V K Bhutani

Stanford University, Palo Alto, California, United States

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Publications (185)618.91 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND 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 levels because albumin binding of bilirubin is confounded by a variety of molecular, biologic, and metabolic factors.METHODS 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.RESULTSTB and BBC levels ranged from 0.7-22.8 and 6.3-47.5mg/dL, respectively. GA correlated with BBC (r=0.54, P <0.0002) with a slope of 0.93mg/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.CONCLUSION We speculate that the spread of BBC levels around the regression line (±5.8mg/dL) suggests that individualized BBC assays would provide a robust approach to gauge risk of bilirubin neurotoxicity compared to TB and GA.Pediatric Research (2014); doi:10.1038/pr.2014.191.
    Pediatric research. 11/2014;
  • Sanjiv B Amin, Vinod K Bhutani, Jon F Watchko
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    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.
    Seminars in perinatology. 09/2014;
  • Yassar H Arain, Vinod K Bhutani
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    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.
    The Indian Journal of Pediatrics 04/2014; · 0.72 Impact Factor
  • V K Bhutani
    Journal of perinatology: official journal of the California Perinatal Association 01/2014; 34(1):81. · 1.59 Impact Factor
  • Matthew B Wallenstein, Vinod K Bhutani
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    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.
    Clinics in perinatology 12/2013; 40(4):679-88. · 1.54 Impact Factor
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    ABSTRACT: Background:Rhesus (Rh) disease and extreme hyperbilirubinemia (EHB) result in neonatal mortality and long-term neurodevelopmental impairment, yet there are no estimates of their burden.Methods: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.Results: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.Conclusion: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.
    Pediatric Research 12/2013; 74 Suppl 1:86-100. · 2.67 Impact Factor
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    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.
    Journal of Tropical Pediatrics 05/2013; · 1.01 Impact Factor
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    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.
    Pediatric Research 04/2013; · 2.67 Impact Factor
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    Vinod K Bhutani
    Indian pediatrics 04/2013; 50(4):365-6. · 1.04 Impact Factor
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    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.Journal of Perinatology advance online publication, 21 February 2013; doi:10.1038/jp.2013.14.
    Journal of perinatology: official journal of the California Perinatal Association 02/2013; · 1.59 Impact Factor
  • Vinod K Bhutani
    Evidence-based medicine 01/2013;
  • Vinod K Bhutani, Ronald J Wong
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    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.
    Journal of clinical neonatology. 01/2013; 2(2):61-69.
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    ABSTRACT: OBJECTIVE: 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. STUDY DESIGN: 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. RESULTS: 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). CONCLUSIONS: 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.
    The Journal of pediatrics 10/2012; · 4.02 Impact Factor
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    Vinod K Bhutani
    Indian pediatrics 09/2012; 49(9):704-5. · 1.04 Impact Factor
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    ABSTRACT: We provide an approach to the use of phototherapy and exchange transfusion in the management of hyperbilirubinemia in preterm infants of <35 weeks of gestation. Because there are limited data for evidence-based recommendations, these recommendations are, of necessity, consensus-based. The recommended treatment levels are based on operational thresholds for bilirubin levels and represent those levels beyond which it is assumed that treatment will likely do more good than harm. Long-term follow-up of a large population will be needed to evaluate whether or not these recommendations should be modified.
    Journal of perinatology: official journal of the California Perinatal Association 06/2012; 32(9):660-4. · 1.59 Impact Factor
  • Vinod K Bhutani, Ronald J Wong
    Acta Paediatrica 01/2012; 101(5):441-3. · 1.97 Impact Factor
  • Vinod K Bhutani
    The Indian Journal of Pediatrics 12/2011; 79(2):253-5. · 0.72 Impact Factor
  • Tina M Slusher, Alvin Zipursky, Vinod K Bhutani
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    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.
    Seminars in perinatology 06/2011; 35(3):185-91. · 2.33 Impact Factor
  • Lois Johnson, Vinod K Bhutani
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    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.
    Seminars in perinatology 06/2011; 35(3):101-13. · 2.33 Impact Factor
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    Vinod K Bhutani, David K Stevenson
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    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.
    Seminars in perinatology 06/2011; 35(3):97-100. · 2.33 Impact Factor

Publication Stats

3k Citations
618.91 Total Impact Points

Institutions

  • 2005–2014
    • Stanford University
      • • Division of Neonatal and Developmental Medicine
      • • Department of Pediatrics
      Palo Alto, California, United States
  • 2013
    • Magee-Womens Hospital
      • Department of Pediatrics
      Pittsburgh, Pennsylvania, United States
  • 2006–2013
    • Lucile Packard Children’s Hospital at Stanford
      Palo Alto, California, United States
    • Virginia Commonwealth University
      • Department of Neurology
      Richmond, VA, United States
    • Baylor College of Medicine
      • Department of Pediatrics
      Houston, TX, United States
  • 2012
    • Beaumont Health System
      Detroit, Michigan, United States
  • 2011
    • University of Minnesota Duluth
      Duluth, Minnesota, United States
  • 2007–2011
    • Stanford Medicine
      • Division of Neonatal and Developmental Medicine
      Stanford, California, United States
  • 1996–2008
    • Pennsylvania Medical Society
      Philadelphia, Pennsylvania, United States
    • Boston Children's Hospital
      Boston, Massachusetts, United States
  • 1986–2008
    • The Children's Hospital of Philadelphia
      • • Division of General Pediatrics
      • • Division of Neonatology
      • • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 1990–2005
    • University of Pennsylvania
      • • Department of Pediatrics
      • • Department of Medicine
      Philadelphia, Pennsylvania, United States
  • 1988–2005
    • Hospital of the University of Pennsylvania
      • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 1994
    • Medical University of Graz
      Gratz, Styria, Austria
  • 1991
    • Thomas Jefferson University Hospitals
      Philadelphia, Pennsylvania, United States
  • 1981–1990
    • Temple University
      • Department of Physiology
      Philadelphia, PA, United States