Academic Appointments

Research & Scholarship

Current Research and Scholarly Interests

Neonatology, neurobehavioral development, outcomes in premature infants.


All Publications

  • 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


    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

  • Diffusion tensor brain imaging findings at term-equivalent age may predict neurologic abnormalities in low birth weight preterm infants AMERICAN JOURNAL OF NEURORADIOLOGY Arzoumanian, Y., Mirmiran, M., Barnes, P. D., Woolley, K., Ariagno, R. L., Moseley, M. E., Fleisher, B. E., Atlas, S. W. 2003; 24 (8): 1646-1653


    Low birth weight preterm infants are at high risk of brain injury, particularly injury to the white matter. Diffusion tensor imaging is thought to be more sensitive than conventional MR imaging for detecting subtle white matter abnormalities. The objective of this study was to examine whether diffusion tensor imaging could detect abnormalities that may be associated with later neurologic abnormalities in infants with otherwise normal or minimally abnormal conventional MR imaging findings.We prospectively studied 137 low birth weight (<1800 g) preterm infants. Neonatal conventional MR imaging and diffusion tensor imaging were performed near term-equivalent age before discharge, and neurologic development of the infants was later followed up at 18 to 24 months of age.Among the preterm infants who were fully studied, 63 underwent normal conventional MR imaging. Three of these infants developed cerebral palsy, and 10 others showed abnormal neurologic outcome. Diffusion tensor imaging results for these infants showed a significant reduction of fractional anisotropy in the posterior limb of the internal capsule in neurologically abnormal infants (including those with cerebral palsy) compared with control preterm infants with normal neurologic outcomes.These results suggest that neonatal diffusion tensor imaging may allow earlier detection of specific anatomic findings of microstructural abnormalities in infants at risk for neurologic abnormalities and disability. The combination of conventional MR imaging and diffusion tensor imaging may increase the predictive value of neonatal MR imaging for later neurologic outcome abnormalities and may become the basis for future interventional clinical studies to improve outcomes.

    View details for Web of Science ID 000185400100031

    View details for PubMedID 13679287

  • Follow-up of children of depressed mothers exposed or not exposed to antidepressant drugs during pregnancy 1st International Conference on Womens Mental Health Casper, R. C., Fleisher, B. E., Lee-Ancajas, J. C., Gilles, A., Gaylor, E., DeBattista, A., Hoyme, H. E. MOSBY-ELSEVIER. 2003: 402–8


    To compare the structural growth and developmental outcome of children born to mothers diagnosed with major depressive disorder during pregnancy who were exposed or not exposed to selective serotonin reuptake inhibitors (SSRIs) in utero.Children whose mothers were diagnosed with major depressive disorder in pregnancy and elected not to take medication (n = 13) were compared with children of depressed mothers treated with SSRIs (n = 31) on birth outcomes and postnatal neurodevelopmental functioning between ages 6 and 40 months. Children underwent blinded standardized pediatric and dysmorphology examinations and evaluations of their mental and psychomotor development with the use of the Bayley Scales of Infant Development (BSID II).The Bayley mental developmental indexes were similar in both groups. Children exposed to SSRIs during pregnancy had lower APGAR scores and scored lower on the Bayley psychomotor development indexes and the motor quality factor of the Bayley Behavioral Rating Scale than unexposed children.The findings that SSRIs during fetal development might have subtle effects on motor development and motor control are consistent with the pharmacologic properties of the drugs.

    View details for DOI 10.1067/mpd.203.139

    View details for Web of Science ID 000182733800011

    View details for PubMedID 12712058

  • The need for long-term audiologic follow-up of neonatal intensive care unit (NICU) graduates INTERNATIONAL JOURNAL OF PEDIATRIC OTORHINOLARYNGOLOGY Yoon, P. J., Price, M., Gallagher, K., Fleisher, B. E., Messner, A. H. 2003; 67 (4): 353-357


    To evaluate the adequacy of newborn hearing screening in the identification of hearing loss in post-neonatal intensive care unit (NICU) infants.Eighty-two post-NICU infants who had initially passed automated auditory brainstem response (AABR) screening were studied prospectively between November 1997 and July 1999. Tympanometry and transient evoked otoacoustic emissions (TEOAE) were used to evaluate middle ear status and screen the hearing of subjects when they were seen routinely in the Mary L. Johnson Infant Development Clinic, where NICU graduates are followed at our institution. TEOAEs were not performed in subjects with abnormal tympanometry, defined as negative pressures greater than 200 daPa or flat tympanograms.Of the 82 subjects, 31 (37%) had abnormal tympanometry in at least one ear, with 24 (29%) exhibiting abnormal values bilaterally. Two subjects were identified with delayed-onset or previously undiagnosed sensorineural hearing loss. One had a history of persistent pulmonary hypertension (PPHN) and extracorporeal membrane oxygenation. The other infant had no risk factors for sensorineural hearing loss.Our data indicate that newborn hearing screening programs may not provide adequate vigilance for NICU graduates. The high incidence of abnormal middle ear status and the identification of delayed-onset hearing loss in an infant without known risk factors highlights the need for close audiologic and speech/language follow-up in the post-NICU population.

    View details for DOI 10.1016/S0165-5876(02)00400-7

    View details for Web of Science ID 000182263300007

    View details for PubMedID 12663106

  • Infant heart transplantation at Stanford: Growth and neurodevelopmental outcome PEDIATRICS Fleisher, B. E., Baum, D., Brudos, G., Burge, M., Carson, E., Constantinou, J., Duckworth, J., Gamberg, P., Klein, P., Luikart, H., Miller, J., Stach, B., Bernstein, D. 2002; 109 (1): 1-7


    To evaluate the growth and neurodevelopmental outcome of 18 surviving Stanford patients who received heart transplantations before their second birthday.We compared the growth and neurodevelopmental outcome of these 18 patients with a second group of age-matched comparison patients who underwent other heart surgery requiring cardiopulmonary bypass.Difficulties with growth and development were more common in the transplant group as were neurologic abnormalities. Speech and language delays as well as hearing problems were also more common in the transplant group.Multicenter prospective longitudinal neurodevelopmental outcome studies of infant heart transplant patients should be conducted to provide a more efficient basis for evaluating management protocols and assessment of long-term outcomes and of the need for early intervention services.

    View details for Web of Science ID 000173006600019

    View details for PubMedID 11773534

  • Effects of skin-to-skin holding on general movements of preterm infants CLINICAL PEDIATRICS Constantinou, J. C., Adamson-Macedo, E. N., Stevenson, D. K., Mirmiran, M., Fleisher, B. E. 1999; 38 (8): 467-471


    The study objective was to test the hypothesis that the effect of skin-to-skin (STS) holding increases the ratio of rest to activity in low birth weight preterm infants. Ten infants with birthweight < 2,000 grams were videotaped before and after STS holding. Video recordings were analyzed to determine the number of general movements. We found no statistically significant difference between the percentage of general movements over the two periods. We conclude that the ratio of rest-activity before and after STS holding does not change as measured by occurrence of general movements.

    View details for Web of Science ID 000081864400005

    View details for PubMedID 10456242

  • Supplemental oxygen may decrease progression of prethreshold disease to threshold retinopathy of prematurity. Journal of perinatology Gaynon, M. W., Stevenson, D. K., Sunshine, P., Fleisher, B. E., Landers, M. B. 1997; 17 (6): 434-438


    The optimum level of oxygen saturation for infants with prethreshold retinopathy of prematurity (ROP) is unknown. We reviewed our conversion rate from prethreshold to threshold ROP between 1985 and 1993 during which time target levels of oxygen saturation rose in a stepwise fashion. A retrospective study of 153 infants with prethreshold ROP was performed at Stanford University between 1985 and 1993 that showed that target minimum oxygen saturation rose from 92% (1985-1987) to 95% (1988) to 96% (1989) to 99% (1990-1993). In addition, we looked at 26 infants between 1994 and 1996 who were excluded from the STOP-ROP study and who were not receiving supplemental oxygen in an effort to maintain equipoise for that study. Infant characteristics were tabulated, and rates of progression from prethreshold to threshold ROP were calculated. Rates of progression to threshold varied little between 1985 and 1989 (average 37%), but dropped to 7% for the period between 1990 and 1993. From 1994 through 1996 the rate of progression to threshold disease rose again, to 38%. Moderate supplemental oxygen (target saturation 99% with PO2 no higher than 100 mm Hg) was associated with regression of prethreshold ROP, without appearing to arrest retinal vascular maturation.

    View details for PubMedID 9447528

  • Sedation administered to very low birth weight premature infants. Journal of perinatology Heller, C., Constantinou, J. C., Vandenberg, K., Benitz, W., Fleisher, B. E. 1997; 17 (2): 107-112


    The aim of this study was to evaluate the impact of individualized developmental care for very low birth weight infants on the amount of sedation used in their treatment.A randomized control trial was conducted. Each infant in the experimental group underwent evaluation weekly, and individualized behaviorally oriented care plans, aimed at reducing stress and promoting self-regulatory behaviors, were prepared and implemented. Control infants received the usual standard of nursery care. Total doses of opioids and chloral hydrate were calculated. Severity of illness during the initial hospital stay was stratified with use of the Neonatal Medical Index.Severely ill infants in the treatment group required less chloral hydrate than those in the control group. Infants who were not severely ill received little or no sedation, and among this subgroup treatment and control infants did not differ.We speculate that developmentally based care reduces stress levels in severely ill very low birth weight infants and thus decreases sedation requirements.

    View details for PubMedID 9134507

  • INDIVIDUALIZED DEVELOPMENTAL CARE FOR VERY-LOW-BIRTH-WEIGHT PREMATURE-INFANTS CLINICAL PEDIATRICS Fleisher, B. E., Vandenberg, K., Constantinou, J., Heller, C., Benitz, W. E., Johnson, A., Rosenthal, A., Stevenson, D. K. 1995; 34 (10): 523-529


    Forty very-low-birth-weight neonatal intensive care unit (NICU) infants with birth weights < or = 1,250 g were randomly assigned to treatment or control groups. Behavior of the treatment infants was systematically evaluated, and individualized developmentally oriented care plans were implemented to enhance stability. Treatment babies required fewer days of intermittent mandatory ventilation and continuous positive airway pressure and achieved full enteral feedings sooner. Length of hospital stay and hospital charges were less for treatment than control infants. There were favorable effects on treatment infants' behavioral performance at 42 weeks' postconceptional age. These results support the hypothesis that behaviorally sensitive, developmentally oriented care improves medical and neurodevelopmental outcome in the NICU.

    View details for Web of Science ID A1995RZ28800003

    View details for PubMedID 8591679



    Computed tomography scans of the head and early neurodevelopmental assessment (Bayley Scales of Infant development) were recorded for 24 surviving infants who received venovenous extracorporeal membrane oxygenation and were compared with those of infants treated with venoarterial bypass matched by diagnosis and oxygenation index before extracorporeal membrane oxygenation. A comparable neuroradiographic and early neurodevelopmental outcome was documented for survivors of venoarterial and venovenous extracorporeal membrane oxygenation.

    View details for Web of Science ID A1994PA95200025

    View details for PubMedID 8040782


    View details for Web of Science ID A1991FF72700027

    View details for PubMedID 2011440



    The incidence of respiratory distress syndrome (RDS) is higher in male than in female infants. The lung profiles--lecithin/sphingomyelin (L/S) ratios, percent disaturated (acetone precipitated) lecithin, phosphatidylglycerol, and phosphatidylinositol--were obtained in amniotic fluid during 164 normal pregnancies of 30 or more weeks' gestation. The profiles were evaluated to determine any sex differences in fetal development of the surfactant components. According to regression analysis the L/S ratios for females reached 2:1 at 33.7 weeks, which is 1.4 weeks earlier than males. A similar trend was evident for disaturated lecithin. Phosphatidylglycerol first appeared at 34 weeks' gestation for females and 35 weeks for males. The rate of the increase in phosphatidylglycerol was higher in females than in males. Phosphatidylinositol began to decrease after 36 weeks for females and fell to levels below that of males after 37 weeks' gestation. All four indexes of the lung profile revealed a higher degree of lung maturity in female than in male fetuses during the last two months of normal pregnancy. This explains a higher incidence of RDS in male than in female infants.

    View details for Web of Science ID A1985APU2500006

    View details for PubMedID 4022494