Invited Commentary: Does Neonatal Hyperbilirubinemia Cause Asthma?

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

Lower incidence of seizure among neonates treated with therapeutic hypothermia.

Animal studies suggest that hypothermia decreases seizure burden, whereas limited human data are inconclusive. This retrospective cohort study examines the relationship between therapeutic hypothermia and seizure in neonates with hypoxic-ischemic encephalopathy. Our center admitted 224 neonates from July 2004 to December 2011 who met institutional cooling criteria. Seventy-three neonates were born during the pre-cooling era, prior to November 2007, and 151 were born during the cooling era. Among neonates with moderate encephalopathy, the incidence of seizure in cooled infants was less than half the incidence in those not cooled (26% cooling, 61% pre-cooling era; risk ratio = 0.43, 95% confidence interval = 0.30-0.61). Among neonates with severe encephalopathy, there was no difference in the incidence (83% vs. 87%; risk ratio = 1.05, 95% confidence interval = 0.78-1.39). These results support animal data and suggest a mechanism by which neonates with moderate encephalopathy can benefit more from cooling than neonates with severe encephalopathy

Outcomes of Admissions for Preterm Labor

Objective  This study aims to quantitate the incidence of preterm labor (PTL) admissions and determine the frequency and predictors of preterm delivery (PTD) during these admissions. Study Design  Retrospective cohort of singleton pregnancies within Kaiser Permanente Northern California, 2001 to 2011. PTL admissions were defined as inpatient encounters > 24 hours with an International Classification of Diseases, 9th Revision code for PTL. Results  Total study population was 365,897 with PTL admission rate 11%. PTD occurred in 85% of pregnancies with PTL admission. Delivery occurred within 48 hours of admission in 96% ≥34 weeks, 67% 31 to 33 weeks, and 51.9% <31 weeks. Predictors of delivery during PTL admission included gestational age 34 to 36 weeks (adjusted odds ratio [aOR], 6.90), chorioamnionitis (aOR, 105.58), and preterm rupture of membranes (aOR 19.29). Conclusion  We demonstrate a high rate of PTD per PTL admission in a highly integrated health care system. More work is needed to determine optimal practices for hospitalization and treatment of women diagnosed with PTL

Neonatal Neurocritical Care Service Is Associated With Decreased Administration of Seizure Medication.

This cohort study examines medication use in term neonates with hypoxic-ischemic encephalopathy and seizures before and after implementation of a Neonatal Neurocritical Care Service (N = 108), which included increased seizure monitoring. Nearly all neonates received phenobarbital (96% pre- vs 95% post-Neonatal Neurocritical Care Service) and total loading dose did not vary among groups (33 [95% confidence interval 29-37] vs 30 [26-34] mg/kg). After adjustment for seizure burden, neonates managed during the Neonatal Neurocritical Care Service era, on average, received 30 mg/kg less cumulative phenobarbital (95% confidence interval 15-46 mg/kg) and were on maintenance 5 fewer days (95% confidence interval 3-8 days) than those who were treated prior to implementation of the service. In spite of the enhanced ability to detect seizures because of improved monitoring and increased vigilance by bedside practitioners, implementation of the Neonatal Neurocritical Care Service was associated with decreased use of potentially harmful phenobarbital treatment among neonates with hypoxic-ischemic encephalopathy

Neonatal Phototherapy and Infantile Cancer.

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 <15 days and discharge diagnoses of cancer at 61 to 365 days. We adjusted for potential confounding variables by using traditional and propensity-adjusted logistic regression models.ResultsCancer was diagnosed in 58/178 017 infants with diagnosis codes for phototherapy and 1042/4 966 832 infants without such codes (32.6/100 000 vs 21.0/100 000; relative risk 1.6; 95% confidence interval [CI], 1.2-2.0, P = .002). In propensity-adjusted analyses, associations were seen between phototherapy and overall cancer (adjusted odds ratio [aOR] 1.4; 95% CI, 1.1-1.9), myeloid leukemia (aOR 2.6; 95% CI, 1.3-5.0), and kidney cancer (aOR 2.5; 95% CI, 1.2-5.1). The marginal propensity-adjusted absolute risk increase for cancer after phototherapy in the total population was 9.4/100 000 (number needed to harm of 10 638). Because of the higher baseline risk of cancer in infants with Down syndrome, the number needed to harm was 1285.ConclusionsPhototherapy may slightly increase the risk of cancer in infancy, although the absolute risk increase is small. This risk should be considered when making phototherapy treatment decisions, especially for infants with bilirubin levels below current treatment guidelines

Neonatal Neurocritical Care Service Is Associated With Decreased Administration of Seizure Medication.

This cohort study examines medication use in term neonates with hypoxic-ischemic encephalopathy and seizures before and after implementation of a Neonatal Neurocritical Care Service (N = 108), which included increased seizure monitoring. Nearly all neonates received phenobarbital (96% pre- vs 95% post-Neonatal Neurocritical Care Service) and total loading dose did not vary among groups (33 [95% confidence interval 29-37] vs 30 [26-34] mg/kg). After adjustment for seizure burden, neonates managed during the Neonatal Neurocritical Care Service era, on average, received 30 mg/kg less cumulative phenobarbital (95% confidence interval 15-46 mg/kg) and were on maintenance 5 fewer days (95% confidence interval 3-8 days) than those who were treated prior to implementation of the service. In spite of the enhanced ability to detect seizures because of improved monitoring and increased vigilance by bedside practitioners, implementation of the Neonatal Neurocritical Care Service was associated with decreased use of potentially harmful phenobarbital treatment among neonates with hypoxic-ischemic encephalopathy