Vinod K. Bhutani

Lucile Packard Children’s Hospital at Stanford, Palo Alto, California, United States

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Publications (226)783.73 Total impact

  • David K. Stevenson · Ronald J. Wong · Vinod K. Bhutani

    No preview · Article · Jan 2016
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    ABSTRACT: Aim: Relative contributions of increased production [by end-tidal carbon monoxide (ETCOc) concentrations] and decreased elimination of bilirubin to pre-discharge hour-specific total bilirubin (TB) levels were assessed in healthy late preterm and term newborns. Secondly, we report pre-discharge ETCOc ranges to guide clinical management of hyperbilirubinemia. Methods: TB and ETCOc (≤3 timepoints) determinations of newborns aged between 6 h and <6 days (n = 79) were stratified by postnatal age epochs. Hyperbilirubinemia risk was assessed by plotting TB values as a function of ETCOc. Results: Stratifications of ETCOc (in ppm, mean, median, and interquartile ranges) by postnatal age epochs (0-24, 24-48, and 48-72) were: 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 hemolysis 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). Conclusion: Near-simultaneous ETCOc and TB measurements in infants with TB > 75(th) percentile accurately identifies hemolytic hyperbilirubinemia. This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2016 · Acta Paediatrica
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    ABSTRACT: Background and objectives: 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. 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. Results: 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. Conclusions: Pending further validation, a digital microfluidics platform could be an accurate point-of-care screening tool for rapid newborn G6PD screening.
    No preview · Article · Oct 2015 · PEDIATRICS
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    ABSTRACT: Background: 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. Methods: 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. Results: 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. Conclusions: 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.
    Full-text · Article · Sep 2015 · BMC Pregnancy and Childbirth
  • Alvin Zipursky · Vinod K Bhutani

    No preview · Article · Aug 2015 · The Lancet
  • M Kaplan · C Hammerman · V K Bhutani
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    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.Journal of Perinatology advance online publication, 16 July 2015; doi:10.1038/jp.2015.77.
    No preview · Article · Jul 2015 · Journal of perinatology: official journal of the California Perinatal Association
  • V K Bhutani · R J Wong · H J Vreman · D K Stevenson
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    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.Journal of Perinatology advance online publication, 16 April 2015; doi:10.1038/jp.2015.32.
    No preview · Article · Apr 2015 · Journal of perinatology: official journal of the California Perinatal Association
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    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). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to
    No preview · Article · Mar 2015 · Archives of Disease in Childhood - Fetal and Neonatal Edition
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    ABSTRACT: Elevated levels of end-tidal carbon monoxide corrected for inhaled carbon monoxide (ETCOc), have been correlated with blood carboxyhemoglobin corrected for inhaled carbon monoxide (COHbc) and increased bilirubin production in both healthy newborn infants and those with haemolysis. Elevated bilirubin production has also been reported in infants born premature, born to mothers with diabetes, with bruising or birth trauma, with iso-immune haemolytic disorders, such as maternal-fetal blood group incompatibilities with ABO, Rh, or other minor groups, glucose-6-phosphate dehydrogenase (G6PD) deficiency, structural and functional red blood cell abnormalities and perinatal sepsis (1-6). The 2004 American Academy of Pediatrics (AAP) guideline (7) specifically recommends that ETCOc measurements be used to identify the presence of haemolysis in infants and their subsequent risk for hyperbilirubinemia based on observations that heme degradation from senescing red blood cells leads to the equimolar production of carbon monoxide (CO) and bilirubin in the absence of exposure to high ambient CO or active tissue injury (8).This article is protected by copyright. All rights reserved.
    No preview · Article · Jan 2015 · Acta Paediatrica
  • Alvin Zipursky · Vinod K. Bhutani
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    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. Copyright © 2014. Published by Elsevier Ltd.
    No preview · Article · Jan 2015 · Seminars in Fetal and Neonatal Medicine
  • Vinod K. Bhutani · Ronald Wong

    No preview · Article · Jan 2015 · Seminars in Fetal and Neonatal Medicine
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    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.
    No preview · Article · Nov 2014 · Pediatric Research
  • 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.
    No preview · Article · Sep 2014 · Seminars in Perinatology
  • 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.
    No preview · Article · Apr 2014 · The Indian Journal of Pediatrics
  • V K Bhutani
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    ABSTRACT: JPER is a multi-disciplinary journal that promotes the health of the preterm infant.
    No preview · Article · Jan 2014 · Journal of perinatology: official journal of the California Perinatal Association
  • 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.
    No preview · Article · Dec 2013 · Clinics in perinatology
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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.
    Full-text · Article · Dec 2013 · Pediatric Research
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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.
    No preview · Article · May 2013 · Journal of Tropical Pediatrics
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    ABSTRACT: Background: The therapeutic phototherapy action spectrum ranges from 420 to 500 nm. However, a recent report of improved efficacy of fluorescent "turquoise" light (~490 nm) as compared with blue 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 the optical properties of skin for robust calculations of the fraction of light absorbed by bilirubin at various wavelengths that could be confounded by hemoglobin (Hb), melanin, and skin thickness. Applying assumptions regarding the wavelength dependence of bilirubin photochemistry, "action spectra" were assembled 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. Of note, the relative amplitudes of the action spectra showed an inverse relationship with hematocrit (Hct). Conclusion: We speculate that a narrow range of light at 476 nm would be 60% more effective than blue (broadband) fluorescent lamps. Because Hb serves as a major competitor of bilirubin for light absorption, the calculations also predict that the efficacy of phototherapy is dependent on the Hct. A high Hct could reduce therapeutic efficiency.
    No preview · Article · Apr 2013 · Pediatric Research
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    Vinod K Bhutani

    Preview · Article · Apr 2013 · Indian pediatrics

Publication Stats

5k Citations
783.73 Total Impact Points


  • 2008-2015
    • Lucile Packard Children’s Hospital at Stanford
      Palo Alto, California, United States
  • 2001-2015
    • Stanford University
      • • Department of Pediatrics
      • • Division of Neonatal and Developmental Medicine
      • • Department of Medicine
      Palo Alto, California, United States
  • 1985-2008
    • The Children's Hospital of Philadelphia
      • • Division of General Pediatrics
      • • Division of Neonatology
      • • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
    • Philadelphia ZOO
      Filadelfia, Pennsylvania, United States
  • 1984-2005
    • University of Pennsylvania
      • Department of Pediatrics
      Filadelfia, Pennsylvania, United States
  • 2004
    • Virginia Commonwealth University
      • Department of Pediatrics
      Ричмонд, Virginia, United States
  • 1994-2004
    • William Penn University
      Filadelfia, Pennsylvania, United States
  • 2003
    • University of Wisconsin–Madison
      • Department of Pediatrics
      Madison, Wisconsin, United States
  • 1988-2002
    • Pennsylvania Medical Society
      Filadelfia, Pennsylvania, United States
    • Thomas Jefferson University Hospitals
      Philadelphia, Pennsylvania, United States
  • 1999
    • Northside Hospital
      Atlanta, Georgia, United States
  • 1997
    • University of Illinois at Chicago
      • Department of Pediatrics (Peoria)
      Chicago, Illinois, United States
  • 1991
    • Thomas Jefferson University
      Filadelfia, Pennsylvania, United States
  • 1981-1990
    • Temple University
      • • Department of Physiology
      • • Department of Pediatrics
      Philadelphia, Pennsylvania, United States
  • 1986-1988
    • Hospital of the University of Pennsylvania
      Filadelfia, Pennsylvania, United States