Vinod (Vinny) K. Bhutani

All Publications

• Identification of risk for neonatal haemolysis. Acta paediatrica (Oslo, Norway : 1992) Bhutani, V. K., Maisels, M. J., Schutzman, D. L., Castillo Cuadrado, M. E., Aby, J. L., Bogen, D. L., Christensen, R. D., Watchko, J. F., Wong, R. J., Stevenson, D. K. 2018

  Abstract

  AIM: To identify neonates at risk of haemolytic hyperbilirubinaemia through near-concurrent measurements of total serum/plasma bilirubin (TB) or transcutaneous bilirubin (TcB) and end-tidal breath carbon monoxide (CO), corrected for ambient CO (ETCOc), an index of bilirubin production and haemolysis.METHODS: Paired TB/TcB (mg/dL) and ETCOc (ppm) measurements were obtained in newborns (n = 283) at 20 to <60 hours of age in five nurseries. TB/TcB values were assigned TB/TcB percentile risk values using the Bhutani hour-specific nomogram. In infants having two serial TB/TcB measurements (n = 76), TB rate of rise (ROR, mg/dL/h) was calculated.RESULTS: For the entire cohort (n = 283), 67.1% and 32.9% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.79 ± 1.84 vs 9.14 ± 2.25 mg/dL) and ETCOc (1.61 ± 0.45 vs 2.02 ± 1.35 ppm, p = 0.0002) were different between the groups. About 36.6% of infants with TB/TcB ≥75th percentile had ETCOc ≥ 2.0 ppm. In the subcohort of infants with serial TB/TcB measurements (n = 76), 44.7% and 55.3% had TB/TcB<75th and ≥75th percentile, respectively. TB/TcB (5.28 ± 1.97 vs 9.53 ± 2.78 mg/dL), ETCOc (1.72 ± 0.48 vs 2.38 ± 1.89 ppm, p = 0.05) and TB ROR (0.011 ± 0.440 vs 0.172 ± 0.471 mg/dL/h) were different between the groups.CONCLUSION: The combined use of TB/TcB percentile risk assessments and ETCOc measurements can identify infants with haemolytic hyperbilirubinaemia. The addition of TB ROR can identify those infants with elimination disorders.

  View details for PubMedID 29532503

• Extreme hyperbilirubinemia and rescue exchange transfusion in California from 2007 to 2012. Journal of perinatology Bhutani, V. K., Meng, N. F., Knauer, Y., Danielsen, B. H., Wong, R. J., Stevenson, D. K., Gould, J. B. 2016; 36 (10): 853-857

  Abstract

  To evaluate the impact of statewide learning collaboratives that used national guidelines to manage jaundice on the serial prevalence of extreme hyperbilirubinemia (EHB, total bilirubin ⩾25 mg dl(-1)) and exchange transfusions introduced in California Perinatal Quality Care Collaborative (CPQCC) hospitals in 2007.Adverse outcomes were retrieved from statewide databases on re-admissions for live births ⩾35 weeks' gestation (2007 to 2012) in diverse CPQCC hospitals. Individual and cumulative select perinatal risk factors and frequencies were the outcomes measures.For 3 172 762 babies (2007 to 2012), 92.5% were ⩾35 weeks' gestation. Statewide EHB and exchange rates decreased from 28.2 to 15.3 and 3.6 to 1.9 per 100 000 live births, respectively. From 2007 to 2012, the trends for TB>25 mg dl(-1) rates were -0.92 per 100 000 live births per year (95% CI: -3.71 to 1.87, P=0.41 and R(2)=0.17).National guidelines complemented by statewide learning collaboratives can decrease or modify outcomes among all birth facilities and impact clinical practice behavior.

  View details for DOI 10.1038/jp.2016.106

  View details for PubMedID 27442156

• Clinical trial of tin mesoporphyrin to prevent neonatal hyperbilirubinemia JOURNAL OF PERINATOLOGY Bhutani, V. K., Poland, R., Meloy, L. D., Hegyi, T., Fanaroff, A. A., Maisels, M. J. 2016; 36 (7): 533-539

  Abstract

  To assess the efficacy of the heme oxygenase inhibitor, tin mesoporphyrin (SnMP), to reduce total bilirubin (TB) levels.Masked, SnMP (4.5 mg kg(-1)), placebo-controlled, multicenter trial of single intramuscular injection to newborns ⩾35 weeks gestational age whose predischarge screening transcutaneous bilirubin (TcB) was >75th percentile.Two hundred and thirteen newborns (median age 30 h) were randomized to treatment with SnMP (n=87) or 'sham' (n=89). We found that the duration of phototherapy was halved. Within 12 h of SnMP administration, the natural TB trajectory was reversed. At age 3 to 5 days, TB in the SnMP-treated group was +8% but sixfold lower than the 47% increase in the sham-treated group (P<0.001). At age 7 to 10 days, mean TB declined 18% (P<0.001) compared with a 7.1% increase among controls. No short-term adverse events from SnMP treatment were noted other than photoreactivity due to inadvertent exposure to white light phototherapy.Early, predischarge SnMP administration decreased the duration of phototherapy, reversed TB trajectory and reduced the severity of subsequent hyperbilirubinemia.

  View details for DOI 10.1038/jp.2016.22

  View details for Web of Science ID 000378649300008

  View details for PubMedID 26938918

• The clinical syndrome of bilirubin-induced neurologic dysfunction SEMINARS IN FETAL & NEONATAL MEDICINE Bhutani, V. K., Johnson-Hamerman, L. 2015; 20 (1): 6-13

  Abstract

  Clinicians have hypothesized a spectrum of minor neurologic manifestations, consistent with neuroanatomical reports and collectively termed as a "syndrome of bilirubin-induced neurologic dysfunction (BIND)," which can occur in the absence of classical kernicterus. The current review builds on these initial reports with a focus on clinical signs and symptoms that are assessed by standardized tools and manifest from neonatal age to childhood. These clinical manifestations are characterized by the following domains: (i) neuromotor signs; (ii) muscle tone abnormalities; (iii) hyperexcitable neonatal reflexes; (iv) variety of neurobehavior manifestations; (v) speech and language abnormalities; and (vi) evolving array of central processing abnormalities, such as sensorineural audiology and visuomotor dysfunctions. Concerns remain that the most vulnerable infants are likely to acquire BIND, either because their exposure to bilirubin is not identified as severe enough to need treatment or is prolonged but slightly below current threshold levels for intervention. Knowing that a total serum/plasma bilirubin (TB) level is not the most precise indicator of neurotoxicity, the role of expanded biomarkers or a "bilirubin panel" has yet to be validated in prospective studies. Future studies that correlate early "toxic" bilirubin exposure to long-term academic potential of children are needed to explore new insights into bilirubin's effect on the structural and functional maturation of an infant's neural network topology.

  View details for DOI 10.1016/j.siny.2014.12.008

  View details for Web of Science ID 000350926500003

  View details for PubMedID 25577653

• Neonatal hyperbilirubinemia and Rhesus disease of the newborn: incidence and impairment estimates for 2010 at regional and global levels PEDIATRIC RESEARCH Bhutani, V. K., Zipursky, A., Blencowe, H., Khanna, R., Sgro, M., Ebbesen, F., Bell, J., Mori, R., Slusher, T. M., Fahmy, N., Paul, V. K., Du, L., Okolo, A. A., de Almeida, M., Olusanya, B. O., Kumar, P., Cousens, S., Lawn, J. E. 2013; 74: 86-100

  Abstract

  Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.Systematic reviews and meta-analyses were undertaken of national prevalence, mortality, and kernicterus due to Rh disease and EHB. We applied a compartmental model to estimate neonatal survivors and impairment cases for 2010.Twenty-four million (18% of 134 million live births ≥ 32 wk gestational age from 184 countries; uncertainty range: 23-26 million) were at risk for neonatal hyperbilirubinemia-related adverse outcomes. Of these, 480,700 (0.36%) had either Rh disease (373,300; uncertainty range: 271,800-477,500) or developed EHB from other causes (107,400; uncertainty range: 57,000-131,000), with a 24% risk for death (114,100; uncertainty range: 59,700-172,000), 13% for kernicterus (75,400), and 11% for stillbirths. Three-quarters of mortality occurred in sub-Saharan Africa and South Asia. Kernicterus with Rh disease ranged from 38, 28, 28, and 25/100,000 live births for Eastern Europe/Central Asian, sub-Saharan African, South Asian, and Latin American regions, respectively. More than 83% of survivors with kernicterus had one or more impairments.Failure to prevent Rh sensitization and manage neonatal hyperbilirubinemia results in 114,100 avoidable neonatal deaths and many children grow up with disabilities. Proven solutions remain underused, especially in low-income countries.

  View details for DOI 10.1038/pr.2013.208

  View details for PubMedID 24366465

• Predischarge screening for severe neonatal hyperbilirubinemia identifies infants who need phototherapy. journal of pediatrics Bhutani, V. K., Stark, A. R., Lazzeroni, L. C., Poland, R., Gourley, G. R., Kazmierczak, S., Meloy, L., Burgos, A. E., Hall, J. Y., Stevenson, D. K. 2013; 162 (3): 477-482 e1

  Abstract

  To test whether the combined use of total plasma/serum bilirubin (TSB) levels and clinical risk factors more accurately identifies infants who receive phototherapy than does the use of either method alone.We recruited healthy infants of ≥35 weeks' gestation at 6 centers that practiced universal predischarge TSB screening. Transcutaneous bilirubin (TcB) was measured at 24 hours, with TSB at 24-60 hours and at 3- to 5- and 7- to 14-day follow-up visits. Clinical risk factors were identified systematically.Of 1157 infants, 1060 (92%) completed follow-up, and 982 (85%) had complete datasets for analysis. Infant characteristics included 25% were nonwhite and 55% were Hispanic/Latino; >90% were breastfed. During the first week, jaundice was documented in 84% of subjects. Predischarge TSB identified the 41 (4.2%) and 34 (3.5%) infants who received phototherapy before and after discharge, respectively. Prediction of postdischarge phototherapy was similar for combined clinical risk factors (earlier gestational age [GA], bruising, positive direct antiglobulin test, Asian race, exclusive breastfeeding, blood type incompatibility, jaundice extent) and age-adjusted TSB (area under the curve [AUC] = .86 vs .87), but combined screening was better (AUC = .95). TcB/TSB combined with GA alone was equally predictive (AUC = .95; 95% CI .93-.97).Jaundice is present in 4 of 5 (84%) healthy newborns. Predischarge TcB/TSB (adjusted for postnatal age) combined with specific clinical factors (especially GA) best predicts subsequent phototherapy use. Universal implementation of this strategy in the US should improve outcomes of healthy newborns discharged early.

  View details for DOI 10.1016/j.jpeds.2012.08.022

  View details for PubMedID 23043681

• Building Evidence to Manage Newborn Jaundice Worldwide INDIAN JOURNAL OF PEDIATRICS Bhutani, V. K. 2012; 79 (2): 253-255

  View details for DOI 10.1007/s12098-011-0631-6

  View details for Web of Science ID 000302360700015

  View details for PubMedID 22183759

• The Need for Technologies to Prevent Bilirubin-Induced Neurologic Dysfunction Syndrome SEMINARS IN PERINATOLOGY Bhutani, V. K., Stevenson, D. K. 2011; 35 (3): 97-100

  Abstract

  Dramatic improvements in the overall socioeconomic conditions have yet to impact the unacceptably high maternal (approximately 1500 maternal deaths daily, worldwide) and neonatal morbidity and mortality (more than 10,000 deaths per daily 200,000 live-births, worldwide) in the developing nations. Thus, nations with emerging markets have unique health-societal needs. All infants require a safer transition from a birthing facility to home during the first week after birth and providing for a nurturing environment to prevent neonatal illnesses is integral to "good clinical practice." The unmonitored occurrence of severe hyperbilirubinemia and kernicterus are emblematic of a fractured maternal child healthcare system. The "know-do" gaps that span private versus public health care systems in the emerging markets have led us to conclude that building an interdisciplinary leadership approach to provide innovative strategies and affordable technologies will help bridge and access existing social barriers in the micro- and macro-health environments. Thus, unfettered access, global benchmarks, and culturally relevant strategies are dependent on evidence-based affordable technologies to successfully transform societal health care practices. Implementation of jaundice-related technologies should serve as a template for other affordable newborn health products.

  View details for DOI 10.1053/j.semperi.2011.02.002

  View details for PubMedID 21641481

• Predictive ability of a predischarge hour-specific serum bilirubin for subsequent significant hyperbilirubinemia in healthy term and near-term newborns PEDIATRICS Bhutani, V. K., Johnson, L., Sivieri, E. M. 1999; 103 (1): 6-14

  Abstract

  To assess the predictive ability of a universal predischarge serum bilirubin measurement to screen for risk of subsequent significant hyperbilirubinemia in the direct Coombs negative healthy term and near-term newborn during the first postnatal week.Total serum bilirubin (TSB) levels were obtained at the time of the routine metabolic screen in all term and near-term newborns cared for in the Pennsylvania Hospital Well Baby Nursery (n = 13 003). Postnatal age (in hours) at the time of TSB measurement was recorded. A percentile-based bilirubin nomogram for the first week was constructed from hour-specific predischarge and postdischarge TSB values of newborns (n = 2840; median BW = 3230 g and median gestational age = 39 weeks) who met classification criteria for healthy newborns (excluding those with a positive direct Coombs test or those requiring phototherapy before age 60 hours) and who were enrolled in a hospital supervised home or outpatient follow-up program. The accuracy of the predischarge TSB as a predictor of subsequent degree of hyperbilirubinemia was determined.The study patients in the nomogram were racially diverse. Nearly 60% were breastfed. Predischarge, 6.1% of the study population (172/2840) had TSB values in the high-risk zone (>/=95th percentile) at 18 to 72 hours; of these, 39.5% (68/172) remained in that zone (likelihood ratio [LR] = 14.08, sensitivity = 54%; specificity = 96.2%, probability = 39.5%). Predischarge, 32.1% of the population (912/2840) had TSB values in the intermediate-risk zone. In a clinically significant minority of these newborns (58/912 or 6.4%), the postdischarge TSB moved into the high-risk zone (LR of this move: 3.2 from the upper-intermediate zone and.48 from the lower-intermediate risk zone). The predischarge TSB in 61.8% of the newborns (1756/2840) was in the low-risk zone (<40th percentile) and there was no measurable risk for significant hyperbilirubinemia (LR = 0, sensitivity = 100%; specificity = 64.7%; probability = 0%).An hour-specific TSB before hospital discharge can predict which newborn is at high, intermediate or low risk for developing clinically significant hyperbilirubinemia (specifically defined as TSB levels >/=95th percentile for age in hours). Risk designation and subsequent increases or decreases of in TSB can be easily monitored on an hour-specific percentile based predictive bilirubin nomogram. A predischarge TSB measured as a universal policy would facilitate targeted intervention and follow-up in a safe, cost-effective manner. In conjunction with bilirubin practice parameter of the American Academy of Pediatrics, it could reduce the potential risk for bilirubin-induced neurologic dysfunction.

  View details for Web of Science ID 000078060900002

  View details for PubMedID 9917432

• A multi-center evaluation of a device for measurement of bilirubin binding capacity in neonates: the effects of gestational age, Intralipid exposure and illness severity JOURNAL OF PERINATOLOGY Schutzman, D. L., Bhutani, V. K., Cuadrado, M., Lamola, A. A., Frantz, I., Obregon, E., Wong, R. J. 2019; 39 (6): 883–88

  View details for DOI 10.1038/s41372-019-0365-2

  View details for Web of Science ID 000468895300016

• A multi-center evaluation of a device for measurement of bilirubin binding capacity in neonates: the effects of gestational age, Intralipid exposure and illness severity. Journal of perinatology : official journal of the California Perinatal Association Schutzman, D. L., Bhutani, V. K., Castillo Cuadrado, M. E., Lamola, A. A., Frantz, I., Obregon, E., Wong, R. J. 2019

  Abstract

  OBJECTIVE: Measure daily bilirubin-binding capacity (BBC) variation using an automated, not as-yet FDA approved, Point-of-Care hematofluorometer. Measure the effects of prematurity, clinical instability and exposure to Intralipid on BBC.SUBJECTS: Convenience sample of 109 infants from well-baby and intensive care nurseries. Gestational ages 28-41 weeks. 261 specimens obtained from postnatal ages 1-4 days. Unstable neonates were defined by need for at least noninvasive respiratory support and FiO2≥0.25.RESULTS: Median interday variation was 2.9±5.1mg/dL. BBC (0.254mg/dL/wk) and albumin (0.037g/dL/wk) increased for each week of gestation. BBC was lower in unstable compared to well infants (26.1±7.6mg/dL v 28.6±6.3mg/dL). BBC was not significantly different in infants receiving or not receiving IL.CONCLUSIONS: BBC measurements using the device had acceptable intraspecimen reproducibility and interday variability. BBC may be helpful in guiding the assessment of aggressive versus conservative management decisions in preterm and sick infants with hyperbilirubinemia.

  View details for PubMedID 30918342

• The Neonatal Acute Bilirubin Encephalopathy Registry (NABER): Background, Aims, and Protocol. Neonatology Bahr, T. M., Christensen, R. D., Agarwal, A. M., George, T. I., Bhutani, V. K. 2019; 115 (3): 242–46

  Abstract

  BACKGROUND: Acute bilirubin encephalopathy (ABE) is a potentially devastating condition that can lead to death or life-long neurodevelopmental handicaps. ABE is particularly tragic because it is, in theory, completely preventable. Progress toward its prevention has been hampered by the perception that the extreme hyperbilirubinemia giving rise to ABE typically has no clear causation, with the majority of previous cases being labeled as "idiopathic" neonatal jaundice.OBJECTIVES: This research briefing is intended to inform readers of a new prospective study aimed at clarifying the causes of ABE. This is accomplished by identifying qualifying patients with ABE anywhere in the USA and then documenting their clinical characteristics and the results of testing 28 specific genetic associations in a web-based, institutional review board-approved, REDCap (research electronic data capture) deidentified registry.METHODS: In this research briefing, we present an overview of ABE and discuss the problem that most patients in the past have been labeled as having "idiopathic" hyperbilirubinemia. We also present data supporting a new theory that most (perhaps all) ABE patients have mutations or polymorphisms in genes involved in bilirubin production or metabolism. We introduce a new registry seeking to enroll 100 neonates with ABE as a voluntary, deidentified database, with next generation sequencing of 28 genes involved in bilirubin production/metabolism provided to enrollees at no cost.RESULTS AND CONCLUSIONS: The Neonatal Acute Bilirubin Encephalopathy Registry (NABER) study will correlate deidentified clinical and genetic data in order to clarify the underlying causes of hyperbilirubinemia in current ABE patients. We maintain that the improved understanding this study produces will constitute a needed step toward devising new clinical pathways and strategies for preventing ABE in neonates.

  View details for PubMedID 30669144

• A NOVEL POINT-OF-CARE DEVICE FOR MEASURING GLUCOSE-6-PHOSPHATE DEHYDROGENASE ENZYME DEFICIENCY Montiel, C., Kunda, M., Stevenson, D. K., Wong, R. J., Bhutani, V. K. BMJ PUBLISHING GROUP. 2019: 117

  View details for DOI 10.1136/jim-2018-000939.116

  View details for Web of Science ID 000457712500126

• ACUTE BILIRUBIN ENCEPHALOPATHY: A REGISTRY AND DATABASE INCLUDING NEXT GENERATION SEQUENCING OF POTENTIAL GENETIC ASSOCIATIONS Bahr, T. M., Christensen, R. D., Agarwal, A. M., George, T. I., Bhutani, V. K. BMJ PUBLISHING GROUP. 2019: 262–63

  View details for DOI 10.1136/jim-2018-000939.455

  View details for Web of Science ID 000457712500465

• The Neonatal Acute Bilirubin Encephalopathy Registry (NABER): Background, Aims, and Protocol NEONATOLOGY Bahr, T. M., Christensen, R. D., Agarwal, A. M., George, T., Bhutani, V. K. 2019; 115 (3): 242–46

  View details for DOI 10.1159/000495518

  View details for Web of Science ID 000467681100010

• Acute neonatal bilirubin encephalopathy in the State of Utah 2009-2018 BLOOD CELLS MOLECULES AND DISEASES Christensen, R. D., Agarwal, A. M., George, T., Bhutani, V. K., Yaish, H. M. 2018; 72: 10–13

  Abstract

  Herein we report a case series of seven newborn infants, all apparently well at birth, who in the period since 2009 were cared for in the State of Utah with acute bilirubin encephalopathy (ABE). This report summarizes our attempts to define common features of these seven through a state-wide voluntary registry, as a step toward devising new means of preventing such cases in the future. In previous reports of ABE, many of the affected neonates had no clearly defined explanation for their progressive hyperbilirubinemia. Our efforts to identify clear explanations in all seven cases included next generation DNA sequencing, testing a panel of 28 genes involved in bilirubin production and metabolism. We found that hemolytic disease was a unifying feature of these seven; two had DAT (+) Anti-D or anti-c hemolysis, while five had confirmed mutations in genes involved in bilirubin production and or metabolism that were previously unrecognized in these families.

  View details for PubMedID 29880417

• Bilirubin binding in jaundiced newborns: from bench to bedside? Pediatric research Ahlfors, C. E., Bhutani, V. K., Wong, R. J., Stevenson, D. K. 2018

  Abstract

  BACKGROUND: Bilirubin-induced neurologic dysfunction (BIND) is a spectrum of preventable neurological sequelae in jaundiced newborns. Current total plasma bilirubin (BT) concentration thresholds for phototherapy and/or exchange transfusion poorly predict BIND.METHODS: The unbound (free) bilirubin (Bf) measured at these BT thresholds provides additional information about the risk for BIND. Bf can be readily adapted to clinical use by determining Bf population parameters at current BT thresholds. These parameters can be established using a plasma bilirubin binding panel (BBP) consisting of BT, Bf, and two empiric constants, the maximum BT (BTmax) and the corresponding equilibrium association bilirubin constant (K).RESULTS: BTmax and K provide the variables needed to accurately estimate Bf at BT

  View details for PubMedID 29967530

• Neurodevelopmental disorders in children aged 2-9 years: Population-based burden estimates across five regions in India PLOS MEDICINE Arora, N. K., Nair, M. C., Gulati, S., Deshmukh, V., Mohapatra, A., Mishra, D., Patel, V., Pandey, R. M., Das, B. C., Divan, G., Murthy, G. S., Sharma, T. D., Sapra, S., Aneja, S., Juneja, M., Reddy, S. K., Suman, P., Mukherjee, S. B., Dasgupta, R., Tudu, P., Das, M. K., Bhutani, V. K., Durkin, M. S., Pinto-Martin, J., Silberberg, D. H., Sagar, R., Ahmed, F., Babu, N., Bavdekar, S., Chandra, V., Chaudhuri, Z., Dada, T., Dass, R., Gourie-Devi, M., Remadevi, S., Gupta, J. C., Handa, K. K., Kalra, V., Karande, S., Konanki, R., Kulkarni, M., Kumar, R., Maria, A., Masoodi, M. A., Mehta, M., Mohanty, S., Nair, H., Natarajan, P., Niswade, A. K., Prasad, A., Rai, S. K., Russell, P. S., Saxena, R., Sharma, S., Singh, A. K., Singh, G. B., Sumaraj, L., Suresh, S., Thakar, A., Parthasarathy, S., Vyas, B., Panigrahi, A., Saroch, M. K., Shukla, R., Rao, K., Silveira, M. P., Singh, S., Vajaratkar, V. 2018; 15 (7): e1002615

  Abstract

  Neurodevelopmental disorders (NDDs) compromise the development and attainment of full social and economic potential at individual, family, community, and country levels. Paucity of data on NDDs slows down policy and programmatic action in most developing countries despite perceived high burden.We assessed 3,964 children (with almost equal number of boys and girls distributed in 2-<6 and 6-9 year age categories) identified from five geographically diverse populations in India using cluster sampling technique (probability proportionate to population size). These were from the North-Central, i.e., Palwal (N = 998; all rural, 16.4% non-Hindu, 25.3% from scheduled caste/tribe [SC-ST] [these are considered underserved communities who are eligible for affirmative action]); North, i.e., Kangra (N = 997; 91.6% rural, 3.7% non-Hindu, 25.3% SC-ST); East, i.e., Dhenkanal (N = 981; 89.8% rural, 1.2% non-Hindu, 38.0% SC-ST); South, i.e., Hyderabad (N = 495; all urban, 25.7% non-Hindu, 27.3% SC-ST) and West, i.e., North Goa (N = 493; 68.0% rural, 11.4% non-Hindu, 18.5% SC-ST). All children were assessed for vision impairment (VI), epilepsy (Epi), neuromotor impairments including cerebral palsy (NMI-CP), hearing impairment (HI), speech and language disorders, autism spectrum disorders (ASDs), and intellectual disability (ID). Furthermore, 6-9-year-old children were also assessed for attention deficit hyperactivity disorder (ADHD) and learning disorders (LDs). We standardized sample characteristics as per Census of India 2011 to arrive at district level and all-sites-pooled estimates. Site-specific prevalence of any of seven NDDs in 2-<6 year olds ranged from 2.9% (95% CI 1.6-5.5) to 18.7% (95% CI 14.7-23.6), and for any of nine NDDs in the 6-9-year-old children, from 6.5% (95% CI 4.6-9.1) to 18.5% (95% CI 15.3-22.3). Two or more NDDs were present in 0.4% (95% CI 0.1-1.7) to 4.3% (95% CI 2.2-8.2) in the younger age category and 0.7% (95% CI 0.2-2.0) to 5.3% (95% CI 3.3-8.2) in the older age category. All-site-pooled estimates for NDDs were 9.2% (95% CI 7.5-11.2) and 13.6% (95% CI 11.3-16.2) in children of 2-<6 and 6-9 year age categories, respectively, without significant difference according to gender, rural/urban residence, or religion; almost one-fifth of these children had more than one NDD. The pooled estimates for prevalence increased by up to three percentage points when these were adjusted for national rates of stunting or low birth weight (LBW). HI, ID, speech and language disorders, Epi, and LDs were the common NDDs across sites. Upon risk modelling, noninstitutional delivery, history of perinatal asphyxia, neonatal illness, postnatal neurological/brain infections, stunting, LBW/prematurity, and older age category (6-9 year) were significantly associated with NDDs. The study sample was underrepresentative of stunting and LBW and had a 15.6% refusal. These factors could be contributing to underestimation of the true NDD burden in our population.The study identifies NDDs in children aged 2-9 years as a significant public health burden for India. HI was higher than and ASD prevalence comparable to the published global literature. Most risk factors of NDDs were modifiable and amenable to public health interventions.

  View details for PubMedID 30040859

• Rhesus disease: a global prevention strategy LANCET CHILD & ADOLESCENT HEALTH Zipursky, A., Bhutani, V. K., Odame, I. 2018; 2 (7): 536–42

  View details for DOI 10.1016/S2352-4642(18)30071-3

  View details for Web of Science ID 000437267600020

• A PILOT PROSPECTIVE COHORT STUDY ON BILIRUBIN BINDING CAPACITY AND INTRALIPID INFUSION RATE Pham, O., Chetta, K. E., Pedroza, C., Tyson, J., Lamola, A., Bhutani, V., Arnold, C. BMJ PUBLISHING GROUP. 2018: 559

  View details for DOI 10.1136/jim-2017-000697.507

  View details for Web of Science ID 000428919000520

• MEASURING BILIRUBIN BINDING CAPACITY IN VERY LOW BIRTHWEIGHT NEWBORNS Chetta, K. E., Pham, O., Pedroza, C., Tyson, J., Lamola, A., Bhutani, V., Arnold, C. BMJ PUBLISHING GROUP. 2018: 627

  View details for DOI 10.1136/jim-2017-000697.677

  View details for Web of Science ID 000428919000689

• Rhesus disease: a global prevention strategy. The Lancet. Child & adolescent health Zipursky, A., Bhutani, V. K., Odame, I. 2018; 2 (7): 536–42

  Abstract

  After nearly five decades of effective prophylaxis in high-income countries, the incidence of rhesus haemolytic disease (also known as haemolytic disease of the fetus and newborn) has substantially decreased, and as a result, clinical experience of the disease among health-care providers is insufficient. By contrast, a worldwide study found that rhesus haemolytic disease continues to be a public health problem in low-income and middle-income countries, affecting annually in more than 150 000 children, and causing thousands of stillbirths, neonatal deaths, and cases of hyperbilirubinaemia with its sequelae (kernicterus and bilirubin-induced neurological dysfunction). Solutions to this problem will require the combined and integrated effort of physicians and other health-care workers, international agencies, manufacturers of the prophylactic agent (rhesus immunoglobulin), health policy makers, and governments of low-income and middle-income countries.

  View details for PubMedID 30169325

• NEONATAL HYPERBILIRUBINEMIA AFTER MECHANICAL CIRCULATORY SUPPORT Bhombal, S., Dasani, R., Davis, A., Axelrod, D. M., Wong, R. J., Bhutani, V. K. BMJ PUBLISHING GROUP. 2018: 164–65

  View details for DOI 10.1136/jim-2017-000663.236

  View details for Web of Science ID 000432007400247

• Rh sensitization in Canada is not obsolete PAEDIATRICS & CHILD HEALTH Baker, J. M., Campbell, D. M., Bhutani, V. K., Sgro, M. 2017; 22 (4): 238–39

  View details for PubMedID 29479222

  View details for PubMedCentralID PMC5804569

• Skin-to-skin contact after birth and the natural course of neurosteroid levels in healthy term newborns. Journal of perinatology McCallie, K. R., Gaikwad, N. W., Castillo Cuadrado, M. E., Aleman, M., Madigan, J. E., Stevenson, D. K., Bhutani, V. K. 2017

  Abstract

  To determine the postnatal course of neurosteroid levels in relation to gender, mode of delivery and the extent of skin-to-skin (STS) contact during the first days of life in healthy term newborns.Prospective observational study of 39 neonates in which parents recorded total duration of STS in the first 2 days and nine neurosteroids (dehydroepiandrosterone-sulfate, progesterone, pregnenolone, pregnenolone-sulfate, allopregnanolone, isopregnanolone, epipregnanolone, pregnanolone and pregnanolone-sulfate) were assayed from blood samples at birth and at 1-2 days of age.All nine neurosteroid levels declined significantly during the first 2 days of life. Gender did not significantly affect the change in neurosteroid levels. The decline in neurosteroid levels was generally more pronounced in vaginal deliveries, and there was a trend toward a larger decline with more exposure to STS.Ongoing studies may better characterize the role of neurosteroids and the influence of STS in more critically ill and premature neonates.

  View details for DOI 10.1038/jp.2016.268

  View details for PubMedID 28102853

• CYCLED PHOTOTHERAPY IS A SAFE AND EFFECTIVE TREATMENT FOR SMALL PREMATURE INFANTS WITH HYPERBILIRUBINEMIA Arnold, C. C., Tyson, J. E., Cuadrado, C. E., Dempsey, A. G., Khan, A. M., Pedroza, C., Bhutani, V. K., Wong, R. J., Stevenson, D. K. BMJ PUBLISHING GROUP. 2017: 150–51

  View details for DOI 10.1136/jim-2016-000365.120

  View details for Web of Science ID 000433055100121

• The Importance of Hemolysis and Its Clinical Detection in Neonates with Hyperbilirubinemia. Current pediatric reviews Wong, R. J., Bhutani, V. K., Stevenson, D. K. 2017; 13 (3): 193–98

  Abstract

  BACKGROUND: Hyperbilirubinemia is a benign transitional phenomenon that occurs in 60% to 80% of all term infants. The degree of hyperbilirubinemia and hence risk for developing bilirubin-induced neurologic dysfunction or BIND is dependent upon two major processes: (i) bilirubin production and its elimination.OBJECTIVE: The aim of this review is to address the importance of hemolysis and its clinical detection in neonates with hyperbilirubinemia.RESULTS: In newborns, an increased bilirubin production rate due to hemolysis is often the primary cause of hyperbilirubinemia during the first week of life. If undiagnosed or untreated, it may lead to an increased risk for BIND. Therefore, the ability to identify infants with hemolytic disease is important in assessing those at risk for developing BIND. In addition, an infant's genetic profile and bilirubin binding status can also affect their overall capacity to cope with the resultant tissue bilirubin load and affect risk and guide appropriate management strategies.CONCLUSION: Therefore, the determination of a newborn's bilirubin production rate is critical to the assessment of a newborn's risk for developing unpredictable extreme hyperbilirubinemia and preventing BIND.

  View details for PubMedID 28782473

• IDENTIFICATION OF RISK FOR NEONATAL HEMOLYSIS: A MULTI-CENTER STUDY Bhutani, V. K., Cuadrado, C. E., Schutzman, D. L., Aby, J. L., Bogen, D. L., Christensen, R. D., Watchko, J. F., Maisels, M., Wong, R. J., Stevenson, D. K. BMJ PUBLISHING GROUP. 2017: 123

  View details for DOI 10.1136/jim-2016-000365.57

  View details for Web of Science ID 000433055100058

• Risk profiles for haemolytic and nonhaemolytic neonatal jaundice ACTA PAEDIATRICA Bhutani, V. K., Wong, R. J. 2016; 105 (12): 1387–88

  View details for PubMedID 27870210

• Hyperbilirubinemia in Preterm Neonates CLINICS IN PERINATOLOGY Bhutani, V. K., Wong, R. J., Stevenson, D. K. 2016; 43 (2): 215-?

  Abstract

  Preterm neonates with increased bilirubin production loads are more likely to sustain adverse outcomes due to either neurotoxicity or overtreatment with phototherapy and/or exchange transfusion. Clinicians should rely on expert consensus opinions to guide timely and effective interventions until there is better evidence to refine bilirubin-induced neurologic dysfunction or benefits of bilirubin. In this article, we review the evolving evidence for bilirubin-induced brain injury in preterm infants and highlight the clinical approaches that minimize the risk of bilirubin neurotoxicity.

  View details for DOI 10.1016/j.clp.2016.01.001

  View details for PubMedID 27235203

• The Preterm Infant A High-Risk Situation for Neonatal Hyperbilirubinemia Due to Glucose-6-Phosphate Dehydrogenase Deficiency CLINICS IN PERINATOLOGY Kaplan, M., Hammerman, C., Bhutani, V. K. 2016; 43 (2): 325-?

  Abstract

  Prematurity and glucose-6-phosphate dehydrogenase (G6PD) deficiency are risk factors for neonatal hyperbilirubinemia. The 2 conditions may interact additively or synergistically, contributing to extreme hyperbilirubinemia, with the potential for bilirubin neurotoxicity. This hyperbilirubinemia is the result of sudden, unpredictable, and acute episodes of hemolysis in combination with immaturity of bilirubin elimination, primarily of conjugation. Avoidance of contact with known triggers of hemolysis in G6PD-deficient individuals will prevent some, but not all, episodes of hemolysis. All preterm infants with G6PD deficiency should be vigilantly observed for the development of jaundice both in hospital and after discharge home.

  View details for DOI 10.1016/j.clp.2016.01.008

  View details for Web of Science ID 000378367300011

  View details for PubMedID 27235211

• Preterm Neonates: Beyond the Guidelines for Neonatal Hyperbilirubinemia CLINICS IN PERINATOLOGY Stevenson, D. K., Bhutani, V. K. 2016; 43 (2): XVII-XVIII

  View details for PubMedID 27235216

• Identification of neonatal haemolysis: an approach to predischarge management of neonatal hyperbilirubinemia. Acta paediatrica (Oslo, Norway : 1992) Bhutani, V. K., Srinivas, S., Castillo Cuadrado, M. E., Aby, J. L., Wong, R. J., Stevenson, D. K. 2016; 105 (5): e189-94

  Abstract

  Relative contributions of increased production [by end-tidal carbon monoxide concentrations (ETCOc)] and decreased elimination of bilirubin to predischarge hour-specific total bilirubin (TB) levels were assessed in healthy late-preterm and term newborns. Secondly, we report predischarge ETCOc ranges to guide clinical management of hyperbilirubinemia.TB and ETCOc (≤3 timepoints) determinations of newborns aged between six hours and <6 days (n = 79) were stratified by postnatal age epochs. Hyperbilirubinemia risk was assessed by plotting TB values as a function of ETCOc.Stratifications of ETCOc (in ppm, mean, median and interquartile ranges) by postnatal age epochs (0-24, 24-48 and 48-72) were as follows: 2.0, 1.9, 1.8-2.2 (n = 11); 1.6, 1.5, 1.1-2.0 (n = 58); and 2.0, 1.8, 1.6-2.3 (n = 9), respectively. Infants with ETCOc ≥ 2.5 were at high risk, between 1.5 and 2.5 at moderate risk and ≤1.5 were at low risk. Risk due to haemolysis alone was not independent (p < 0.01). For infants with TB >75th percentile (n = 31), 23% had ETCO ≤1.5, and 77% had ETCOc > 1.5 (p < 0.00003).Near-simultaneous ETCOc and TB measurements in infants with TB >75th percentile accurately identify haemolytic hyperbilirubinemia.

  View details for DOI 10.1111/apa.13341

  View details for PubMedID 26802319

• Filtered sunlight noninferior to conventional phototherapy JOURNAL OF PEDIATRICS Bhutani, V. K. 2016; 170: 341–42

  View details for PubMedID 26922768

• Point-of-Care Quantitative Measure of Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency PEDIATRICS Bhutani, V. K., Kaplan, M., Glader, B., Cotten, M., Kleinert, J., Pamula, V. 2015; 136 (5): E1268-E1275

  Abstract

  Widespread newborn screening on a point-of-care basis could prevent bilirubin neurotoxicity in newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We evaluated a quantitative G6PD assay on a digital microfluidic platform by comparing its performance with standard clinical methods.G6PD activity was measured quantitatively by using digital microfluidic fluorescence and the gold standard fluorescence biochemical test on a convenience sample of 98 discarded blood samples. Twenty-four samples were designated as G6PD deficient.Mean ± SD G6PD activity for normal samples using the digital microfluidic method and the standard method, respectively, was 9.7 ± 2.8 and 11.1 ± 3.0 U/g hemoglobin (Hb), respectively; for G6PD-deficient samples, it was 0.8 ± 0.7 and 1.4 ± 0.9 U/g Hb. Bland-Altman analysis determined a mean difference of -0.96 ± 1.8 U/g Hb between the digital microfluidic fluorescence results and the standard biochemical test results. The lower and upper limits for the digital microfluidic platform were 4.5 to 19.5 U/g Hb for normal samples and 0.2 to 3.7 U/g Hb for G6PD-deficient samples. The lower and upper limits for the Stanford method were 5.5 to 20.7 U/g Hb for normal samples and 0.1 to 2.8 U/g Hb for G6PD-deficient samples. The measured activity discriminated between G6PD-deficient samples and normal samples with no overlap.Pending further validation, a digital microfluidics platform could be an accurate point-of-care screening tool for rapid newborn G6PD screening.

  View details for DOI 10.1542/peds.2015-2122

  View details for Web of Science ID 000363969600012

  View details for PubMedID 26459646

  View details for PubMedCentralID PMC4621802

• Point-of-Care Quantitative Measure of Glucose-6-Phosphate Dehydrogenase Enzyme Deficiency. Pediatrics Bhutani, V. K., Kaplan, M., Glader, B., Cotten, M., Kleinert, J., Pamula, V. 2015; 136 (5): e1268-75

  Abstract

  Widespread newborn screening on a point-of-care basis could prevent bilirubin neurotoxicity in newborns with glucose-6-phosphate dehydrogenase (G6PD) deficiency. We evaluated a quantitative G6PD assay on a digital microfluidic platform by comparing its performance with standard clinical methods.G6PD activity was measured quantitatively by using digital microfluidic fluorescence and the gold standard fluorescence biochemical test on a convenience sample of 98 discarded blood samples. Twenty-four samples were designated as G6PD deficient.Mean ± SD G6PD activity for normal samples using the digital microfluidic method and the standard method, respectively, was 9.7 ± 2.8 and 11.1 ± 3.0 U/g hemoglobin (Hb), respectively; for G6PD-deficient samples, it was 0.8 ± 0.7 and 1.4 ± 0.9 U/g Hb. Bland-Altman analysis determined a mean difference of -0.96 ± 1.8 U/g Hb between the digital microfluidic fluorescence results and the standard biochemical test results. The lower and upper limits for the digital microfluidic platform were 4.5 to 19.5 U/g Hb for normal samples and 0.2 to 3.7 U/g Hb for G6PD-deficient samples. The lower and upper limits for the Stanford method were 5.5 to 20.7 U/g Hb for normal samples and 0.1 to 2.8 U/g Hb for G6PD-deficient samples. The measured activity discriminated between G6PD-deficient samples and normal samples with no overlap.Pending further validation, a digital microfluidics platform could be an accurate point-of-care screening tool for rapid newborn G6PD screening.

  View details for DOI 10.1542/peds.2015-2122

  View details for PubMedID 26459646

• Parental education and the WHO neonatal G-6-PD screening program: a quarter century later. Journal of perinatology Kaplan, M., Hammerman, C., Bhutani, V. K. 2015; 35 (10): 779-784

  Abstract

  Neonatal screening for glucose-6-phosphate dehydrogenase (G-6-PD) deficiency in any population with a male frequency >3-5%, combined with parental education regarding the dietary, environmental and sepsis-related triggers for hemolysis was recommended by the WHO (World Health Organization) Working Group in 1989. As the aim of identifying G-6-PD deficiency in the newborn period is to avert or detect extreme hyperbilirubinemia developing at home, before the development of kernicterus, the parental role in identifying evolving icterus was considered integral to any screening program. Now, a quarter century after publication of this report, severe bilirubin neurotoxicity associated with G-6-PD deficiency continues to be encountered worldwide. Screening programs have not been universally introduced but several national or regional maternal child health programs have implemented neonatal G-6-PD screening. Some reports detail the role of parental education, based on the above mentioned principles, through a variety of audio-visual materials. The paucity of randomized controlled trials or validated evidence to demonstrate the effectiveness of the contribution of parental education fails to meet the ideal testable evidence-based approach. However, our review of the cumulative experience and evidence currently available does supply certain information reflecting a positive impact of screening programs combined with parental input. We propose that the current information is sufficient to continue to support and apply the Working Group's recommendations. In order not to waste unnecessary time available, data may be used in lieu of randomized trials to continue to recommend screening programs, as suggested, in high-risk regions. If the incidence of kernicterus associated with G-6-PD deficiency is to be diminished, G-6-PD screening in combination with parental explanation may be one instance in which the consensus approach suggested by the WHO Working Group, rather than reliance on (nonexistent) evidence-based studies, should continue to be practiced.

  View details for DOI 10.1038/jp.2015.77

  View details for PubMedID 26181718

• Bilirubin production and hour-specific bilirubin levels JOURNAL OF PERINATOLOGY Bhutani, V. K., Wong, R. J., Vreman, H. J., Stevenson, D. K. 2015; 35 (9): 735-738

  Abstract

  We assessed the relative contributions of increased bilirubin production (indexed by end-tidal carbon monoxide (CO) concentrations, corrected for ambient CO (ETCOc)) to hour-specific total bilirubin (TB) levels in healthy late preterm and term newborns.Post hoc analyses of concurrent ETCOc and TB (at 30±6 h of age) and follow-up TB levels at age 96±12 h and up to 168 h after birth were performed in a cohort of 641 term and late preterm infants.Increased bilirubin production (hour-specific ETCOc ⩾1.7 p.p.m. at age 30±6 h) was noted in ~80%, 42% and 32% of infants in the high-, intermediate- and low-risk TB zones, respectively. One infant with TB <40th percentile and ETCOc <1.7 p.p.m. developed TB ⩾95th percentile at age 168 h, probably due to decreased bilirubin elimination.Infants in the high-risk quartile of the hour-specific bilirubin nomogram have a higher mean bilirubin production. Infants with TB levels ⩾95th percentile without increased bilirubin production have impaired bilirubin elimination.

  View details for DOI 10.1038/jp.2015.32

  View details for Web of Science ID 000360408600015

• Bilirubin production and hour-specific bilirubin levels. Journal of perinatology Bhutani, V. K., Wong, R. J., Vreman, H. J., Stevenson, D. K. 2015; 35 (9): 735-738

  Abstract

  We assessed the relative contributions of increased bilirubin production (indexed by end-tidal carbon monoxide (CO) concentrations, corrected for ambient CO (ETCOc)) to hour-specific total bilirubin (TB) levels in healthy late preterm and term newborns.Post hoc analyses of concurrent ETCOc and TB (at 30±6 h of age) and follow-up TB levels at age 96±12 h and up to 168 h after birth were performed in a cohort of 641 term and late preterm infants.Increased bilirubin production (hour-specific ETCOc ⩾1.7 p.p.m. at age 30±6 h) was noted in ~80%, 42% and 32% of infants in the high-, intermediate- and low-risk TB zones, respectively. One infant with TB <40th percentile and ETCOc <1.7 p.p.m. developed TB ⩾95th percentile at age 168 h, probably due to decreased bilirubin elimination.Infants in the high-risk quartile of the hour-specific bilirubin nomogram have a higher mean bilirubin production. Infants with TB levels ⩾95th percentile without increased bilirubin production have impaired bilirubin elimination.

  View details for DOI 10.1038/jp.2015.32

  View details for PubMedID 25880796

• Rhesus disease: a major public health problem LANCET Zipursky, A., Bhutani, V. K. 2015; 386 (9994): 651

  View details for PubMedID 26334154

• Keeping babies warm: a non-inferiority trial of a conductive thermal mattress. Archives of disease in childhood. Fetal and neonatal edition Bhat, S. R., Meng, N. F., Kumar, K., Nagesh, K. N., Kawale, A., Bhutani, V. K. 2015; 100 (4): F309-12

  Abstract

  External thermal support is critical for preterm or ill infants due to altered thermoregulation. Incubators are the gold standard for long-term support and have been adopted successfully in many countries. Alternatives such as radiant warmers, blankets and others are often used as standard of care (SoC) in resource-limited settings when infants are otherwise not in Kangaroo Mother Care (KMC).In this pilot study, we evaluate the feasibility of a conductive thermal mattress (CTM) using phase change materials as a low-cost warmer. We conducted a prospective multicentre open-label randomised controlled trial to determine non-inferiority of this CTM to SoC warming practices in low birthweight infants. The primary outcome was maintenance of axillary temperature.We equally randomised 160 infants to CTM or SoC. The latter cohort continued to receive warmth by radiant warmers (n=48), blankets (n=18), warmed cradles (n=7) or KMC (n=7) before, during and subsequent to the study. CTM was deemed non-inferior since warmed babies had higher axillary temperature compared with SoC (mean increase 0.11±0.03°C SEM; p<0.001). Post hoc comparison to radiant warmers alone showed that CTM led to a higher axillary temperature (mean increase by 0.14±0.03°C SEM; p<0.001).Short-term use of CTM compared with radiant warmers and other modes of warming is non-inferior to SoC and efficacious in maintaining body temperature. No adverse effects were reported. An extended multinational trial, preferably one that demonstrates longer-term thermoregulation, is warranted.Clinical Trials Registry of India (CTRI/2010/091/002916 and CTRI/2011/04/001696).

  View details for DOI 10.1136/archdischild-2014-306269

  View details for PubMedID 25791056

• Evaluation of a new end-tidal carbon monoxide monitor from the bench tothe bedside ACTA PAEDIATRICA Cuadrado, M. E., Bhutani, V. K., Aby, J. L., Vreman, H. J., Wong, R. J., Stevenson, D. K. 2015; 104 (6): E279-E282

  View details for DOI 10.1111/apa.12938

  View details for Web of Science ID 000354528100008

• Preventing visuocotical bilirubin induced neurological dysfunction Good, W. V., Hou, C., Bhutani, V., Norcia, A., Wong, R., Lewis, K., Slagel, T. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2015

  View details for Web of Science ID 000362882201300

• Evaluation of a new end-tidal carbon monoxide monitor from the bench to the bedside. Acta paediatrica (Oslo, Norway : 1992) Castillo Cuadrado, M. E., Bhutani, V. K., Aby, J. L., Vreman, H. J., Wong, R. J., Stevenson, D. K. 2015; 104 (6): e279-82

  View details for DOI 10.1111/apa.12938

  View details for PubMedID 25640053

• Neonatal bilirubin binding capacity discerns risk of neurological dysfunction. Pediatric research Lamola, A. A., Bhutani, V. K., Du, L., Castillo Cuadrado, M., Chen, L., Shen, Z., Wong, R. J., Stevenson, D. K. 2015; 77 (2): 334-339

  Abstract

  Bilirubin binding capacity (BBC) defines the dynamic relationship between an infant's level of unbound or "free" bilirubin and his/her ability to "tolerate" increasing bilirubin loads. BBC is not synonymous with albumin (Alb) levels because Alb binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors.We utilized a novel modification of a previously developed hematofluorometric method to directly assay BBC in whole blood from preterm and term neonates and then combined these data with an archived database. Total bilirubin (TB) was also measured, and multiple regression modeling was used to determine whether BBC in combination with TB measurements can assess an infant's risk for developing bilirubin-induced neurotoxicity.TB and BBC levels ranged from 0.7-22.8 to 6.3-47.5 mg/dl, respectively. Gestational age (GA) correlated with BBC (r = 0.54; P < 0.0002) with a slope of 0.93 mg/dl/wk by logistic regression. Our calculations demonstrate that recently recommended GA-modulated TB thresholds for phototherapy and exchange transfusion correspond to 45 and 67% saturation of our observed regression line, respectively.We speculate that the spread of BBC levels around the regression line (±5.8 mg/dl) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared with TB and GA.

  View details for DOI 10.1038/pr.2014.191

  View details for PubMedID 25420178

• Bilirubin-induced neurologic dysfunction (BIND) SEMINARS IN FETAL & NEONATAL MEDICINE Bhutani, V. K., Wong, R. 2015; 20 (1): 1

  View details for PubMedID 25577656

• Impact of Rhesus disease on the global problem of bilirubin-induced neurologic dysfunction SEMINARS IN FETAL & NEONATAL MEDICINE Zipursky, A., Bhutani, V. K. 2015; 20 (1): 2-5

  Abstract

  Clinical experience with Rhesus (Rh) disease and its post-icteric sequelae is limited among high-income countries because of nearly over four decades of effective prevention care. We hypothesized that Rh disease is prevalent in other regions of the world because it is likely that protection is limited or non-existent. Following a worldwide study, it has been concluded that Rh hemolytic disease is a significant public health problem resulting in stillbirths and neonatal deaths, and is a major cause of severe hyperbilirubinemia with its sequelae, kernicterus and bilirubin-induced neurologic dysfunction. Knowing that effective Rh-disease prophylaxis depends on maternal blood-type screening, healthcare afforded to the high-risk mothers needs to be free of bottlenecks and coupled with unfettered access to effective Rh-immunoglobulin. Future studies that match the universal identification of Rh-negative status of women and targeted use of immunoprophylaxis to prevent childhood bilirubin neurotoxicity are within reach, based on vast prior experiences.

  View details for DOI 10.1016/j.siny.2014.12.001

  View details for Web of Science ID 000350926500002

  View details for PubMedID 25582277

• Neonatal bilirubin binding capacity discerns risk of neurological dysfunction. Pediatric research Lamola, A. A., Bhutani, V. K., Du, L., Castillo Cuadrado, M., Chen, L., Shen, Z., Wong, R. J., Stevenson, D. K. 2015; 77 (2): 334-339

  View details for DOI 10.1038/pr.2014.191

  View details for PubMedID 25420178

• Inpatient care of small and sick newborns: a multi-country analysis of health system bottlenecks and potential solutions. BMC pregnancy and childbirth Moxon, S. G., Lawn, J. E., Dickson, K. E., Simen-Kapeu, A., Gupta, G., Deorari, A., Singhal, N., New, K., Kenner, C., Bhutani, V., Kumar, R., Molyneux, E., Blencowe, H. 2015; 15: S7-?

  Abstract

  Preterm birth is the leading cause of child death worldwide. Small and sick newborns require timely, high-quality inpatient care to survive. This includes provision of warmth, feeding support, safe oxygen therapy and effective phototherapy with prevention and treatment of infections. Inpatient care for newborns requires dedicated ward space, staffed by health workers with specialist training and skills. Many of the estimated 2.8 million newborns that die every year do not have access to such specialised care.The bottleneck analysis tool was applied in 12 countries in Africa and Asia as part of the Every Newborn Action Plan process. Country workshops involved technical experts to complete the survey tool, which is designed to synthesise and grade health system "bottlenecks" (or factors that hinder the scale up) of maternal-newborn intervention packages. For this paper, we used quantitative and qualitative methods to analyse the bottleneck data, and combined these with literature review, to present priority bottlenecks and actions relevant to different health system building blocks for inpatient care of small and sick newborns.Inpatient care of small and sick newborns is an intervention package highlighted by all country workshop participants as having critical health system challenges. Health system building blocks with the highest graded (significant or major) bottlenecks were health workforce (10 out of 12 countries) and health financing (10 out of 12 countries), followed by community ownership and partnership (9 out of 12 countries). Priority actions based on solution themes for these bottlenecks are discussed.Whilst major bottlenecks to the scale-up of quality inpatient newborn care are present, effective solutions exist. For all countries included, there is a critical need for a neonatal nursing cadre. Small and sick newborns require increased, sustained funding with specific insurance schemes to cover inpatient care and avoid catastrophic out-of-pocket payments. Core competencies, by level of care, should be defined for monitoring of newborn inpatient care, as with emergency obstetric care. Rather than fatalism that small and sick newborns will die, community interventions need to create demand for accessible, high-quality, family-centred inpatient care, including kangaroo mother care, so that every newborn can survive and thrive.

  View details for DOI 10.1186/1471-2393-15-S2-S7

  View details for PubMedID 26391335

  View details for PubMedCentralID PMC4577807

• Apnea in acute bilirubin encephalopathy SEMINARS IN PERINATOLOGY Amin, S. B., Bhutani, V. K., Watchko, J. F. 2014; 38 (7): 407-411

  Abstract

  Central apnea, defined as cessation of breathing for ≥20s, is frequent in premature infants born at <34 weeks׳ gestation but uncommon among healthy late preterm (34(0/7)-36(6/7) weeks׳ gestation) and term (≥37 weeks׳ gestation) infants, where it is usually a clinical manifestation of a neurological or metabolic problem. There is growing evidence that marked unconjugated hyperbilirubinemia is associated with central apnea in neonates. This article explores the reported association between acute bilirubin encephalopathy and symptomatic apneic events in newborns and the possible mechanisms involved in the pathogenesis of this phenomenon. The prevalence of symptomatic apneic events in reports of acute bilirubin encephalopathy suggests this clinical finding should be considered a sign of bilirubin neurotoxicity.

  View details for DOI 10.1053/j.semperi.2014.08.003

  View details for Web of Science ID 000343960900003

  View details for PubMedID 25239473

  View details for PubMedCentralID PMC4285431

• INCLEN Diagnostic Tool for Neuromotor Impairments (INDT-NMI) for primary care physician: Development and validation INDIAN PEDIATRICS Gulati, S., Aneja, S., Juneja, M., Mukherjee, S., Deshmukh, V., Silberberg, D., Bhutani, V. K., Pinto, J. M., Durkin, M., Tudu, P., Pandey, R. M., Nair, M. K., Arora, N. K. 2014; 51 (8): 613-619

  Abstract

  To develop and validate a diagnostic tool for use by primary care physicians for diagnosing neuro-motor impairment among 2-9 year old children in primary care settings.Modified Delphi technique involving national (n=49) and international (n=6) experts was used for development of INDT-NMI. The tool was then validated through a cross sectional study.Neurology specialty clinics of three tertiary care pediatric centers in New Delhi, India.454 children aged 2-9 years [mean (SD) age: 60.4 (23.7) mo], selected through systematic random sampling, underwent assessment for identification and classification of neuromotor impairments (NMI).All study subjects were first administered INDT-NMI (candidate test) by a trained physician followed by expert assessment for NMI and other neurodevelopment disorders (NDD) by team of two pediatric neurologists (Gold standard).According to expert evaluation, 171 (37.8%) children had neuromotor impairments. There were four categories of subjects: NMI alone (n=66); NMI+other NDDs (n=105); Other NDDs without NMI (n=225) and 'Normal' group (n=58). Using expert evaluation as gold standard, overall sensitivity of the INDT-NMI was 75.4% and specificity was 86.8%. INDT-NMI helped graduate physicians to correctly classify 86.6% (112/129) children with NMI into different types (cerebral palsy, neuromotor diseases and other NMI). Graduate physicians assigned 40 children (8.8%) as 'indeterminate', 38 (95%) of whom had either NDD and/or NMI and thus merited referral. Misclassification of NMI occurred in those with mild changes in muscle tone, dystonia, or ataxia and associated NDDs.Graduate primary care physicians with a structured short training can administer the new tool and diagnose NMI in 2-9 year old children with high validity. INDT-NMI requires further evaluation in actual primary care settings.

  View details for DOI 10.1007/s13312-014-0463-3

  View details for Web of Science ID 000342114900005

  View details for PubMedID 25128993

• Prevention of Kernicterus in South Asia: Role of Neonatal G6PD Deficiency and its Identification INDIAN JOURNAL OF PEDIATRICS Arain, Y. H., Bhutani, V. K. 2014; 81 (6): 599-607

  Abstract

  Extreme hyperbilirubinemia (EHB) caused by neonatal glucose-6-phosphate dehydrogenase (G6PD) deficiency is strongly associated with mortality and long-term neurodevelopmental impairment, yet there are limited national strategies to reduce this burden in South Asia. Current known and predicted prevalence of G6PD deficiency in Afghanistan, Bangladesh, Bhutan, India, Nepal, and Pakistan ranges from 3.8 to 15 %, with regional "hot spots" exceeding 22 %. Annually, 3.14 million infants are born at risk for this condition. In 2010, South Asian countries reported 37 million (27 %) of world-wide livebirths ≥ 32 wk gestational-age and G6PD deficiency accounted for > 33 % of the global EHB burden, in contrast to 2.2 % for those born in high-income nations. Traditional national approach includes universal newborn screening in malaria-endemic countries or those with prevalence >3.5 %. However, screening implementation should be best optimized using timely quantitative enzyme assay and identification of at-risk female newborns. Furthermore, economic and social constraints, in context of sub-regional variances, call for flexible problem-solving methods in anticipation of changing community demographics. Thus, incremental and need-based newborn screening programs could be the most optimal approach. A human-centered design (HCD) approach, as an alternate pathway, could build the evidence to translate the complex biology of G6PD deficiency and the biodesign of affordable technologies, allowing facilitation of access to knowledge and services, in order to deliver on a long-term public health mandate. Key steps would encompass the initiation of local inquiry of both quantitative and qualitative data to identify at-risk communities and to prospectively design for local innovative solutions.

  View details for DOI 10.1007/s12098-014-1410-y

  View details for Web of Science ID 000341631900012

  View details for PubMedID 24763814

• INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD): Development and Validation INDIAN PEDIATRICS Mukherjee, S., Aneja, S., Russell, P. S., Gulati, S., Deshmukh, V., Sagar, R., Silberberg, D., Bhutani, V. K., Pinto, J. M., Durkin, M., Pandey, R. M., Nair, M. K., Arora, N. K. 2014; 51 (6): 457-462

  Abstract

  To develop and validate INCLEN Diagnostic Tool for Attention Deficit Hyperactivity Disorder (INDT-ADHD).Diagnostic test evaluation by cross sectional design.Tertiary care pediatric centers.156 children aged 65-117 months.After randomization, INDT-ADHD and Connors 3 Parent Rating Scale (C3PS) were administered, followed by an expert evaluation by DSM-IV-TR diagnostic criteria.Psychometric evaluation of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency.INDT-ADHD had 18 items that quantified symptoms and impairment. Attention deficit hyperactivity disorder was identified in 57, 87 and 116 children by expert evaluation, INDT-ADHD and C3PS, respectively. Psychometric parameters of INDT-ADHD for differentiating attention deficit hyperactivity disorder and normal children were: sensitivity 87.7%, specificity 97.2%, positive predictive value 98.0% and negative predictive value 83.3%, whereas for differentiating from other neuro-developmental disorders were 87.7%, 42.9%, 58.1% and 79.4%, respectively. Internal consistency was 0.91. INDT-ADHD has a 4-factor structure explaining 60.4% of the variance. Convergent validity with Conner's Parents Rating Scale was moderate (r =0.73, P= 0.001).INDT-ADHD is suitable for diagnosing attention deficit hyperactivity disorder in Indian children between the ages of 6 to 9 years.

  View details for Web of Science ID 000338271800008

  View details for PubMedID 24986281

• INCLEN diagnostic tool for autism spectrum disorder (INDT-ASD): Development and validation INDIAN PEDIATRICS Juneja, M., Mishra, D., Russell, P. S., Gulati, S., Deshmukh, V., Tudu, P., Sagar, R., Silberberg, D., Bhutani, V. K., Pinto, J. M., Durkin, M., Pandey, R. M., Nair, M. K., Arora, N. K. 2014; 51 (5): 359-365

  Abstract

  To develop and validate INCLEN Diagnostic Tool for Autism Spectrum Disorder (INDT-ASD).Diagnostic test evaluation by cross sectional design.Four tertiary pediatric neurology centers in Delhi and Thiruvanthapuram, India.Children aged 2-9 years were enrolled in the study. INDT-ASD and Childhood Autism Rating Scale (CARS) were administered in a randomly decided sequence by trained psychologist, followed by an expert evaluation by DSM-IV TR diagnostic criteria (gold standard).Psychometric parameters of diagnostic accuracy, validity (construct, criterion and convergent) and internal consistency.154 children (110 boys, mean age 64.2 mo) were enrolled. The overall diagnostic accuracy (AUC=0.97, 95% CI 0.93, 0.99; P<0.001) and validity (sensitivity 98%, specificity 95%, positive predictive value 91%, negative predictive value 99%) of INDT-ASD for Autism spectrum disorder were high, taking expert diagnosis using DSM-IV-TR as gold standard. The concordance rate between the INDT-ASD and expert diagnosis for 'ASD group' was 82.52% [Cohen's k=0.89; 95% CI (0.82, 0.97); P=0.001]. The internal consistency of INDT-ASD was 0.96. The convergent validity with CARS (r = 0.73, P= 0.001) and divergent validity with Binet-Kamat Test of intelligence (r = -0.37; P=0.004) were significantly high. INDT-ASD has a 4-factor structure explaining 85.3% of the variance.INDT-ASD has high diagnostic accuracy, adequate content validity, good internal consistency high criterion validity and high to moderate convergent validity and 4-factor construct validity for diagnosis of Autistm spectrum disorder.

  View details for DOI 10.1007/s13312-014-0417-9

  View details for Web of Science ID 000336049800005

  View details for PubMedID 24953575

• Visual Acuity is Reduced at One Year in Infants with Neonatal Physiological Jaundice Good, W. V., Bhutani, V., Hou, C., Slagel, T., Wong, R., Lewis, K., Ahlfors, C., Norcia, A. M. ASSOC RESEARCH VISION OPHTHALMOLOGY INC. 2014

  View details for Web of Science ID 000433199701386

• Multidisciplinary guidelines for the care of late preterm infants JOURNAL OF PERINATOLOGY Bhutani, V. K. 2014; 34 (1): 81

  View details for PubMedID 24374869

• Jaundice and Kernicterus in the Moderately Preterm Infant CLINICS IN PERINATOLOGY Wallenstein, M. B., Bhutani, V. K. 2013; 40 (4): 679-?

  Abstract

  Moderate preterm infants remain at increased risk for adverse outcomes, including acute bilirubin encephalopathy (ABE). Evidence-based guidelines for management of hyperbilirubinemia in preterm infants less than 35 weeks' gestational age are not yet optimized. High concentrations of unconjugated bilirubin can cause permanent posticteric neurologic sequelae (kernicterus). Clinical manifestations of ABE in preterm infants are similar to, but often more subtle than, those of term infants. This review outlines clinical strategies to operationalize management of hyperbilirubinemia in moderately preterm infants to meet recently published consensus-based recommendations.

  View details for DOI 10.1016/j.clp.2013.07.007

  View details for Web of Science ID 000327560000008

  View details for PubMedID 24182955

• Jaundice and kernicterus in the moderately preterm infant. Clinics in perinatology Wallenstein, M. B., Bhutani, V. K. 2013; 40 (4): 679-688

  Abstract

  Moderate preterm infants remain at increased risk for adverse outcomes, including acute bilirubin encephalopathy (ABE). Evidence-based guidelines for management of hyperbilirubinemia in preterm infants less than 35 weeks' gestational age are not yet optimized. High concentrations of unconjugated bilirubin can cause permanent posticteric neurologic sequelae (kernicterus). Clinical manifestations of ABE in preterm infants are similar to, but often more subtle than, those of term infants. This review outlines clinical strategies to operationalize management of hyperbilirubinemia in moderately preterm infants to meet recently published consensus-based recommendations.

  View details for DOI 10.1016/j.clp.2013.07.007

  View details for PubMedID 24182955

• Phototherapy Device Effectiveness in Nigeria: Irradiance Assessment and Potential for Improvement JOURNAL OF TROPICAL PEDIATRICS Cline, B. K., Vreman, H. J., Faber, K., Lou, H., Donaldson, K. M., Amuabunosi, E., Ofovwe, G., Bhutani, V. K., Olusanya, B. O., Slusher, T. M. 2013; 59 (4): 321-325

  Abstract

  This study investigated the effectiveness of simple-to-implement adjustments of phototherapy devices on irradiance levels in a cross-section of Nigerian hospitals. A total of 76 phototherapy devices were evaluated in 16 hospitals while adjustments were implemented for a subset of 25 devices for which consent was obtained. The mean irradiance level was 7.6 ± 5.9 µW/cm(2)/nm for all devices prior to adjustments. The average irradiance level improved from 9.0 µW/cm(2)/nm to 27.3 µW/cm(2)/nm for the adjusted group (n = 25) compared with 6.8 ± 5.4 µW/cm(2)/nm for the unadjusted group (n = 51). Simple, inexpensive adjustments to phototherapy devices with sub-optimal irradiance levels can significantly improve their effectiveness to acceptable international standards and should be widely promoted in resource-constrained settings.

  View details for DOI 10.1093/tropej/fmt027

  View details for Web of Science ID 000322665200013

  View details for PubMedID 23666953

• The effect of hematocrit on the efficacy of phototherapy for neonatal jaundice PEDIATRIC RESEARCH Lamola, A. A., Bhutani, V. K., Wong, R. J., Stevenson, D. K., McDonagh, A. F. 2013; 74 (1): 54-60

  Abstract

  Background:The therapeutic phototherapy action spectrum ranges from 420 to 500nm. However, a recent report of improved efficacy offluorescent "turquoise"light (~490 nm) compared toblue light(~450 nm) underscores the need to define an optimal action spectrum for precision-targeted phototherapy using very narrow wavelength ranges.Methods:We used a current semi-empirical model of theoptical properties of skinfor robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin, melanin and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra"wereassembled from the calculated values.Results:All the calculated action spectra displayed a peak between 472 and 480 nm (most at 476 nm), which is a significant shift from the well-reported 460 nm absorption peak of bilirubin. Interestingly, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit.Conclusion:We speculate that narrow range of light at 476 nmshould be 60% more effective than blue (broad-band) fluorescent lamps. Because hemoglobin serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the hematocrit.A high hematocrit could reduce therapeutic efficiency.Pediatric Research (2013); doi:10.1038/pr.2013.67.

  View details for DOI 10.1038/pr.2013.67

  View details for PubMedID 23604171

• Should we screen newborns for glucose-6-phosphate dehydrogenase deficiency in the United States? JOURNAL OF PERINATOLOGY Watchko, J. F., Kaplan, M., Stark, A. R., Stevenson, D. K., Bhutani, V. K. 2013; 33 (7): 499-504

  Abstract

  Glucose-6-phosphate dehydrogenase (G6PD) deficiency, a common X-linked enzymopathy can lead to severe hyperbilirubinemia, acute bilirubin encephalopathy and kernicterus in the United States. Neonatal testing for G6PD deficiency is not yet routine and the American Academy of Pediatrics recommends testing only in jaundiced newborns who are receiving phototherapy whose family history, ethnicity, or geographic origin suggest risk for the condition, or for infants whose response to phototherapy is poor. Screening tests for G6PD deficiency are available, are suitable for use in newborns and have been used in birth hospitals. However, US birth hospitals experience is limited and no national consensus has emerged regarding the need for newborn G6PD testing, its effectiveness or the best approach. Our review of current state of G6PD deficiency screening highlights research gaps and informs specific operational challenges to implement universal newborn G6PD testing concurrent to bilirubin screening in the United States.

  View details for DOI 10.1038/jp.2013.14

  View details for Web of Science ID 000321000800001

  View details for PubMedID 23429543

• Bilirubin nomogram, a prediction tool or natural history profile? Indian pediatrics Bhutani, V. K. 2013; 50 (4): 365-366

  View details for PubMedID 23665596

• Bilirubin neurotoxicity in preterm infants: risk and prevention. Journal of clinical neonatology Bhutani, V. K., Wong, R. J. 2013; 2 (2): 61-69

  Abstract

  Hemolytic conditions in preterm neonates, including Rhesus (Rh) disease, can lead to mortality and long-term impairments due to bilirubin neurotoxicity. Universal access to Rh immunoprophylaxis, coordinated perinatal-neonatal care, and effective phototherapy has virtually eliminated the risk of kernicterus in many countries. In the absence of jaundice due to isoimmunization and without access to phototherapy or exchange transfusion (in 1955), kernicterus was reported at 10.1%, 5.5%, and 1.2% in babies <30, 31-32, and 33-34 wks gestational age, respectively. Phototherapy initiated at 24±12 hr effectively prevented hyperbilirubinemia in infants <2,000 g even in the presence of hemolysis. This approach (in 1985) reduced exchange transfusions from 23.9% to 4.8%. Now with 3 decades of experience in implementing effective phototherapy, the need for exchange transfusions has virtually been eliminated. However, bilirubin neurotoxicity continues to be associated with prematurity alone. The ability to better predict this risk, other than birthweight and gestation, has been elusive. Objective tests such as total bilirubin, unbound or free bilirubin, albumin levels, and albumin-bilirubin binding, together with observations of concurrent hemolysis, sepsis, and rapid rate of bilirubin rise have been considered, but their individual or combined predictive utility has yet to be refined. The disruptive effects of immaturity, concurrent neonatal disease, cholestasis, use of total parenteral nutrition or drugs that alter bilirubin-binding abilities augment the clinical risk of neurotoxicity. Current management options rely on the "fine-tuning" of each infant's exposure to beneficial antioxidants and avoidance of silent neurotoxic properties of bilirubin navigated within the safe spectrum of operational thresholds demarcated by experts.

  View details for DOI 10.4103/2249-4847.116402

  View details for PubMedID 24049745

  View details for PubMedCentralID PMC3775137

• Neuro-Developmental Disorders in India - An INCLEN Study Silberberg, D., Arora, N., Bhutani, V., Durkin, M., Gulati, S. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332068603118

• Neuro-Developmental Disorders in India - An INCLEN Study Silberberg, D., Arora, N., Bhutani, V., Durkin, M., Gulati, S. LIPPINCOTT WILLIAMS & WILKINS. 2013

  View details for Web of Science ID 000332068600082

• Need remains for evidence-based reassurance for absence of bilirubin neurotoxicity with severe hyperbilirubinaemia. Evidence-based medicine Bhutani, V. K. 2013

  View details for PubMedID 23335271

• Late preterm births: Major cause of prematurity and adverse outcomes of neonatal hyperbilirubinemia INDIAN PEDIATRICS Bhutani, V. K. 2012; 49 (9): 704-705

  View details for DOI 10.1007/s13312-012-0149-7

  View details for Web of Science ID 000309225900004

  View details for PubMedID 23024077

• Neonatal phototherapy: choice of device and outcome ACTA PAEDIATRICA Bhutani, V. K., Wong, R. J. 2012; 101 (5): 441-443

  View details for DOI 10.1111/j.1651-2227.2012.02605.x

  View details for Web of Science ID 000302349200016

  View details for PubMedID 22251098

• The Need to Implement Effective Phototherapy in Resource-Constrained Settings SEMINARS IN PERINATOLOGY Bhutani, V. K., Cline, B. K., Donaldson, K. M., Vreman, H. J. 2011; 35 (3): 192-197

  Abstract

  Phototherapy is the treatment of choice to reduce the severity of neonatal unconjugated hyperbilirubinemia regardless of its etiology. Its implementation requires a technical framework that conforms to existing evidence-based guidelines that promote its safer and effective use worldwide. Optimal use of phototherapy has been defined by specific ranges of total serum bilirubin thresholds configured to an infant's postnatal age (in hours) and potential risk for bilirubin neurotoxicity. Effective phototherapy implies its use at specific blue light wavelengths (peak emission, 450 ± 20 nm) and emission spectrum (range, 400-520 nm), preferably in a narrow bandwidth that is delivered at an irradiance of ≥30 μW/cm(2)/nm to up to 80% of an infant's body surface area. However, this is often not feasible in clinical settings with limited or constrained resources. To identify and bridge implementation barriers, we propose minimum criteria for device performance for safe and practical use of phototherapy as a prophylactic intervention to prevent severe hyperbilirubinemia.

  View details for DOI 10.1053/j.semperi.2011.02.015

  View details for Web of Science ID 000292057900014

  View details for PubMedID 21641494

• A Global Need for Affordable Neonatal Jaundice Technologies SEMINARS IN PERINATOLOGY Slusher, T. M., Zipursky, A., Bhutani, V. K. 2011; 35 (3): 185-191

  Abstract

  Globally, health care providers worldwide recognize that severe neonatal jaundice is a "silent" cause of significant neonatal morbidity and mortality. Untreated neonatal jaundice can lead to death in the neonatal period and to kernicterus, a major cause of neurologic disability (choreo-athetoid cerebral palsy, deafness, language difficulty) in children who survive this largely preventable neonatal tragedy. Appropriate technologies are urgently needed. These include tools to promote and enhance visual assessment of the degree of jaundice, such as simpler transcutaneous bilirubin measurements and readily available serum bilirubin measurements that could be incorporated into routine treatment and follow-up. Widespread screening for glucose-6-phoshate dehydrogenase deficiency is needed because this is often a major cause of neonatal jaundice and kernicterus worldwide. Recognition and treatment of Rh hemolytic disease, another known preventable cause of kernicterus, is critical. In addition, effective phototherapy is crucial if we are to make kernicterus a "never-event." Finally it is essential that we conduct appropriate population-based studies to accurately elucidate the magnitude of the problem. However, knowledge alone is not sufficient. If we are to implement these and other programs and technologies to relegate severe neonatal jaundice and its sequelae to the history books, screening and interventions must be low cost and technologically appropriate for low and middle income nations.

  View details for DOI 10.1053/j.semperi.2011.02.014

  View details for Web of Science ID 000292057900013

  View details for PubMedID 21641493

• The Clinical Syndrome of Bilirubin-Induced Neurologic Dysfunction SEMINARS IN PERINATOLOGY Johnson, L., Bhutani, V. K. 2011; 35 (3): 101-113

  Abstract

  We believe that the syndrome of bilirubin-induced neurologic dysfunction [BIND] represents a spectrum of neurologic manifestations among vulnerable infants who have experienced an exposure to bilirubin of lesser degree than generally described in previous publications. Clinical neuro-motor manifestations extend to a range of subtle processing disorders with objective disturbances of visual-motor, auditory, speech, cognition, and language among infants with a previous history of moderate-to-severe hyperbilirubinemia of varied duration. Confounding effects include prematurity, hemolysis, perinatal-neonatal complications, altered bilirubin-albumin binding, severity and duration of bilirubin exposure, and the individual vulnerability of the infant related to genetic, family, social, and educational predilection, regardless of the cause of neonatal jaundice. Tools to better assess BIND specific domains of multisensory processing disorders, identified by pyschometric, audiologic, speech, language and visual-motor, and neuromotor examination would allow for prospective surveillance of infants at risk for the syndrome.

  View details for DOI 10.1053/j.semperi.2011.02.003

  View details for Web of Science ID 000292057900002

  View details for PubMedID 21641482

• Severe Neonatal Hyperbilirubinemia and Adverse Short-Term Consequences in Baghdad, Iraq NEONATOLOGY Hameed, N. N., Na' ma, A. M., Vilms, R., Bhutani, V. K. 2011; 100 (1): 57-63

  Abstract

  Severe neonatal hyperbilirubinemia, when unmonitored or untreated, can progress to acute bilirubin encephalopathy (ABE). Initiatives to prevent and eliminate post-icteric sequelae (kernicterus) are being implemented to allow for timely interventions for bilirubin reduction.We report an observational study to determine the clinical risk factors and short-term outcomes of infants admitted for severe neonatal jaundice.A post-discharge medical chart review was performed for a cohort of infants admitted for management of newborn jaundice to the Children Welfare Teaching Hospital during a 4-month period in 2007 and 2008. Immediate outcomes included severity of hyperbilirubinemia, association of ABE, need and impact of exchange transfusion, and survival. Short-term post-discharge follow-up assessed for post-icteric sequelae.A total of 162 infants were admitted for management of severe jaundice. Incidences of severe sequelae were: advanced ABE (22%), neonatal mortality within 48 h of admission (12%) and post-icteric sequelae (21%). Among the cohort, 85% were <10 days of age (median 6 days, IQR 4-7 days). Readmission total serum bilirubin ranged from 197 to 770 μM; mean 386 ± 108 SD μM (mean 22.6 ± 6.3 SD mg/dl; median 360, IQR 310-445 μM). The major contributory risk factor for the adverse outcome of kernicterus/death was admission with advanced ABE (OR 8.03; 95% CI 3.44-18.7). Other contributory factors to this outcome, usually significant, but not so for this cohort, included home delivery, sepsis, ABO or Rh disease. Absence of any detectable signs of ABE on admission and treatment of severe hyperbilirubinemia was associated with no adverse outcome (OR 0.34; 95% CI 0.16-0.68).Risks of mortality and irreversible brain injury among healthy infants admitted for newborn jaundice are urgent reminders to promote education of communities, families and primary health care providers, especially in a fractured health system. Known risk factors for severe hyperbilirubinemia were overwhelmed by the effect of advanced ABE.

  View details for DOI 10.1159/000321990

  View details for Web of Science ID 000291160900011

  View details for PubMedID 21212697

• Universal bilirubin screening for severe neonatal hyperbilirubinemia 5th Annual Meeting on Evidence vs Experience in Neonatal Practices Bhutani, V. K., Vilms, R. J., Hamerman-Johnson, L. NATURE PUBLISHING GROUP. 2010: S6–S15

  Abstract

  To reduce the incidence of severe neonatal hyperbilirubinemia affecting newborns with jaundice in the United States and to prevent kernicterus, there is a need to implement proven prevention strategies for severe neonatal hyperbilirubinemia as recommended in the 2004 American Academy of Pediatrics Guidelines for newborns >35 weeks gestational age. The purpose of universal predischarge bilirubin screening is to identify infants with bilirubin levels >75th percentile for age in hours and track those with rapid rates of bilirubin rise (>0.2 mg per 100 ml per h). Early identification has been reported to predict severe hyperbilirubinemia and allow for evidence-based targeted interventions. A systems approach is likely to reduce the preventable causes of acute bilirubin encephalopathy. To do so, highest priority should be given to (i) designating extreme hyperbilirubinemia (total serum bilirubin >427 μmol l(-1) or >25 mg per 100 ml) as a reportable condition by laboratories and health-care providers through public health mandates; (ii) implementation of Joint Commission's Sentinel Report for kernicterus; (iii) nursing outreach to communities for education of prospective parents; (iv) development of clinical pathways to monitor, evaluate and track infants with extreme hyperbilirubinemia; and (v) societal awareness. These efforts should be monitored by a state and national surveillance system in order to critically improve the timeliness and completeness of notifications and to allow evaluation and interventions at the policy and individual family level.

  View details for Web of Science ID 000282744100003

  View details for PubMedID 20877410

• Transcutaneous bilirubinometry reduces the need for blood sampling in neonates with visible jaundice ACTA PAEDIATRICA Mishra, S., Chawla, D., Agarwal, R., Deorari, A. K., Paul, V. K., Bhutani, V. K. 2009; 98 (12): 1916-1919

  Abstract

  We determined usefulness of transcutaneous bilirubinometry to decrease the need for blood sampling to assay serum total bilirubin (STB) in the management of jaundiced healthy Indian neonates.Newborns, > or =35 weeks' gestation, with clinical evidence of jaundice were enrolled in an institutional approved randomized clinical trial. The severity of hyperbilirubinaemia was determined by two non-invasive methods: i) protocol-based visual assessment of bilirubin (VaB) and ii) transcutaneous bilirubin (TcB) determination (BiliCheck). By a random allocation, either method was used to decide the need for blood sampling, which was defined to be present if assessed STB by allocated method exceeded 80% of hour-specific threshold values for phototherapy (2004 AAP Guidelines).A total of 617 neonates were randomized to either TcB (n = 314) or VaB (n = 303) groups with comparable gestation, birth weight and postnatal age. Need for blood sampling to assay STB was 34% lower (95% CI: 10% to 51%) in the TcB group compared with VaB group (17.5% vs 26.4% assessments; risk difference: -8.9%, 95% CI: -2.4% to -15.4%; p = 0.008).Routine use of transcutaneous bilirubinometry compared with systematic visual assessment of bilirubin significantly reduced the need for blood sampling to assay STB in jaundiced term and late-preterm neonates. (ClinicalTrials.gov number, NCT00653874).

  View details for DOI 10.1111/j.1651-2227.2009.01505.x

  View details for Web of Science ID 000271465200015

  View details for PubMedID 19811459

• Hyperbilirubinemia in the Newborn Infant >= 35 Weeks' Gestation: An Update With Clarifications PEDIATRICS Maisels, J., Bhutani, V. K., Bogen, D., Newman, T. B., Stark, A. R., Watchko, J. F. 2009; 124 (4): 1193–98

  View details for DOI 10.1542/peds.2009-0329

  View details for Web of Science ID 000270274300021

• Clinical report from the Pilot USA Kernicterus Registry (1992 to 2004) JOURNAL OF PERINATOLOGY Johnson, L., Bhutani, V. K., Karp, K., Sivieri, E. M., Shapiro, S. M. 2009; 29: S25-S45

  Abstract

  To identify antecedent clinical and health services events in infants (>/=35 weeks gestational age (GA)) who were discharged as healthy from their place of birth and subsequently sustained kernicterus. We conducted a root-cause analysis of a convenience sample of 125 infants >/=35 weeks GA cared for in US healthcare facilities (including off-shore US military bases). These cases were voluntarily reported to the Pilot USA Kernicterus Registry (1992 to 2004) and met the eligibility criteria of acute bilirubin encephalopathy (ABE) and/or post-icteric sequelae. Multiple providers at multiple sites managed this cohort of infants for their newborn jaundice and progressive hyperbilirubinemia. Clinical signs of ABE, verbalized by parents, were often inadequately elicited or recorded and often not recognized as an emergency. Clinical signs of ABE were reported in 7 of 125 infants with a subsequent diagnosis of kernicterus who were not re-evaluated or treated for hyperbilirubinemia, although jaundice was noted at outpatient visits. The remaining infants (n=118) had total serum bilirubin (TSB) levels >20 mg per 100 ml (342 micromol l(-1); range: 20.7 to 59.9 mg per 100 ml). No specific TSB threshold coincided with onset of ABE. Of infants <37 weeks GA with kernicterus, 34.9% were LGA (large for gestational age) as compared with 24.7% of term infants (>37 weeks GA). Although >90% mothers initiated breast-feeding, assessment of milk transfer and lactation support was suboptimal in most. Mortality was 4% (5 of 125) in infants readmitted at age 0.2 mg per 100 ml per hour), contributing factors, alone or in combination, included undiagnosed hemolytic disease, excessive bilirubin production related to extra-vascular hemolysis and delayed bilirubin elimination (including increased enterohepatic circulation, diagnosed and undiagnosed genetic disorders) in the context of known late prematurity (<37 weeks), glucose 6-phosphate-dehydrogenase deficiency, infection and dehydration. Readmission was at age 35 mg per 100 ml had post-icteric sequelae (n=73). There was a narrow margin of safety between birthing hospital discharge or home birth and readmission to a tertiary neonatal/pediatric facility. Progression of hyperbilirubinemia to hazardous levels and onset of neurological signs were often not identified as infant's care and medical supervision transitioned during the first week after birth. The major underlying root cause for kernicterus was systems failure of services by multiple providers at multiple sites and inability to identify the at-risk infant and manage severe hyperbilirubinemia in a timely manner.

  View details for DOI 10.1038/jp.2008.211

  View details for Web of Science ID 000263604400007

  View details for PubMedID 19177057

• Synopsis report from the Pilot USA Kernicterus Registry JOURNAL OF PERINATOLOGY Bhutani, V. K., Johnson, L. 2009; 29: S5-S7

  Abstract

  Breakdown in systems for safe newborn health-care delivery accounts for the majority of kernicterus cases encountered in the United States. Traditional epidemiologic investigations do not track the national incidence of severe hyperbilirubinemia and kernicterus or recognize its recent surge. Innovative investigative strategies are needed to seek more sensitive surrogates for kernicterus (often diagnosed late in infancy) and to overcome the limitations of retrospective continuity of adverse neonatal experiences because of severe hyperbilirubinemia. Root cause analysis of a cohort of infants who manifested kernicterus in the past two decades attests to some of the clinical and health-service barriers encountered by families as they negotiate health care from multiple providers at multiple sites during the first week after birth. Clinicians, health-care organizations, parents, and payors and purchasers of health care were often unaware of the ongoing patterns of care that may have obstructed preventive care. Now, partly based on these analyses, key recommendations have led to clinical usable guidelines for practitioners and have contributed to systems-oriented national guidelines for evidence-based safer management of newborn jaundice.(1) Clinician- and family-oriented tool kits have been made available, based on the report presented in this study, to facilitate effective implementation and thus optimize and institutionalize these guidelines (http://www.cdc.gov/jaundice). An informed partnership of parents and clinicians seems to be the most effective strategy to prevent severe neonatal hyperbilirubinemia and 'near-miss' cases of kernicterus in the United States.

  View details for DOI 10.1038/jp.2008.210

  View details for Web of Science ID 000263604400003

• A proposal to prevent severe neonatal hyperbilirubinemia and kernicterus JOURNAL OF PERINATOLOGY Bhutani, V. K., Johnson, L. 2009; 29: S61-S67

  Abstract

  To address systems failures and promote a safer management of newborn jaundice, we propose an 'aviation safety standard' for newborn health-care services during the first week after birth. Systems failure in newborn jaundice management has been characterized by lapses in concern, loss of continuity, and delays in care by multiple providers at multiple sites. Components for a six-step national strategy to prevent severe neonatal hyperbilirubinemia and possibly kernicterus are being implemented as delineated in the 2004 AAP guidelines. The clinical guidelines for safer and evidence-based practice have been characterized by both healthcare and societal communities. Professional and community organizations are optimizing outreach resources and facilitating institutionalization of these practices. Nationwide implementation at individual birthing hospitals concurrent with surveillance feedback needs to be initiated. Implementation of a 'six-sigma' approach, as proposed to the current Center for Disease Control and Prevention-initiated partnership (health-care providers, public health and community advocates) may be achieved through collaboration with state and national agencies.

  View details for DOI 10.1038/jp.2008.213

  View details for Web of Science ID 000263604400011

  View details for PubMedID 19177062

• Kernicterus in the 21st century: frequently asked questions JOURNAL OF PERINATOLOGY Bhutani, V. K., Johnson, L. 2009; 29: S20-S24

  Abstract

  Acute kernicterus remains a clinical emergency and its delayed management represents an easily preventable neonatal brain injury. Yet, practitioners encounter recurrent questions regarding the risk and timing of bilirubin-related neurotoxicity. These include the following: does bilirubin damage the brain of healthy infants? Is there a re-emergence of kernicterus in the United States? Was kernicterus previously prevented in the United States? What was the public health impact of 1994 American Academy of Pediatrics Guidelines? What is the current incidence of kernicterus and severe neonatal hyperbilirubinemia? What is the estimated risk of kernicterus in infants with excessive hyperbilirubinemia? Is there a specific bilirubin threshold total serum bilirubin (TSB) value for neurotoxicity? Are there sequelae of severe or prolonged moderate hyperbilirubinemia in the absence of recognized acute bilirubin encephalopathy? Can we define a bilirubin level that is safe in newborns? We address these questions in the context of available data and evidence, and estimate the current risk of chronic kernicterus is about one in seven in infants with TSB >30 mg per 100 ml (513 micromol l(-1)).

  View details for DOI 10.1038/jp.2008.212

  View details for Web of Science ID 000263604400006

  View details for PubMedID 19177056

• Synopsis report from the pilot USA Kernicterus Registry. Journal of perinatology Bhutani, V. K., Johnson, L. 2009; 29: S4-7

  Abstract

  Breakdown in systems for safe newborn health-care delivery accounts for the majority of kernicterus cases encountered in the United States. Traditional epidemiologic investigations do not track the national incidence of severe hyperbilirubinemia and kernicterus or recognize its recent surge. Innovative investigative strategies are needed to seek more sensitive surrogates for kernicterus (often diagnosed late in infancy) and to overcome the limitations of retrospective continuity of adverse neonatal experiences because of severe hyperbilirubinemia. Root cause analysis of a cohort of infants who manifested kernicterus in the past two decades attests to some of the clinical and health-service barriers encountered by families as they negotiate health care from multiple providers at multiple sites during the first week after birth. Clinicians, health-care organizations, parents, and payors and purchasers of health care were often unaware of the ongoing patterns of care that may have obstructed preventive care. Now, partly based on these analyses, key recommendations have led to clinical usable guidelines for practitioners and have contributed to systems-oriented national guidelines for evidence-based safer management of newborn jaundice.(1) Clinician- and family-oriented tool kits have been made available, based on the report presented in this study, to facilitate effective implementation and thus optimize and institutionalize these guidelines (http://www.cdc.gov/jaundice). An informed partnership of parents and clinicians seems to be the most effective strategy to prevent severe neonatal hyperbilirubinemia and 'near-miss' cases of kernicterus in the United States.

  View details for DOI 10.1038/jp.2008.210

  View details for PubMedID 19177058

• Performance Evaluation for Neonatal Phototherapy INDIAN PEDIATRICS Bhutani, V. K. 2009; 46 (1): 19-21

  View details for Web of Science ID 000262840800003

  View details for PubMedID 19179712

• Developing a systems approach to prevent meconium aspiration syndrome: lessons learned from multinational studies 1st International Conference on Meconium Aspiration Syndrome and Meconium-Induced Lung Injury Bhutani, V. K. NATURE PUBLISHING GROUP. 2008: S30–S35

  Abstract

  Passage of fetal bowel movement (meconium) is common (in about one out of six births), and in some the staining of the amniotic fluid is a sign of fetal distress. Inhalation of meconium (aspiration syndrome, in upto one out of five to eight such births) just before or at birth may be preventable by a coordinated approach by well-trained and informed birth attendants. Respiratory failure secondary to meconium aspiration syndrome (MAS) remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of MAS, persistent pulmonary hypertension of the newborn and pneumonia/sepsis have an increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options earlier limited to inotropic support, continuous airway pressure (CPAP), conventional ventilatory management, respiratory alkalosis, paralysis and intravenous vasodilators have been replaced by synchronized intermittent mandatory ventilation (SIMV), high-frequency oscillatory ventilation (HFOV), surfactant and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe the enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting that surfactant deficiency or inactivation may contribute to neonatal respiratory failure, exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. However, these innovative interventions are costly, require a sophisticated infrastructure and are not universally accessible. In this paper, a context of systems-approach for prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized and the least number of babies require innovative ventilatory support is described. Previously reported data from a single urban perinatal center (Philadelphia, PA, USA), over a 6-year period (1995-2000), demonstrated that 14.5% (3370/23175 of live births babies were delivered with MSAF. These data also showed that 4.6% of babies (155/3370) with MSAF sustained MAS. Overall, 26% of babies (40/155) with MAS needed ventilatory support (or 0.17% of all live births); of these, only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the components for a systems approach to prevent and manage adverse outcomes related to MSAF at the regional level II or III perinatal center. Replication of a similar strategy may be more relevant to cost containment and be a safer approach for neonates at risk for MAS-related respiratory failure. This paper assess the evidence for pivotal steps needed to prevent MAS and ensuing neonatal death and disease in the context of diverse perinatal health services.

  View details for Web of Science ID 000261417200007

  View details for PubMedID 19057608

• Inhibition of heme oxygenase activity in newborn mice by azalanstat CANADIAN JOURNAL OF PHYSIOLOGY AND PHARMACOLOGY Morisawa, T., Wong, R. J., Bhutani, V. K., Vreman, H. J., Stevenson, D. K. 2008; 86 (10): 651-659

  Abstract

  Inhibition of heme oxygenase (HO), the rate-limiting enzyme in heme catabolism, may be an ideal strategy for preventing neonatal jaundice. Although natural and synthetic heme analogs, called metalloporphyrins (Mps), have been extensively investigated for this purpose, some Mps are phototoxic, affect the activity of other enzymes, or induce HO-1 transcription-properties that may limit their clinical use. Another class of compounds, imidazole-dioxolanes, has been shown to selectively inhibit the inducible isozyme HO-1. Therefore, we investigated the efficacy of azalanstat (AZA), an imidazole-dioxolane, towards inhibiting HO activity in 7-day-old mice. We found that a single dose of AZA at 500 micromol.kg(-1) body mass (BM) administered i.p. significantly inhibited HO activity and reduced in vivo bilirubin production. In the spleen, HO inhibition (>50%) was observed within 0.25-3 h after administration. After 24 h, however, spleen HO activity, HO-1 protein, and HO-1 mRNA levels significantly increased 1.2-, 2.4-, and 4.0-fold, respectively. We conclude that AZA effectively inhibits in vivo HO activity only at a high dose and that it also induces spleen HO-1 gene transcription. Therefore, other imidazole-dioxolanes should be evaluated to determine whether they are more potent than AZA for use in treating neonatal jaundice.

  View details for DOI 10.1139/Y08-069

  View details for PubMedID 18841169

• The Jaundiced Newborn in the Emergency Department: Prevention of Kernicterus CLINICAL PEDIATRIC EMERGENCY MEDICINE Bhutani, V. K., Johnson, L. 2008; 9 (3): 149–59

  View details for DOI 10.1016/j.cpem.2008.06.004

  View details for Web of Science ID 000219550500004

• Neonatal hyperbilirubinemia: Don't let glucose-6-phosphate dehydrogenase deficiency off the hook - Reply PEDIATRICS Keren, R., Friedman, S., Bhutani, V. 2008; 122 (1): 217–18

  View details for DOI 10.1542/peds.2008-1163

  View details for Web of Science ID 000257271200043

• Management of jaundice and prevention of severe neonatal hyperbilirubinemia in infants >= 35 weeks gestation NEONATOLOGY Bhutani, V. K., Maisels, M. J., Stark, A. R., Buonocore, G. 2008; 94 (1): 63-67

  Abstract

  Kernicterus is still occurring but should be largely preventable if health care personnel follow the recommendations listed in this guideline. These recommendations emphasize the importance of universal, systematic assessment of the risk of severe hyperbilirubinemia, lactation support, close follow-up, and prompt intervention when necessary. A systems-based approach to prevent severe neonatal hyperbilirubinemia should be implemented at all birthing facilities and coordinated with continuing ambulatory care. Translational research is needed to better understand the mechanisms of bilirubin neurotoxicity and potential therapeutic interventions.

  View details for DOI 10.1159/000113463

  View details for PubMedID 18204221

• A comparison of alternative risk-assessment strategies for predicting significant neonatal hyperbilirubinemia in term and near-term infants PEDIATRICS Keren, R., Luan, X., Friedman, S., Saddlemire, S., Cnaan, A., Bhutani, V. K. 2008; 121 (1): E170-E179

  Abstract

  The purpose of this work was to compare the predictive accuracy of alternative risk-assessment strategies used to screen for the risk of significant neonatal hyperbilirubinemia.We conducted a prospective cohort study of 823 term and near-term newborns admitted to the well-infant nursery at the Hospital of the University of Pennsylvania. Maternal, infant, and delivery risk factors for significant hyperbilirubinemia were obtained from chart review, structured interviews with parents, and nurse assessments before discharge. Transcutaneous bilirubin measurement was performed daily until discharge and once by a visiting home nurse between 3 and 8 days of life. We used the c statistic to compare the predictive accuracy of 3 risk-assessment strategies for estimating the risk of significant neonatal hyperbilirubinemia, defined as a bilirubin level that at any time after birth exceeded or was within 1 mg/dL (17 micromol/L) of the hour-specific phototherapy treatment threshold recommended by the American Academy of Pediatrics in 2004. The compared strategies included those that use (1) a predischarge bilirubin level (obtained before 52 hours) expressed as a risk zone on an hour-specific bilirubin nomogram, (2) clinical risk factors other than the predischarge bilirubin level, and (3) a combination of the predischarge bilirubin risk zone and additional clinical risk factors.Forty-eight patients (6%) developed significant neonatal hyperbilirubinemia. The predischarge (<52 hours) bilirubin level expressed as a risk zone on the bilirubin nomogram and a prediction model that combined multiple other clinical risk factors had similar accuracy for predicting significant hyperbilirubinemia. The only clinical risk factor that could be added to the predischarge risk zone to improve overall predictive accuracy was gestational age. The predischarge bilirubin risk zone and gestational age could be used to stratify patients into a large group (n = 523 [70%]) of infants with a very low (0.2%) risk of developing significant hyperbilirubinemia, a small group of infants (n = 127 [17%]) with a low (4%) risk of developing significant hyperbilirubinemia, and an even smaller group of infants (n = 100 [13%]) with a high (42%) risk of developing significant hyperbilirubinemia.An infant's risk of developing significant hyperbilirubinemia can be simply and accurately assessed by using just the infant's predischarge bilirubin level and gestational age.

  View details for DOI 10.1542/peds.2006-3499

  View details for Web of Science ID 000252096300061

  View details for PubMedID 18166536

• Efficacy of chromium mesoporphyrin in inhibiting heme oxygenase activity in heme-loaded newborn mice Western Regional Meeting of the American-Federation-for-Medical-Research Morisawa, T., Xiao, H. H., Wong, R. J., Bhutani, V. K., Vreman, H. J., Stevenson, D. K. LIPPINCOTT WILLIAMS & WILKINS. 2008: 198–98

  View details for Web of Science ID 000252793300297

• Early recognition of neonatal hyperbilirubinemia Bhutani, V. K. BLACKWELL PUBLISHING. 2007: 74–75

  View details for Web of Science ID 000251907200195

• Prevention of severe neonatal hyperbilirubinemia in healthy infants of 35 or more weeks of gestation: implementation of a systems-based approach JORNAL DE PEDIATRIA Bhutani, V. K., Ohnson, L. 2007; 83 (4): 289–93

  View details for DOI 10.2223/JPED.1673

  View details for Web of Science ID 000254506500001

  View details for PubMedID 17676232

• G6PD deficiency as significant contributor of mortality and morbidity in infants with excessive postnatal hyperbilirubinemia Johnson, L., Bhutani, V. K., Sivieri, E. M., Karp, K. WILEY-LISS. 2007: 628

  View details for Web of Science ID 000246013900117

• Efficacy of azalanstat in inhibiting heme oxygenase activity in newborn mice. 8th Conference of the Western Student Medical Research Forum/Western Section of the American-Federation-for-Medical-Research/Western Association-of-Physicians/Western-Society-for-Pediatric-Research/Western-Society-for-Clinical-Investigation Morisawa, T., Wong, R. J., Bhutani, V. K., Vreman, H. J., Stevenson, D. K. LIPPINCOTT WILLIAMS & WILKINS. 2007: S89–S89

  View details for Web of Science ID 000247692400087

• Early inhaled nitric oxide therapy in premature newborns with respiratory failure NEW ENGLAND JOURNAL OF MEDICINE Kinsella, J. P., Cutter, G. R., Walsh, W. F., Gerstmann, D. R., Bose, C. L., Hart, C., Sekar, K. C., Auten, R. L., Bhutani, V. K., Gerdes, J. S., George, T. N., Southgate, W. M., Carriedo, H., Couser, R. J., Mammel, M. C., Hall, D. C., Pappagallo, M., Sardesai, S., Strain, J. D., Baier, M., Abman, S. H. 2006; 355 (4): 354-364

  Abstract

  The safety and efficacy of early, low-dose, prolonged therapy with inhaled nitric oxide in premature newborns with respiratory failure are uncertain.We performed a multicenter, randomized trial involving 793 newborns who were 34 weeks of gestational age or less and had respiratory failure requiring mechanical ventilation. Newborns were randomly assigned to receive either inhaled nitric oxide (5 ppm) or placebo gas for 21 days or until extubation, with stratification according to birth weight (500 to 749 g, 750 to 999 g, or 1000 to 1250 g). The primary efficacy outcome was a composite of death or bronchopulmonary dysplasia at 36 weeks of postmenstrual age. Secondary safety outcomes included severe intracranial hemorrhage, periventricular leukomalacia, and ventriculomegaly.Overall, there was no significant difference in the incidence of death or bronchopulmonary dysplasia between patients receiving inhaled nitric oxide and those receiving placebo (71.6 percent vs. 75.3 percent, P=0.24). However, for infants with a birth weight between 1000 and 1250 g, as compared with placebo, inhaled nitric oxide therapy reduced the incidence of bronchopulmonary dysplasia (29.8 percent vs. 59.6 percent); for the cohort overall, such treatment reduced the combined end point of intracranial hemorrhage, periventricular leukomalacia, or ventriculomegaly (17.5 percent vs. 23.9 percent, P=0.03) and of periventricular leukomalacia alone (5.2 percent vs. 9.0 percent, P=0.048). Inhaled nitric oxide therapy did not increase the incidence of pulmonary hemorrhage or other adverse events.Among premature newborns with respiratory failure, low-dose inhaled nitric oxide did not reduce the overall incidence of bronchopulmonary dysplasia, except among infants with a birth weight of at least 1000 g, but it did reduce the overall risk of brain injury. (ClinicalTrials.gov number, NCT00006401 [ClinicalTrials.gov].).

  View details for Web of Science ID 000239282600004

  View details for PubMedID 16870914

• A systems approach for neonatal hyperbilirubinemia in term and near-term newborns JOGNN-JOURNAL OF OBSTETRIC GYNECOLOGIC AND NEONATAL NURSING Bhutani, V. K., Johnson, L. H., Schwoebel, A., Gennaro, S. 2006; 35 (4): 444-455

  Abstract

  To propose and implement a family-centered systems approach to manage newborn jaundice for safer outcomes.Observational study for known adverse outcomes.Semiprivate urban birthing hospital.31,059 well babies discharged as healthy from a cohort of 41,961 live births (1990-2000).Incremental implementation of a systems approach that incorporated a hospital policy to (a) authorize nurses to obtain a bilirubin (total serum/transcutaneous) measurement for clinical jaundice, (b) universal predischarge total serum bilirubin (at routine metabolic screening), and (c) targeted follow-up, using the bilirubin nomogram (hour-specific, percentile-based total serum bilirubin/transcutaneous bilirubin).Known adverse outcomes assessed for early- and late-onset severe hyperbilirubinemia before, during, and after systems approach implementation.Adverse outcomes decreased for well babies: exchange transfusion, intensive phototherapy, and readmission. During the study period, there were no "never events" (total serum bilirubin greater than or equal to 30 mg/dl), while "close calls" (total serum bilirubin greater than or equal to 25 mg/dl) were 1 in 15,000 as compared to a reported incidence of 1 in 625.Reduced adverse events, significant reduction in close calls, and no never events met family expectations for safer experiences with this approach.

  View details for DOI 10.1111/J.1552-6909.2006.00044.x

  View details for Web of Science ID 000239009100002

  View details for PubMedID 16881988

• Hyperbilirubinemia and kernicterus CLINICS IN PERINATOLOGY Shapiro, S. M., Bhutani, V. K., Johnson, L. 2006; 33 (2): 387-?

  Abstract

  This article describes new findings concerning the basic science of bilirubin neurotoxicity, new considerations of the definition of clinical kernicterus, and new and useful tools to diagnose kernicterus in older children, and discusses treatments for kernicterus beyond the newborn period and why proper diagnosis is important.

  View details for DOI 10.1016/j.clp.2006.03.010

  View details for Web of Science ID 000238956600011

  View details for PubMedID 16765731

• Early recognition of neonatal hyperbilirubinemia and its emergent management SEMINARS IN FETAL & NEONATAL MEDICINE Smitherman, H., Stark, A. R., Bhutani, V. K. 2006; 11 (3): 214-224

  Abstract

  Hyperbilirubinemia and kernicterus are re-emerging as prominent clinical concerns and have been hypothesized to be secondary to increased breast-feeding rates, early hospital discharges and overall lack of concern for the potential impact of severe hyperbilirubinemia on healthy term newborns. Although the clinical symptoms can be non-specific and vague, they could be early, insidious and heralding signs of acute bilirubin encephalopathy (ABE) or acute stage kernicterus. Because it is highly prevalent, evaluation of a jaundiced neonate requires detailed questions about specific signs, review of birth and postnatal histories, evaluation of predischarge data, and possibly an emergency clinical evaluation of the neurological status of the infant. Medical urgency to evaluate, investigate and monitor such a newborn ensues from the possibility of rapid progression that might lead to permanent sequelae of bilirubin-induced neurologic dysfunction (BIND). Early recognition of the urgency and rapid transition to treatment seem to be the major barriers leading to delay in therapy. However, because there is a well-established and relatively safe treatment for neonatal jaundice, there should be zero tolerance for kernicterus, and BIND prevention has become a national priority in the USA. This paper reviews the clinical signs and epidemiology of ABE and BIND and presents a system-based strategy for preventing their occurrence, focusing particularly on the transition from recognition of clinical jaundice to actual treatment. A novel emergency-room-based protocol is presented as an example of how to expedite and facilitate rapid progression to treatment.

  View details for DOI 10.1016/j.siny.2006.02.002

  View details for Web of Science ID 000238020800010

  View details for PubMedID 16603425

• Abuse of casein hydrolysate formulas for treating infants with severe hyperbilirubinemia PEDIATRICS Bhutani, V. K. 2006; 117 (6): 2317

  View details for DOI 10.1542/peds.2006-0321

  View details for Web of Science ID 000237979000058

  View details for PubMedID 16740882

• Kernicterus in late preterm infants cared for as term healthy infants Workshop on Optimizing Care and Outcome of the Near-Term Pregnancy and the Near-Term Newborn Infant Bhutani, V. K., Johnson, L. W B SAUNDERS CO-ELSEVIER INC. 2006: 89–97

  Abstract

  To compare the clinical profile and health care experiences related to management of newborn jaundice and hyperbilirubinemia in preterm infants (<37(0/7) weeks gestation) who are cared for as term infants (> or =37(0/7) weeks) and develop acute and/or chronic posticteric sequelae.Retrospective study of a convenient sample of term and near term infants voluntarily reported to the Pilot Kernicterus Registry (1992-2003). Study infants were required to meet the clinical definitions for acute bilirubin encephalopathy (moderate or advanced severity) and/or the classical signs of kernicterus. Main outcome measures were the comparison of etiology, severity and duration of extreme hyperbilirubinemia (TSB levels >20 mg/dL), response to interventions of intensive phototherapy and exchange transfusion, and health care delivery experiences in preterm as compared with term infants.No targeted attention was accorded to preterm infants during their neonatal health care experiences as related to predischarge risk assessment, feeding, discharge follow-up instructions, or breastfeeding, regardless of the known vulnerability of preterm infants to safely transition during the first week after birth. The TSB levels, age at re-hospitalization, and birth weight distribution were similar for late preterm and term infants. Large for gestational age and late preterm infants disproportionately developed kernicterus as compared with those who were appropriate for gestational age and term. Clinical management of extreme of hyperbilirubinemia, by the attending clinical providers, was not impacted or influenced by the gestational age, clinical signs, or risk assessment. This resulted in severe posticteric sequelae which was more severe and frequent in late preterm infants.Late prematurity (34(0/7) to 36(6/7) weeks) of healthy infants was not recognized as a risk factor for hazardous hyperbilirubinemia by clinical practitioners. Unsuccessful lactation experience was the most frequent experience; being large for gestational age as well as the other known biologic risk factors for hyperbilirubinemia and bilirubin neurotoxicity were not identified by the clinical care providers either before discharge or at immediate postdischarge follow up.

  View details for DOI 10.1053/j.semperi.2006.04.001

  View details for Web of Science ID 000238327000008

  View details for PubMedID 16731283

• Toward understanding kernicterus: A challenge to improve the management of jaundiced newborns PEDIATRICS Wennberg, R. P., Ahlfors, C. E., Bhutani, V. K., Johnson, L. H., Shapiro, S. M. 2006; 117 (2): 474-485

  Abstract

  We sought to evaluate the sensitivity and specificity of total serum bilirubin concentration (TSB) and free (unbound) bilirubin concentration (Bf) as predictors of risk for bilirubin toxicity and kernicterus and to examine consistency between these findings and proposed mechanisms of bilirubin transport and brain uptake.A review of literature was undertaken to define basic principles of bilirubin transport and brain uptake leading to neurotoxicity. We then reviewed experimental and clinical evidence that relate TSB or Bf to risk for bilirubin toxicity and kernicterus.There are insufficient published data to precisely define sensitivity and specificity of either TSB or Bf in determining risk for acute bilirubin neurotoxicity or chronic sequelae (kernicterus). However, available laboratory and clinical evidence indicate that Bf is better than TSB in discriminating risk for bilirubin toxicity in patients with severe hyperbilirubinemia. These findings are consistent with basic pharmacokinetic principles involved in bilirubin transport and tissue uptake.Experimental and clinical data strongly suggest that measurement of Bf in newborns with hyperbilirubinemia will improve risk assessment for neurotoxicity, which emphasizes the need for additional clinical evaluation relating Bf and TSB to acute bilirubin toxicity and long-term outcome. We speculate that establishing risk thresholds for neurotoxicity by using newer methods for measuring Bf in minimally diluted serum samples will improve the sensitivity and specificity of serum indicators for treating hyperbilirubinemia, thus reducing unnecessary aggressive intervention and associated cost and morbidity.

  View details for DOI 10.1542/peds.2005-0395

  View details for Web of Science ID 000235491100027

  View details for PubMedID 16452368

• Combining clinical risk factors with serum bilirubin levels to predict hyperbilirubinemia in newborns. journal of pediatrics Bhutani, V. K. 2005; 147 (1): 123-124

  View details for PubMedID 16027713

• Identifying newborns at risk of significant hyperbilirubinaemia: a comparison of two recommended approaches ARCHIVES OF DISEASE IN CHILDHOOD Keren, R., Bhutani, V. K., Luan, X., Nihtianova, S., Cnaan, A., Schwartz, J. S. 2005; 90 (4): 415-421

  Abstract

  To compare the predictive performance of clinical risk factor assessment and pre-discharge bilirubin measurement as screening tools for identifying infants at risk of developing significant neonatal hyperbilirubinaemia (post-discharge total serum bilirubin (TSB) >95th centile).Retrospective cohort study of term and near term infants born in an urban community teaching hospital in Pennsylvania (1993-97). A clinical risk factor scoring system was developed and its predictive performance compared to a pre-discharge TSB expressed as a risk zone on a bilirubin nomogram. Main outcome measures were prediction model discrimination, range of predicted probabilities, and sensitivity, specificity, positive and negative predictive values, and likelihood ratios for various positivity criteria.The clinical risk factor scoring system developed included birth weight, gestational age <38 weeks, oxytocin use during delivery, vacuum extraction, breast feeding, and combination breast and bottle feeding. The pre-discharge bilirubin risk zone had better discrimination (c = 0.83; 95% CI 0.80 to 0.86) than the clinical risk factor score (c = 0.71; 95% CI 0.66 to 0.76) and predicted risk of significant hyperbilirubinaemia as high as 59% compared with a maximum of 44% for the clinical risk factor score. Neither the risk score nor the pre-discharge TSB risk zone predicted the outcome with > or =0.98 sensitivity without significantly compromising specificity (0.13 and 0.21, respectively). Multi-level clinical risk factor scores and TSB risk zones produced likelihood ratios of 0.15-3.25 and 0.05-9.43, respectively.The pre-discharge bilirubin expressed as a risk zone on an hour specific bilirubin nomogram is more accurate and generates wider risk stratification than a clinical risk factor score.

  View details for DOI 10.1136/adc.2004.060079

  View details for Web of Science ID 000227805500026

  View details for PubMedID 15781937

• Risk management of severe neonatal hyperbilirubinemia to prevent kernicterus CLINICS IN PERINATOLOGY Bhutani, V. K., Donn, S. M., Johnson, L. H. 2005; 32 (1): 125-?

  Abstract

  Our approach for risk management of severe neonatal hyperbilirubinemia to prevent kernicterus--one of the most easily preventable causes of neonatal brain damage--includes management of certain high-risk clinical situations, identification of systems failure, and suggestions for implementation strategies to enhance patient safety.

  View details for DOI 10.1016/j.clp.2004.11.002

  View details for Web of Science ID 000227662400009

  View details for PubMedID 15777825

• Postnatal changes in pulmonary mechanics and energetics of infants with respiratory distress syndrome following surfactant treatment. Biology of the neonate Bhutani, V. K., Bowen, F. W., Sivieri, E. M. 2005; 87 (4): 323-331

  Abstract

  Postnatal alterations in pulmonary mechanics, energetics and functional residual capacity (FRC) describe the structural maturation of the preterm respiratory system.To evaluate longitudinal changes in pulmonary function in infants with respiratory distress syndrome (RDS) treated with oxygen, positive pressure ventilation and synthetic surfactant (Exosurf).Serial pulmonary function tests were performed in surfactant-treated infants [mean +/- SD birth weight (BW) = 1,112 +/- 276 g, gestational age (GA) = 29 +/- 3 weeks] at postnatal ages: <3 days, 1, 2, 3, 4 and 6-8 weeks until term postmenstrual age (PMA). Tidal volume, pulmonary compliance (C(L)), pulmonary resistance (R(T)) and flow-resistive work were analyzed following simultaneous measurements of airflow and transpulmonary pressure signals. Serial FRC measurements were made in a randomly selected group. Results: Prior to 28 weeks' PMA, C(L) was unchanged irrespective of GA. At age 1 week the likelihood ratio (LR) for bronchopulmonary dysplasia (BPD) based on C(L), R(T) and GA was predicted to be >90% for those with BW <750 g (LR >100) as compared to <10% probability (LR = 0.3) for infants >1,500 g. Significant linear increase in C(L) to PMA was evident >28 weeks' PMA (r = 0.86, p < 0.01) at 0.17 ml/cm H2O/kg/week. By term PMA, mean C(L) was 2.60 +/- 0.07 ml/cm H2O. Improvements in FRC of preterm infants with RDS who recovered occur at a more rapid rate ( approximately 25 ml/kg) compared to those who developed BPD ( approximately 20 ml/kg).Slow but incremental postnatal pulmonary improvement, minimal <28 weeks' PMA, were comparable for all infants. Along with diminished FRC, these changes reflect persistent deleterious effects of positive pressure ventilation, alveolar hyperoxia and unrecognized pulmonary overdistension.

  View details for PubMedID 15985755

• Kernicterus as a 'Never-Event': a newborn safety standard? Indian journal of pediatrics Bhutani, V. K. 2005; 72 (1): 53-56

  Abstract

  Kernicterus, preventable in most cases but with untreatable and tragic sequelae, is a matter of public health concern that requires implementation of safer community healthcare standards to prevent its occurrence.

  View details for PubMedID 15684449

• Kernicterus in sick and preterm infants (1999-2002): A need for an effective preventive approach SEMINARS IN PERINATOLOGY Bhutani, V. K., Johnson, L. H., Shapiro, S. M. 2004; 28 (5): 319-325

  Abstract

  Kernicterus in sick and preterm infants is a rarity. Universal availability of phototherapy and concerted clinical efforts to identify, effectively manage and establish clinical guidelines have been instrumental in preventing kernicterus in US intensive care nurseries. However, in sick and preterm infants the absence of precise data on prevalence of bilirubin induced neurologic injury, the lack of proven predictive indices and the absence of evidence-based studies that clearly demonstrate the actual risk of kernicterus. These leave questions regarding the basis for clinical strategies and recommendations for the management of neonatal jaundice in this select population. This article reviews 6 preterm infants selected from the Pilot Kernicterus Registry who had recovered from life-threatening neonatal illnesses, briefly discusses current indices used to ascertain risk, and offers an initial bilirubin level based identification of infants while future directions and studies are conducted to supplement our presently incomplete knowledge for safer clinical practice.

  View details for DOI 10.1053/j.demperi.2004.09.006

  View details for Web of Science ID 000226212000002

  View details for PubMedID 15686262

• Introduction. Newborn jaundice. Seminars in perinatology Bhutani, V. K., Stevenson, D. K., Johnson, L. H. 2004; 28 (5): 317-318

  View details for PubMedID 15686261

• Kernicterus: epidemiological strategies for its prevention through systems-based approaches. Journal of perinatology Bhutani, V. K., Johnson, L. H., Jeffrey Maisels, M., Newman, T. B., Phibbs, C., Stark, A. R., Yeargin-Allsopp, M. 2004; 24 (10): 650-662

  Abstract

  Kernicterus, thought to be due to severe hyperbilirubinemia, is an uncommon disorder with tragic consequences, especially when it affects healthy term and near-term infants. Early identification, prevention and treatment of severe hyperbilirubinemia should make kernicterus a preventable disease. However, national epidemiologic data are needed to monitor any preventive strategies. Recommendations are provided to obtain prospective data on the prevalence and incidence of severe hyperbilirubinemia and associate mortality and neurologic injury using standardized definitions, explore the clinical characteristics and root causes of kernicterus in children identified in the Kernicterus Pilot Registry, identify and test an indicator for population surveillance, validating systems-based approaches to the management of newborn jaundice, and explore the feasibility of using biologic or genetic markers to identify infants at risk for hyperbilirubinemia. Increased knowledge about the incidence and consequences of severe hyperbilirubinemia is essential to the planning, implementation and assessment of interventions to ensure that infants discharged as healthy from their birth hospitals have a safer transition to home, avoiding morbidity due to hyperbilirubinemia and other disorders. At a recent NIHCD-sponsored conference, key questions were raised about kernicterus and the need for additional strategies for its prevention. These questions and an approach to their answers form the basis of this report.

  View details for PubMedID 15254556

• Diagnosis and management of hyperbilirubinemia in the term neonate: for a safer first week PEDIATRIC CLINICS OF NORTH AMERICA Bhutani, V. K., Johnson, L. H., Keren, R. 2004; 51 (4): 843-?

  Abstract

  New data support restructuring the approach toward diagnosis and management of hyperbilirubenia in the term neonate to make it more physician-friendly and gain wider implementation. The authors advocate clear criteria for patient safety, preventive approaches, and timely interventions. Structural changes to facilitate a system-based approach should include predischarge bilirubin management; follow-up bilirubin management; and lactational support and nutritional management. The authors advocate total serum bilirubin screening and a scoring system based on clinical risk factors as predischarge screening strategies; we should screen all babies for hyperbilirubinemia and for targeted follow-up based on an hour-specific total serum bilirubin measured for risk assessment. We should also provide focused universal education emphasizing adequate lactational nutrition, to decrease severe hyperbilirubinemia and thus prevent kernicterus.

  View details for DOI 10.1016/j.pcl.2004.03.011

  View details for Web of Science ID 000223511000002

  View details for PubMedID 15275978

• Management of hyperbilirubinemia in the newborn infant 35 or more weeks of gestation PEDIATRICS Maisels, M. J., Baltz, R. D., Bhutani, V. K., Newman, T. B., Palmer, H., Rosenfeld, W., Stevenson, D. K., Weinblatt, H. B. 2004; 114 (1): 297-316

  Abstract

  Jaundice occurs in most newborn infants. Most jaundice is benign, but because of the potential toxicity of bilirubin, newborn infants must be monitored to identify those who might develop severe hyperbilirubinemia and, in rare cases, acute bilirubin encephalopathy or kernicterus. The focus of this guideline is to reduce the incidence of severe hyperbilirubinemia and bilirubin encephalopathy while minimizing the risks of unintended harm such as maternal anxiety, decreased breastfeeding, and unnecessary costs or treatment. Although kernicterus should almost always be preventable, cases continue to occur. These guidelines provide a framework for the prevention and management of hyperbilirubinemia in newborn infants of 35 or more weeks of gestation. In every infant, we recommend that clinicians 1) promote and support successful breastfeeding; 2) perform a systematic assessment before discharge for the risk of severe hyperbilirubinemia; 3) provide early and focused follow-up based on the risk assessment; and 4) when indicated, treat newborns with phototherapy or exchange transfusion to prevent the development of severe hyperbilirubinemia and, possibly, bilirubin encephalopathy (kernicterus).

  View details for Web of Science ID 000222439200072

  View details for PubMedID 15231951

• Effects of morphine analgesia in ventilated preterm neonates: primary outcomes from the NEOPAIN randomised trial LANCET Anand, K. J., Hall, R. W., Desai, N., Shephard, B., Bergqvist, L. L., Young, T. E., Boyle, E. M., Carbajal, R., Bhutani, V. K., Moore, M. B., Kronsberg, S. S., Barton, B. A. 2004; 363 (9422): 1673-1682

  Abstract

  Opioid analgesia is commonly used during neonatal intensive care. We undertook the Neurologic Outcomes and Pre-emptive Analgesia in Neonates (NEOPAIN) trial to investigate whether pre-emptive morphine analgesia decreases the rate of a composite primary outcome of neonatal death, severe intraventricular haemorrhage (IVH), and periventricular leucomalacia (PVL) in preterm neonates.Ventilated preterm neonates (n=898) from 16 centres were randomly assigned masked placebo (n=449) or morphine (n=449) infusions. After a loading dose (100 microg/kg), morphine infusions (23-26 weeks of gestation 10 microg kg(-1) h(-1); 27-29 weeks 20 microg kg(-1) h(-1); 30-32 weeks 30 microg kg(-1) h(-1)) were continued as long as clinically justified (maximum 14 days). Open-label morphine could be given on clinical judgment (placebo group 242/443 [54.6%], morphine group 202/446 [45.3%]). Analyses were by intention to treat.Baseline variables were similar in the randomised groups. The placebo and morphine groups had similar rates of the composite outcome (105/408 [26%] vs 115/419 [27%]), neonatal death (47/449 [11%] vs 58/449 [13%]), severe IVH (46/429 [11%] vs 55/411 [13%]), and PVL (34/367 [9%] vs 27/367 [7%]). For neonates who were not given open-label morphine, rates of the composite outcome (53/225 [24%] vs 27/179 [15%], p=0.0338) and severe IVH (19/219 [9%] vs 6/189 [3%], p=0.0209) were higher in the morphine group than the placebo group. Placebo-group neonates receiving open-label morphine had worse rates of the composite outcome than those not receiving open-label morphine (78/228 [34%] vs 27/179 [15%], p<0.0001). Morphine-group neonates receiving open-label morphine were more likely to develop severe IVH (36/190 [19%] vs 19/219 [9%], p=0.0024).Pre-emptive morphine infusions did not reduce the frequency of severe IVH, PVL, or death in ventilated preterm neonates, but intermittent boluses of open-label morphine were associated with an increased rate of the composite outcome. The morphine doses used in this study decrease clinical signs of pain but can cause significant adverse effects in ventilated preterm neonates.

  View details for Web of Science ID 000221546300007

  View details for PubMedID 15158628

• For a safer outcome with newborn jaundice. Indian pediatrics Bhutani, V. K. 2004; 41 (4): 321-326

  View details for PubMedID 15123860

• Urgent clinical need for accurate and precise bilirubin measurements in the United States to prevent kernicterus CLINICAL CHEMISTRY Bhutani, V. K., Johnson, L. H. 2004; 50 (3): 477-480

  View details for DOI 10.1373/clinchem.2003.024489

  View details for Web of Science ID 000189287500006

  View details for PubMedID 14726464

• Innovative neonatal ventilation and meconium aspiration syndrome. Indian journal of pediatrics Bhutani, V. K., Chima, R., Sivieri, E. M. 2003; 70 (5): 421-427

  Abstract

  Respiratory failure remains a major cause of morbidity and mortality in the neonatal population. Infants with hypoxemic respiratory failure because of meconium aspiration syndrome (MAS), persistent pulmonary hypertension of the newborn (PPHN), and pneumonia/sepsis have a potential for increased survival with extracorporeal membrane oxygenation (ECMO). Other treatment options previously limited to inotropic support, conventional ventilatory management, respiratory alkalosis, paralysis and intravenousvasodilators have been replaced by high-frequency oscillatory ventilation (HFOV), surfactant, and inhaled nitric oxide (iNO). HFOV has been advocated for use to improve lung inflation while potentially decreasing lung injury through volutrauma. Other reports describe enhanced efficacy of HFOV when combined with iNO. Subsequent to studies reporting surfactant deficiency or inactivation may contribute to neonatal respiratory failure exogenous surfactant therapy has been implemented with apparent success. Recent studies have shown that iNO therapy in the neonate with hypoxemic respiratory failure can result in improved oxygenation and decreased need for ECMO. In this article, the authors place in context of a system-based strategy the prenatal, natal and postnatal management of babies delivered through meconium stained amniotic fluid (MSAF) so that adverse outcomes are minimized, and the least number of babies require innovative ventilatory support. At Pennsylvania Hospital, over a six-year period (1995 to 2000), 14.5% (3370/23,175 of live births babies were delivered with MSAF. These data show that 4.6% (155/3370) of babies with MSAF sustained MAS. Overall, 26% (40/155) of babies with MAS needed ventilatory support (or 0.17% of all live-births); of these only 20% (8/40 or 0.035% of live births) needed innovative ventilatory support. None died or needed ECMO. These data describe the impact of a system-based approach to prevent and manage adverse outcomes related to MSAF at regional Level III perinatal center.

  View details for PubMedID 12841404

• Newborn jaundice and kernicterus--health and societal perspectives. Indian journal of pediatrics Bhutani, V. K., Johnson, L. H. 2003; 70 (5): 407-416

  Abstract

  Kernicterus, a preventable injury to the brain from severe neonatal jaundice, has re-emerged in the United States as a public and societal health concern. Kernicterus, in its usually recognized form, causes devastating disabilities, including athetoid cerebral palsy and speech and hearing impairment. This condition not only ranks amongst the highest cost per new case (per CDCs Financial Burden of Disability study, 1992), but also results in profound and uncompromising grief for the family and loss to siblings of healthy, talkative playmates. And for the child with kernicterus (usually remarkably intelligent, but trapped in an uncontrollable body), grief and frustration are enormous. In 2001 national healthcare organizations, including Centers for Disease Control (CDC), the Joint Commission for the Accreditation of Healthcare Organizations (JACHO) and the American Academy of Pediatrics (AAP) issued alerts to all accredited hospitals and public health professionals in the United States that all healthy infants are at potential risk of kernicterus if their newborn jaundice is unmonitored and inadequately treated. The re-emergence of kernicterus in the United States is the result of interacting phenomena including (a) Early hospital discharge (before extent of jaundice is known and signs of impending brain damage have appeared); (b) Lack of adequate concern for the risks of severe jaundice in healthy term and near newborns; (c) An increase in breast feeding; (d) Medical care cost constraints; (e) Paucity of educational materials to enable parents to participate in safeguarding their newborns; and (f) Limitations within in healthcare systems to monitor the outpatient progression of jaundice. A multidisciplinary approach that encompasses both healthcare and societal needs should be evaluated at a national level for practical and easy to implement strategies. An approach that is based on principles of evidence-based medicine, patient-safety and family centeredness is presented in this article. These strategies should also be based on public awareness campaign such that the healthcare providers can attempt to achieve a "Zero Tolerance of Kernicterus" and thereby decrease both childhood disabilities and infant mortality within the community.

  View details for PubMedID 12841402

• Measuring bilirubin through the skin? PEDIATRICS Bhutani, V. K., Johnson, L. H., Gourley, G. 2003; 111 (4): 919-919

  View details for Web of Science ID 000181960600037

  View details for PubMedID 12671137

• Clinical applications of pulmonary function and graphics. Seminars in neonatology : SN Bhutani, V. K. 2002; 7 (5): 391-399

  Abstract

  Pulmonary function and mechanics testing are emerging as a valuable tool to aid clinical decision making in the management of ventilated infants. Although there are as yet no published randomized controlled trials to suggest that pulmonary mechanics testing reduces mortality or morbidity, it has--in conjunction with clinical, radiological, and blood gas monitoring--changed neonatal ventilation from "good judgement" to "informed judgement". It is not surprising that pulmonary graphics are increasingly being used as a tool for assessment of patient status, therapeutic evaluation, and management guidance of infants who become dependent on ventilator. A working knowledge of pulmonary graphics also improves understanding of pulmonary physiology and pathophysiology, and their responses to mechanical ventilatory support. Recent advances in microprocessor technology for on-line analysis of pulmonary mechanics have made such evaluations easily available for bedside clinical application.

  View details for PubMedID 12464501

• System-based approach to management of neonatal jaundice and prevention of kernicterus JOURNAL OF PEDIATRICS Johnson, L. H., Bhutani, V. K., Brown, A. K. 2002; 140 (4): 396-403

  View details for DOI 10.1067/mpd.2002.123098

  View details for Web of Science ID 000175524400007

  View details for PubMedID 12006952

• Jaundice technologies: prediction of hyperbilirubinemia in term and near-term newborns. Journal of perinatology Bhutani, V. K., Johnson, L. H. 2001; 21: S76-82

  View details for PubMedID 11803423

• Neonatal hyperbilirubinemia and the potential risk of subtle neurological dysfunction PEDIATRIC RESEARCH Bhutani, V. K. 2001; 50 (6): 679-680

  View details for Web of Science ID 000172398500006

  View details for PubMedID 11726722

• Prediction of hyperbilirubinemia in near-term and term infants. Journal of perinatology Stevenson, D. K., Fanaroff, A. A., Maisels, M. J., Young, B. W., Wong, R. J., Vreman, H. J., MacMahon, J. R., Yeung, C. Y., Seidman, D. S., Gale, R., Oh, W., Bhutani, V. K., Johnson, L. H., Kaplan, M., Hammerman, C., Nakamura, H. 2001; 21: S63-72

  Abstract

  The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life.From nine multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998 through February 22, 1999. Measurements of both ETCOc and STB were performed at 30+/-6 hours of life; STB also was measured at 96+/-12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study.A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breast-fed infants was 8.92+/-4.37 mg/dl at 96 hours versus 7.63+/-3.58 mg/dl in those fed formula only. The mean ETCOc at 30+/-6 hours for the total population was 1.48+/-0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45+/-0.47 and 1.81+/-0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30+/-6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB > or =95th percentile. When infants with STB > or =95th percentile at <36 hours of age were excluded, the STB at 30+/-6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these two measurements at 30+/-6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV.This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30+/-6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

  View details for PubMedID 11803421

• Clinical use of pulmonary mechanics and waveform graphics CLINICS IN PERINATOLOGY Bhutani, V. K., Sivieri, E. M. 2001; 28 (3): 487-?

  Abstract

  Decades of research have led to the understanding of neonatal pulmonary physiology and have influenced the clinical care that neonatologists provide to the sick newborn. Advances in microprocessor technology have allowed for clinical access of the research-based measurements of neonatal pulmonary functions. These evaluations are not only the integrated evaluation of the three primary vectors of respiration (driving pressure, air flow, and volume measured over time) but also values calculated by known physiologic equations. Clinical use of these data may not only be relevant and helpful in the bedside management, but also provides a uniquely objective and research-oriented data collection for individual newborns.

  View details for Web of Science ID 000171029800002

  View details for PubMedID 11570150

• Prediction of hyperbilirubinemia in near-term and term infants PEDIATRICS Stevenson, D. K., Fanaroff, A. A., Maisels, M. J., Young, B. W., Wong, R. J., Vreman, H. J., MacMahon, J. R., Yeung, C. Y., Seidman, D. S., Gale, R., Oh, W., Bhutani, V. K., Johnson, L. H., Kaplan, M., Hammerman, C., Nakamura, H. 2001; 108 (1): 31-39

  Abstract

  The purpose of this study was to determine whether end-tidal carbon monoxide (CO) corrected for ambient CO (ETCOc), as a single measurement or in combination with serum total bilirubin (STB) measurements, can predict the development of hyperbilirubinemia during the first 7 days of life.From 9 multinational clinical sites, 1370 neonates completed this cohort study from February 20, 1998, through February 22, 1999. Measurements of both ETCOc and STB were performed at 30 +/- 6 hours of life; STB also was measured at 96 +/- 12 hours and subsequently following a flow diagram based on a table of hours of age-specific STB. An infant was defined as hyperbilirubinemic if the hours of age-specific STB was greater than or equal to the 95th percentile as defined by the table at any time during the study.A total of 120 (8.8%) of the enrolled infants became hyperbilirubinemic. Mean STB in breastfed infants was 8.92 +/- 4.37 mg/dL at 96 hours versus 7.63 +/- 3.58 mg/dL in those fed formula only. The mean ETCOc at 30 +/- 6 hours for the total population was 1.48 +/- 0.49 ppm, whereas those of nonhyperbilirubinemic and hyperbilirubinemic infants were 1.45 +/- 0.47 ppm and 1.81 +/- 0.59 ppm, respectively. Seventy-six percent (92 of 120) of hyperbilirubinemic infants had ETCOc greater than the population mean. An ETCOc greater than the population mean at 30 +/- 6 hours yielded a 13.0% positive predictive value (PPV) and a 95.8% negative predictive value (NPV) for STB >/=95th percentile. When infants with STB >95th percentile at <36 hours of age were excluded, the STB at 30 +/- 6 hours yielded a 16.7% PPV and a 98.1% NPV for STB >75th percentile. The combination of these 2 measurements at 30 +/- 6 hours (either ETCOc more than the population mean or STB >75th percentile) had a 6.4% PPV with a 99.0% NPV. Conclusions. This prospective cohort study supports previous observations that measuring STB before discharge may provide some assistance in predicting an infant's risk for developing hyperbilirubinemia. The addition of an ETCOc measurement provides insight into the processes that contribute to the condition but does not materially improve the predictive ability of an hours of age-specific STB in this study population. The combination of STB and ETCOc as early as 30 +/- 6 hours may identify infants with increased bilirubin production (eg, hemolysis) or decreased elimination (conjugation defects) as well as infants who require early follow-up after discharge for jaundice or other clinical problems such as late anemia. Depending on the incidence of hyperbilirubinemia within an institution, the criteria for decision making should vary according to its unique population.

  View details for Web of Science ID 000169571400025

  View details for PubMedID 11433051

• Newborn jaundice and Kernicterus: Predictive role of system-based application of jaundice technologies 5th World Congress of Perinatal Medicine Bhutani, V. K., Johnson, L. H. MEDIMOND S R L. 2001: 996–1007

  View details for Web of Science ID 000174742200182

• Managing the assessment of neonatal jaundice: importance of timing. Indian journal of pediatrics Bhutani, V. K., Johnson, L. H. 2000; 67 (10): 733-737

  Abstract

  In view of the limitations in the accurate visual assessment of jaundice and its potential role as a predictive vector for serious neurologic sequelae, we propose that a universal screening of bilirubin be considered concurrent to the routine pre-discharge metabolic screening. Universal bilirubin screening in the term and near-term newborns when plotted on "Hour-specific Bilirubin Nomogram" in lieu of the usual "day-specific" value will predict the high-risk and the low-risk groups and facilitate cost-effective and individualized follow-up of those babies at risk. A percentile based bilirubin nomogram for the first week of age was constructed from hour-specific pre- and post-discharge bilirubin values of 2840 healthy term and near-term babies. The accuracy of the pre-discharge bilirubin values was determined as a predictive vector. Pre-discharge (18-72 hours age), 6.1% of the study population had bilirubin values in the high-risk zone (> 95th percentile). Of these, 39.5% remained in that zone (likelihood ratio ¿LR¿ = 14.08). Pre-discharge, 32.1% of the study population had bilirubin values in the intermediate risk zone (40-75th percentiles). In a clinically significant minority of these babies (6.4%), the post-discharge values moved to the high-risk zone (L-R = 3.2 for the move from the upper-intermediate zone and 0.48 from the lower-intermediate zone). In the remainder 61.8% of the population who were identified to be at low risk, there was no measurable risk for significant hyperbilirubinemia (L-R = 0). The bilirubin nomogram can predict which infant is at high, intermediate, and low risk for subsequent excessive hyperbilirubinemia and allows for the individualized follow-up of these high-risk babies with particular attention to those who may need evaluation and intervention. Whereas, identification of the low risk group allows for a less intense bilirubin follow-up and in whom a visual check by an experienced care-provider may suffice.

  View details for PubMedID 11105424

• Noninvasive measurement of total serum bilirubin in a multiracial predischarge newborn population to assess the risk of severe hyperbilirubinemia PEDIATRICS Bhutani, V. K., Gourley, G. R., Adler, S., Kreamer, B., Dalin, C., Johnson, L. H. 2000; 106 (2)

  Abstract

  Jaundice in near-term and term newborns is a frequent diagnosis that may prompt hospital readmission in the first postnatal week. Hyperbilirubinemia, when excessive, can lead to potentially irreversible bilirubin-induced neurotoxicity. Predischarge risk assessment (at 24-72 hours of age) for subsequent excessive hyperbilirubinemia is feasible by a laboratory-based assay of total serum bilirubin (TSB). Hypothesis. Noninvasive, transcutaneous, point-of-care measurement of transcutaneous bilirubin (TcB) predischarge by multiwavelength spectral analysis, using a portable BiliCheck device (SpectRx Inc, Norcross, GA), is clinically equivalent to measurement of TSB in a diverse, multiracial term and near-term newborn population and predictive of subsequent hyperbilirubinemia.We evaluated a hand-held device that uses multiwavelength spectral reflectance analysis to measure TcB (BiliCheck). The study population (490 term and near-term newborns) was racially diverse (59.1% white, 29.5% black, 3.46% Hispanic, 4.48% Asian, and 3.46% other) and was evaluated at 2 separate institutions using multiple (11) devices. The postnatal age ranged from 12 to 98 hours and the ranges of birth weights and gestational ages were 2000 to 5665 g and 35 to 42 weeks, respectively. All transcutaneous evaluations were performed contemporaneously and paired with a heelstick TSB measurement. All TSB assays were performed by high performance liquid chromatography, as well as by diazo dichlorophenyldiazonium tetrafluoroborate techniques.TSB values ranged from .2 to 18.2 mg/dL (mean +/- standard deviation: 7.65 +/- 3.35 mg/dL). The overall correlation of TSB (by high performance liquid chromatography technique) to TcB (by BiliCheck devices) was linear and statistically significant (r =.91; r(2) =.83; TcB =.84; TSB = +.75; standard error of regression line = 1.38; P <.001; n = 490 infants; 1788 samples). Similar regression statistics were evident in subset populations categorized by race (white: r =.91 [n = 289 infants]; black: r =.91 [n = 145 infants]) as well as by gestation (term: r =. 91 [n = 1625 samples]; near-term: r =.89 [n = 163 samples]). Intradevice precision was determined to be.59 mg/dL (2-3 measurements per infant with 1 device; n = 210 infants; 510 samples in a separate subset). Interdevice evaluation of 11 devices determined the precision to be.68 mg/dL (2-4 devices used for measurements per patient). In 23 of 419 of the study population infants who were in the 24- to 72-hour age range, the predischarge TSB values designated them to be at high risk for subsequent excessive hyperbilirubinemia (above the 95th percentile track on the hour-specific bilirubin nomogram). For these infants, the paired BiliCheck TcB values were all above the 75th percentile track (negative predictive value = 100%; positive predictive value = 32. 86%; sensitivity = 100%; specificity = 88.1%; likelihood ratio = 8. 43).Our data demonstrate the accuracy and reproducibility of the predischarge BiliCheck measurements in term and near-term newborn infants of diverse races and ethnicities. Infants with predischarge BiliCheck values above the 75th percentile of hour-specific TSB values on the bilirubin nomogram may be considered to be at high risk for subsequent excessive hyperbilirubinemia. Further studies are needed to assess the efficacy of this technique in preterm infants, those undergoing phototherapy, and those with TSB values of >/=15 mg/dL (>/=256 micromol/L).

  View details for Web of Science ID 000088538100003

  View details for PubMedID 10920173

• Inhaled nitric oxide in premature neonates with severe hypoxaemic respiratory failure: a randomised controlled trial LANCET Kinsella, J. P., Walsh, W. F., Bose, C. L., Gerstmann, D. R., LaBella, J. J., Sardesai, S., Walsh-Sukys, M. C., McCaffrey, M. J., Cornfield, D. N., Bhutani, V. K., Cutter, G. R., Baier, M., Abman, S. H. 1999; 354 (9184): 1061-1065

  Abstract

  Inhaled nitric oxide improves oxygenation and lessens the need for extracorporeal-membrane oxygenation in full-term neonates with hypoxaemic respiratory failure and persistent pulmonary hypertension, but potential adverse effects are intracranial haemorrhage and chronic lung disease. We investigated whether low-dose inhaled nitric oxide would improve survival in premature neonates with unresponsive severe hypoxaemic respiratory failure, and would not increase the frequency or severity of intracranial haemorrhage or chronic lung disease.We did a double-blind, randomised controlled trial in 12 perinatal centres that provide tertiary care. 80 premature neonates (gestational age < or = 34 weeks) with severe hypoxaemic respiratory failure were randomly assigned inhaled nitric oxide (n=48) or no nitric oxide (n=32, controls). Our primary outcome was survival to discharge. Analysis was by intention to treat. We studied also the rate and severity of intracranial haemorrhage, pulmonary haemorrhage, duration of ventilation, and chronic lung disease at 36 weeks' postconceptional age.The two groups did not differ for baseline characteristics or severity of disease. Inhaled nitric oxide improved oxygenation after 60 min (p=0.03). Survival at discharge was 52% in the inhaled-nitric-oxide group and 47% in controls (p=0.65). Causes of death were mainly related to extreme prematurity and were similar in the two groups. The two groups did not differ for adverse events or outcomes (intracranial haemorrhage grade 2-4, 28% inhaled nitric oxide and 33% control; pulmonary haemorrhage 13% and 9%; chronic lung disease 60% and 80%).Low-dose inhaled nitric oxide improved oxygenation but did not improve survival in severely hypoxaemic premature neonates. Low-dose nitric oxide in the most critically ill premature neonates does not increase the risk of intracranial haemorrhage, and may decrease risk of chronic lung injury.

  View details for Web of Science ID 000082777500010

  View details for PubMedID 10509496

• Reply journal of pediatrics Raju, Langenberg, Bhutani, Quinn 1999; 134 (2): 249-?

  View details for PubMedID 9931548

• Perinatal bacterial infection: an update. Indian journal of pediatrics Yeagley, T. J., Tolosa, J. E., Bhutani, V. K. 1998; 65 (6): 841-848

  Abstract

  This article reviews the current trends in the evaluation and management of bacterial infection involving the uterus, placenta, membranes, amniotic fluid, and fetus occurring near the time of birth. The discussion includes information regarding risk, incidence, pathophysiology, bedside diagnosis, interventional options including antibiotics, corticosteroids, fetal monitoring, and delivery, and possible preventive measures which affect the outcome. The adequate evaluation and management of perinatal infection requires a team approach with obstetricians and pediatricians. Clinical screening is useful in developing the diagnosis, but amniotic fluid evaluation remains the proposed gold standard. The role of cytokines is becoming increasingly important, as is seen in the association of IL-6 with positive amniotic fluid cultures and periventricular leukomalacia. Prompt recognition and management of the pregnancy affected by infection can improve perinatal outcomes. A management protocol is presented to help structure the approach to suspected infection. Premature delivery due to perinatal infection may be preventable.

  View details for PubMedID 10773948

• Guidelines for management of the jaundiced term and near-term infant CLINICS IN PERINATOLOGY Johnson, L., Bhutani, V. K. 1998; 25 (3): 555-?

  Abstract

  Factors believed to have contributed to the reemergence of kernicterus in the United States during the 1990's are discussed: these include decreased concern about toxicity of bilirubin in term and near-term infants, increased prevalence of breastfeeding, and increasingly shortened postnatal hospital stays. The rationale for a universal predischarge bilirubin measurement at the time of the routine predischarge metabolic screen is presented: the hour-specific level of bilirubin at discharge, plotted on an Hour-Specific Bilirubin Nomogram, improves prediction of risk of excessive jaundice postdischarge and facilitates safe, cost-effective follow-up. This minimizes repeat bilirubin measurements and maximizes recognition of confounding variables and risk of hyperbilirubinemia so that timely, minimally invasive, preventive therapy can be instituted if needed.

  View details for Web of Science ID 000076016000005

  View details for PubMedID 9779334

• Respiratory and systemic effects of inhaled dexamethasone on ventilator dependant preterm infants at risk for bronchopulmonary dysplasia. Indian journal of pediatrics Pappagallo, M., Abbasi, S., Bhutani, V. K. 1998; 65 (2): 273-282

  Abstract

  Short-term inhaled dexamethasone therapy was evaluated in a double blind placebo controlled trial in 36 ventilator dependent preterm neonates (BW < 1500 gm, postnatal age > 7 days) who were at risk for bronchopulmonary dysplasia. Pulmonary and systemic effects were compared at early (day 3), late (7-10 days) and post (14 days after initiation) phases of therapy. Airflow mechanics improved as demonstrated by a net 101% improvement in pulmonary resistance (a decrease from 139 to 101 cm H2O/L/s in the dexamethasone treated infants as compared to an increase from 153 to 267 cmH2O/L/s in the placebo treated infants during the early phase of therapy); this was associated with a 45% increase in inspiratory airflow (1.29 +/- 0.43 to 1.87 +/- 0.978 L/min; p < 0.01), and 37% increase in expiratory airflow. These changes resulted in a significant reduction in the work of breathing such that the mean tidal driving pressure significantly decreased from 13.6 cmH2O to 9.4 cm H2O with inhaled steroid administration. Though the brief duration of therapy did not result in cessation of ventilatory support, the level of support was significantly reduced (decreased values of oxygen supplementation, mean airway pressure and oxygenation index and increased ventilatory efficiency index). The inhaled dexamethasone therapy was also associated with systemic absorption of the drug as evidenced by transient but apparently reversible reduction in serum cortisol levels. No systemic side effects of hypertension, hyperglycemia or nosocomial sepsis were observed. These data demonstrate beneficial effects of short-term inhaled dexamethasone on the resistive airflow properties of preterm infants at risk for BPD and may provide adjunctive means to facilitate weaning in the ventilator dependent neonates.

  View details for PubMedID 10771973

• Vitamin E prophylaxis to reduce retinopathy of prematurity: A reappraisal of published trials JOURNAL OF PEDIATRICS Raju, T. N., Langenberg, P., Bhutani, V., Quinn, G. E. 1997; 131 (6): 844-850

  Abstract

  We conducted a meta-analysis of the published randomized clinical trials of vitamin E prophylaxis designed to reduce retinopathy of prematurity (ROP) to determine whether increased serum concentrations of vitamin E reduced the incidence of severe, threshold (Stage 3+) ROP in the very low birth weight (VLBW) infant subset.Among the six trials considered eligible for analyses, the incidence for all stages of ROP and for Stage 3+ ROP was computed for all randomly assigned infants (intention-to-treat analysis) and for those infants completing the trials. Odds ratios (ORs) and pooled estimates for event rate reductions (and the respective 95% confidence intervals [CIs]) were calculated for these outcome end points.There were 704 VLBW infants in the vitamin E prophylaxis groups and 714 in control groups; 536 (76.1%) infants in the vitamin E and 551 (77.2%) in the control groups completed the trials. In all trials the mean serum vitamin E concentrations were within or above the physiologic range in the vitamin-treated groups and at or below the physiologic ranges in the control groups. The overall incidence of any stage ROP was similar between the groups: 39.8% in the vitamin E group and 43.5% in the control group. The overall incidence for Stage 3+ ROP was lower in the vitamin E-treated groups than in the control group (2.4% in vitamin E vs 5.3% in control). The pooled OR for developing Stage 3+ ROP with vitamin E prophylaxis was 0.44 (95% CI, 0.21, 0.81, p < 0.02). The reciprocal of the pooled estimate of mean risk reduction (2.8%, 95% CI: 0.55%, 5.1%) for Stage 3+ ROP revealed that on average, vitamin E prophylaxis given to 35 VLBW infants would prevent one case of threshold, Stage 3+ ROP.Considering that there was a 52% reduction in the incidence of Stage 3+ ROP, we suggest that the role of vitamin E in reducing severe ROP be re-evaluated. We could not assess the adverse effect rates from vitamin E therapy in the trials analyzed; therefore, we recommend a well-controlled and focused trial in which the issues of benefit, adverse effects, and cost can be assessed with vitamin E prophylaxis in extremely low birth weight (< 1000 gm) infants.

  View details for Web of Science ID 000071165100013

  View details for PubMedID 9427888

• Evolution of neonatal and pediatric critical care in India CRITICAL CARE CLINICS Vidyasagar, D., Singh, M., BHAKOO, O. N., Paul, V. K., Narang, A., Bhutani, V., Beligere, N., Deorari, A. 1997; 13 (2): 331-?

  Abstract

  During the last decade, the disciplines of neonatal and pediatric critical care have rapidly progressed in India. The growth of Neonatal Intensive Care has paced the growth of Pediatric Critical Care. The substantial growth of discipline and the positive improvements in neonatal outcomes are the results of the concerted efforts of the National Neonatal Forum and commitment of expatriate physicians residing in the United States. This article provides the background information regarding perinatal, neonatal, and infant mortalities in India. It also describes the maternal child health care delivery system in the Indian subcontinent.

  View details for Web of Science ID A1997WT70400009

  View details for PubMedID 9107511

• Accidental administration of an ergot alkaloid to a neonate PEDIATRICS Baum, C. R., HILPERT, P. L., Bhutani, V. K. 1996; 98 (3): 457-458

  View details for Web of Science ID A1996VF50600020

  View details for PubMedID 8784375

• Effects of sweet taste stimulation on growth and sucking in preterm infants. Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG Mattes, R. D., Maone, T., Wager-Page, S., Beauchamp, G., Bernbaum, J., Stallings, V., Pereira, G. R., Gibson, E., Russell, P., Bhutani, V. 1996; 25 (5): 407-414

  Abstract

  To evaluate the effect of sweet taste stimulation in augmenting the reported growth-enhancing effects of nonnutritive sucking in preterm infants who are gavage-fed.Random assignment of preterm infants to receive stimulation by one of three methods during each feeding until totally orally fed.Hospital intensive-care and infant transitional units.Eligibility criteria included body weight greater than or equal to 1,250 g, gestational age younger than 34 weeks, growth parameters appropriate for gestational age, tolerating at least 100 kcals/kg/day by gavage feeding with evidence of weight gain, and no clinical evidence of health complications. Data are presented for 42 infants who completed 14 days of treatment.Exposure to a sweet pacifier, a latex pacifier, or maternal heartbeat sounds during gavage feedings.Growth, time to total oral feeding, and sucking responses.No significant differences in sucking measures were noted among treatment groups. Differences in progression time to total oral feedings and weight gain favored the sweet-pacifier group but were not statistically significant.Oral stimulation of gavage-fed, preterm infants during a 2-week hospitalization was not sufficient to elicit a significant improvement in growth efficiency, progression to total oral feedings, or sucking maturation. Additional studies may show a beneficial effect of chemosensory stimulation in preterm infants.

  View details for PubMedID 8791228

• SEVERE RETINOPATHY OF PREMATURITY IN INFANTS WITH BIRTH WEIGHTS LESS-THAN 1250 GRAMS - INCIDENCE AND OUTCOME OF TREATMENT WITH PHARMACOLOGICAL SERUM LEVELS OF VITAMIN-E IN ADDITION TO CRYOTHERAPY FROM 1085 TO 1991 JOURNAL OF PEDIATRICS Johnson, L., Quinn, G. E., Abbasi, S., Gerdes, J., Bowen, F. W., Bhutani, V. 1995; 127 (4): 632-639

  Abstract

  To determine the effect of vitamin E prophylaxis and treatment on the sequelae of severe (threshold) retinopathy of prematurity (ROP) in infants treated with cryotherapy at Pennsylvania Hospital from 1985 to 1991.Beginning on day 0, all infants with birth weights < or = 1250 gm received supplements of vitamin E using standard preparations. Serum E levels of 23 to 58 mumol/L (1 to 2.5 mg/dl) were targeted for infants with immature retinal vasculature or ROP of stage 2 or less in severity, and levels of 58 to 81 mumol/L (2.5 to 3.5 mg/dl) for infants with prethreshold ROP. At diagnosis of threshold ROP, treatment with a parenteral investigational new drug preparation of alpha-tocopherol was begun to raise serum levels to the pharmacologic range (93 to 116 mumol/L or 4 to 5 mg/dl). Within 3 days of diagnosis, and at the discretion of the retinal specialist, one or both eyes were treated with cryotherapy. Visual outcome at 4 years was compared with the 42-month outcome reported for eyes in the infants randomly assigned to treatment in the 1986-1987 Multicenter Trial of Cryotherapy for ROP (CRYO-ROP).Threshold ROP developed in 22 of 450 surviving infants (age 3 months). All were treated with pharmacologic serum levels of vitamin E; 17 infants were also treated with cryotherapy (10 in one eye and 7 in both eyes). These 17 infants, in comparison with infants in the CRYO-ROP trial (n = 187), were at least at equal risk for poor visual outcome on the basis of birth weight, gestational age, the percentage of zone 1 ROP, and mean interval from appearance of ROP to diagnosis of prethreshold ROP, which was shorter at Pennsylvania Hospital (4.1 days for the Pennsylvania Hospital group, 10.3 days for the CRYO-ROP group). However, on the basis of the mean number of days from diagnosis of prethreshold to threshold ROP (12.5 days for Pennsylvania Hospital, 10.5 days for CRYO-ROP) and the extent of extraretinal neovascularization at threshold (mean 7.9 sectors for Pennsylvania Hospital, 9.7 for CRYO-ROP), progression of retinopathy beyond the prethreshold stage had slowed and visual outcome in the eyes of infants at Pennsylvania Hospital treated with both cryotherapy and vitamin E (worse eye used for those treated with bilateral cryotherapy) was better than that reported for the treated eye of infants in the CRYO-ROP group (percentage of favorable visual acuity, 76% vs 48%, p = 0.04; percentage of normal structure posterior retinal pole, 71% vs 38%, p < or = 0.02).In this small case series, the combination of cryotherapy with anti-oxidant prophylaxis and treatment appeared to decrease the severity and sequelae of threshold ROP. This hypothesis deserves testing in a large, randomized clinical trial.

  View details for Web of Science ID A1995RZ08400023

  View details for PubMedID 7562291

• GASTROINTESTINAL AND RENAL BLOOD-FLOW VELOCITY PROFILE IN NEONATES WITH BIRTH ASPHYXIA JOURNAL OF PEDIATRICS Akinbi, H., Abbasi, S., HILPERT, P. L., Bhutani, V. K. 1994; 125 (4): 625-627

  Abstract

  Pulsed Doppler ultrasound blood flow profiles were studied, before the initiation of enteral feedings, in 23 neonates with birth asphyxia. We observed a significant direct correlation between the reduction of peak velocity and increased resistance in the renal and superior mesenteric arteries to the severity of asphyxia (r = 0.8; p < 0.05); the changes often persisted up to 3 days of age. Longitudinal evaluation of flow in these vessels might help to time the initiation of enteral nutrition in neonates with asphyxia.

  View details for Web of Science ID A1994PK52900023

  View details for PubMedID 7931888

• ROLE OF POSITIVE END-EXPIRATORY PRESSURE CHANGES ON FUNCTIONAL RESIDUAL CAPACITY IN SURFACTANT TREATED PRETERM INFANTS PEDIATRIC PULMONOLOGY DASILVA, W. J., Abbasi, S., Pereira, G., Bhutani, V. K. 1994; 18 (2): 89-92

  Abstract

  Both surfactant replacement and positive end-expiratory pressure (PEEP) increase lung volume in infants with respiratory distress syndrome (RDS). We measured pulmonary mechanics and functional residual capacity (FRC) in 21 preterm infants with RDS, > 48 hr post-surfactant therapy (BW, 1,168 +/- 441 g; GA, 28.3 +/- 2.8 weeks; postnatal age, 3-7 days). A non-linear but significant increase in mean FRC was noted as PEEP increased from 2 to 5 cmH2O: 18.4 +/- 4.7 mL/kg at 2 cmH2O; 19.7 +/- 4.3 mL at 3 cmH2O; 22.6 +/- 5.5 ml/kg at 4 cmH2O; and 26.2 +/- 6.2 mL/kg at 5 cmH2O (P < 0.01). Because of the synergistic combined effect on lung volume, surfactant treated neonates should be weaned cautiously from PEEP during ventilatory management. Our study also suggests that the occurrence of inadvertent end-distending pressure during FRC measurement in the ventilated neonate lead to erroneous results.

  View details for Web of Science ID A1994PD75200005

  View details for PubMedID 7970924

• INFLUENCE OF HEAD-NECK POSTURE ON AIR-FLOW AND PULMONARY MECHANICS IN PRETERM NEONATES PEDIATRIC PULMONOLOGY Reiterer, F., Abbasi, S., Bhutani, V. K. 1994; 17 (3): 149-154

  Abstract

  The influence of head-neck posture (neutral, 15 degrees, 30 degrees, and 45 degrees extension and flexion) on airflow and pulmonary mechanics was evaluated in 10 spontaneously breathing healthy preterm neonates (mean +/- SD; birth weight, 1.32 +/- 0.23 kg; gestational age, 29.4 +/- 2.4 weeks; study age, 36.6 +/- 1.6 weeks) who had had respiratory distress syndrome. Head-neck postures were quantified using specially constructed wooden wedges. Airflow was measured by a pneumotachometer via face mask. Lung compliance (CL) and resistance (RL) were measured using an esophageal balloon. Airflow interruption was designated as mild (10-40%), moderate (40-80%), and severe (> 80-100%) decrease of airflow. At neutral head-neck posture, 42.8 +/- 7.5% SEM of breaths had airflow interruption (71.4% mild, 19.9% moderate, 8.7% severe). There was no significant change with 15 degrees and 30 degrees head-neck flexion and extension. However, at 45 degrees flexion the overall incidence of airflow interruption (77.3 +/- 4.8%, P < 0.05) and RL (86.6 +/- 6.7 vs. 64.2 +/- 3.9 cmH2O/L/s, mean +/- SEM; P < 0.05) significantly increased. Extension to 45 degrees caused severe airflow interruption and increased RL in some infants, but no statistically significant change for the whole group. The incidence of severe airflow interruption significantly increased (P < 0.05) from 8.7% at neutral head-neck posture to 26.3% at hyperflexion (45 degrees). No changes in CL were observed. We conclude that minor (15-30 degrees) deviations from neutral neck posture are insignificant, whereas hyperflexion, and in some infants, hyperextension, can significantly affect airflow and pulmonary mechanics.

  View details for Web of Science ID A1994MY96300002

  View details for PubMedID 8196994

• EFFECT OF ENTERAL GAVAGE FEEDING RATE ON PULMONARY FUNCTIONS OF VERY-LOW-BIRTH-WEIGHT INFANTS JOURNAL OF PEDIATRICS Blondheim, O., Abbasi, S., Fox, W. W., Bhutani, V. K. 1993; 122 (5): 751-755

  Abstract

  To compare the effects of intermittent and continuous feedings on pulmonary function, we studied 24 very low birth weight neonates (mean +/- SD: birth weight, 1.2 +/- 0.3 kg; gestational age, 30.5 +/- 1.1 weeks) at 2 to 4 weeks of age. All infants had a previous diagnosis of respiratory distress syndrome but no subsequent diagnosis of bronchopulmonary dysplasia. Pulmonary mechanics were measured before the beginning of intermittent or continuous feedings and 10 minutes after each meal was completed. Twelve infants were randomly assigned to intermittent and 12 to continuous feedings. These infants had similar birth weight, gestational age, study age, and baseline lung function. After intermittent feedings, there was a significant decrease in tidal volume (38%), minute ventilation (44%), and dynamic compliance (28%), whereas pulmonary resistance increased significantly (100%). In comparison, the pulmonary function data remained unchanged after continuous feedings. These data demonstrate that intermittent feeding of very low birth weight infants can lead to airflow and respiratory instability. These adverse effects appear to be dependent on the rate that feedings are administered. A slower pace of feeding may be more advantageous for infants prone to respiratory instability.

  View details for Web of Science ID A1993LC74500018

  View details for PubMedID 8496756

• LONG-TERM PULMONARY CONSEQUENCES OF RESPIRATORY-DISTRESS SYNDROME IN PRETERM INFANTS TREATED WITH EXOGENOUS SURFACTANT JOURNAL OF PEDIATRICS Abbasi, S., Bhutani, V. K., Gerdes, J. S. 1993; 122 (3): 446-452

  Abstract

  The pulmonary outcome for preterm infants 1 year after synthetic surfactant replacement for respiratory distress syndrome was assessed by examining their pulmonary status and the results of pulmonary function tests. A total of 47 infants were followed: 13 infants mean +/- SD: birth weight, 1960 +/- 616 gm; gestation, 32 +/- 1.1 weeks) had been assigned to the placebo group and 34 (birth weight = 1890 +/- 530 gm; gestation = 32 +/- 2.5 weeks) to surfactant treatment. The infants were examined at 3 to 6 months of age (n = 45) and at 9 to 12 months of age (n = 36). There were no significant differences between the two groups in predisposing clinical conditions that would lead to chronic lung disease. The infants had similar patterns of growth, respiratory-related illness, and need for theophylline therapy, diuretic therapy, or both. None had hypoxemia by pulse oximetry. Mean (+/- SEM) values for pulmonary mechanics and energetics in surfactant-treated infants were significantly (p < 0.01) lower for total pulmonary resistance in late infancy (57.7 +/- 11.7 vs 35.3 +/- 4.6 cm H2O/L per second). Lower values (mean +/- SEM) of resistive work of breathing were also measured in the surfactant-treated group (60.7 +/- 12.0 vs 38.2 +/- 3.6 gm-cm/kg per breath). The dynamic pulmonary compliance values were in the low-normal range for both groups, and the mean (+/- SEM) peak-to-peak esophageal pressure values were elevated (11.47 +/- 2.26 cm H2O in the placebo group; 9.24 +/- 0.69 cm H2O in the surfactant group). Forced expiratory flow measurements in late infancy demonstrated significant (p < 0.01) improvement in expiratory reserves and reduced evidence of airflow obstruction in the surfactant-treated infants (peak flow (mean +/- SEM): 287.1 +/- 69 vs 396.9 +/- 27 ml/sec; forced expiratory flow (mean +/- SEM) at functional residual capacity: 56.3 +/- 7.5 vs 83.4 +/- 19.5 ml/sec). No significant differences in pulmonary functions were noted in early infancy. These data suggest that surfactant replacement for respiratory distress syndrome may be associated with beneficial long-term effects on the resistive airflow properties of larger preterm infants.

  View details for Web of Science ID A1993KQ59200023

  View details for PubMedID 8441104

• EVALUATION OF PULMONARY FUNCTIONS DURING PRESSURE-LIMITED MANUAL VENTILATION IN PRETERM NEONATES PEDIATRIC PULMONOLOGY Reiterer, F., Sivieri, E., Abbasi, S., Bhutani, V. K. 1993; 15 (2): 117-121

  Abstract

  Manual ventilation (MAV) or handbagging is a frequent and often life-saving procedure for neonates; however, few studies allow for an objective evaluation of techniques or possible risks. We compared parameters of ventilation and pulmonary mechanics obtained during routine pressure-limited MAV to those obtained during spontaneous breathing (SPB) in the same infant at approximately the same time. We selected 20 preterm neonates in the recovery phase of respiratory distress syndrome who received periodic MAV and were capable of optimum spontaneous minute ventilation (> 300 mL/kg/min). During MAV compared to SPB we measured higher tidal volume (8.1 +/- 0.5 SE vs. 5.4 +/- 0.4 SE mL/kg, P < 0.001), lower total pulmonary compliance (0.65 +/- 0.05 vs. 1.16 +/- 0.11 SE mL/cmH2O, P < 0.001), end-inspiratory compliance, higher pulmonary resistance (121 +/- 11 vs. 61 +/- 7 SE cmH2O/L/s, P < 0.001) and higher peak inspiratory airflow (2.8 +/- 0.2 vs. 1.6 +/- 0.1 L/s, P < 0.001). Inspiratory time (Ti) was consistently longer during MAV (0.49 +/- 0.02 vs. 0.36 +/- 0.02 SE, P < 0.001) such that during MAV the difference between actual Ti and minimal effective Ti (fivefold inspiratory time constant) was larger (0.29 +/- 0.03 vs. 0.13 +/- 0.03 s, P < 0.05). Our study suggests that operator-dependent ventilatory variables such as tidal volume, inspiratory time, frequency, and airflow need to be further evaluated in order to develop standardized guidelines for the safe administration of MAV. Until then the ventilator used for brief or augmented ventilatory support is a reasonable alternative to administering MAV by inconsistent standards.

  View details for Web of Science ID A1993KN86900008

  View details for PubMedID 8474783

• RETINOPATHY OF PREMATURITY (ROP) - EFFECT OF PHYSIOLOGICAL VITAMIN-E PROPHYLAXIS SUPPLEMENTED BY PHARMACOLOGICAL RX AT DX OF SEVERE DISEASE - LONG-TERM VISUAL OUTCOME IN 1001G BW INFANTS (CA 25.6+1.7 WEEKS) 2nd World Congress of Perinatal Medicine Johnson, L., Quinn, G., Abbasi, S., Bhutani, V., Gerdes, J., Bowen, F. MONDUZZI EDITORE. 1993: 955–959

  View details for Web of Science ID A1993BZ92R00199

• LONG-TERM EFFECT OF SURFACTANT REPLACEMENT FOR PRETERM NEONATES WITH RDS AS DETERMINED AT ONE-YEAR OF AGE 2nd World Congress of Perinatal Medicine Abbasi, S., Bhutani, V. K., Gerdes, J. S. MONDUZZI EDITORE. 1993: 1091–1095

  View details for Web of Science ID A1993BZ92R00226

• ALPHA-ADRENERGIC BRONCHOPROVOCATION IN NEONATES WITH BRONCHOPULMONARY DYSPLASIA JOURNAL OF PEDIATRICS MIRMANESH, S. J., Abbasi, S., Bhutani, V. K. 1992; 121 (4): 622-625

  Abstract

  Ophthalmic administration of phenylephrine caused decreased pulmonary compliance, tidal volume, and peak airflow values in infants with bronchopulmonary dysplasia but not in control infants. The alpha-adrenergic effects of phenylephrine may aggravate the bronchospastic component of bronchopulmonary dysplasia.

  View details for Web of Science ID A1992JR92000024

  View details for PubMedID 1328578

• ADAPTIVE-CONTROL OF INSPIRED OXYGEN DELIVERY TO THE NEONATE PEDIATRIC PULMONOLOGY Bhutani, V. K., TAUBE, J. C., Antunes, M. J., DELIVORIAPAPADOPOULOS, M. 1992; 14 (2): 110-117

  Abstract

  Adaptive adjustment of inspired oxygen (FIO2), based on a desired percent arterial hemoglobin saturation (SO2) was achieved by on-line bedside control of the oxygen concentration delivered to the neonate. Fourteen infants with bronchopulmonary dysplasia (BW, 860 +/- 80 g; GA, 26 +/- 1 weeks; study age, 41 +/- 8 days) receiving oxygen-air mixtures by hood were studied. The desired range of SO2 from 92 to 96% with a target value of 95% was determined by pulse oximetry and maintained with adjustment of FIO2 using three modes: 1) standard neonatal intensive care protocol with oxygen delivery evaluated at 20 minutes intervals; 2) bedside manual control with FIO2 manipulation every 2 to 5 minutes; and 3) adaptive control with on-line adjustment of FIO2 according to a specifically designed adaptive program. Each study period was of 40 minute duration. SO2 values within a steady 94 to 96% range was achieved for 54% of the time with standard protocol, compared to 69% (P less than 0.01) with bedside manual control and 81% (P less than 0.01) with adaptive control. In addition, fluctuations in SO2 values and overshoots were less apparent with adaptive control of oxygen delivery. These data describe adaptive FIO2 control as an efficient alternative technique for achieving a stable desired range of oxygenation in neonates.

  View details for Web of Science ID A1992JP73000008

  View details for PubMedID 1437348

• LONG-TERM PULMONARY CONSEQUENCES IN SURVIVORS WITH BRONCHOPULMONARY DYSPLASIA CLINICS IN PERINATOLOGY Bhutani, V. K., Abbasi, S. 1992; 19 (3): 649-671

  Abstract

  The clinical and pulmonary function test evidence of abnormal airway function in infants with BPD is now well established. Studies have shown persistence of airway obstruction into childhood and evidence of residual dysfunction into adulthood. Furthermore, preterm neonates who have been mechanically ventilated but do not meet any of the BPD definitions also have residual pulmonary dysfunction during infancy. As an increasing number of very low birth weight infants survive in the surfactant era, care must be taken to note that their airways are likely to be extremely compliant and thereby exceedingly susceptible to airway barotrauma in the neonatal period. The long-term consequences of airway injury could lead to residual abnormal airway function during infancy. It is hoped that barotrauma can be minimized substantially with a reduction in both the magnitude and duration of ventilatory support following surfactant therapy. With the advent of user-friendly commercial pulmonary function testing equipment, most neonatal follow-up services should include a comprehensive pulmonary follow-up ancillary to the existing neurodevelopmental follow-up services and may thereby reduce the severity of respiratory morbidities and the need for hospital readmissions.

  View details for Web of Science ID A1992LA27000010

  View details for PubMedID 1526076

• PULMONARY MECHANICS AND ENERGETICS IN PRETERM INFANTS WHO HAD RESPIRATORY-DISTRESS SYNDROME TREATED WITH SYNTHETIC SURFACTANT SYMP ON THE SYNTHETIC SURFACTANT EXOSURF NEONATAL ( COLFOSCERIL PALMITATE CETYL ALCOHOL AND TYLOXAPOL ) Bhutani, V. K., Abbasi, S., Long, W. A., Gerdes, J. S. MOSBY-YEAR BOOK INC. 1992: S18–S24

  Abstract

  Pulmonary mechanics and energetics were determined in 32 neonates with respiratory distress syndrome, who were randomly assigned to receive treatment with an exogenous synthetic surfactant, Exosurf Neonatal, or air placebo. Pulmonary mechanics were measured before and 2 hours after surfactant (n = 13) or air placebo (n = 19) treatment, then longitudinally at 24, 48, and 72 hours after treatment, and again at 7, 14, and 28 days of age. There were no significant differences in the values for pulmonary mechanics or energetics 2 hours after the first dose of surfactant. Improvement in pulmonary mechanics was apparent 24 hours after surfactant treatment, when dynamic compliance was 36% greater than in the placebo group (p less than 0.03). Lung compliance values were also higher in surfactant-treated infants 48 and 72 hours after treatment, with a maximal increase of 64% at 7 days of age (p less than 0.03). Surfactant treatment also caused a significant decrease in total pulmonary resistance at 48 and 72 hours after initial treatment and at 14 days of age (p less than 0.04). Similarly, a decrease in flow-resistive work of breathing was demonstrated 24, 48, and 72 hours after surfactant treatment. At 28 days of age, pulmonary mechanics were not different in the two groups. We conclude that beneficial effects of surfactant on pulmonary mechanics were not apparent 2 hours after dosing but were evident 24 hours after dosing and persisted for the first 7 to 14 days of life.

  View details for Web of Science ID A1992HD14200004

  View details for PubMedID 1735846

• PULMONARY MECHANICS IN PRETERM NEONATES WITH RESPIRATORY-FAILURE TREATED WITH HIGH-FREQUENCY OSCILLATORY VENTILATION COMPARED WITH CONVENTIONAL MECHANICAL VENTILATION PEDIATRICS Abbasi, S., Bhutani, V. K., Spitzer, A. R., Fox, W. W. 1991; 87 (4): 487-493

  Abstract

  Pulmonary mechanics were measured in 43 preterm neonates (mean +/- SD values of birth weight 1.2 +/- 0.3 kg, gestational age 30 +/- 2 weeks) with respiratory failure who were concurrently randomly assigned to receive conventional mechanical ventilation (n = 22) or high-frequency ventilation (n = 21). The incidence of bronchopulmonary dysplasia was comparable in the two groups (high-frequency ventilation 57%, conventional ventilation 50%). Pulmonary functions were determined at 0.5, 1.0, 2.0, and 4.0 weeks postnatal ages. Data were collected while subjects were in a nonsedated state during spontaneous breathing. These sequential data show similar patterns of change in pulmonary mechanics during high-frequency ventilation and conventional mechanical ventilation irrespective of gestational age, birth weight stratification, or bronchopulmonary dysplasia. There was no significant difference in the pulmonary functions with either mode of ventilation during the acute phase (less than or equal to 4 weeks) of respiratory disease. When evaluated by the clinical diagnosis of bronchopulmonary dysplasia, the pulmonary data suggested a less severe dysfunction in the high-frequency oscillatory ventilation-treated bronchopulmonary dysplasia group compared with the conventional mechanical ventilation-treated group. These results indicate that high-frequency oscillatory ventilation in preterm neonates does not reduce the risk of acute lung injury; however, the magnitude of the pulmonary dysfunction in the first 2 weeks of life merits a reevaluation.

  View details for Web of Science ID A1991FF72700010

  View details for PubMedID 2011425

• CLOSURE OF THE DUCTUS-ARTERIOSUS WITH INDOMETHACIN IN VENTILATED NEONATES WITH RESPIRATORY-DISTRESS SYNDROME - EFFECTS ON PULMONARY COMPLIANCE AND VENTILATION AMERICAN REVIEW OF RESPIRATORY DISEASE Stefano, J. L., Abbasi, S., Pearlman, S. A., Spear, M. L., ESTERLY, K. L., Bhutani, V. K. 1991; 143 (2): 236-239

  Abstract

  The reported effects of indomethacin on pulmonary compliance are variable depending upon the patient population and on the degree to which indomethacin resulted in successful ductal closure. Eleven fluid-restricted, furosemide-treated premature infants being mechanically ventilated for respiratory distress syndrome (RDS) who also had a significant patent ductus arteriosus (PDA) had pulmonary function testing performed before and after successful closure of the PDA. The diagnosis of a significant PDA was made by clinical and echocardiographic criteria. Indomethacin was administered at a dosage of 0.2 mg/kg/dose every 12 to 18 h for 1 to 3 doses. To control for the 48-h time interval to achieve ductal closure, nine premature infants being ventilated for RDS but who did not have a significant PDA also had pulmonary function evaluations performed before and after the 48 h. Also, to control for the independent effect of fluid restriction and diuretic therapy on pulmonary compliance, eight such premature infants with a PDA had pulmonary function evaluations performed at a 48-h interval. Successful closure of the ductus with indomethacin was associated with an improvement in compliance and ventilation parameters in all infants in the indomethacin-treated infants. In the indomethacin-treated group, the mean percent improvements were noted in the following parameters: CLdyn, 59.2%; CLI, 78.3%; CLE, 63.3%; VT, 63.3%; VE, 54.6%. There were no significant changes in the pulmonary functions in the 48-h RDS or the 48-h PDA fluid-restricted, furosemide-treated control groups. In conclusion, successful closure of the ductus with indomethacin causes a significant improvement in compliance and ventilation parameters in infants being mechanically ventilated for RDS.

  View details for Web of Science ID A1991EX24500006

  View details for PubMedID 1990934

• A RANDOMIZED PLACEBO-CONTROLLED STUDY TO EVALUATE THE EFFECTS OF ORAL ALBUTEROL ON PULMONARY MECHANICS IN VENTILATOR-DEPENDENT INFANTS AT RISK OF DEVELOPING BPD PEDIATRIC PULMONOLOGY Stefano, J. L., Bhutani, V. K., Fox, W. W. 1991; 10 (3): 183-190

  Abstract

  Albuterol is a specific beta-2 agonist that has been reported to be effective in treating infants and children with bronchospastic pulmonary disease. The use of oral albuterol has not been investigated in patients with bronchopulmonary dysplasia (BPD). Thirty premature infants were randomized to receive oral albuterol (0.15 mg/kg/dose q8h) or a volume- and color-matched placebo (D5/W). Pulmonary functions were evaluated at baseline and at 48 and 96 hours after entry to the study. The study was also designed for crossover from placebo to albuterol or albuterol to caffeine in the event that the infant's total pulmonary resistance did not improve at the time of the 48 hour pulmonary function evaluation. Heart rate and respiratory rate showed a statistically significant but clinically unimportant increase in the albuterol-treated infants. There were no significant differences noted in systolic or diastolic blood pressure. Percent improvement in the pulmonary function indices were calculated from baseline to 48 hours and from baseline to 96 hours for the placebo and albuterol-treated groups. The results indicate that at 48 hours there were statistically significant improvements in total resistance (14.5%), inspiratory resistance (10.8%), and expiratory resistance (12.9%) in the albuterol-treated infants as compared to the spontaneous deterioration of the same values by 25%, 81%, and 11%, respectively, in the placebo-treated infants. In conclusion, oral albuterol therapy of 48 hours duration improved pulmonary resistance without major cardiovascular side effects in ventilator-dependent premature infants.

  View details for Web of Science ID A1991FL38700006

  View details for PubMedID 1852516

• AUTOMATIC-CONTROL OF NEONATAL FRACTIONAL INSPIRED OXYGEN 1991 ANNUAL INTERNATIONAL CONF OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOC Taube, J., Bhutani, V. I E E E. 1991: 2176–2177

  View details for Web of Science ID A1991BV15B01080

• ROLE OF FUROSEMIDE THERAPY AFTER BOOSTER-PACKED ERYTHROCYTE TRANSFUSIONS IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA JOURNAL OF PEDIATRICS Stefano, J. L., Bhutani, V. K. 1990; 117 (6): 965-968

  View details for Web of Science ID A1990EM11600027

  View details for PubMedID 2246701

• MATERNAL AND FETAL PLASMA VITAMIN-E TO TOTAL LIPID RATIO AND FETAL RBC ANTIOXIDANT FUNCTION DURING GESTATIONAL DEVELOPMENT JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION Abbasi, S., LUDOMIRSKI, A., Bhutani, V. K., Weiner, S., Johnson, L. 1990; 9 (4): 314-319

  Abstract

  Placental transfer of vitamin E was investigated from 19 to 35 weeks of gestation by analysis of fetal and maternal blood samples for total tocopherol, total lipids, and fetal red blood cell antioxidant reserves. Fifty-two fetal blood samples were obtained under ultrasonographic guide by percutaneous umbilical blood sampling. Thirteen were from fetuses with gestational age less than or equal to 22 weeks (x serum vitamin E = 0.4 +/- 0.14 mg/dl), 12 were from fetuses at 23-27 weeks gestation (x serum vitamin E = 0.4 +/- 0.21 mg/dl), and 27 were from fetuses with gestational age 28-38 weeks (x serum level = 0.37 +/- 0.18). Total lipid levels ranged from 140 to 216 mg/dl. Maternal plasma vitamin E concentrations correlated significantly with concurrent values in the fetus. There were no significant differences in serum vitamin E levels or vitamin E to total lipid ratio in samples from early, mid, or late gestation in either the mother or fetus. Red blood cell antioxidant reserve on samples from 18 fetuses were grossly abnormal by three different functional assays. On the basis of these data, placental transfer of vitamin E appears to be relatively constant through advancing gestation. Red blood cell antioxidant reserve is uniformly low.

  View details for Web of Science ID A1990DQ46000006

  View details for PubMedID 2212388

• SYSTEMIC COMPLICATIONS ASSOCIATED WITH RETINAL CRYOABLATION FOR RETINOPATHY OF PREMATURITY 1989 ANNUAL MEETING OF THE AMERICAN ACAD OF OPHTHALMOLOGY Brown, G. C., TASMAN, W. S., Naidoff, M., Schaffer, D. B., Quinn, G., Bhutani, V. K. LIPPINCOTT-RAVEN PUBL. 1990: 855–58

  Abstract

  Eighty infants with proliferative retinopathy of prematurity (ROP) were treated with peripheral retinal cryoablation. Among the serious systemic complications encountered were three instances of respiratory arrest and one of cardiorespiratory arrest. Recommendations that may help prevent these adverse systemic effects in premature infants include: (1) avoidance of excess subconjunctival anesthetic doses, (2) preoperative administration of systemic atropine to minimize the oculocardiac reflex, (3) consideration of an analgesic agent to decrease the pain and exhaustion, and (4) cardiorespiratory monitoring in a hospital setting, with an intravenous line in place, at the time of treatment.

  View details for Web of Science ID A1990DN66300013

  View details for PubMedID 2381697

• EFFECT OF SINGLE DOSE SURFACTANT ON PULMONARY-FUNCTION CRITICAL CARE MEDICINE Bhat, R., Dziedzic, K., Bhutani, V. K., Vidyasagar, D. 1990; 18 (6): 590-595

  Abstract

  Sequential changes in pulmonary mechanics in response to single dose exogenous surfactant instillation were studied in 15 preterm neonates who had hyaline membrane disease (HMD). The infants were part of a larger double-blind national study. Birth weight ranged from 0.88 to 1.55 kg, and gestational age was between 27 to 32 wk. There were six infants in the surfactant group and nine in the placebo group. Pulmonary mechanics were studied before and at 2, 24, 60, and 96 h after surfactant or sham instillation using a pneumotachometer and an esophageal balloon catheter. The variables studied were dynamic compliance (Cdyn), pulmonary resistance, work of breathing, tidal volume, and minute ventilation. Infants in the surfactant group showed an immediate and significant (p less than .05) improvement in gas exchange ratio, decreased mean airway pressure (9.7 +/- 0.9 to 7.9 +/- 0.4 cm H2O) and airway resistance (133 +/- 6.3 to 92 +/- 14.9 cm H2O/L.sec) (p less than .05). Changes in Cdyn were noted only at 24 h after surfactant instillation. In the control group, gradual improvement occurred after the initial deterioration. The findings suggest that the immediate improvement in oxygenation after surfactant instillation is the result of factors other than changes in lung compliance, such as improved ventilation/perfusion and better capillary stability with decreased leakage of fluid into alveoli.

  View details for Web of Science ID A1990DH23600002

  View details for PubMedID 2111754

• EMERGENCE OF THE BRAIN-STEM AUDITORY EVOKED-POTENTIAL IN THE PREMATURE LAMB ELECTROENCEPHALOGRAPHY AND CLINICAL NEUROPHYSIOLOGY Wolfson, M. R., DURRANT, J. D., TRAN, N. N., Bhutani, V. K., Shaffer, T. H. 1990; 75 (3): 242-250

  Abstract

  Brain-stem auditory evoked potentials (BAEPs) were elicited by bone conducted stimuli in the very immature lamb following delivery, wherein liquid ventilation techniques were utilized to control cardiopulmonary and acid-base conditions, independent of umbilical-placenta support. Unlike previous studies of the in utero fetal lamb in which the BAEP could not be elicited by earphone delivered stimuli until 117 days gestation, our results demonstrate that the BAEP emerges at least as early as 106 days gestation in the lamb and consists of a full complement of readily discernible and reproducible wave forms. In addition, the results demonstrate substantial maturation of the BAEP from 106 to 122 days gestation during which time there is a significant decrease in absolute and interpeak latencies with an increase in developmental age. It is concluded that the ability to elicit the BAEP utilizing bone conduction at this early stage of gestation is related to improved stimuli delivery. Furthermore, this study demonstrates the feasibility and flexibility afforded by liquid ventilation and bone conduction BAEP techniques to study brain-stem function at particularly vulnerable stages of development.

  View details for Web of Science ID A1990CT88700013

  View details for PubMedID 1689647

• PULMONARY MECHANICS AND ENERGETICS OF NORMAL, NONVENTILATED LOW-BIRTH-WEIGHT INFANTS PEDIATRIC PULMONOLOGY Abbasi, S., Bhutani, V. K. 1990; 8 (2): 89-95

  Abstract

  Pulmonary mechanics and energetics were determined in 33 healthy low birthweight infants (less than 1,500 g, 28-34 weeks gestation) who had never received ventilatory support. Tidal volume, dynamic pulmonary compliance, pulmonary resistance, pressure-volume relationships, and tidal flow-volume measurements were obtained by pneumotachography and the esophageal balloon technique. Standardized data collection and software data analysis by least mean squares technique yielded data at 0.5, 1, 2, and 4 weeks postnatally, as a function of gestational age (less than 30, 30-32, and greater than 32 weeks gestation). Relatively stable values were obtained for tidal volume and minute ventilation (normalized for body weight); these were associated with values of peak-to-peak esophageal pressure significantly (P less than 0.001) increasing from 4.4 +/- 0.3 SEM cmH2O at 0.5 weeks to 8.1 +/- 0.8 SEM cmH2O at 4 weeks of age. Dynamic pulmonary compliance ranged from 2.0 to 2.4 mL/cmH2O in the first 4 weeks of life. When normalized for weight, compliance decreased with age, which may suggest a slower pulmonary maturation as compared to increase of body weight. Mean pulmonary resistance decreased from 62.9 cmH2O/L/s at less than 30 weeks gestation to 32.5 cmH2O/L/s at greater than 32 weeks gestation, 0.5 weeks postnatally. Pulmonary resistance peaked at 2 weeks postnatally (P less than 0.05), at all gestational ages, then decreased. Changes in pulmonary mechanics resulted in increasing resistive work of breathing. Our findings suggest a postnatal retardation of pulmonary and airway growth, relative to gestation maturation. These data can provide an objective base of comparison for data in sick, low birthweight neonates.

  View details for Web of Science ID A1990CR92000004

  View details for PubMedID 2352789

• PHARMACOKINETICS OF INTRAVENOUS VITAMIN-E IN PRETERM INFANTS ANNALS OF THE NEW YORK ACADEMY OF SCIENCES Abbasi, S., Jensen, B. K., Gerdes, J. S., Bhutani, V. K., Johnson, L. 1989; 570: 345-351

  View details for Web of Science ID A1989CV07100031

  View details for PubMedID 2629603

• STRUCTURAL-CHANGES IN THE TRACHEAE OF PRETERM LAMBS INDUCED BY VENTILATION PEDIATRIC RESEARCH Deoras, K. S., Wolfson, M. R., Bhutani, V. K., Shaffer, T. H. 1989; 26 (5): 434-437

  Abstract

  Compliant immature airways sustain significant deformation following positive pressure ventilation. To evaluate the structural changes induced by in vivo positive pressure ventilation, tracheae of preterm lambs (107-116 d gestational age) were studied histologically. Nonventilated (group I: n = 7) and ventilated (group II: n = 7) tracheal segments were excised and studied by histologic and morphometric techniques. Computerized image analysis was used to measure dimensions of tracheal wall components and of the tracheal section. The circumference, diameter, and cross-sectional area of the section as well as the length of the trachealis muscle were significantly greater; although the thickness of the muscle and cartilage were seen to be significantly lower in group II sections compared to group I sections. Also, in comparison to group I, in group II sections there was lesser overlap of the posterior free ends of tracheal cartilage and the epithelial layer was flattened and focally abraded. Our findings demonstrate structural changes in the airway of preterm animals and characterize alterations in the geometric arrangement of muscle and cartilage after PPV. These results suggest possible structural mechanisms for the functional changes seen during and subsequent to mechanical ventilation.

  View details for Web of Science ID A1989AX12100009

  View details for PubMedID 2682500

• AIRWAY REACTIVITY AS DETERMINED BY A COLD AIR CHALLENGE IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA JOURNAL OF PEDIATRICS Greenspan, J. S., DEGIULIO, P. A., Bhutani, V. K. 1989; 114 (3): 452-454

  View details for Web of Science ID A1989T561100022

  View details for PubMedID 2921689

• ETHICAL DILEMMAS OF NEONATAL PERINATAL SURGERY CLINICS IN PERINATOLOGY Rostain, A. L., Bhutani, V. K. 1989; 16 (1): 275-302

  Abstract

  This article reviews historical developments and ethical problems, including quality of life determinations, surrogate decision making, informed consent, and medical uncertainty. Procedural aspects of ethical decision making and a framework for resolving ethical dilemmas are described, and case examples are provided.

  View details for Web of Science ID A1989T887700019

  View details for PubMedID 2656064

• INVIVO MECHANICAL-PROPERTIES OF THE DEVELOPING AIRWAY PEDIATRIC RESEARCH Shaffer, T. H., Bhutani, V. K., Wolfson, M. R., Penn, R. B., TRAN, N. N. 1989; 25 (2): 143-146

  Abstract

  The inherent mechanical characteristics of the airways are determined in part by their elastic and viscoelastic properties. As compliant structures during early development, the airways are susceptible to significant distention and collapse, depending on the proportionality between airway volume and transmural pressure. To characterize the age-related changes in airway mechanical properties, the elastic and viscoelastic behavior of in vivo tracheal segments were evaluated in preterm and newborn lambs over a wide range of developmental age (108 to 154 days postconceptional age). Tracheal pressure-vol relationships and concomitant airway compliance measurements were used to determine elastic behavior. Calculations of the tracheal relaxation time constant on the same tracheal segments were used to evaluate airway viscoelastic behavior. Data demonstrated a significant (p less than 0.01) correlation with developmental age. With increasing age, the airways were found to be less compliant, and the tracheal relaxation time constant was observed to decrease. The difference in elastic properties of the trachea, in vivo compared to in vitro, suggest that neural-humoral and surrounding connective tissue factors may affect the elasticity of the developing airway. Although the modulating effects of smooth muscle tone and supporting connective tissue assist in the control of airway dimension and resistance to airflow in the intact airway, the age-related differences in the elastic properties may be a factor that predisposes the more immature airway to positive pressure-induced damage.

  View details for Web of Science ID A1989R964600007

  View details for PubMedID 2919128

• PHARMACOKINETICS OF INTRAVENOUS VITAMIN-E IN PRETERM INFANTS CONF ON VITAMIN E : BIOCHEMISTRY AND HEALTH IMPLICATIONS Abbasi, S., Jensen, B. K., Gerdes, J. S., Bhutani, V. K., Johnson, L. NEW YORK ACAD SCIENCES. 1989: 345–351

  View details for Web of Science ID A1989BQ32R00031

• CHANGES IN PULMONARY MECHANICS FOLLOWING CAFFEINE ADMINISTRATION IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA PEDIATRIC PULMONOLOGY Davis, J. M., Bhutani, V. K., Stefano, J. L., Fox, W. W., Spitzer, A. R. 1989; 6 (1): 49-52

  Abstract

  The effects of caffeine upon pulmonary mechanics were measured in 16 infants with bronchopulmonary dysplasia (BPD). Pulmonary function tests were performed immediately prior to and 1 hour following a dose of 10 mg/kg of caffeine. A 37% increase in minute ventilation (mean +/- SEM; 436.6 +/- 26.3 to 580.8 +/- 30.7 ml/min/kg) was seen with caffeine administration (P less than 0.001), primarily from a 42% increase in tidal volume (6.2 +/- 0.4 to 8.5 +/- 0.4 ml/kg) (P less than 0.001). Total lung resistance decreased by 20% (134.6 + 24.2 to 105.3 +/- 20.1 cmH2O/L/sec) (P = 0.01), and total pulmonary compliance improved by 47% (0.642 +/- 0.104 to 0.908 +/- 0.190 ml/cmH2O/kg) (P less than 0.01). In five matched control infants with BPD, no effects of placebo upon pulmonary mechanics were detected. Since caffeine has a wide therapeutic index with few side effects, it may be an effective adjunct in the treatment of infants with BPD.

  View details for Web of Science ID A1989R964400009

  View details for PubMedID 2704583

• Care of the neonate with erythroblastosis fetalis. Journal of obstetric, gynecologic, and neonatal nursing : JOGNN / NAACOG Dunn, P. A., Bhutani, V., Weiner, S., LUDOMIRSKI, A. 1988; 17 (6): 382-386

  Abstract

  Erythroblastosis fetalis, hemolytic disease of the newborn, occurs when an isoimmunized mother produces antibodies that cross the placenta and cause hemolysis of fetal red blood cells. This hemolysis can be accompanied by severe anemia, ascites, pleural and pericardial effusions, congestive heart failure, and neurological damage with resultant perinatal mortality. Rh isoimmunization in pregnancy still occurs in spite of the advent of Rh immune globulin. This article describes the complex management and nursing implications associated with caring for the neonate with erythroblastosis fetalis.

  View details for PubMedID 3148028

• SEQUENTIAL-CHANGES IN PULMONARY MECHANICS IN THE VERY LOW BIRTH-WEIGHT (LESS-THAN-OR-EQUAL-TO-1000 GRAMS) INFANT JOURNAL OF PEDIATRICS Greenspan, J. S., Abbasi, S., Bhutani, V. K. 1988; 113 (4): 732-737

  Abstract

  Pulmonary function tests were performed on 36 very low birth weight neonates (birth weight less than or equal to 1000 gm, gestational age less than or equal to 30 weeks, appropriate size for gestational age) from birth until 8 weeks of age. Tidal airflow was measured by means of a pneumotachygraph, and the transpulmonary pressure changes were determined by the esophageal balloon technique. Pulmonary mechanics and energetics were calculated by the least mean square analysis technique at 1/2, 1, 2, 4, 6, and 8 weeks of age. Compliance was lowest at 2 weeks and subsequently increased linearly (at approximately 0.1 ml/cm H2O/wk). When compliance was based on body weight, however, no change was noted with advancing age. Resistance was greatest at 2 weeks and subsequently decreased. The infants maintained a normal minute ventilation with a slightly increased resistive work of breathing. Despite our ability to wean 53% of the infants to room air by 8 weeks, none of them had pulmonary mechanics considered normal for term infants. Infants with and without bronchopulmonary dysplasia (BPD) had similar patterns of pulmonary development. At 8 weeks of age, the pulmonary mechanics in infants with BPD who had been weaned to room air were comparable to those in infants without BPD, an observation that calls into question the rationale for defining BPD at 4 weeks in this population. These data suggest that such pulmonary function profiles provide evidence of persistent lung parenchymal abnormalities.

  View details for Web of Science ID A1988Q533800022

  View details for PubMedID 3171798

• A NEW EXPERIMENTAL APPROACH FOR THE STUDY OF CARDIOPULMONARY PHYSIOLOGY DURING EARLY DEVELOPMENT JOURNAL OF APPLIED PHYSIOLOGY Wolfson, M. R., Tran, N., Bhutani, V. K., Shaffer, T. H. 1988; 65 (3): 1436-1443

  Abstract

  In this report, an experimental approach and newly designed apparatus for liquid ventilation of preterm animals are described. Findings of age-related changes in cardiopulmonary function of this animal preparation are presented. Thirty-one lambs, 102-137 days gestation (term 147 +/- 3 days), were studied. The carotid artery, jugular vein, and trachea of the exteriorized fetus were cannulated under local anesthesia. Immediately after cesarean section delivery, ventilation commenced; warmed (39 degrees C) and oxygenated (PIO2 greater than 500 Torr) liquid fluorocarbon (RIMAR 101) was delivered to the lung by a mechanically assisted liquid ventilation system. Skeletal muscle paralysis, low-dose exogenous buffering, and thermal support were maintained during the 3-h experiment. Pulmonary gas exchange, acid-base status, and cardiopulmonary and metabolic function were assessed. By utilizing these techniques, effective arterial oxygenation, CO2 elimination, acid-base status, and cardiovascular stability were supported independent of gestational age. The results demonstrate a developmental increase in specific lung compliance and mean arterial pressure and decrease in heart rate and systemic O2 consumption per kilogram with advancing gestational age. These findings demonstrate that liquid ventilation negates the dependency of effective pulmonary gas exchange on surfactant development, thereby extending the limits of viability of the immature extrauterine lamb. As such this new experimental approach is useful for the study of physiological development over an age range previously limited to fetal animal preparations and, therefore, may provide insight regarding adaptation of the premature to the extrauterine environment.

  View details for Web of Science ID A1988Q092100062

  View details for PubMedID 3182511

• CHANGES IN PULMONARY MECHANICS AFTER THE ADMINISTRATION OF SURFACTANT TO INFANTS WITH RESPIRATORY-DISTRESS SYNDROME NEW ENGLAND JOURNAL OF MEDICINE Davis, J. M., VENESSMEEHAN, K., Notter, R. H., Bhutani, V. K., Kendig, J. W., Shapiro, D. L. 1988; 319 (8): 476-479

  Abstract

  We assessed pulmonary mechanics in 35 premature infants with respiratory distress syndrome just before and one hour after the administration of 90 mg of surfactant to each infant. Transpulmonary pressure was measured between the airway opening and an esophageal balloon with use of a differential transducer, and flow rates were measured by a pneumotachometer. Values for pulmonary mechanics were then calculated by microcomputer processing. The administration of surfactant produced a large decrease (56 percent) in the mean (+/- SEM) ratio of alveolar to arterial oxygen, from 7.1 +/- 0.5 to 3.1 +/- 0.2 (P less than 0.0001)--a change that indicates improvement in gas exchange. Associated changes in pulmonary mechanics were not demonstrable when 10 of the infants were studied during continuous mechanical ventilation. However, in the 25 infants examined during spontaneous breathing with continuous positive airway pressures (identical airway pressures before and after treatment), large and consistent improvements in pulmonary mechanics were found after the administration of surfactant. Tidal volume increased by 32 percent (P less than 0.03), minute ventilation by 38 percent (P less than 0.02), dynamic compliance by 29 percent (P less than 0.004), and inspiratory flow rates by 54 percent (P less than 0.01). We conclude that significant improvement in pulmonary mechanics results from surfactant-replacement therapy for respiratory distress syndrome, but that these mechanical changes are apparent only during spontaneous respiration and can be masked if measurements are made during mechanical ventilation.

  View details for Web of Science ID A1988P821000004

  View details for PubMedID 3405254

• TRACHEO-BRONCHIAL ABNORMALITIES COMPLICATING BRONCHOPULMONARY DYSPLASIA JOURNAL OF PEDIATRICS Bhutani, V. K. 1988; 112 (5): 843-844

  View details for Web of Science ID A1988N308700039

  View details for PubMedID 3361400

• CONTINUOUS SKELETAL-MUSCLE PARALYSIS - EFFECT ON NEONATAL PULMONARY MECHANICS PEDIATRICS Bhutani, V. K., Abbasi, S., Sivieri, E. M. 1988; 81 (3): 419-422

  Abstract

  Pancuronium bromide (Pavulon) is used to induce skeletal muscle paralysis in preterm infants, presumably for effective ventilatory support during acute respiratory failure. Twelve infants with respiratory failure were evaluated for sequential changes in pulmonary mechanics during continuous pancuronium administration (0.1 mg/kg every two to three hours) for more than 48 hours. The study weight of the neonates ranged from 980 to 2,950 g, and the postconceptional age ranged from 27 to 41 weeks. Pulmonary compliance, resistance, and resistive work of breathing were determined, using least mean square analysis technique, daily for three days and after discontinuation of pancuronium (even though there was no clinical improvement in ventilatory management). The dynamic pulmonary compliance decreased from 0.38 +/- 0.05 to 0.30 +/- 0.04 mL/cm H2O/kg (mean +/- SE) (P less than .05) and the total pulmonary resistance increased 51% from 115.6 +/- 21.3 to 174.9 +/- 27.3 cm H2O/L/s (P less than .005) during prolonged skeletal muscle paralysis. Upon discontinuation of pancuronium, the dynamic pulmonary compliance increased 43% to 0.43 +/- 0.4 mL/cm H2O/kg (P less than .05) and the total pulmonary resistance decreased by 41% (P less than .005). These data question the advisability of prolonged skeletal muscle paralysis in neonates and suggest the need for further detailed evaluation of the effects of prolonged paralysis on neonatal pulmonary mechanics.

  View details for Web of Science ID A1988M438800015

  View details for PubMedID 3344185

• EVALUATION OF NEONATAL PULMONARY MECHANICS AND ENERGETICS - A 2-FACTOR LEAST MEAN-SQUARE ANALYSIS PEDIATRIC PULMONOLOGY Bhutani, V. K., Sivieri, E. M., Abbasi, S., Shaffer, T. H. 1988; 4 (3): 150-158

  Abstract

  Pulmonary mechanics, using a two factor least mean square analysis technique, were determined in 22 preterm neonates with respiratory failure. The respiratory system is modelled as a linear mechanical system. Concurrent signals of airflow and transpulmonary pressure were utilized to calculate values of dynamic lung compliance and pulmonary resistances; these determinations were made over the entire tidal volume range. In addition, values of resistive work of breathing, pulmonary time constants, scalar records of sequential breaths, pressure-volume and flow-volume relationships were available for data review and interpretation. The mean +/- SEM value of tidal volume was 7.4 +/- 0.6 ml/kg; dynamic lung compliance was 0.44 +/- 0.04 ml/cmH2O/kg; and the pulmonary resistance of the whole breath was 106 +/- 9.1 cmH2O/liter/s. The resistive work of breathing (hysteresis) was 41.8 +/- 5.9 gm.cm/kg. In correlating the measured values of pressure and flow to those predicted by the model, the mean value of the correlation coefficient for the least mean square analysis for all 22 studies was 0.995 +/- 0.001; the standard error of estimate of the predicted pressure was less than 4.4% of the range of pressures measured. Thereby, the model was considered to be appropriate for the neonatal respiratory system. In addition to the traditional procedures of evaluating the respiratory status of a sick neonate, bedside analysis of pulmonary mechanics provide graphical information, and quantitative data which should be useful in day-to-day pulmonary management.

  View details for Web of Science ID A1988N147300004

  View details for PubMedID 3374983

• ENERGETICS AND MECHANICS OF NUTRITIVE SUCKING IN THE PRETERM AND TERM NEONATE JOURNAL OF PEDIATRICS Jain, L., Sivieri, E., Abbasi, S., Bhutani, V. K. 1987; 111 (6): 894-898

  Abstract

  Energetics and mechanics of sucking in preterm and term neonates were determined by simultaneous records of intraoral pressure, flow, volume, and work of individual sucks. Nine term infants (mean postconceptional age: 38.6 +/- 0.7 SD weeks; mean postnatal age: 18.4 +/- 6.1 SD days) and nine preterm infants (mean postconceptional age: 35.2 +/- 0.7 SD weeks; mean postnatal age: 21.9 +/- 5.4 SD days) were studied under identical feeding conditions. Preterm infants generated significantly lower peak pressure (mean values of 48.5 cm H2O compared with 65.5 cm H2O in term infants; P less than 0.01), and the volume ingested per such was generally less than or equal to 0.5 mL. Term infants demonstrated a higher frequency of sucking, a well-defined suck-pause pattern, and a higher minute consumption of formula. Energy and caloric expenditure estimations revealed significantly lower work performed by preterm infants for isovolumic feeds (1190 g/cm/dL in preterm infants compared with 2030 g.cm/dL formula ingested in term infants; P less than 0.01). Furthermore, work performed by term infants was disproportionately higher for volumes greater than or equal to 0.5 mL ingested. This study indicates that preterm infants expend less energy than term infants to suck the same volume of feed and also describes an objective technique to evaluate nutritive sucking during growth and development.

  View details for Web of Science ID A1987L199300023

  View details for PubMedID 3681557

• A CHRONIC LUNG DISORDER FOLLOWING ABDOMINAL PREGNANCY AMERICAN JOURNAL OF DISEASES OF CHILDREN Bell, J. B., Gerdes, J. S., Bhutani, V. K., Wilmott, R. W. 1987; 141 (10): 1111-1113

  Abstract

  Abdominal pregnancy is a rare condition that is associated with a high infant mortality, as well as orthopedic and pulmonary deformations. This article describes the clinical and radiological courses of two infants born after abdominal pregnancies. Evidence of pulmonary hypoplasia secondary to fetal compression was present. The morbidity and mortality for infants born of abdominal pregnancies may depend on the extent of pulmonary involvement, which may relate to the length of fetal compression.

  View details for Web of Science ID A1987K198800031

  View details for PubMedID 3630998

• ULTRASONIC RATIO OF FETAL THORACIC TO ABDOMINAL CIRCUMFERENCE - AN ASSOCIATION WITH FETAL PULMONARY HYPOPLASIA AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY Johnson, A., Callan, N. A., Bhutani, V. K., Colmorgen, G. H., Weiner, S., BOLOGNESE, R. J. 1987; 157 (3): 764-769

  Abstract

  Real time ultrasound was used in pregnant women who were considered to be at risk for development of pulmonary hypoplasia (n = 26). The population consisted of women who had either premature rupture of membranes (n = 16) or oligohydramnios (n = 10). The ratio calculated by comparing the fetal thoracic circumference to abdominal circumference was obtained in all cases within 10 days of delivery. This ratio correlated strongly with neonatal outcome. Multivariate regression models of neonatal outcome were developed to analyze the relationship of gestational age at which premature membrane rupture occurred, the duration of premature rupture, date of birth, and prenatal diagnosis. The addition of the thoracic circumference to the abdominal circumference ratio increased significantly the proportion of explained variability. Application of this ratio should be considered in evaluating fetal status in oligohydramnios and in the expectant management of premature rupture of membranes.

  View details for Web of Science ID A1987K198900046

  View details for PubMedID 3307430

• USE OF CAFFEINE IN INFANTS UNRESPONSIVE TO THEOPHYLLINE IN APNEA OF PREMATURITY PEDIATRIC PULMONOLOGY Davis, J. M., Spitzer, A. R., Stefano, J. L., Bhutani, V., Fox, W. W. 1987; 3 (2): 90-93

  Abstract

  Eleven premature infants with severe apnea unresponsive to therapeutic theophylline levels were studied to determine if caffeine is an effective treatment in such cases. Apnea was documented and quantitated with thermistor-pneumocardiograms measuring heart rate, thoracic impedance, and nasal air flow. Infants with prolonged central or mixed apnea were then treated with caffeine and restudied. Caffeine reduced the total number of apneic episodes of greater than 10 sec duration by 80% (P less than 0.01) and prolonged episodes of apnea (greater than 20 sec) by 88% (P less than 0.05). These data suggest that caffeine may be effective in the management of apnea of prematurity, particularly the prolonged type, unresponsive to theophylline.

  View details for Web of Science ID A1987H125700007

  View details for PubMedID 3588062

• INTERRELATIONSHIPS OF VITAMIN-E AND ZINC-DEFICIENCY IN THE GROWING PRETERM INFANT TRACE ELEMENTS IN MEDICINE Abbasi, S., Johnson, L., Bhutani, V. K. 1987; 4 (3): 93-98

  View details for Web of Science ID A1987K167200001

• THE ROLE OF TRACHEAL SMOOTH-MUSCLE CONTRACTION ON NEONATAL TRACHEAL MECHANICS PEDIATRIC RESEARCH KOSLO, R. J., Bhutani, V. K., Shaffer, T. H. 1986; 20 (12): 1216-1220

  Abstract

  The ability of tracheal smooth muscle tone to modulate the mechanical properties of neonatal airways was evaluated in six newborn lambs. Tracheal pressure-volume relationships, isovolumic compliance, hysteresis, and the relaxation time constant of the smooth muscle were evaluated as a function of incremental cholinergic stimulation. Tracheal active tensions were also determined at the graded levels of cholinergic stimulation. Data show that a maximal cholinergic stimulation resulted in a mean developed active tension value of 14.3 +/- 2.13 SEM X 10(3) dynes/cm. The resultant 55% decrease in tracheal compliance was linearly correlated to the increase in active tension (r = 0.90, p less than 0.01). Cholinergic stimulation also resulted in a 18.4% decrease (p less than 0.02) in the relaxation time constant of the smooth muscle, and in a 82% increase (p less than 0.01) in tracheal hysteresis. This study demonstrates that both elastic and viscoelastic properties of the neonatal lamb trachea are effected by tracheal smooth muscle contraction. Since neonatal airways are more compliant than adult airways, cholinergic stimulation could conceivably enhance airway rigidity and may provide a protective mechanism against pressure-induced deformation.

  View details for Web of Science ID A1986F145800002

  View details for PubMedID 3797112

• ASPIRATION OF PACIFIERS PEDIATRICS Jain, L., Sivieri, E., Bhutani, V. K. 1986; 78 (5): 955-956

  View details for Web of Science ID A1986E633300038

  View details for PubMedID 3763314

• EFFECT OF HIGH-FREQUENCY JET VENTILATION ON PRETERM AND RABBIT TRACHEAL MECHANICS PEDIATRIC PULMONOLOGY Bhutani, V. K., Shaffer, T. H., Abbasi, S., Spitzer, A. R., Fox, W. W. 1986; 2 (6): 327-331

  Abstract

  The effect of high-frequency jet ventilation (HFJV) on both tracheal dimensions and mechanics was evaluated in preterm and term rabbit airways. Seven tracheal segments were studied at 27 days (group I) and 31 days (group II) of gestation, respectively. Tracheal dimensions and segmental pressure-volume relationships were determined before and after 60 minutes of HFJV (peak pressure 20 cm H2O; mean airway pressure 6.7 to 6.8 cm H2O at 10 Hz). Both tracheal lengths and diameters increased significantly (p less than 0.01) in each group and resulted in increased tracheal volumes: 109% in group I (p less than 0.01) and 60% in group II (p less than 0.01). The mean specific tracheal compliance decreased in group I, from 0.036 cm H2O-1 to 0.015 cm H2O-1 (p less than 0.01), and in group II from 0.029 cm H2O-1 to 0.021 cm H2O-1 (p less than 0.01). Furthermore, the collapsing transmural pressure (the pressure required for total collapse of tracheal segments) decreased significantly (p less than 0.01) in both groups. These data demonstrate significant dimensional and mechanical deformation of tracheal segments after HFJV. An increased propensity toward collapsibility is also observed following HFJV. These changes are similar to those with tracheomalacia. The influence of such deformation on tracheal gas flow during HFJV needs to be further investigated.

  View details for Web of Science ID A1986F158100002

  View details for PubMedID 3808774

• PHYSIOLOGICAL-EFFECTS OF TERBUTALINE ON PULMONARY-FUNCTION OF INFANTS WITH BRONCHOPULMONARY DYSPLASIA PEDIATRIC PULMONOLOGY SOSULSKI, R., Abbasi, S., Bhutani, V. K., Fox, W. W. 1986; 2 (5): 269-273

  Abstract

  This study defines the physiologic changes in pulmonary mechanics induced by subcutaneous terbutaline administration in ventilator-dependent infants with severe bronchopulmonary dysplasia (BPD). Eight such infants (mean +/- SEM weight = 2.56 +/- 0.32 kg, postnatal age = 13.0 +/- 3.2 weeks) were chosen for the study. Pulmonary mechanics and arterial blood gases were measured in the control state and at 30 and 60 minutes following the subcutaneous injection of 5 micrograms/kg terbutaline. There was a significant (p less than 0.001) improvement in lung compliance from baseline values at 30 minutes and at 60 minutes (38%). A significant (p less than 0.05) decrease of 23% in the average pulmonary resistance at 30 minutes and a 26% decrease at 60 minutes from control values were observed. An increase in the I/E ratio occurred in all patients at 60 minutes (p less than 0.01). In addition, clinical improvement was noted in six of eight infants. Administration of terbutaline demonstrated a significant improvement in the pulmonary mechanics of infants with severe BPD.

  View details for Web of Science ID A1986E394600002

  View details for PubMedID 3774383

• IMPROVED SURVIVAL AND SHORT-TERM OUTCOME OF INBORN MICROPREMIES CLINICAL PEDIATRICS Gerdes, J. S., Abbasi, S., Bhutani, V. K., Bowen, F. W. 1986; 25 (8): 391-394

  Abstract

  Survival and significant chronic morbidity were determined by retrospective chart review for 107 inborn "micropremies." "Micropremies" are defined as appropriate-for-gestational age neonates of less than 1,001 grams and less than or equal to 28 weeks gestation. The overall survival rate for "micropremies" was 64 percent, ranging from 20 percent at 24 weeks to 83 percent at 27 weeks gestation. Race and sex are important determinants of survival in these infants. The incidence of severe, chronic morbidity in "micropremies" is relatively low. The acceptable outcome for "micropremies" supports aggressive perinatal management for fetuses as low as 24 to 25 weeks gestation. However, it is important for physicians to use current statistics from their own institutions when counseling parents and making management decisions.

  View details for Web of Science ID A1986D516900001

  View details for PubMedID 3731666

• NEONATAL PULMONARY MANIFESTATIONS DUE TO PROLONGED AMNIOTIC LEAK AMERICAN JOURNAL OF PERINATOLOGY Bhutani, V. K., Abbasi, S., Weiner, S. 1986; 3 (3): 225-230

  Abstract

  Neonatal pulmonary manifestations of prolonged (2-8 weeks) amniotic fluid leak (PAL) were evaluated in 22 neonates. The severity of respiratory insufficiency was evaluated by a profile scoring system based on arterial blood gases, ventilatory support, and evidence of "fetal compression". The spectrum included acute respiratory failure with pulmonary hypoplasia (3), pulmonary hemorrhage (2), severe bronchopulmonary dysplasia (3), subacute lung disease (5), and transient respiratory disease (2). Seven neonates were completely asymptomatic. Clinical manifestations were correlated to age of onset and duration of PAL. The onset of PAL in the asymptomatic babies had occurred after 32 weeks gestation (mean +/- SEM, 33.5 +/- 1.1 wk; duration was 4.4 +/- 1.1 wk). In symptomatic neonates the onset of PAL was 24.0 +/- 1.0 weeks; duration being 6.0 +/- 0.6 weeks. When PAL occurred before 22 weeks and the duration of leak was longer than 6 weeks, the pulmonary profile score was less than 3 and associated with severe respiratory sequelae. These manifestations culminated in neonatal demise despite aggressive conventional ventilatory techniques. Onset of PAL between 23 and 28 weeks gestation and continuing longer than 8 weeks also was associated with a similar outcome. Duration of PAL between 2 and 7 weeks in this group was associated with less severe pulmonary manifestations and higher scores. Pulmonary morbidity was significantly correlated to the initial profile score (P less than .05) and was influenced by the prenatal reduction in thoracic volume.

  View details for Web of Science ID A1986D108300015

  View details for PubMedID 3718644

• THE EFFECT OF TRACHEAL SMOOTH-MUSCLE TONE ON NEONATAL AIRWAY COLLAPSIBILITY PEDIATRIC RESEARCH Bhutani, V. K., KOSLO, R. J., Shaffer, T. H. 1986; 20 (6): 492-495

  Abstract

  The effect of smooth muscle tone on the functional characteristics of neonatal airways was studied in six newborn lambs. Tracheal mechanics, resistance, and collapsibility were determined in tracheal segments of uniform length which were surgically isolated just caudal to the cricoid cartilage. Resistance to airflow through uncompressed (zero transmural pressure) and compressed (increased transmural pressure) trachea was evaluated over a range of physiological flows both before and after induced contraction of airway smooth muscle. Results demonstrate that neonatal tracheal smooth muscle does respond to cholinergic stimulation and that there was a significant decrease in airway compliance. Furthermore, the consequent increase in airway rigidity may play a role in resisting collapse or compression of the intrathoracic airway during expiration.

  View details for Web of Science ID A1986C430200002

  View details for PubMedID 2872649

• ACQUIRED TRACHEOMEGALY IN VERY PRETERM NEONATES AMERICAN JOURNAL OF DISEASES OF CHILDREN Bhutani, V. K., RITCHIE, W. G., Shaffer, T. H. 1986; 140 (5): 449-452

  Abstract

  Proximal airways are compliant structures at early gestational ages and may be susceptible to pressure-induced deformation following prolonged ventilatory support. Sixteen neonates (mean +/- SD gestational age, 27.0 +/- 0.6 weeks; mean +/- SD birth weight, 847 +/- 68 g) were studied to assess tracheal volume deformation. The neonates received ventilatory support for a mean +/- SD duration of 25.4 +/- 4.9 days. During this period the maximum peak inspiratory pressures ranged from 15 to 25 cm H2O, and respirations ranged from 20/min to 60/min. These neonates were studied at seven days postextubation and were individually matched for body weight with 16 nonventilated neonates. The width of the tracheal air column was measured at the lower border of the first thoracic (T-1) and third thoracic (T-3) vertebrae. The average tracheal width (average of T-1 and T-3) was significantly (38%) wider in the ventilated group, and the mean +/- SD tracheal width values were 3.79 +/- 0.29 mm, as compared with the control values of 2.74 +/- 0.31 mm. Based on these data it was estimated that the tracheal volume was 91% greater in the ventilated group. These observations demonstrate tracheal volume deformation and acquired tracheomegaly in neonates who have received mechanical ventilatory support. In addition to increased dead space ventilation, these findings also indicate underlying mechanical deformation of the tracheal wall.

  View details for Web of Science ID A1986C085200024

  View details for PubMedID 3962939

• A NEW APPROACH TO INDUCED HYPOTHERMIA JOURNAL OF SURGICAL RESEARCH Forman, D. L., Bhutani, V. K., Tran, N., Shaffer, T. H. 1986; 40 (1): 36-42

  Abstract

  A variety of methods have been employed for the induction of hypothermia; however, there are still some inherent problems that remain with current techniques. Liquid ventilation, a process used in several other environmental and clinical research areas, may be a feasible method since it takes advantage of the effectiveness of the pulmonary architecture as a heat exchanger. Hypothermia induced by liquid ventilation was studied in 8 newborn lambs, mean age = 10 +/- 8 SEM days. Each lamb was anesthetized with sodium pentobarbitol (20 mg/kg) and intubated. Cardiopulmonary measurements were taken during a control period prior to induced hypothermia. Liquid temperatures of 20 and 30 degrees C were used in cooling the animal while monitoring rectal and surface temperatures. Temperatures decreased producing rectal cooling rates of 8.4 and 4.8 degrees C/hr, respectively. Blood gas analysis showed adequate physiological gas exchange for all lambs during the liquid ventilation period. Based on the data, the process of liquid ventilation offers a unique potential both in experimental and clinical areas as a new approach to the technique of induced hypothermia.

  View details for Web of Science ID A1986AXQ1100006

  View details for PubMedID 3941549

• MECHANICS AND ENERGETICS OF BREATHING HELIUM IN INFANTS WITH BRONCHOPULMONARY DYSPLASIA JOURNAL OF PEDIATRICS Wolfson, M. R., Bhutani, V. K., Shaffer, T. H., Bowen, F. W. 1984; 104 (5): 752-757

  Abstract

  The mechanics and energetics of breathing were studied in preterm infants with bronchopulmonary dysplasia while spontaneously breathing control gas and helium-oxygen (Heliox) gas mixtures. During Heliox breathing, there was a significant decrease in pulmonary resistance, resistive work of breathing, and mechanical power of breathing, whereas ventilation remained unchanged. Breathing a lower density gas mixture (Heliox) may have therapeutic value by decreasing the demands on the respiratory muscles and the caloric requirements for breathing. Therefore, this modality may reduce potential respiratory muscle fatigue and avail additional calories for growth and recovery in the preterm infant with bronchopulmonary dysplasia.

  View details for Web of Science ID A1984SR58100025

  View details for PubMedID 6546945

• TRACHEAL VOLUME DEFORMATION IN A DEVELOPMENTAL RABBIT MODEL BIOLOGY OF THE NEONATE Snyder, S. M., Shaffer, T. H., Bhutani, V. K. 1984; 46 (4): 192-197

  Abstract

  Alterations in tracheal volume were evaluated in a developmental in vivo rabbit model during and following the application of continuous positive pressure (CPP). Sequential volume changes were recorded during 60 min of CPP to a bypassed tracheal segment. The distal trachea was utilized for spontaneous ventilation. CPP of 10 cm H2O was applied to three developmental groups: group I, 5 term newborn pups; group II, 5, 7-day-old pups, and group III, 5 adult female rabbits of 18 +/- 6 months old. Changes in tracheal volume were measured by a micropipette system. Following 60 min of CPP, tracheal volumes increased (p less than 0.01) by 39.8% in group I; 36.1% in group II and 5.1% in group III. During a recovery period (60 min), return towards initial resting volume was observed in all groups, though maximal persistent volume deformation was observed in groups I and II. Thus, these data indicate tracheal barotrauma in the form of persistent dimensional deformation at early stages of development in an in vivo rabbit model.

  View details for Web of Science ID A1984TK78000006

  View details for PubMedID 6386060

• LIQUID VENTILATION - EFFECTS ON PULMONARY-FUNCTION IN DISTRESSED MECONIUM-STAINED LAMBS PEDIATRIC RESEARCH Shaffer, T. H., Lowe, C. A., Bhutani, V. K., Douglas, P. R. 1984; 18 (1): 47-52

  Abstract

  Seven lambs (0.93 term gestation) were delivered by cesarean section with evidence of meconium in the amniotic fluid, meconium staining, and respiratory distress. The initial arterial blood gas and acid-base status indicated severe hypoxemia and acidosis. Three of these lambs developed pneumothoraces and died on control gas ventilation with positive end expiratory pressure. During the control period (90 min) with ventilatory support, there were no significant alterations in mean arterial oxygen tension (PaO2) and alveolar-arterial oxygen gradient (A-aDO2). The initial hypercarbia and acidosis were effectively controlled and corrected using mechanical ventilation and bicarbonate infusion. Fifteen min after the onset of fluorocarbon ventilation mean PaO2 significantly increased and A-aDo2 decreased. After 90 min of fluorocarbon ventilation, lambs were returned to gas ventilation. During this recovery period, PaO2 and A-aDo2 remained significantly improved compared with control gas values. Dynamic lung compliance increased, alveolar and peak tracheal pressure decreased and inspiratory elastic work of breathing decreased during liquid ventilation.

  View details for Web of Science ID A1984RX66100009

  View details for PubMedID 6422432

• GALLBLADDER MECHANICS IN NEWBORN PIGLETS PEDIATRIC RESEARCH Kaplan, G. S., Bhutani, V. K., Shaffer, T. H., Tran, N., KOSLO, R. J., Wolfson, M. R. 1984; 18 (11): 1181-1184

  Abstract

  The mechanical properties of the newborn piglet gallbladder were evaluated in both the stimulated and unstimulated states. The pressure-volume relationships, compliance, and the estimated active tension of the gallbladder were determined in 10 newborn piglets (2-7 days of age). Agonist stimulation was achieved by administration of histamine (25 micrograms/kg/h) and cholecystokinin (CCK) (60 ng/kg/h). Both histamine and CCK increased the intracholecystic pressure at the 50% resting volume from 12.4 cm H2O to 18.9 and 15.5 cm H2O, respectively. This resulted in a significant (p less than 0.05) increase in the active tension. However, no significant changes were observed in the gallbladder compliance after stimulation. These findings characterize the mechanical properties of the normal neonatal gallbladder. The low magnitude of intracholecystic pressure response to agonist stimulation, when compared to adult data, may explain the occurrence of decreased neonatal choledochal bile flow.

  View details for Web of Science ID A1984TQ20200026

  View details for PubMedID 6514445

• ECHOGENIC INTRAVASCULAR AND HEPATIC MICROBUBBLES ASSOCIATED WITH NECROTIZING ENTEROCOLITIS JOURNAL OF PEDIATRICS MALIN, S. W., Bhutani, V. K., RITCHIE, W. W., Hall, M. L., Paul, D. 1983; 103 (4): 637-640

  View details for Web of Science ID A1983RL51300033

  View details for PubMedID 6620027

• THE EFFECTS OF LIQUID VENTILATION ON CARDIOPULMONARY FUNCTION IN PRETERM LAMBS PEDIATRIC RESEARCH Shaffer, T. H., Douglas, P. R., Lowe, C. A., Bhutani, V. K. 1983; 17 (4): 303-306

  Abstract

  The effects of fluorocarbon ventilation on cardiopulmonary function were studied in 8 preterm lambs, 132-136 days gestation. After mechanical ventilation with 100% oxygen (control period), the lambs were ventilated with fluorocarbon (PIO2 = 622 torr). The liquid was then removed from their lungs and gas ventilation resumed (recovery period). During normothermic liquid breathing the alveolar-arterial O2 gradient (A-a DO2) decreased (P less than 0.01) from control by 154 torr and remained decreased (P less than 0.05) by 85 torr during recovery. Dynamic lung compliance (CL) increased 50% (P less than 0.05); PaO2 increased 50% (P less than 0.05); and PaCO2 decreased 29% (P less than 0.01) as compared to control values. The change in A-a DO2 and PaO2 before and after liquid ventilation was correlated (r = 0.79 and P less than 0.01) with control CL. There was a gradual decrease (P less than 0.01) in mean arterial pressure from 62 +/- 5.4 torr (control) to 53,1 +/- 9,3 torr (recovery); however, there were no significant alterations in mean central venous pressure, heart rate, or mean electrical axis.

  View details for Web of Science ID A1983QJ21600017

  View details for PubMedID 6856391

• CARDIOPULMONARY FUNCTION IN VERY PRETERM LAMBS DURING LIQUID VENTILATION PEDIATRIC RESEARCH Shaffer, T. H., Tran, N., Bhutani, V. K., Sivieri, E. M. 1983; 17 (8): 680-684

  Abstract

  Cardiopulmonary function was evaluated in very preterm lambs (106 +/- 0.7 S.E. days gestation, 1.66 +/- 0.12 S.E. kg birth weight) during fluorocarbon ventilation. Lambs were delivered by cesarean section after epidural anesthesia. Indwelling arterial, venous, and tracheal cannulae were placed before clamping the cord. Lambs were then mechanically ventilated with oxygenated fluorocarbon for approximately 2 h. During this period it was possible to maintain adequate gas exchange and stable cardiac function. Transpulmonary pressure, liquid flow, and tidal volume tracings enabled determination of lung compliance, CL = 0.58 +/- 0.12 S.E. ml X cmH2O-1 X kg-1, inspiratory resistance, RI = 3600 +/- 604 S.E. cmH2O X liter-1 X sec-1, and expiratory resistance, RE = 4034 +/- 2183 S.E. cmH2O/liter/sec. Lung compliance of the 106-day-old fluorocarbon-filled lung is similar to the more mature 138-143-day-old air-filled lung in preterm lambs. Based on the data presented herein we have extended the viability of the preterm lamb to the limit of pulmonary capillary development rather than that of the pulmonary surfactant system.

  View details for Web of Science ID A1983QZ96100016

  View details for PubMedID 6889011

• EFFECT OF LIQUID VENTILATION ON PRETERM LAMB TRACHEAL MECHANICS BIOLOGY OF THE NEONATE Bhutani, V. K., Shaffer, T. H. 1983; 44 (5): 257-263

  Abstract

  Liquid ventilation with fluorocarbon has been demonstrated as a viable mode of ventilatory support to preterm or distressed lambs. The effect of liquid ventilation and its high inflation pressures in proximal airways was evaluated on the mechanical behavior of the preterm trachea. 7 preterm lambs (134 +/- 1.5 SE days of gestation; 90% term) were ventilated with fluorocarbon (Rimar) for 58.6 +/- 8 min. The tracheae were dissected and the ventilated, distal segments were compared to nonventilated proximal segments. Pressure-volume curves were determined by plethysmography and specific tracheal compliance was computed. Tracheal dimensions increased 13.6 and 25.6% in diameter and volume (p less than 0.05), respectively, and the compliance decreased 29.9% (p less than 0.05). The magnitude of these changes is comparable to that observed during gaseous ventilation of term animals.

  View details for Web of Science ID A1983RM75200001

  View details for PubMedID 6639995

• TIME-DEPENDENT TRACHEAL DEFORMATION IN FETAL, NEONATAL, AND ADULT-RABBITS PEDIATRIC RESEARCH Bhutani, V. K., Shaffer, T. H. 1982; 16 (10): 830-833

  Abstract

  Sequential magnitude and the rate of change in tracheal mechanics after application of intermittent positive pressure (IPP), and the time constant, tau, of this deformation were determined in fetal (21 and 27 days gestation), neonatal (term, 31 days gestation) and adult rabbits. In vitro tracheal mechanics were determined by liquid plethysmography before and after IPP, (25 cm H2O at 30 cycles/min) of 20, 40, 60, and 120 min duration. A sequential decrease in tracheal compliance was documented at all ages. This was associated with increased values of tau as the maturational age advanced. Further, the rate of tracheal deformation was 0.008 cm H2O min-1 at 21 days gestation compared to 0.00025 cm H2O min-1 at adulthood. The decrease in rate of deformation was related to the gestational maturity and duration of IPP. The rate of deformation, as predicted by calculated deformation time constants, appears to be a function of structural elastic and viscoelastic properties of the trachea as well as the duration and magnitude of applied pressure. The deformation time constant may be defined as a useful index to predict the rate of airway deformation. Utilizing the rabbit model, this provides a measure of comparing barotrauma with different modes of ventilation in preterms.

  View details for Web of Science ID A1982PJ85500006

  View details for PubMedID 6755370

• PRESSURE-INDUCED DEFORMATION IN IMMATURE AIRWAYS PEDIATRIC RESEARCH Bhutani, V. K., Rubenstein, D., Shaffer, T. H. 1981; 15 (5): 829-832

  Abstract

  The effect of positive pressure ventilation on the highly compliant fetal airways was evaluated utilizing fetal rabbit tracheal segments. The degree of mechanical and dimensional deformation was quantified to the pressure applied intermittently (IPP) or continuously (CPAP) for 60 min. Excised tracheal segments were obtained at 21, 27, and 31 days fetal rabbit gestation (term = 31 days) and from 18 +/- 6-month-old adults. Internal diameter, resting length, and volume of the tracheal segments were measured, and their pressure-volume relationships were determined by plethysmography. Tracheal specific compliance at deflation pressure of 0 to 10 cm H2O was calculated from these data. In all fetal groups, the application of positive pressure resulted in a decrease of both tracheal distensibility and the slope of the pressure-volume curves; in addition, a highly significant decrease in tracheal specific compliance was documented. At 21 days gestation, the tracheal specific compliance decreased from 0.089 to 0.034 cm H20-1 (P less than 0.001) after CPAP and to 0.025 cm H2O (P less than 0.001) after IPP. For the same group, the resting tracheal volume increased by a dramatic 89% (P less than 0.001) after CPAP and by 124% (P less than 0.001) after IPP. The magnitude of these alterations decreased as gestational age advanced; the changes were not significant by adulthood. These data indicate that significant pressure-induced deformation (barotrauma) is sustained by susceptible immature airways.

  View details for Web of Science ID A1981LM90000009

  View details for PubMedID 7017562

• PRESSURE-VOLUME RELATIONSHIPS OF TRACHEAE IN FETAL NEWBORN AND ADULT-RABBITS RESPIRATION PHYSIOLOGY Bhutani, V. K., Rubenstein, S. D., Shaffer, T. H. 1981; 43 (3): 221-231

  Abstract

  The physical properties of the trachea in fetal, newborn, and adult rabbits change with age. Tracheal dimensions and pressure--volume relationships were determined in excised tracheae at a wide developmental age range (from early gestational age to infancy and adulthood). At intraluminal pressures of 0 to 10 cm H2O, the tracheal specific compliance was 0.089 (cm H2O)(-1) for a 21 day old fetus. By adulthood, the tracheal specific compliance decreased five fold to 0.017 (cm H2O)(-1); a dramatic proportion of this reduction occurred during fetal life itself, followed by a steady, progressive decline to adult age. The volume of the tracheal segment, at intraluminal pressure of 20 cm H2O, increased by 29% (adult), 41.5% (31 day fetus) and 113% (21 day fetus). Developmental alterations in the specific airway compliance suggest significant changes in anatomical dead space would occur as a function of maturation and airway transmural pressure.

  View details for Web of Science ID A1981LK88600005

  View details for PubMedID 7280379

• RESPIRATORY MUSCLE FUNCTION, ASSESSMENT, AND TRAINING PHYSICAL THERAPY Shaffer, T. H., Wolfson, M. R., Bhutani, V. K. 1981; 61 (12): 1711-1723

  Abstract

  This article presents a brief overview of respiratory muscle mechanics and the effects of lung disease and neuromuscular disease on pulmonary function. A variety of current specific and general muscle training techniques are described and discussed. Also presented is a current review of training studies and the effects of muscle training on cardiopulmonary function, muscle strength, endurance and fatigue, and exercise tolerance.

  View details for Web of Science ID A1981MU67800002

  View details for PubMedID 7312944

• EFFECT OF INTERMITTENT POSITIVE PRESSURE APPLICATION ON THE BULK MODULUS OF THE DEVELOPING RABBIT TRACHEA RESPIRATION Bhutani, V. K., Shaffer, T. H. 1981; 41 (3): 192-198

  Abstract

  Tracheal dimension, pressure-volume relationships and bulk modulus (K) were determined in excised fetal and adult rabbit tracheal segments before and after application of intermittent positive pressure (IPP) which was 0--25 cm H2O pressure, at 30 cycles/min, and for a duration of 60 min. Both tracheal elastic behavior and dimensions underwent dramatic changes following IPP. At 21, 27, 31 days gestation age, the bulk modulus, K, of the rabbit trachea approximated those of the adult control values. However, the adult values of K did not vary significantly after IPP. The associated increase in tracheal dimensions were also related to the maturity of the animal. Significant structural and functional barotrauma is thus sustained by immature airways, and may account for the tracheal deformation frequently observed as a result of IPP.

  View details for Web of Science ID A1981MC19300007

  View details for PubMedID 7025137

• ALTERATIONS IN BULK MODULUS OF TRACHEA DURING DEVELOPMENT RESPIRATION Shaffer, T. H., Bhutani, V. K. 1980; 39 (6): 344-350

  Abstract

  Tracheal dimensions, pressure-volume relationships, and bulk moduli, K, were determined in excised tracheae at different developmental ages: 21-, 27-1, and 31-day rabbit fetuses; 7-day pups; and adult rabbits 18 +/- 6 months of age. Alterations in tracheal dimensions paralleled the growth of the animal. At low segmental pressures such as 10 cm H2O, the tracheal segments became stiffer with age (K = 20.4 cm H2O for the 21-day fetus to K = 58.0 cm H2O for the adult). However, at segmental pressures greater than 15 cm H2O, the overdistended immature trachea became stiffer than even those of the adults. Developmental alterations in bulk modulus suggest significant changes in the material and mechanical properties of the wirways as a function of both pressure and developmental age.

  View details for Web of Science ID A1980KK22100006

  View details for PubMedID 7423068