conditions.

  View details for Web of Science ID A1988N081100006

  View details for PubMedID 3383729

• LACK OF INHIBITION OF INTESTINAL HEME OXYGENASE BY ANTIBIOTICS AND TIN-PROTOPORPHYRIN PEDIATRIC RESEARCH Hintz, S. R., Kim, C. B., Vreman, H. J., Stevenson, D. K. 1988; 23 (1): 50-53

  Abstract

  We assessed the in vivo and in vitro effects of antibiotics and tin-protoporphyrin (TP) on intestinal heme oxygenase (HO) activity using a gas chromatographic assay. This method measures the carbon monoxide produced from heme in the presence of NADPH. After in vivo administration of kanamycin (10 mg/kg body weight), ampicillin (200 mg/kg body weight) or neomycin (60 mg/kg body weight) with or without TP (65 mumol/kg body weight) to suckling rats, no significant difference in HO activity along the small intestine was observed. In vitro exposure of adult rat intestinal preparations to the antibiotics showed no significant decrease in HO activity between control and experimental tissue preparations. A concentration-dependent stimulatory effect of neomycin was observed. Subcutaneous administration of TP (25 mumol/kg body weight) to adult male Wistar rats revealed no significant inhibition of the intestine. However, in vitro addition of TP (12.5 microM) to the control tissue preparations of adult Wistar rats revealed highly significant inhibition in liver and spleen when compared to the unexposed control tissues. In contrast, when TP was added to control intestinal preparations no inhibition was observed. These findings suggest that suckling rat intestinal heme oxygenase is not inhibited by in vivo treatment with high concentrations of kanamycin, ampicillin, or neomycin. Furthermore, these antibiotics are not in vitro inhibitors of adult rat intestinal HO. Finally, adult rat intestinal HO is not inhibited either in vivo or in vitro by a concentration of TP that significantly inhibits liver and spleen activity.

  View details for Web of Science ID A1988L542200010

  View details for PubMedID 3340445

• EFFECT OF ENTERAL TIN-PROTOPORPHYRIN AND ZINC-PROTOPORPHYRIN ON HEME OXYGENASE ACTIVITY HINTZ, KIM, C. B., VREMAN, H. J., STEVENSON, D. K. SLACK INC. 1988: A205

  View details for Web of Science ID A1988L516801199

• UNDERSTANDING CO PRODUCTION BY SUCKLING RATS AFTER TIN-PROTOPORPHYRIN THERAPY - INTESTINAL SOURCES OF CO STEVENSON, D. K., KIM, C. B., HINTZ, VREMAN, H. J. WILLIAMS & WILKINS. 1987: A242

  View details for DOI 10.1203/00006450-198704010-00448

  View details for Web of Science ID A1987G700500410

• RECOVERY OF EXOGENOUS HEME AS CARBON-MONOXIDE AND BILIARY HEME IN ADULT-RATS AFTER TIN PROTOPORPHYRIN TREATMENT JOURNAL OF PEDIATRIC GASTROENTEROLOGY AND NUTRITION Hintz, S. R., Kwong, L. K., Vreman, H. J., Stevenson, D. K. 1987; 6 (2): 302-306

  Abstract

  We studied the effect of tin protoporphyrin (TP) on bilirubin production in adult Wistar rats by quantifying in vivo carbon monoxide (CO) excretion and the simultaneous excretion of biliary heme after common bile duct cannulation. A known amount of heme was injected intravenously as red blood cells (RBC) damaged with a sulfhydryl inhibitor, N-ethylmaleimide. The recovery of heme as CO or biliary heme in the cannulated animals was calculated as the molar percent of heme recovered over heme injected. For cannulated controls (n = 4), the recovery was 89 +/- 6% SD, and no heme appeared in bile. Cannulated rats treated with TP (n = 4) had 64 +/- 11% recovered as CO and 30 +/- 11% as heme in bile. Our findings suggest that TP is an effective in vivo inhibitor of exogenous heme catabolism and bilirubin production in adult rats. Furthermore, this inhibition results in increased excretion of heme into the bile proportional to the degree of inhibition.

  View details for Web of Science ID A1987G188100025

  View details for PubMedID 3694354

• TIN PROTOPORPHYRIN INHIBITS CARBON-MONOXIDE PRODUCTION IN SUCKLING MICE BIOLOGY OF THE NEONATE Stevenson, D. K., Watson, E. M., Hintz, S. R., Kim, C. B., Vreman, H. J. 1987; 51 (1): 40-44

  Abstract

  The carbon monoxide excretion rate (VeCO) of groups of 1-day-old mice was measured after administration of two separate doses of 50 nmol of tin protoporphyrin (TP) per gram of body weight. The mean VeCO of the saline-treated control groups over the study period was 1.50 +/- 0.26 nmol/g/h, and that of the TP-treated groups was 1.35 +/- 0.29 nmol/g/h. Tin protoporphyrin treatment reduced the CO excretion by approximately 14% in 2-day-old mice over 24-48 h.

  View details for Web of Science ID A1987G021800007

  View details for PubMedID 3828416

• INVITRO CARBON-MONOXIDE PRODUCTION BY THE RAT SMALL-INTESTINE KIM, C. B., HINTZ, VREMAN, H. J., STEVENSON, D. K. SLACK INC. 1987: A208

  View details for Web of Science ID A1987F528501198

• CARBON-MONOXIDE (CO) EXCRETION AS AN ACCURATE MEASURE OF SUPPRESSED EXOGENOUS HEME CATABOLISM IN BILE-DUCT CANNULATED ADULT WISTAR RATS AFTER TIN PROTOPORPHYRIN (TP) Hintz, S. R., Kwong, L. K., Vreman, H. J., Stevenson, D. K. INT PEDIATRIC RESEARCH FOUNDATION, INC. 1986: A350?A350

  View details for Web of Science ID A1986A712001182

• COMPLETE RECOVERY OF EXOGENOUS HEME AS CO AND BILIARY HEME IN WISTAR RATS AFTER TIN-PROTOPORPHYRIN (TP) Hintz, S. R., Kwong, L. K., Vreman, H. J., Stevenson, D. K. SLACK INC. 1986: A143?A143

  View details for Web of Science ID A1986C748300840

• COMPARATIVE EFFECT OF TIN PROTOPORPHYRIN (TP) ON CARBON-MONOXIDE EXCRETION (VECO) IN ADULT AND NEWBORN WISTAR RATS Kim, C. B., Hintz, S. R., Watson, E. M., Kwong, L. K., Vreman, H. J., Stevenson, D. K. SLACK INC. 1986: A144?A144

  View details for Web of Science ID A1986C748300847