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ObjectiveTo 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.Study designProspective 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.ResultsAll 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.ConclusionOngoing studies may better characterize the role of neurosteroids and the influence of STS in more critically ill and premature neonates.

Background: Near-term neonates (Babies of 36 to 37 weeks GA and with BW [is greater than] 2000g as well as those of 35 weeks GA and BW [is greater than] 2500g) are frequently managed as healthy, well newborns. They are subject to early discharge without mandated specialized pre or post discharge care. Epidemiologic studies have placed them at risk for higher rate of readmission, excessive weight loss, feeding difficulties and varying risk of dehydration and hyperbilirubinemia. Objective: To determine and characterize the level of risk and outcome of neonatal hyperbilirubinemia in these infants. Methods: Identification of a cohort of 326 near-term (n-term) newborns who were enrolled in the bilirubin database that was used to develop the hour-specific bilirubin nomogram (Pediatrics. 1999). Percentile based predischarge risk assessment and subsequent neonatal hyperbilirubinemia, readmission and association with other concomitant epidemiological risk factors were determined from the database. These data were compared to those determined in concurrently enrolled term population (n = 1624). Results: These data show that pre-discharge risk distribution is shifted (*p [is less than] 01) for babies with assisted vaginal deliveries (vacuum/forceps, AVD). Distribution of babies (%) is tabulated below as per their percentile-based risk assignment: Risk All Breast- Status Babies Fed Term N-Term Term N-Term Total (n) 1624 326 827 326 >95 %tile 3.9 4.9 3.9 4.3 40 to 95 53.4 59.9 60.5 61.3 95 %tile 5.2 16.3 27% 50%(*) 40 to 95 59.1 61.3 3.6% 12% Conclusions: These data define the increased risk that near-term babies have for severe bilirubinemia. The magnitude of this risk may be assessed by universal pre-discharge bilirubin screening and efficiently managed by prospective tracking of serial hourspecific post-discharge bilirubin values which designate the ongoing percentile-based risk status. VK Bhutani, MD, FAAP, LH Johnson, MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, Pennsylvania, Hospital, Department of Pediatrics, University of Pennsylvania, Philadelphia, PA3, VK Bhutani, MD, FAAP, LH Johnson, MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, Pennsylvania, Hospital, Department of Pediatrics, University of Pennsylvania, Philadelphia, [...]

Background: Newborn babies can be evaluated and assessed for risk for severe hyperbilirubinemia prior to discharge and effectively targeted for follow-up and interventional strategies (Pediatrics, 1999). Objective: To develop practical and physician-friendly tools for hospital and office based application of the bilirubin nomogram. Methods: Healthy babies, both term and near-term (N-Term, [is less than or equal to] 37 weeks, 36 weeks with BW [is greater than] 2000 g, and 35 weeks with BW [is greater than] 2500 g), had a pre-discharge total serum bilirubin (TSB) test and were also evaluated for known epidemiologic and clinical risk factors for excessive hyperbilirubinemia. Babies were assigned to percentile based risk tracts on their pre-discharge TSB values = high ([is greater than] 95th percentile zone), intermediate (40 to 75th percentile zone) and low ([is less than] 40th percentile). Results: Percent of babies in each risk zone were compared for known risk groups: breast-fed (BF), N-Term, vacuum/forceps (assisted) vaginal delivery (AVD), gender, ancestry, as well as ABO ([+ or -] Coombs) sensitization. Risk Status Term Term Term N-Term ABO (BF) (AVD) Total (n) (1624) (827) (232) (326) (553) >95th %lie 3.9 3.9 5.2 4.9 9.9%(*) 40-95th %ile 53.4 60.5 59.1 59.9 42.1% >40th %ile 42.7 35.6 35.7 35.2 49.0% These data described distribution of risk status for babies based on their epidemiologic/clinical risk factors. As anticipated, a significant shift in risk pattern (p [is less than] 0.01) was seen for the ABO population, and a trend for increased risk distribution is evident for the AVD and near term population. These singled them out for closer follow-up. With the use of a software based program, predischarge coupled with hour-specific TSB values, when expressed in percentiles or visually tracked on the nomogram, facilitated risk assessment by indicating rate of rise and upward or downward change in percentile track. Thus, the impact of epidemiologic and clinical factors may be individualized for each baby. Direct reporting of TSB data from laboratories as percentile values (actual percentile or in quintiles) is also possible. Conclusion: Individualized care and risk assessment for each baby can be achieved in a practical and efficient manner by reporting TSB as hour-specific percentile values, so that they can be tracked by a busy pediatrician's office for safe, efficient, targeted management. VK Bhutani, MD, FAAP, LH Johnson. MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, PA Hospital, Department of Pediatrics, University of PA, Phila, PA3, VK Bhutani, MD, FAAP, LH Johnson. MD, FAAP, EM Sivieri, MS; Newborn Pediatrics, PA Hospital, Department of Pediatrics, University of PA, Phila, [...]

Background: Accurate and reproducible measures of serum bilirubin (TSB) may be attained in healthy term and near-term newborns by transcutaneous (TcB) measures of bilirubin using the non-invasive multi-wavelength spectral reflectance (BiliCheck TM) device. Hypothesis: A trend comparison between TSB and TcB may be evident in neonates undergoing intensive phototherapy (photoRx). Methods: Study design was generated to assess if an area of skin protected, by a patch, from phototherapy may be used to i) reliably measure TSB and ii) compare the gradient of TSB and TcB, for either exposed or unexposed areas, to define efficacy of photoRx. Measures of TSB (by HPLC and Diazo techniques) and TcB (patched and unpatched areas) were obtained simultaneously prephotoRx, 8 to 12 hours, later, every 24 hours and 8 to 12 hours after cessation of photoRx. Results: Preliminary data in 15 newborns (ranges of BW = 1103-3421g; GA = 29-40wks) show that change in consecutive serial TcB values to matched TSB values correlate by linear regression (r = 0.73). The trending of TcB and TSB is matched, concurrent and evident in a more dramatic manner in one near-term neonate (GA = 35 wks, BW = 2189 g) who had a double volume exchange transfusion (Ex Tx) while undergoing intensive phothoRx. As shown in the Figure, there is consistent gradient for TSB and TcB after the initiation of photoRx. Importantly, the rapid decline in TSB during the exchange was concurrently reflected in TcB values both for the areas exposed and unexposed to photoRx. Fall in tissue bilirubin is especially significant. Conclusions: Whereas, these preliminary data and case report suggest that, in babies receiving photoRx, skin deposition of bilirubin acutely reflects TSB values and that this trend is immediately apparent; accurate measure of TSB by TcB techniques, in babies receiving PhotoRx, requires continued study. (Supported in part by Spectrx Inc. Norcross, VA), VK Bhutani, MD, FAAP, LH Johnson, MD, FAAP, G Gourley, MD, FAAP, and C Dalin; Newborn Pediatrics, PA Hospital, Department of Pediatrics, Universities of Pennsylvania, Phila, PA, and Wisconsin--Madison, Madison, [...]

Background: Readmission of infants for treatment of excessive neonatal hyperbilirubinemia is not uncommon now as a result of hospital discharge before the extent of serum bilirubin rise is known or breast feeding has been established. Hypothesis: A scoring system to define presence and severity of signs of neurologic compromise associated with excessive hyperbilirubinemia would be useful as a guide to management and treatment needed to prevent or minimize brain damage. Methods: We based the score presented using generally accepted clinical signs of bilirubin induced neurologic dysfunction from minimal changes which resolve without apparent sequelae to those indicative of severe nervous system damage with a high potential for permanent sequelae in spite of aggressive treatment. Results: Characteristics of mental state, muscle tone and cry are grouped into three levels of increasing abnormality: Stage IA: Minimal Signs, Stage IB: Progressive but reversible with treatment, Stage II: Advanced-largely irreversible, but severely decreased by treatment. Characteristics for each category are given a weight of 1, 2, or 3 according to their severity stage and then summed to give an overall score. The higher the number (0 to 9) the greater the risk. This is the reverse of the Apgar Score, on which BIND has been modeled. The score may represent characteristics of more than one Stage, ie, Stage IA for cry and Stage IB for mental state muscle tone, resulting in a score of 5. The maximum score of 9 is given for advanced signs in each category. Stage 1A Stage 1B Stage II * Subtle * Progressive * Largely irre- signs signs versible signs * Reversible * Largely * Severity No reversible decreased by apparent with prompt sequale aggressive Rx aggressive Rx Weight for Signs 1 2 3 Mental * Too * Very poor * Semi-coma Status sleepy feeding * Poor * Marked leth- * Intermittent feeding argy or apnea * Irritability * Seizures Muscle * Slight but * Moderate hy- * Severe hyper Tone persistent per or hypoto- or hypotonia decrease nia depending in tone on arousal state * Posturing, bicycling, * Mild nuchal * Opisthotonos and * Truncal * Fever arching Cry * High * Shrill and * Inconsolable or pitched frequent or only with stimulation Too infrequent Range of 1-3 4-6 7-9 Scores Conclusions: The goal of the Clinical BIND Score is to encourage standardized, more rigorous assessment of risk from exposure to increasing levels and duration of hyperbilirubinemia. Serial scores should be useful in relating treatment response to initial severity, hospital course, and long term outcome and help define aggressiveness and type of treatment needed. (Laboratory and Audiology BIND Scores in progress) J Johnson, MD, FAAP, AK Brown, MD, FAAP, VK Bhutani, MD, FAAP; PA Hosp, Dept of Peds, Univ PA, Phila, PA, and SUNY Brooklyn, NY3, J Johnson, MD, FAAP, AK Brown, MD, FAAP, VK Bhutani, MD, FAAP; PA Hosp, Dept of Peds, Univ PA, Phila, PA, and SUNY Brooklyn, [...]

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. [ABSTRACT FROM AUTHOR]

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 µmol 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 <1 week. Along with a rapid rise of TSB (>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 <5 days in 81 of 118 (69%) infants and <10 days in 101 of 118 (86%) infants. TSB levels were <35 mg per 100 ml (598 µmol l-¹) in 46 (39%) infants, of whom one died before exchange transfusion, one was untreated and one was lost to follow-up. Timely and efficacious bilirubin reduction interventions defined by 'crash-cart' initiation of immediate intensive phototherapy and urgent exchange transfusion were accomplished in 11 of 43 infants, which were compared with 12 of 43 infants in whom a timely exchange sometimes could not be accomplished. No overt sequelae were found in 8 of 11 infants (73%) treated with a 'crash-cart' approach compared with none without sequelae when exchange was delayed by pre-admission delays, technical factors or need to transfer to a tertiary facility. None of the remaining 20 of 43 infants treated only with phototherapy escaped sequelae. Regardless of age at readmission and intervention, infants with peak measured TSB >35mg 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. [ABSTRACT FROM AUTHOR]

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. 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: 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.Methods: 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.Findings: 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%).Interpretation: 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. [ABSTRACT FROM AUTHOR]

Prevention of neonatal bilirubin injury exemplifies success of systems approach to avert adverse neonatal and childhood outcomes that rely on strategies including prenatal identification of Rhesus sensitization, universal maternal blood typing, risk assessment for neonatal extreme hyperbilirubinemia (EHB), unfettered access to safe, effective phototherapy, and application of patient safety principles. India's diverse landscape suggests varied real-time experiences of neonatal hyperbilirubinemia and consequent infant mortality rates (IMR). Utilizing Global Burden of Disease (GBD) database, the authors examined national and subnational trends, infant mortality timing, and the disease burden from hemolytic and perinatal jaundice over 30 y (1999 to 2019). They also assessed the correlation of EHB-IMR with socio-demographic index and health expenditure per capita, estimating economic losses from EHB-related infant mortality to guide policy decisions at national and state domains. From 1990 to 2019, India delivered 811,078,415 livebirths of which, 1,189,856 infant deaths were due to EHB. EHB-related deaths decreased from 57,773 in 1990 to 19,664 in 2019, a 60% reduction vs. 40% in overall IMR. Early (0-6 d), late (7-27 d), and post-neonatal (28-364 d) deaths accounted for 61%, 34%, and 5% of mortality, respectively. Uttar Pradesh and Bihar contributed to 38% of all EHB deaths. Economic analysis estimate losses between US $7.2 and 11.7 billion for the year 2019 secondary to EHB-related mortality. The present analysis reveals consistent declines across all states to reach current EHB-IMR of 0.8 per 1,000 live-births in India by 2019. Significant economic impact of lost human productivity highlight ongoing need for targeted life-saving public health strategies., Competing Interests: Declarations Conflict of Interest None., (© 2024. The Author(s), under exclusive licence to Dr. K C Chaudhuri Foundation.)

Background: Limited data exist on population-level mortality outcomes related to extreme neonatal hyperbilirubinemia (EHB) and this study examines trends in annual infant mortality rate (IMR) attributed to hemolytic and perinatal jaundice among Germany, France, Italy, Portugal, Greece and Spain from 1990 to 2019., Methods: Data on annual incident cases and disability-adjusted life years were collected from the 2019 Global Burden of Disease study. Live birth cohort data were sourced from UN World Population Prospects. We quantified temporal trends, with relative percent changes. Average annual percent changes (AAPCs) were evaluated using the Joinpoint Regression Program., Results: EHB-related infant mortality decreased from 21.4 (95%CI: 16.1, 27.1) in 1990 to 4.2 (95%CI: 1.9, 7.6) per million live births in 2019. Germany demonstrated lowest AAPC of -3.2% (95% CI: -3.8, -2.5), while Portugal had the highest AAPC of -8.6% (95% CI -11.9, -5.1) in reducing infant mortality due to EHB. There were distinct divergences in the trajectories of declining EHB mortality among the studied countries., Conclusion: This study highlights a significant decline in infant mortality due to extreme hyperbilirubinemia, emphasizing the need for national surveillance and tailored guidelines to prevent bilirubin induced neurological damage., Impact: This cross-sectional analysis revealed a marked decline in infant mortality rates attributed to extreme hyperbilirubinemia across the selected European countries. The rates of decline varied significantly between countries, demonstrating notable heterogeneity in mortality trends when stratified by age at death. Implementing data-driven surveillance systems can optimize the alignment of equitable healthcare services, strengthen accountability measures, and identify critical operational inefficiencies. In the European Union, country-specific hyperbilirubinemia guidelines should be reinforced to ensure effective screening and post-discharge follow-up protocols that are tailored to risk burden and available healthcare resources., Competing Interests: Competing interests The authors declare no competing interests. Consent statement As the study used publicly available data with no patient specific information, it was deemed exempt from Institutional Review Board review., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Neonatal G6PD deficiency (G6PDd) prevalence explains its recent recognition as a major contributory cause of extreme hyperbilirubinemia (EHB). Disparate global EHB burden reveals comparative racial prevalence of leading conditions, Rh negativity and G6PDd: 15-17% vs. < 5% in Caucasians, 4 to 8% vs. up to 17% in Blacks and 0.1 to 4% vs. 5-8% in Asians, respectively. G6PDd also burdens malaria endemic countries planning malarial elimination. Binary expression of male G6PDd is reliably diagnostic but is complex and uncertain for heterozygous females. Unlike the RhD disease and its prevention, the medical and hematological life burdens of female G6PDd and heterozygosity have been vastly understudied. Three silent global health crises intersect: EHB, Malaria, and women's health. Regardless of race, sex, or geography, clinical practice needs optimization with dual (phenotypic and genotypic) screening to allow women plan and anticipate safe pregnancies, birthing, breastfeeding and enjoy their newborns' healthy childhood in a society freed of malaria., Competing Interests: Competing interests The author declares no competing interests. Statement of financial support This study has not been funded by any commercial public grants. Consent statement This study does not involve any human participant, and no patient consent is required., (© 2024. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Neonatal encephalopathy (NE) is a significant cause of neonatal mortality in low- and middle-income (LAMI) countries, with far-reaching impacts on families and national human capital. Quantifying the disease burden in monetary terms is crucial for resource allocation and public health prioritization, yet data on the economic impact of NE-related neonatal mortality and prevention is limited. This study estimates the country-specific disease burden and economic impacts of NE for the ten countries with the highest death tolls in 2019. Using data from the Global Burden of Disease (GBD) Collaborative Network, we analyzed NE-specific mortality trends and calculated years of life lost (YLLs) based on life expectancy, with and without age weighting and discounting. Economic losses were evaluated using the value per statistical life (VSL) and value per statistical life year (VSLY) methodologies, with sensitivity analyses incorporating variable discount rates. In 2019, the ten countries with the highest NE burden was estimated at 138,763 neonatal deaths. YLLs ranged from 4.5 million with discounting to 9.8 million without. While nine of these countries reduced overall neonatal mortality from 2010 to 2019, six saw rising NE-specific mortality. Economic losses were estimated at $80 billion using the VSL method and between $72 billion and $163 billion using VSLY. Despite overall progress in reducing neonatal mortality, targeted funded strategies are needed to address NE in LAMI countries. Burden of NE could be reduced with improved strategic access to quality antenatal care and effective peripartum practices through efficient and enhanced resource allocation., Competing Interests: Declaration of competing interest The authors have no conflicts of interest relevant to this article to disclose., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Competing Interests: We declare no competing interests. We thank our Global Bilirubin team: Ramesh Vidavalur, Iman Iskander, Praveen Kumar, Zubaida Farouk, Lizhong Du, Monica Villa Guillen, Esterlita Uy, Numan N Hameed, Claudio Tiribelli, and Ronald J Wong for their insightful comments and endorsement.

Objective: To summarize the principles and application of phototherapy consistent with the current 2022 American Academy of Pediatrics "Clinical Practice Guideline Revision for the Management of Hyperbilirubinemia in the Newborn Infant 35 or More Weeks of Gestation.", Methods: Relevant literature was reviewed regarding phototherapy devices in the United States, specifically those that incorporate blue to blue-green light-emitting diode, fluorescent, halogen, or fiberoptic light sources, and their currently marketed indications., Results: The efficacy of phototherapy devices varies widely because of nonstandardized use of light sources and configurations and irradiance meters. In summary, the most effective and safest devices have the following characteristics: (1) incorporation of narrow band blue-to-green light-emitting diode lamps (∼460-490 nm wavelength range; 478 nm optimal) that would best overlap the bilirubin absorption spectrum; (2) emission of irradiance of at least 30 µW/cm2/nm (in term infants); and (3) illumination of the exposed maximal body surface area of an infant (35% to 80%). Furthermore, accurate irradiance measurements should be performed using the appropriate irradiance meter calibrated for the wavelength range delivered by the phototherapy device., Conclusions: With proper administration of effective phototherapy to an infant without concurrent hemolysis, total serum or plasma bilirubin concentrations will decrease within the first 4 to 6 hours of initiation safely and effectively., (Copyright © 2024 by the American Academy of Pediatrics.)

We describe the implementation of universal glucose-6-phosphate dehydrogenase (G6PD) screening during the first year of New York State mandated testing, as well as operational challenges and clinical knowledge gained. All infants born at or transferred to our center between June 21, 2022 and June 30, 2023, underwent testing for G6PD enzyme deficiency and were included in the study cohort. Infant blood samples were collected and sent to a reference laboratory for quantitative assay. After initiation of universal screening, a quality improvement initiative was launched to: monitor and improve the suitability of blood sample collection to ensure timely return of results;improve the reliability and validity of the reference laboratory enzyme assay; andestablish accurate reference ranges for G6PD deficiency in newborns.A total of 5601 newborns were included. Within the first year of implementation, the percentage of samples yielding any test result increased from 76% to 85%, and most patients had a G6PD result available within 1 day of discharge. We established a more accurate threshold for G6PD deficiency in newborns of <4.9 U/g Hb and G6PD intermediate of <10.0 U/g Hb. Using the updated reference ranges, 224 patients in our cohort were identified as G6PD deficient or intermediate (4.0%). Through a quality-sensitive process, we identified the importance of a standardized approach, improved sample collection processes, decreased sample turnaround time, and established more accurate reference ranges. We hope our experiences will help others seeking to improve processes and implement similar programs at other institutions., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: The American Academy of Pediatrics and the Canadian Paediatric Society both advise that all newborns should undergo bilirubin screening before leaving the hospital, and this has become the standard practice in both countries. However, the US Preventive Task Force has found no strong evidence to suggest that this practice of universal screening for bilirubin reduces the occurrence of significant outcomes such as bilirubin-induced neurologic dysfunction or kernicterus., Objectives: To evaluate the effectiveness of transcutaneous screening compared to visual inspection for hyperbilirubinemia to prevent the readmission of newborns (infants greater than 35 weeks' gestation) for phototherapy., Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL, ClinicalTrials.gov, ICTRP, and ISRCTN in June 2023. We also searched conference proceedings, and the reference lists of included studies., Selection Criteria: We included randomized controlled trials (RCTs), quasi-randomized, cluster-randomized, or prospective cohort studies with control arm that evaluated the use of transcutaneous bilirubin (TcB) screening for hyperbilirubinemia in newborns before hospital discharge., Data Collection and Analysis: We used standard methodologic procedures expected by Cochrane. We evaluated treatment effects using a fixed-effect model with risk ratio (RR) and 95% confidence intervals (CI) for categorical data and mean, standard deviation (SD), and mean difference (MD) for continuous data. We used the GRADE approach to evaluate the certainty of evidence., Main Results: We identified one RCT that met our inclusion criteria. The study included 1858 African newborns at 35 weeks' gestation or greater who were receiving routine care at a well-baby nursery, and were randomly recruited prior to discharge to undergo TcB screening. The study had good methodologic quality. TcB screening versus visual assessment of hyperbilirubinemia in newborns: - probably reduces readmission to the hospital for hyperbilirubinemia (RR 0.25, 95% CI 0.14 to 0.46; P < 0.0001; moderate-certainty evidence); - may have little or no effect on the rate of exchange transfusion (RR 0.20, 95% CI 0.01 to 14.16; low-certainty evidence); - probably increases the number of newborns who require phototherapy prior to discharge (RR 2.67, 95% CI 1.56 to 4.55; moderate-certainty evidence). - may have little or no effect on the rate of acute bilirubin encephalopathy (RR 0.33, 95% CI 0.01 to 8.18; low-certainty evidence). The study did not evaluate or report cost of care., Authors' Conclusions: Moderate-certainty evidence suggests that TcB screening probably reduces hospital readmission for hyperbilirubinemia compared to visual inspection. Low-certainty evidence also suggests that TcB screening may have little or no effect on the rate of exchange transfusion compared to visual inspection. However, moderate-certainty evidence suggests that TcB screening probably increases the number of newborns that require phototherapy before discharge compared to visual inspection. Low-certainty evidence suggests that TcB screening may have little or no effect on the rate of acute bilirubin encephalopathy compared to visual inspection. Given that we have only identified one RCT, further studies are necessary to determine whether TcB screening can help to reduce readmission and complications related to neonatal hyperbilirubinemia. In settings with limited newborn follow-up after hospital discharge, identifying newborns at risk of severe hyperbilirubinemia before hospital discharge will be important to plan targeted follow-up of these infants., (Copyright © 2024 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Objective: Glucose-6-phosphate dehydrogenase deficiency (G6PDd) is the most common inherited enzyme deficiency disorder worldwide and a major risk factor for the development of severe hyperbilirubinemia. Racial diversity of phenotypes and genotypes in affected individuals is likely to exist in the United States because of changing population demographics. The aim of the present study was to predict an empirical estimate of annual prevalence of G6PDd in newborns adjusted for geography (state of birth), maternal racial identity, and sex of the infant., Study Design: Birth statistics (2019) from National Center for Vital Statistics and CDC-WONDER data and race-specific prevalence of G6PDd in the United States were evaluated from published sources. We developed Simpson's diversity index (DI) for each State and correlated these to rates of G6PDd in neonates. Descriptive statistics including modeled prevalence and its association with DI were assessed using the Spearman's rho correlation test. We modeled state-specific prevalence for six states (California, Washington DC, Illinois, Massachusetts, New York, and Pennsylvania) using population-level allele frequencies and race, based on Hardy-Weinberg equilibrium., Results: We estimated 78,010 (95% confidence interval: 76,768-79,252) newborns had G6PDd at birth in 2019 with cumulative median prevalence of 17.3 (interquartile range: 12.4-23.2) per 1,000 live births for United States. A strong association was noted for DI and prevalence of G6PDd ( p  < 0.0005). Five states (Washington DC, Mississippi, Louisiana, Georgia, and Maryland) have the highest projected G6PDd prevalence, with a range of 35 to 48 per 1,000 live births. The probability of G6PDd for female heterozygotes, based on male prevalence, ranged from 1.1 to 7.5% for each cohort in the select six states., Conclusion: States with diverse populations are likely to have higher rates of G6PDd. These prevalence estimates exceeded by several-fold when compared with disorders screened by existing state mandated newborn screening panels. These discrepancies are further confounded by known risk of severe neonatal hyperbilirubinemia that results with G6PDd and the life-long risk of hemolysis. Combined universal newborn predischarge screening for G6PDd and bilirubin could alert and guide a clinician's practices for parental education and closer medical surveillance during the vulnerable neonatal time period., Key Points: · G6PDd is a common X-linked disorder that can present with varied phenotypes among newborns.. · Prevalence of G6PDd and genotype distribution varies with sex, race, and ethnicity.. · We present regional race- and sex-based estimates of G6PDd in the United States.., Competing Interests: None declared., (Thieme. All rights reserved.)

Objective: Initiatives, "Every Newborn Action Plans" and "Sustainable Developmental Goals," are profoundly shaping global infant mortality trends. Concurrently, professional organizations recommended curricula to prevent extreme hyperbilirubinemia (EHB) sequelae. Therefore we assessed if these efforts have successfully decreased EHB-related mortality over time., Study Design: We used the Global Burden of Diseases 2019 database to determine neonatal and infant mortality and the burden of kernicterus from 1990-2019., Results: Globally, kernicterus accounted for 2.8 million infant deaths and trended downwards significantly from 1990 to 2019. By 2019, kernicterus-related mortality was 4 and 293 per million livebirths in high (HICs) and low income countries (LICs), respectively. 82% of deaths occurred in LICs and lower-middle income-countries. Average declines of mortality rates were 6.2% and 3.0% for HICs and LICs, respectively., Conclusions: Kernicterus-related mortality has been effectively reduced to <5 per million in HICs. Skills and knowledge transfer can potentially transform frontline services to bridge discordant kernicteric outcomes worldwide., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Extreme hyperbilirubinemia leading to neurologic disability and death is disproportionately higher in low- and middle-income countries (LMIC) such as Bangladesh, and is largely preventable through timely treatment. In LMICs, an estimated half of all newborns are born at home and few receive screening or treatment for hyperbilirubinemia, leading to 6 million newborns per year who need phototherapy treatment for hyperbilirubinemia but are untreated. Household screening and treatment for neonatal hyperbilirubinemia with phototherapy administered by a trained community health worker (CHW) may increase indicated treatment for neonatal hyperbilirubinemia in comparison to the existing care system in Bangladesh., Methods: 530 Bangladeshi women in their second or third trimester of pregnancy from the rural community of Sakhipur, Bangladesh will be recruited for a cluster randomized trial and randomized to the intervention arm - home screening and treatment for neonatal hyperbilirubinemia - or the comparison arm to receive usual care. In the intervention arm, CHWs will provide mothers with two prenatal visits, visit newborns by 2 days of age and then daily for 3 days to measure transcutaneous bilirubin (TcB) and monitor for clinical danger signs. Newborns without danger signs but with a TcB above the treatment threshold, but >15 mg/dL will be treated with light-emitting diode (LED) phototherapy at home. Newborns with danger signs or TcB ≥15 mg/dL will be referred to a hospital for treatment. Treatment rates for neonatal hyperbilirubinemia in each arm will be compared., Conclusion: This study will evaluate the effectiveness of CHW-led home phototherapy to increase neonatal hyperbilirubinemia treatment rates in rural Bangladesh. LMICs are expanding access to postnatal care by using CHWs, and our work will give CHWs a curative treatment option for neonatal hyperbilirubinemia. Similar projects in other LMICs can be pursued to dramatically extend healthcare access to vulnerable newborns with hyperbilirubinemia., Competing Interests: No competing interests were disclosed., (Copyright: © 2024 Foote EM et al.)

Identifying "gold standard" diagnostic tests can promote evidence-based neonatology practice. Hemolysis is a pathological shortening of the erythrocyte lifespan, differing from erythrocyte senescence in responsible mechanisms and clinical implications. Diagnosing hemolysis goes beyond a binary (yes vs. no) determination. It is characterized according to magnitude, and as acute vs. chronic, and genetically based vs. not. For neonates with significant hyperbilirubinemia or anemia, detecting hemolysis and quantifying its magnitude provides diagnostic clarity. The 2022 American Academy of Pediatrics (AAP) Clinical Practice Guideline on management of hyperbilirubinemia in the newborn states that hemolysis is a risk factor for developing significant hyperbilirubinemia and neurotoxicity. The guideline recommends identifying hemolysis from any cause, but specific guidance is not provided. A spectrum of laboratory tests has been endorsed as diagnostic methods for hemolysis. Herein we examine these laboratory tests and recommend one as the "gold standard" for diagnosing and quantifying hemolysis in neonates and infants., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Jaundice is a very common condition in newborns, affecting up to 60% of term newborns and 80% of preterm newborns in the first week of life. Jaundice is caused by increased bilirubin in the blood from the breakdown of red blood cells. The gold standard for measuring bilirubin levels is obtaining a blood sample and processing it in a laboratory. However, noninvasive transcutaneous bilirubin (TcB) measurement devices are widely available and used in many settings to estimate total serum bilirubin (TSB) levels., Objectives: To determine the diagnostic accuracy of transcutaneous bilirubin measurement for detecting hyperbilirubinaemia in newborns., Search Methods: We searched CENTRAL, MEDLINE, Embase, CINAHL and trial registries up to 18 August 2022. We also checked the reference lists of all included studies and relevant systematic reviews for other potentially eligible studies., Selection Criteria: We included cross-sectional and prospective cohort studies that evaluated the accuracy of any TcB device compared to TSB measurement in term or preterm newborn infants (0 to 28 days postnatal age). All included studies provided sufficient data and information to create a 2 × 2 table for the calculation of measures of diagnostic accuracy, including sensitivities and specificities. We excluded studies that only reported correlation coefficients., Data Collection and Analysis: Two review authors independently applied the eligibility criteria to all citations from the search and extracted data from the included studies using a standard data extraction form. We summarised the available results narratively and, where possible, we combined study data in a meta-analysis., Main Results: We included 23 studies, involving 5058 participants. All studies had low risk of bias as measured by the QUADAS 2 tool. The studies were conducted in different countries and settings, included newborns of different gestational and postnatal ages, compared various TcB devices (including the JM 101, JM 102, JM 103, BiliChek, Bilitest and JH20-1C) and used different cutoff values for a positive result. In most studies, the TcB measurement was taken from the forehead, sternum, or both. The sensitivity of various TcB cutoff values to detect significant hyperbilirubinaemia ranged from 74% to 100%, and specificity ranged from 18% to 89%., Authors' Conclusions: The high sensitivity of TcB to detect hyperbilirubinaemia suggests that TcB devices are reliable screening tests for ruling out hyperbilirubinaemia in newborn infants. Positive test results would require confirmation through serum bilirubin measurement., (Copyright © 2023 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.)

Background: Targeted rapid degradation of bilirubin has the potential to thwart incipient bilirubin encephalopathy. We investigated a novel spinel-structured citrate-functionalized trimanganese tetroxide nanoparticle (C-Mn 3 O 4 NP, the nanodrug) to degrade both systemic and neural bilirubin loads., Method: Severe neonatal unconjugated hyperbilirubinemia (SNH) was induced in neonatal C57BL/6j mice model with phenylhydrazine (PHz) intoxication. Efficiency of the nanodrug on both in vivo bilirubin degradation and amelioration of bilirubin encephalopathy and associated neurobehavioral sequelae were evaluated., Results: Single oral dose (0.25 mg kg -1 bodyweight) of the nanodrug reduced both total serum bilirubin (TSB) and unconjugated bilirubin (UCB) in SNH rodents. Significant (p < 0.0001) UCB and TSB-degradation rates were reported within 4-8 h at 1.84 ± 0.26 and 2.19 ± 0.31 mg dL -1 h -1 , respectively. Neural bilirubin load was decreased by 5.6 nmol g -1 (p = 0.0002) along with improved measures of neurobehavior, neuromotor movements, learning, and memory. Histopathological studies confirm that the nanodrug prevented neural cell reduction in Purkinje and substantia nigra regions, eosinophilic neurons, spongiosis, and cell shrinkage in SNH brain parenchyma. Brain oxidative status was maintained in nanodrug-treated SNH cohort. Pharmacokinetic data corroborated the bilirubin degradation rate with plasma nanodrug concentrations., Conclusion: This study demonstrates the in vivo capacity of this novel nanodrug to reduce systemic and neural bilirubin load and reverse bilirubin-induced neurotoxicity. Further compilation of a drug-safety-dossier is warranted to translate this novel therapeutic chemopreventive approach to clinical settings., Impact: None of the current pharmacotherapeutics treat severe neonatal hyperbilirubinemia (SNH) to prevent risks of neurotoxicity. In this preclinical study, a newly investigated nano-formulation, citrate-functionalized Mn 3 O 4 nanoparticles (C-Mn 3 O 4 NPs), exhibits bilirubin reduction properties in rodents. Chemopreventive properties of this nano-formulation demonstrate an efficacious, efficient agent that appears to be safe in these early studies. Translation of C-Mn 3 O 4 NPs to prospective preclinical and clinical trials in appropriate in vivo models should be explored as a potential novel pharmacotherapy for SNH., (© 2022. The Author(s), under exclusive licence to the International Pediatric Research Foundation, Inc.)

Background and Objectives: Glucose-6-Phosphate Dehydrogenase (G6PD) deficiency is frequent inherited enzymopathy that poses potentially preventable risk for extreme hyperbilirubinemia (EHB) which can, rarely, lead to acute bilirubin encephalopathy, childhood kernicterus and death. We aimed to estimate quality adjusted life years (QALY) lost due to G6PD deficiency associated with EHB and economic costs to best estimate value of universal pre-discharge screening., Methods: We did a cost utility analysis for US birth cohort utilizing pre-discharge screening decision tree model to estimate population burden and EHB outcomes, based on literature search and expert opinions. Employing human capital approach, we measured health benefits in terms of QALYs and economic losses. QALYs and costs were discounted at 3%; one-way sensitivity analysis was used for decision variables., Results: We determined for USA live births of 3.86 million in 2017, 1464 cases of EHB were estimated to be due to G6PD deficiency (CI 95%; range: 1270-1656) and contributed 2 deaths (CI 95%; range 1.3-3.2) and 14 (CI 95%; range: 9.1-21.5) cases of kernicterus. Over lifetime horizon, the model predicted undiscounted and discounted gains of 165 (102-252) life years; 241 (183-433) QALYs and 16 (9.9-24.5) life years; 89 (67.9-160.5) QALYs, respectively. Assuming 50% effectiveness, benefit cost ratios ranged from 0.19 to 3.42 for diverse operational settings. The cost to prevent a single case of kernicterus was $2.7 to 6.8 million per annum with cost per QALY gained at $35,946 to $89,159., Conclusion: At incremental cost-effective threshold of $100,000/life year, pre-discharge screening would be expected to prove cost effective in preventing EHB related morbidities and mortality attributed to G6PD deficiency.

Competing Interests: FINANCIAL/CONFLICT OF INTEREST DISCLOSURES: Dr Newman reported providing expert witness consultation in medical malpractice litigation. Dr Maisels reported providing expert witness review and testimony in kernicterus medical malpractice litigation. Dr Watchko disclosed a financial relationship with McGraw Hill. Dr Grout reported receiving grant funding from Pfizer for a non-pediatric study. Dr Bogen disclosed a Board of Directors relationship with Mid-Atlantic Mothers’ Milk Bank. No other disclosures were reported., (Copyright © 2022 by the American Academy of Pediatrics.)

Objective: To develop a statistically rigorous, hour-specific bilirubin nomogram for newborns based on a very large data set; and use it prospectively as a replacement for the 1999 Bhutani nomogram., Study Design: This was a retrospective analysis of first total serum bilirubin (TSB) measurements from 15 years of universal bilirubin screening during birth hospitalizations at 20 Intermountain Healthcare hospitals. Hour-specific TSB values were assembled into a nomogram by percentile, and subgroups were compared., Results: The information obtained included robust data in the first 12 hours after birth (which was not included in the 1999 nomogram), general agreement with the 1999 nomogram for values in the first 60 hours, but higher 75th and 95th percentile TSB values thereafter in the new version, no difference in TSB between male and female infants, higher TSB values among earlier gestation neonates (35 0/7 -36 6/7  weeks vs ≥37 weeks, P < .0001), and lower TSB values in neonates of Black race (P < .0001) and higher values in neonates of Asian race (P < .001)., Conclusions: An updated and more informative Bhutani neonatal bilirubin nomogram, based on 140 times the number of subjects included the 1999 version, is now in place in our health care system., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Glucose-6-phosphate dehydrogenase (G6PD) deficiency rarely manifests as extreme hyperbilirubinemia [EHB, total serum/plasma bilirubin > 25 mg/dL (428 µmol/L)]. It is a major preventable cause of newborn morbidity and mortality. In resource-constrained communities of Nigeria, experts have observed its significant clinical burden. We accessed a previously published pooled model of G6PD deficiency and determined its prevalence, subsequent risk of EHB, kernicterus, and death to be 26.4% [95% confidence interval (CI): 19.5, 33.2%]; 33.3% (95%CI: 16.6, 50%); and 22.7% (95% CI: 16.5, 28.9%), respectively. The total number of disability-adjusted life years (DALYs) lost to symptomatic G6PD deficiency was 54,251 (95% CI: 6,039, 189,149). Estimated national average economic deficits due to mortality and disability ranged from $309 to $584 million. G6PD deficiency, when symptomatic in Nigerian newborns, is a significant disease burden, placing 1% of annual births at increased risks of neonatal mortality and morbidity, which contribute to significant economic productivity losses., Competing Interests: Declaration of Competing Interest The authors report no proprietary or commercial interest in any product mentioned or concept discussed in this article., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Extreme hyperbilirubinemia can cause bilirubin neurotoxicity. Infants with glucose-6-phosphate dehydrogenase (G6PD) deficiency can develop hemolysis and thus are at high risk. We evaluated a device that quantitatively measures G6PD activity kinetically using digital microfluidics (DMF). Intra- and inter-instrument and -day imprecision (CVs) were first assessed. G6PD activity in 86 samples was then measured and compared between DMF and 2 reference methods. Overall DMF reproducibility was 3.8% over 5 days by 2 operators on 2 instruments. Mean intra- and inter-instrument variabilities were 3.6% and 3.9%, respectively (n = 28), with a user variability of 4.3%. Mean G6PD activity was 6.40±4.62 and 6.37±4.62 U/g hemoglobin for DMF and Reference Methods 1 (n = 46) and 12.15±3.86 and 11.48±1.55 for DMF and 2 (n = 40), respectively, and strongly correlated (r = 0.95 and 0.95) with mean biases of +0.04±2.90 and +0.67±1.55 for methods 1 and 2, respectively. The novel device could be used for early newborn G6PD screening., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

The predominant cause of elevated total/plasma bilirubin (TB) levels is from an increase in bilirubin production primarily because of ongoing hemolysis. If undiagnosed or untreated, the risk for developing extreme neonatal hyperbilirubinemia and possibly bilirubin-induced neurological dysfunction (BIND) is increased. Since carbon monoxide (CO) and bilirubin are produced in equimolar amounts during the heme catabolic process, measurements of end-tidal CO levels, corrected for ambient CO (ETCOc) can be used as a direct indicator of ongoing hemolysis. A newly developed point-of-care ETCOc device has been shown to be a useful for identifying hemolysis-associated hyperbilirubinemia in newborns. This review summarizes the biology of bilirubin production, the clinical utility of a novel device to identify neonates undergoing hemolysis, and a brief introduction on the use of ETCOc measurements in a cohort of neonates in China., Competing Interests: Declaration of Competing Interest The authors declare no conflicts of interest., (Copyright © 2020 Elsevier Inc. All rights reserved.)

This study assessed a large-scale national distribution of phototherapy (PT) for infants at risk for severe hyperbilirubinemia. We combined healthcare data for infants with jaundice (using local clinical definitions) with a randomized roll-out of PT devices to estimate the causal effect of the national distribution. Pre-intervention, <3.0% of infants were diagnosed as jaundiced, 41.7% of these infants were not tested for bilirubin, and 17.5% and 34.3% were treated with direct sunlight or standard PT, respectively. We found that providing hospitals with PT devices increased care practices: infants with jaundice were more likely to receive PT [+6.26 percentage points (pp)], and less likely to receive sunlight (-6.96 pp) or standard (irradiance < 30 µW/cm 2 /nm) PT (-14.0 pp). However, the intervention did not affect the low diagnosis rate. Our findings suggest that complementary investments in improving diagnosis and monitoring of bilirubin levels increases the benefits of expanding provider access to PT devices., (Copyright © 2020. Published by Elsevier Inc.)

Introduction: As preterm infants are susceptible to hyperbilirubinemia, they require frequent close monitoring. Prior to initiation of phototherapy, hour-specific total serum bilirubin (TSB) percentile cut-points are lacking in these infants, which led to the current study., Methods: A multi-site retrospective cohort study of preterm infants born between January 2013 and June 2017 was completed at 3 NICUs in Ontario, Canada. A total of 2,549 infants born at 290/7-356/7 weeks' gestation contributed 6,143 pre-treatment TSB levels. Hour-specific TSB percentiles were generated using quantile regression, further described by degree of prematurity, and among those who subsequently received phototherapy., Results: Among all infants, at birth, hour-specific pre-treatment, TSB percentiles were 36.1 µmol/L (95% confidence interval [CI]: 34.3-39.3) at the 40th, 52.3 µmol/L (49.4-55.1) at the 75th, and 79.5 µmol/L (72.1-89.6) at the 95th percentiles. The corresponding percentiles were 39.3 μmol/L (35.9-43.2), 55.4 μmol/L (52.1-60.2), and 87.1 μmol/L (CI 70.5-102.4) prior to initiating phototherapy and 24.4 μmol/L (20.4-28.8), 35.3 μmol/L (31.1-41.5), and 52.0 μmol/L (46.1-62.4) among those who did not receive phototherapy. Among infants born at 29-32 weeks, pre-treatment TSB percentiles were 53.9 µmol/L (49.4-61.0) and 95.5 µmol/L (77.5-105.0) at the 75th and 95th percentiles, with respective values of 48.7 µmol/L (43.0-52.3), and 74.1 µmol/L (64.8-83.2) for those born at 33-35 weeks' gestation., Conclusion: Hour-specific TSB percentiles, derived from a novel nomogram, may inform how bilirubin is described in preterm newborns. Further research of pre-treatment TSB levels is required before clinical consideration., (© 2021 The Author(s) Published by S. Karger AG, Basel.)

Objective: Adherence to guidelines for phototherapy initiation in preterm infants was 39% in our academic NICU (61% of phototherapy was initiated at total bilirubin (TB) levels below recommended thresholds). We hypothesized that adoption of an electronic health record integrated clinical decision support (CDS) tool would improve adherence to phototherapy guidelines., Study Design: We developed and implemented Premie BiliRecs (PBR), a novel CDS tool for phototherapy initiation in preterm infants from 27 through 34 weeks postmenstrual age. The primary outcome measure was the proportion of phototherapy initiation events consistent with recommended TB thresholds., Result: Following the implementation of PBR, adherence to guidelines for phototherapy initiation in preterm infants increased to 69.8% (p < 0.001), an improvement of 77%. There was no increase in the incidence of severe hyperbilirubinemia nor exchange transfusions., Conclusion: The adoption of PBR was associated with improved adherence to phototherapy guidelines in preterm infants without increased adverse events.