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Objectives: Our aim was to quantify the associations of both hyperbilirubinemia and phototherapy with childhood asthma using a population-based cohort with total serum bilirubin (TSB) levels., Methods: Retrospective cohort study of infants born at ≥35 weeks' gestation in the Kaiser Permanente Northern California health system ( n = 109 212) from 2010 to 2014. Cox models were used to estimate hazard ratios (HRs) for a diagnosis of asthma., Results: In the study, 16.7% of infants had a maximum TSB level of ≥15 mg/dL, 4.5% of infants had a maximum TSB level of ≥18 mg/dL, and 11.5% of infants received phototherapy. Compared with children with a maximum TSB level of 3 to 5.9 mg/L, children with a TSB level of 9 to 11.9 mg/dL, 12 to 14.9 mg/dL, and 15 to 17.9 mg/dL were at an increased risk for asthma (HR: 1.22 [95% confidence interval (CI): 1.11-1.3], HR: 1.18 [95% CI: 1.08-1.29], and HR: 1.30 [95% CI: 1.18-1.43], respectively). Children with a TSB level of ≥18 mg/dL were not at an increased risk for asthma (HR: 1.04; 95% CI: 0.90-1.20). In propensity-adjusted analyses, phototherapy was not associated with asthma (HR: 1.07; 95% CI: 0.96-1.20)., Conclusions: Modest levels of hyperbilirubinemia were associated with an increased risk of asthma, but an association was not seen at higher levels. No dose-response relationship was seen. Using phototherapy to prevent infants from reaching these modest TSB levels is unlikely to be protective against asthma., Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2018 by the American Academy of Pediatrics.)

Background and Objectives: Total serum bilirubin (TSB) levels ≥ 30 mg/dL are rare but potentially hazardous. A better understanding of their incidence, causes, and outcomes could help inform preventive efforts., Methods: We identified infants born ≥ 35 weeks' gestational age from 1995-2011 in Kaiser Permanente Northern California (n = 525409) and examined the medical records of infants with a TSB ≥ 30 mg/dL to determine etiology and the occurrence of acute bilirubin encephalopathy. We reviewed inpatient and outpatient encounters through 2013 for evidence of sensorineural hearing loss (SNHL) or cerebral palsy (CP)., Results: We identified 47 infants with TSB ≥ 30 mg/dL (8.6 per 100000 births). In 44 infants (94%), the hyperbilirubinemia occurred after the initial birth hospitalization. The etiology was not identified in 33 (70%). Glucose-6-phosphate dehydrogenase (G6PD) activity was measured in only 25 (53%) of whom 10 (40%) were deficient. Four children had acute bilirubin encephalopathy of whom 2 developed both CP and SNHL, and 1 developed isolated SNHL. These 3 infants all had G6PD deficiency and TSB >40 mg/dL. One additional 35-week infant with TSB 38.2 mg/dL had SNHL., Conclusions: Hazardous (≥ 30 mg/dL) hyperbilirubinemia is a rare event. No etiology could be identified from the clinical record in most cases. G6PD deficiency was the leading cause of hazardous hyperbilirubinemia when an etiology was identified, but many were not tested. Chronic, bilirubin-induced neurotoxicity was uncommon and occurred only in the setting of additional risk factors and TSB values well over (>15 mg/dL) the American Academy of Pediatrics exchange transfusion thresholds., (Copyright © 2014 by the American Academy of Pediatrics.)

Although black race is considered protective against hyperbilirubinemia, black infants appear at increased risk of kernicterus. We found that although black infants have a lower risk of developing total serum bilirubin levels ≥ 20 mg/dL than white infants, they appear at greater risk of developing levels ≥ 30 mg/dL., (Copyright © 2013 Mosby, Inc. All rights reserved.)

Background and objectiveIncreases in both phototherapy use and the incidence of type 1 diabetes mellitus (DM-1) have been reported. One large study has suggested a strong association between them. Our objective was to quantify any association between neonatal phototherapy and DM-1 in a northern California integrated health care system.MethodsThis retrospective cohort study included 499 642 children born at ≥35 weeks' gestation in 15 Kaiser Permanente Northern California hospitals from 1995 to 2011 and followed until March 31, 2014. We ascertained phototherapy, bilirubin levels, and other covariates from electronic records. We identified DM-1 cases using a diabetes registry and inpatient and outpatient diagnoses. We used traditional and propensity-adjusted Cox models to quantify associations.ResultsPhototherapy use increased from 2.7% in 1995 to 16.0% in 2011. DM-1 was diagnosed in 37 of 39 406 children who had received phototherapy (15.1 per 100 000 person-years; mean follow-up 6.2 years) and 712 of 460 236 who had not (18.8 per 100 000 person-years; mean follow-up 8.2 years). There was no evidence of increasing diabetes incidence. We found no association between phototherapy and DM-1 in either unadjusted analyses (incidence rate ratio 0.81; 95% confidence interval, 0.56 to 1.12) or analyses adjusted for hyperbilirubinemia and other covariates (hazard ratio 1.06; 95% confidence interval, 0.78 to 1.45). DM-1 incidence was most strongly associated with race and ethnicity, with whites at highest risk (25.6 per 100 000) and Asians at lowest risk (8.9 per 100 000).ConclusionsWe found no evidence of increased DM-1 risk in children who had received phototherapy.

ObjectiveTo determine whether neonatal phototherapy is associated with cancer in the first year after birth.MethodsWe analyzed a data set from the California Office of Statewide Health Planning and Development that was created by linking birth certificates, death certificates, and hospital discharge abstracts up to age 1 year. Subjects were 5 144 849 infants born in California hospitals at ≥35 weeks' gestation from 1998 to 2007. We used International Classification of Diseases, Ninth Revision codes to identify phototherapy at

In an analysis of data from the US Collaborative Perinatal Project, Huang et al. (Am J Epidemiol. 2013;178(12):1691-1697) report an association between neonatal total serum bilirubin levels and childhood asthma. To consider the implications of this finding, we need to evaluate whether the association is causal. The results do not appear to be due to chance or any obvious biases. It is likely that the observed association is the result of a common cause of both hyperbilirubinemia and asthma (confounding). Polymorphisms in the glutathione S-transferase gene are a potential genetic confounder. The glutathione S-transferase M1-null phenotype has been linked to both neonatal hyperbilirubinemia and asthma in several studies. Before making any changes in practice aimed at lowering peak bilirubin levels to reduce asthma risk, it is vital to determine not only whether the association between higher bilirubin levels and asthma risk is causal, but also whether interventions to reduce peak bilirubin levels (or their duration) are associated with decreased risk of asthma (without evidence of other adverse effects). The study by Huang et al. should encourage further investigation of these questions.

BACKGROUND AND OBJECTIVES: The neonatal hereditary spherocytosis (HS) index, defined as the mean corpuscular hemoglobin concentration divided by the mean corpuscular volume, has been proposed as a screening tool for HS in neonates. In a population of mostly white infants, an HS Index >0.36 was 97% sensitive and >99% specific. We evaluated the utility of the HS Index among a more racially and ethnically diverse population and determined if its discrimination varies with total serum bilirubin (TSB) levels. METHODS: Infants born at $35 weeks' gestation at 15 Kaiser Permanente Northern California hospitals from 1995 to 2015 were eligible (N 5 670 272). Erythrocyte indices from the first complete blood count drawn at #7 days and TSB levels drawn at #30 days were obtained. Diagnoses of HS were confirmed via chart review. RESULTS: HS was confirmed in 79 infants, 1.2 per 10 000. HS was more common among infants of white and "other" race or ethnicity and among those with higher peak TSB levels. The area under the receiver operating characteristic curve for the HS Index was 0.84 (95% confidence interval 0.78-0.90). Likelihood ratios ranged from 10.1 for an HS Index $0.380 to 0.1 for an HS Index <0.310. Dichotomized at 0.36, the HS Index was 56% sensitive and 93% specific. Discrimination of the HS Index appeared best among infants with TSB levels <10 mg/dL. CONCLUSIONS: The HS Index, when obtained from a CBC drawn within the first week after birth, had only modest ability to alter the probability of HS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The goal was to assess the impact of universal bilirubin screening on severe hyperbilirubinemia and phototherapy use. METHODS: In this retrospective cohort study of 358 086 infants of ⩾35 weeks and ⩾2000 g born between January 1,1995, and June 30, 2007, we obtained demographic data, bilirubin levels, and codes for inpatient phototherapy from existing databases. We compared the incidence of high total serum bilirubin (TSB) levels and phototherapy before and after implementation of universal screening and examined riskfactors for high TSB levels. RESULTS: A total of 38 182 infants (10.6%) were born at facilities that had implemented universal bilirubin screening. Compared with infants born at facilities that were not screening, these infants had a 62% lower incidence of TSB levels exceeding the American Academy of Pediatrics exchange guideline (0.17% vs 0.45%; P< .001), received twice the inpatient phototherapy (9.1% vs 4.2%; p < .001), and had slightly longer birth hospitalization lengths of stay (50.9 vs 48.7 hours; P < .001). Of those receiving phototherapy, 56% after initiation of universal screening had TSB levels at which phototherapy was recommended by the guideline, compared with 70% before screening. The adjusted odds ratio for developing TSB levels exceeding the guideline value was 0.28 (95% confidence interval: 0.20-0.40) for those born at a facility using TSB screening and 0.28 (95% confidence interval: 0.19-0.42) for those born at a facility using transcutaneous bilirubin screening. CONCLUSION: Universal bilirubin screening was associated with a significantly lower incidence of severe hyperbilirubinemia but also with increased phototherapy use. [ABSTRACT FROM AUTHOR]

BACKGROUND AND OBJECTIVES: High bilirubin levels are associated with sensorineural hearing loss (SNHL). However, few large studies of relative and excess risk exist. We sought to quantify the risk of SNHL in newborns who had bilirubin levels at or above American Academy of Pediatrics exchange transfusion thresholds (ETT). METHODS: Infants born at ≥35 weeks gestation in 15 Kaiser Permanente Northern California hospitals from 1995-2011 were eligible (N = 525 409). We used a nested double cohort design. The exposed cohort included subjects with ≥1 bilirubin level at or above ETT. The unexposed cohort was a 3.6% random sample of subjects with all bilirubin levels below ETT (10 unexposed per exposed). An audiologist, blinded to bilirubin levels, reviewed the charts of children in whom SNHL had been diagnosed before age 8 years to confirm the diagnosis. We calculated Cox proportional hazard ratios for time to diagnosis of SNHL. RESULTS: SNHL was confirmed in 11 (0.60%) of the 1834 exposed subjects and in 43 (0.23%) of the 19 004 unexposed. Only bilirubin levels ≥10 mg/dL above ETT were associated with a statistically significant increased risk of SNHL (hazard ratio: 36 [95% confidence interval (CI): 13 to 101]). Likewise, only bilirubin levels ≥35 mg/dL were associated with a statistically significant increased risk of SNHL (hazard ratio: 91 [95% CI: 32 to 255]). For subjects with total serum bilirubin levels 0 to 4.9 mg/dL above ETT, the upper limit of the 95% CI for excess risk was 0.5%. CONCLUSIONS: Only bilirubin levels well above ETT were associated with SNHL. At lower bilirubin levels, the excess risk of SNHL was low. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The objective of this study was to determine whether either hyperbilirubinemia or inpatient phototherapy is associated with increased subsequent outpatient visit rates, a possible effect of the "vulnerable child syndrome." METHODS: We compared 3 groups of otherwise well term and latepreterm infants who were born between 1995 and 2004 in Northern California Kaiser hospitals: group 1 never had a documented total serum bilirubin (TSB) level ⩾12 mg/dL (n = 128 417); group 2 had a TSB level ⩾17 and <23 mg/dL as outpatients between 48 hours and 7 days of age and did not receive inpatient phototherapy (n = 6777); and group 3 met criteria for group 2 but did receive inpatient phototherapy (n = 1765). We compared outpatient visit rates from 15 to 364 days of age adjusting for other predictors of visit rates by using Poisson and linear regression. RESULTS: The mean total number of visits between 15 and 364 days was 9.83. Compared with group 1, adjusted total first-year visit rates were slightly increased in group 2 (adjusted incidence rate ratio: 1.04 [95% confidence interval: 1.02-1.051) and group 3 (incidence rate ratio: 1.07 [95% confidence interval: 1.05-1.101). The increases in visit rates were greatest for visits from 15 to 59 days of age, for specialty visits, and for unspecified diagnoses. These rates correspond to adjusted increases in total first-year visits (compared with group 1) of 0.36 visits in group 2 and 0.73 visits in group 3. CONCLUSIONS: Neonatal jaundice and inpatient phototherapy are associated with only small increases in first-year outpatient visit rates, consistent with mild or infrequent contribution to the vulnerable child syndrome in this population. [ABSTRACT FROM AUTHOR]