A Significant Increase in the Incidence of Neonatal Hyperbilirubinemia and Phototherapy Treatment Due to a Routine Change in Laboratory Equipment.

CONTEXT.­: Total serum bilirubin (TSB) analysis is pivotal for diagnosing neonatal hyperbilirubinemia. Because of a routine change in laboratory equipment, our TSB assay changed from a diazo to a vanadate oxidase method. Upon implementation, TSB results were substantially higher in newborns than expected based on the validation. OBJECTIVE.­: To investigate the application of TSB and intermethod differences in neonates and their impact on phototherapy treatment. DESIGN.­: The diazo and vanadate methods were compared directly using neonatal and adult samples. Anonymized external quality control data were analyzed to explore interlaboratory differences among 8 commercial TSB assays. Clinical patient data were extracted from the medical records to investigate the number of newborns receiving phototherapy. RESULTS.­: The mean bias of the vanadate versus the diazo TSB method was +17.4% and +3.7% in neonatal and adult samples, respectively. External quality control data showed that the bias of commercial TSB methods compared with the reference method varied from -3.6% to +20.2%. Within-method variation ranged from 5.2% to 16.0%. After implementation of the vanadate TSB method, the number of neonates treated with phototherapy increased approximately threefold. CONCLUSIONS.­: Currently available TSB assays lack harmonization for the diagnosis of neonatal hyperbilirubinemia. Between-methods differences are substantially higher in neonatal compared with adult samples, highlighting the importance of including neonatal samples during assay validation. Close collaboration between laboratory specialists and clinicians is essential to prevent overtreatment or undertreatment upon the implementation of novel analyzers or assays. Also, harmonization of TSB assays, with an emphasis on neonatal application, is warranted.

Automated ABR screening for hearing loss and its clinical determinants among newborns with hyperbilirubinemia in National Hospital, Abuja, Nigeria.

Background: Severe neonatal hyperbilirubinemia is a known risk factor for sensorineural hearing loss which is usually undiagnosed in our environment until school age due to a lack of routine screening programs. Materials and Methods: This cross-sectional study conducted between August 2020 and February 2021 employed a universal sampling of consecutive eligible participants after their mothers' consent. Hearing screening was conducted using an automated auditory brainstem response (AABR) device (Otoport OAE + ABR®). The proportion of AABR screening failure was assessed while associated clinical risk factors were determined using logistic regression. Statistical significance was set at 5% for all comparative analyses. Results: One hundred and sixty newborns below 28 days of age, delivered at 34 weeks gestation and above, who had jaundice were recruited. The prevalence of screening AABR failure in at least one ear was 26.2%. Significant risk factors for AABR screening failure in addition to extreme and hazardous hyperbilirubinemia were acute bilirubin encephalopathy (ABE) (Odds Ratio (OR) =4.44, 95% CI = 3.19-6.17), birth weight below 2500 g (OR = 3.16, 95% CI = 1.48-6.77), dull tympanic membrane (TM) (OR = 5.94, 95% CI = 2.36-14.92) and exchange blood transfusion (OR = 4.84, 95% CI = 1.87-12.58). Conclusion and Recommendations: The prevalence of AABR screening failure was high, and a dull TM was its strongest predictor among late preterm and term neonates with hyperbilirubinemia. Otoscopy should be included in the care of newborn with hyperbilirubinemia and screening programs established to mitigate hearing loss among high-risk neonates in Abuja.

Prospective cohort study of neurodevelopmental outcomes following extreme neonatal hyperbilirubinaemia in Australia.

AIM: This study aimed to establish the incidence and nature of neurodevelopmental outcomes following extreme neonatal hyperbilirubinaemia in an Australian cohort. METHODS: A prospective cohort study of neurodevelopmental outcomes up to 3 years of age of infants born between 2010 and 2013 at ≥34 weeks gestation, with total serum bilirubin ≥450 µmol/L and/or clinical signs of acute bilirubin encephalopathy. Outcome measures comprised neurological examination, Bayley Scales of Infant and Toddler Development, 3rd edition and Ages and Stages Questionnaire, 3rd edition. RESULTS: The Australian estimated incidence of kernicterus is 0.35 per 100 000 live births. Within the follow-up cohort of 26, three children have clinical neurodevelopmental impairment: one has gross motor function classification system level 4 cerebral palsy, audiological deficiency and visual impairment; the second has gross motor function classification system level 1 cerebral palsy and the third has global developmental delay with autism spectrum disorder. Mean Bayley Scales of Infant and Toddler Development, 3rd edition scores were: cognition 10.3 (SD 1.5), receptive communication 9.4 (SD 1.8), expressive communication 9.2 (SD 2.4), fine motor 10.4 (SD 2.6) and gross motor 9.2 (SD 2.3). CONCLUSION: The Australian national rate of kernicterus compares favourably with global estimates. Future preventative strategies in this context include universal neonatal hyperbilirubinaemia assessment and mandated adverse outcome reporting and investigation.

Neonatal jaundice: magnitude of the problem in Cairo University's neonatal intensive Care unit as a referral center.

Background: Neonatal jaundice is one of the most common physiologic problems requiring medical attention in newborns. It is benign in most cases; however, high levels of bilirubin are neurotoxic and can lead to serious brain damage. Objectives: This study aimed at assessment of magnitude of neonatal jaundice in cases of neonatal hyperbilirubinemia admitted into neonatal intensive care unit (NICU), Cairo University Pediatric Hospital and to detect possible etiologies, management and outcome. Methods: The present work is a retrospective study, included 789 neonates suffered from hyperbilirubinemia over a two-year period. Results: Intensive phototherapy and exchange transfusion were used together in 6 cases. Two hundreds and twenty-two cases (28.1%) had exchange transfusion once, 44 cases had it twice, 6 cases had it 3 times and one case had it 4 times. Number of exchange transfusion significantly affects mortality among cases (P= 0.02). Conclusion: Neonatal hyperbilirubinemia is an existing problem in our NICU. Intensive phototherapy is an excellent substitute for exchange transfusion. Respiratory distress and sepsis are significantly higher among dead cases. Screening for risk factors is needed to avoid critical hyperbilirubenemia.

Association between neonatal hyperbilirubinemia and hypoglycemia in Chinese women with diabetes in pregnancy and influence factors.

This retrospective study aimed to investigate the correlation between neonatal hyperbilirubinemia (NHB) and hypoglycemia (NH) in Chinese women with diabetes in pregnancy (DIP), and the influencing factors. All the data were collected July 1, 2017 and June 30, 2020, and 10,558 Chinese women with DIP and live births were included. Two separate multivariate binary stepwise forward logistic regression analysis calculated OR with 95% CI. The prevalence rates of NHB and NH was respectively 3.65% and 5.82% among women with DIP. The comorbidity of both diseases was 0.59%. NH were 1.81 times (OR 1.81, 1.19-2.76) more likely to have hyperbilirubinemia. NHB is positively correlated with NH (OR 1.93, 1.27-2.92). Increased gestational age has a protective effect on both NH (OR 0.76, 0.68-0.85) and NHB (OR 0.80, 0.69-0.92). Abnormal placental morphology is related to NH (OR 1.55, 1.16-2.08) and NHB (OR 1.64, 1.10-2.45). Regarding neonatal outcomes, congenital heart disease (CHD) (OR 2.16, 1.25-3.73; and OR 10.14, 6.47-15.90) was a risk factor for NH and NHB. NHB and NH were significantly correlated in women with DIP. The offspring of DIP with multiple risk factors have a significantly increased risk of neonatal hyperbilirubinemia.

High rates of neonatal polycythemia and hyperbilirubinemia during the first phase of COVID-19 pandemic in Italy: a single-center experience.

In our third-level Neonatal Unit in Northern Italy, we recorded a high rate of neonatal hyperbilirubinemia requiring phototherapy in March-November 2020, during the first phase of COVID-19 pandemic, compared to the previous year (198/1348, 14.2%, vs 141/1432, 9.8%, p = 0.0004). Supposing it could be the result of neonatal polycythemia, we evaluated capillary hematocrit (Hct) and the rate of hyperbilirubinemia in all newborns ≥36 weeks gestational age born in December 2020. Out of 73 neonates, 37 had Hct ≥65% (50.7%). However, as capillary blood samples may overestimate Hct by 5-15%, even downsizing all values by 15%, Hct was still ≥65% in 9/73 neonates (12.3%), much higher than 0.4-5% prevalence of polycythemia reported in healthy newborns. All those newborns were singleton and healthy, with no clinical signs of hyperviscosity and no underlying factors predisposing to polycythemia. Out of 73 newborns, 13 (17.8%) developed hyperbilirubinemia requiring phototherapy. Their mean Hct value was 66.3 ± 8.2%. Since hyperbilirubinemia is common in the offspring of women with SARS-CoV-2 infection and we recorded increased rates of neonatal hyperbilirubinemia in the first phase of COVID-19 pandemic, it could be hypothesized that even asymptomatic Sars-CoV2 infection during pregnancy might cause placental vascular malperfusion, eliciting polycythemia in the fetus as a compensatory response, that could be the link between COVID-19 in the mothers and hyperbilirubinemia in the newborns.

Severe neonatal hyperbilirubinaemia: lessons learnt from a national perinatal audit.

OBJECTIVES: To describe characteristics of neonates with severe neonatal hyperbilirubinaemia (SNH) and to gain more insight in improvable factors that may have contributed to the development of SNH. DESIGN AND SETTING: Descriptive study, based on national Dutch perinatal audit data on SNH from 2017 to 2019. PATIENTS: Neonates, born ≥35 weeks of gestation and without antenatally known severe blood group incompatibility, who developed hyperbilirubinaemia above the exchange transfusion threshold. MAIN OUTCOME MEASURES: Characteristics of neonates having SNH and corresponding improvable factors. RESULTS: During the 3-year period, 109 neonates met the eligibility criteria. ABO antagonism was the most frequent cause (43%). All neonates received intensive phototherapy and 30 neonates (28%) received an exchange transfusion. Improvable factors were mainly related to lack of knowledge, poor adherence to the national hyperbilirubinaemia guideline, and to incomplete documentation and insufficient communication of the a priori hyperbilirubinaemia risk assessment among healthcare providers. A priori risk assessment, a key recommendation in the national hyperbilirubinaemia guideline, was documented in only six neonates (6%). CONCLUSIONS: SNH remains a serious threat to neonatal health in the Netherlands. ABO antagonism frequently underlies SNH. Lack of compliance to the national guideline including insufficient a priori hyperbilirubinaemia risk assessment, and communication among healthcare providers are important improvable factors. Implementation of universal bilirubin screening and better documentation of the risk of hyperbilirubinaemia may enhance early recognition of potentially dangerous neonatal jaundice.

Increased prevalence of severe neonatal hyperbilirubinaemia during social distancing.

AIM: Social distancing guidelines implemented with the COVID-19 pandemic impacted health-care utilisation and disrupted critical social supports. Resurgence of highly transmissible strains has resulted in revisiting restrictions with potential impacts on newborn health. With concerns for inadequate post-partum support, we sought to determine if social distancing correlated with increased rates of readmission for hyperbilirubinaemia. METHODS: Retrospective chart review identified all readmissions for hyperbilirubinaemia between 1/18 and 4/20 in Western New York. Infant/maternal demographics and data on hospital course were collected on control (1/1/18-31/1/20) and social distancing (1/2/20-30/4/20) cohorts. Nineteen outpatient clinics were surveyed regarding lactation support. RESULTS: Monthly readmissions for hyperbilirubinaemia nearly tripled during social distancing (0.90 ± 0.91 vs. 2.63 ± 2.29 per 1000 births during early COVID, P = 0.015). Comparable severity of disease at readmission was observed with no difference in the need for therapies (phototherapy, intravenous immunoglobulin or exchange transfusion) or length of hospital stay. Mothers were younger (25.8 ± 3.3 vs. 31.3 ± 4.7 years; P = 0.005) with higher rates of primiparity and exclusive breastfeeding than national norms, however not significantly higher than controls in our small cohort (62.5 vs. 37.0% for primiparity; 87.5 vs. 81.5% for breastfeeding). Of 19 clinics surveyed, only six confirmed a telemedicine option for lactation support. CONCLUSIONS: Rates of readmission for hyperbilirubinaemia increased during social distancing. Younger maternal age with high rates of primiparity and exclusive breastfeeding raise concern for inadequate social and/or lactation support. Proactive identification of mothers at risk and expansion of remote lactation services may be indicated with recurrent waves of the pandemic.

Exposure to air pollutants during pregnancy and after birth increases the risk of neonatal hyperbilirubinemia.

OBJECTIVES: Exposure to air pollution is associated with increased risks of several adverse conditions in newborns, such as preterm birth. Whether air pollution is associated with neonatal hyperbilirubinemia remains unclear. We aimed to develop and validate an air-quality-based model to better predict neonatal hyperbilirubinemia. METHODS: A multicenter, population-based cohort of neonates with a gestational age (GA) ≥35 weeks and birth weight ≥2000 g was enrolled in the study. The study was conducted in Shanghai, China, from July 2017 to December 2018. The daily average concentrations of particulate matter (PM) with aerodynamic diameters≤2.5 µm (PM2.5) and ≤10 µm (PM10), sulfur dioxide (SO2), nitrogen dioxide (NO2) and carbon monoxide (CO) were measured. Neonatal hyperbilirubinemia was diagnosed according to the American Academy of Pediatrics (AAP) guidelines by trained neonatologists. We used logistic least absolute shrinkage and selection operator (LASSO) regression to screen air pollutant indicators related to neonatal hyperbilirubinemia and build an air-quality signature for each patient. An air-quality-based nomogram was then established to predict the risk of neonatal hyperbilirubinemia. RESULTS: A total of 11196 neonates were evaluated. Prenatal PM10, CO and NO2 exposure and postpartum SO2 exposure were significantly associated with neonatal hyperbilirubinemia. The air-quality score was calculated according to the hyperbilirubinemia-related pollutants. The air-quality score of the hyperbilirubinemia group was significantly higher than that of the nonhyperbilirubinemia group (P < .01, odds ratio = 2.97). An air-quality-based logistic regression model was built and showed good discrimination (C-statistic of 0.675 [95% CI (confidence interval), 0.658 to 0.692]) and good calibration. Decision curve analysis showed that the air-quality-based model was better than the traditional clinical model in predicting neonatal hyperbilirubinemia. CONCLUSIONS: The findings of this study suggest that ambient air pollution exposure is associated with an increased risk of neonatal hyperbilirubinemia. Our results encourage further exploration of this possibility in future studies.

Maternal Exposure to Air Pollution Is Associated with Neonatal Jaundice: A Retrospective Cohort Study.

OBJECTIVE: To evaluate the association between maternal ambient pollutant exposure and neonatal jaundice in multiple pollutant species and examine sex differences. STUDY DESIGN: Epidemiologic study: Records of 13 297 newborns (6153 male, 7144 female) born in Taichung, Taiwan were obtained from a national database. Average concentrations of prenatal air pollutants 3 months prior to birth were divided into low, middle, and high levels. Neonatal jaundice phototherapy rates between mothers who suffered varying air pollutant levels were compared. Clinical study: Three hundred seventy-six newborns (189 male, 187 female) born and received jaundice treatment with phototherapy in a hospital in Taichung, Taiwan were recruited. The correlation between prenatal exposure to air pollutants 3 months prior to birth, newborn's serum bilirubin, and serum hemoglobin were calculated. RESULTS: Epidemiologic study: Male newborns born to mothers exposed to high carbon monoxide (CO), nitric oxide (NO), nitrogen dioxide (NO2), and methane (CH4) levels had higher phototherapy rates. In female newborns, the same was noted for CO and CH4. Clinical study: Male newborns had a positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO, NO2, nonmethane hydrocarbon, and CH4 exposure 3 months prior to birth and serum bilirubin levels. Female newborns had a positive correlation for CH4. A positive correlation between CO, ≤2.5 µm diameter particles, ≤10 µm diameter particles, NO2, nonmethane hydrocarbon, CH4 exposure, and serum hemoglobin levels was noted in male newborns. CONCLUSION: Maternal exposure to air pollutants may increase neonatal jaundice treatment rates for phototherapy and higher neonatal serum total bilirubin level. Higher hemoglobin levels because of higher pollutant exposures may explain our findings. The association was more obvious in male newborns.

Neonatal hyperbilirubinemia and bilirubin neurotoxicity in hospitalized neonates: analysis of the US Database.

OBJECTIVE: The objective of this study was to assess the prevalence and trends for neonatal hyperbilirubinemia, and the development of bilirubin neurotoxicity in the USA. STUDY DESIGN: We used a de-identified national dataset for the years 2002-2017. The study included all newborn inpatients with postnatal age ≤28 days. Cochran-Armitage trend test was used for trend analyses. Regression analyses were performed and adjusted odds ratios (aOR) were reported. RESULTS: The study included 57,989,476 infants; of them 53,259,758 (91.8%) were term infants and 4,725,178 (8.2%) were preterm infants. Bilirubin neurotoxicity decreased over the years in term infants (Z = 0.36, p = 0.03) without change in preterm infants (Z = 42.5, p = 0.12). Black neonates were less likely to be diagnosed with hyperbilirubinemia than White neonates (aOR = 0.77, 95% confidence interval (CI): 0.77-0.78, p < 0.001) and more likely to develop bilirubin neurotoxicity than White neonates (aOR = 3.0.5, 95% CI: 2.13-4.36, p < 0.001). Bilirubin neurotoxicity rate in the overall population was 2.4 per 100,000 live births. CONCLUSIONS: Bilirubin neurotoxicity has significantly decreased in term infants and did not change in preterm infants. Despite the less diagnosis of hyperbilirubinemia in Black newborns, they are disproportionately at increased risk of developing bilirubin neurotoxicity when compared to White newborns. IMPACT: In this article, we analyzed the National Inpatient Database. This is the largest study of its kind using data on 57,989,476 neonates. The article has multiple novel findings: (1) it demonstrated that utilization of phototherapy has increased significantly over the years, (2) the rate of kernicterus for neonates decreased in term infants and did not change in preterm babies, (3) kernicterus was mostly encountered in infants without isoimmunization jaundice, and (4) there is a clear racial disparity in neonatal jaundice; although Black newborns have less neonatal jaundice, they are at increased risk of developing kernicterus.

Regional variation in the development of neonatal hyperbilirubinemia and relation with sunshine duration in Japan: an ecological study.

BACKGROUND: Few studies have investigated the regional variations in the development of neonatal hyperbilirubinemia. This study aimed to investigate regional variations in medical costs for neonatal hyperbilirubinemia and the correlations between sunshine duration and medical care costs for neonatal hyperbilirubinemia in an ecological study, using the National Database of Japan. METHODS: We obtained data on the annual medical costs for neonatal hyperbilirubinemia, annual live births, and annual sunshine duration in each prefecture from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB) Open Data, Vital Statistics in Japan, and System of Social and Demographic Statistics Prefectural Data Basic Data from 2014 to 2017. We created choropleth maps showing the regional variations (quartiles) in the annual medical costs for neonatal hyperbilirubinemia per 10 live births and the annual sunshine duration in each prefecture. We used Pearson's correlation coefficients to evaluate the associations between the annual sunshine duration and annual medical care costs for neonatal hyperbilirubinemia per 10 live births in each prefecture. RESULTS: The Tohoku region (on the Sea of Japan side) and the Hokuriku region were likely to have higher medical care costs for neonatal hyperbilirubinemia and shorter sunshine duration than the rest of the country. There were weak and negative correlations between the annual sunshine duration and the annual medical care costs for neonatal hyperbilirubinemia. The correlation coefficients ranged from -0.086 to -0.33. CONCLUSION: There could be regional variations in the medical care costs for neonatal hyperbilirubinemia in Japan. Short sunshine duration could be a prognostic factor for the development of neonatal hyperbilirubinemia.

Nursing diagnosis neonatal hyperbilirubinemia: A survival analysis.

PURPOSE: To analyze the short-term survival of the nursing diagnosis of neonatal hyperbilirubinemia in hospitalized neonates within the first 24 h of life and over a maximum of 7 days. METHODS: A prospective open cohort study with a longitudinal design was developed with 120 newborns during the first 24 h of life. The survival rate after a nursing diagnosis of neonatal hyperbilirubinemia was analyzed for 7 days. FINDINGS: The number of new cases of neonatal hyperbilirubinemia during the follow-up was 82 (RR: 90.1%, daily incidence rate: 34.17%). The greatest manifestation of the diagnosis occurred in the first three days (n = 97). The median diagnostic survival time was 2 days (95% CI: 2-2). Yellow-orange skin color (RR = 8.08), yellow mucous membranes (RR = 2.05), yellow sclera (RR = 1.99), and female gender (RR = 1.36) had the highest risk ratios. CONCLUSIONS: A rapid impairment of neonatal hyperbilirubinemia in hospitalized neonates was observed. Some clinical indicators were associated with an increased risk for this diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Studies on the prognostic capacity of the clinical indicators of nursing diagnoses like neonatal hyperbilirubinemia strengthen the clinical reasoning of nurses and subsidize diagnostic inferences and accurate clinical decisions.

Trends in hospitalizations of newborns with hyperbilirubinemia and kernicterus in United States: an epidemiological study.

BACKGROUND: Hyperbilirubinemia is one of the most common diagnosis in newborn nurseries in United States. Universal pre-discharge bilirubin screening decreased the incidence of extreme hyperbilirubinemia and risk of kernicterus. OBJECTIVES: We sought to assess temporal population trends of hyperbilirubinemia, kernicterus and usage of phototherapy, intravenous immunoglobulin (IVIG), and exchange transfusion. DESIGN/METHODS: Data from Healthcare Cost and Utilization Project (HCUP)-the Kids' Inpatient Database (KID) obtained for years 1997-2012. All neonatal discharges with ICD-9 codes for neonatal jaundice (774.2, 774.6), kernicterus (773.4, 774.7) and procedure codes for phototherapy (99.83), IVIG infusion (99.14), exchange transfusion (99.01) were extracted. We compared the trends of diagnosis of hyperbilirubinemia, kernicterus, use of phototherapy, IVIG, and exchange transfusion. RESULTS: During the study period, the proportion of infants diagnosed with hyperbilirubinemia increased by 65% (9.4% vs. 15.5%; p<.001) in term infants and 34.5% (33.5% vs. 45%; p<.001) in preterm infants, respectively. Rate of kernicterus discharges significantly reduced from 7 to 1.9 per 100,000 newborns. Overall, the number of exchange transfusions has decreased by 67% during study period while phototherapy and IVIG use increased by 83% and 170%, respectively. CONCLUSIONS: In last two decades, there was a significant decrease in neonatal discharges with a history of exchange transfusion or with a diagnosis of kernicterus. However, there was a significant increase in number of neonates discharged home with a history of phototherapy during birth hospitalization and decreased number of exchange transfusions were observed during the study period. Incremental implementation of universal predischarge bilirubin screening and treatments based on 2004 AAP recommended risk-based strategies might have contributed to timely interventions in infants with significant hyperbilirubinemia.

The Association between Serum Bilirubin and Kernicterus Spectrum Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Total serum bilirubin (TSB) is used in managing neonates with jaundice, but clear evidence on its association with major outcomes is lacking. OBJECTIVES: We evaluated the association between TSB and kernicterus spectrum disorder (KSD). METHODS: We searched PubMed, EMBASE, and CENTRAL till July 2021. Two authors independently selected relevant cohort studies, extracted data (CHARMS checklist), assessed risk of bias (RoB) (QUIPS tool), and rated certainty-of-evidence (Grades of Recommendation, Assessment, Development, and Evaluation). We pooled adjusted odds ratio (aOR) (random-effect) via generic inverse variance methods. RESULTS: From 2,826 records retrieved, we included 37 studies (n = 648,979). Fifteen studies had low, 16 moderate, and 6 high RoB, with majority having concerns on confounder adjustment and statistical analysis. Twenty-two studies contributed meta-analysis data, and 15 were summarized narratively. TSB appears associated with KSD in infants with certain risk factors (aOR 1.10, 95% CI: 1.07-1.13; 5 studies [n = 4,484]). However, TSB (aOR 1.10, 95% CI: 0.98-1.23; 1 study [n = 34,533]) or hyperbilirubinemia (aOR 1.00, 95% CI: 0.51-1.95; 2 studies [n = 56,578]) have no clear association with kernicterus or neurological diagnosis in overall neonatal population (moderate-certainty-evidence). One study shows that infants with hyperbilirubinemia appear likelier to develop attention-deficit disorder (aOR 1.90, 95% CI: 1.10-3.28) and autistic spectrum disorder (aOR 1.60, 95% CI: 1.03-2.49, n = 56,019) (low-certainty-evidence). Certain clinical factors appear associated with KSD, although very few studies contributed to the analyses. CONCLUSIONS: Despite the importance of this question, there is insufficient high-quality evidence on the independent prognostic value of TSB for adverse neurodevelopmental outcomes in most neonatal populations. Future studies should incorporate all known risk factors alongside TSB in a multivariable analysis to improve certainty-of-evidence.

Sunlight for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates.

BACKGROUND: Acute bilirubin encephalopathy (ABE) and the other serious complications of severe hyperbilirubinemia in the neonate occur far more frequently in low- and middle-income countries (LMIC). This is due to several factors that place babies in LMIC at greater risk for hyperbilirubinemia, including increased prevalence of hematologic disorders leading to hemolysis, increased sepsis, less prenatal or postnatal care, and a lack of resources to treat jaundiced babies. Hospitals and clinics face frequent shortages of functioning phototherapy machines and inconsistent access to electricity to run the machines. Sunlight has the potential to treat hyperbilirubinemia: it contains the wavelengths of light that are produced by phototherapy machines. However, it contains harmful ultraviolet light and infrared radiation, and prolonged exposure has the potential to lead to sunburn, skin damage, and hyperthermia or hypothermia. OBJECTIVES: To evaluate the efficacy of sunlight administered alone or with filtering or amplifying devices for the prevention and treatment of clinical jaundice or laboratory-diagnosed hyperbilirubinemia in term and late preterm neonates. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search CENTRAL (2019, Issue 5), MEDLINE, Embase, and CINAHL on 2 May 2019. We also searched clinical trials databases, conference proceedings, and the reference lists of retrieved articles for randomized controlled trials (RCTs), quasi-RCTs, and cluster RCTs. We updated the searches on 1 June 2020. SELECTION CRITERIA: We included RCTs, quasi-RCTs, and cluster RCTs. We excluded crossover RCTs. Included studies must have evaluated sunlight (with or without filters or amplification) for the prevention and treatment of hyperbilirubinemia or jaundice in term or late preterm neonates. Neonates must have been enrolled in the study by one-week postnatal age. DATA COLLECTION AND ANALYSIS: We used standard methodologic procedures expected by Cochrane. We used the GRADE approach to assess the certainty of evidence. Our primary outcomes were: use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, chronic bilirubin encephalopathy, and death. MAIN RESULTS: We included three RCTs (1103 infants). All three studies had small sample sizes, were unblinded, and were at high risk of bias. We planned to undertake four comparisons, but only found studies reporting on two. Sunlight with or without filters or amplification compared to no treatment for the prevention and treatment of hyperbilirubinemia in term and late preterm neonates One study of twice-daily sunlight exposure (30 to 60 minutes) compared to no treatment reported the incidence of jaundice may be reduced (risk ratio [RR] 0.61, 95% confidence interval [CI] 0.45 to 0.82; risk difference [RD] -0.14, 95% CI -0.22 to -0.06; number needed to treat for an additional beneficial outcome [NNTB] 7, 95% CI 5 to 17; 1 study, 482 infants; very low-certainty evidence) and the number of days that an infant was jaundiced may be reduced (mean difference [MD] -2.20 days, 95% CI -2.60 to -1.80; 1 study, 482 infants; very low-certainty evidence). There were no data on safety or potential harmful effects of the intervention. The study did not assess use of conventional phototherapy, treatment failure requiring exchange transfusion, ABE, and long-term consequences of hyperbilirubinemia. The study showed that sunlight therapy may reduce rehospitalization rates within seven days of discharge for treatment for hyperbilirubinemia, but the evidence was very uncertain (RR 0.55, 95% CI 0.27 to 1.11; RD -0.04, -0.08 to 0.01; 1 study, 482 infants; very low-certainty evidence). Sunlight with or without filters or amplification compared to other sources of phototherapy for the treatment of hyperbilirubinemia in infants with confirmed hyperbilirubinemia Two studies (621 infants) compared the effect of filtered-sunlight exposure to other sources of phototherapy in infants with confirmed hyperbilirubinemia. Filtered-sunlight phototherapy (FSPT) and conventional or intensive electric phototherapy led to a similar number of days of effective treatment (broadly defined as a minimal increase of total serum bilirubin in infants less than 72 hours old and a decrease in total serum bilirubin in infants more than 72 hours old on any day that at least four to five hours of sunlight therapy was available). There may be little or no difference in treatment failure requiring exchange transfusion (typical RR 1.00, 95% CI 0.06 to 15.73; typical RD 0.00, 95% CI -0.01 to 0.01; 2 studies, 621 infants; low-certainty evidence). One study reported ABE, and no infants developed this outcome (RR not estimable; RD 0.00, 95% CI -0.02 to 0.02; 1 study, 174 infants; low-certainty evidence). One study reported death as a reason for study withdrawal; no infants were withdrawn due to death (RR not estimable; typical RD 0.00, 95% CI -0.01 to 0.01; 1 study, 447 infants; low-certainty evidence). Neither study assessed long-term outcomes. Possible harms: both studies showed a probable increased risk for hyperthermia (body temperature greater than 37.5 °C) with FSPT (typical RR 4.39, 95% CI 2.98 to 6.47; typical RD 0.30, 95% CI 0.23 to 0.36; number needed to treat for an additional harmful outcome [NNTH] 3, 95% CI 2 to 4; 2 studies, 621 infants; moderate-certainty evidence). There was probably no difference in hypothermia (body temperature less than 35.5 °C) (typical RR 1.06, 95% CI 0.55 to 2.03; typical RD 0.00, 95% CI -0.03 to 0.04; 2 studies, 621 infants; moderate-certainty evidence). AUTHORS' CONCLUSIONS: Sunlight may be an effective adjunct to conventional phototherapy in LMIC settings, may allow for rotational use of limited phototherapy machines, and may be preferable to families as it can allow for increased bonding. Filtration of sunlight to block harmful ultraviolet light and frequent temperature checks for babies under sunlight may be warranted for safety. Sunlight may be effective in preventing hyperbilirubinemia in some cases, but these studies have not demonstrated that sunlight alone is effective for the treatment of hyperbilirubinemia given its sporadic availability and the low or very low certainty of the evidence in these studies.

Causes of severe neonatal hyperbilirubinemia: a multicenter study of three regions in China.

BACKGROUND: Available evidence suggests that our country bear great burden of severe hyperbilirubinemia. However, the causes have not been explored recently in different regions of China to guide necessary clinical and public health interventions. METHODS: This was a prospective, observational study conducted from March 1, 2018, to February 28, 2019. Four hospitals in three regions of China participated in the survey. Data from infants with a gestational age ≥ 35 weeks, birth weight ≥ 2000 g, and total serum bilirubin (TSB) level ≥ 17 mg/dL (342 µmol/L) were prospectively collected. RESULTS: A total of 783 cases were reported. Causes were identified in 259 cases. The major causes were ABO incompatibility (n = 101), glucose-6-phosphate dehydrogenase deficiency (n = 76), and intracranial hemorrhage (n = 70). All infants with glucose-6-phosphate dehydrogenase deficiency were from the central south region. Those from the central south region had much higher peak total bilirubin levels [mean, 404 µmol/L; standard deviation (SD), 75 µmol/L] than those from the other regions (mean, 373 µmol/L; SD, 35 µmol/L) (P < 0.001). CONCLUSIONS: ABO incompatibility was the leading cause in the east and northwest regions, but cases in the central south region were mainly caused by both ABO incompatibility and glucose-6-phosphate dehydrogenase deficiency, and infants in this region had a much higher peak total bilirubin level. Intracranial hemorrhage may be another common cause. More thorough assessments and rigorous bilirubin follow-up strategies are needed in the central south region.