Neonatal Phototherapy Tied to Small Increased Risk of Seizures in Boys

By Marilynn Larkin

September 26, 2018

NEW YORK (Reuters Health) - Phototherapy in newborn boys is associated with an increased risk of childhood seizures, but the risk is weaker than previously thought, researchers say.

A recent Danish cohort study found that boys who had received phototherapy for neonatal jaundice had approximately double the risk of subsequent epilepsy. The current study confirmed the association in a larger cohort, but found the risk was lower than in the Danish study.

Nonetheless, Dr. Thomas Newman of the University of California, San Francisco, told Reuters Health by email, "These results and others ...have led the UCSF Northern California Neonatology Consortium to raise jaundice treatment thresholds in anticipation of similar changes expected in guidelines currently being updated by the American Academy of Pediatrics."

The current guidelines are online at

Dr. Newman and colleagues studied 37,683 infants born at 35 weeks' gestation or later from 1995 to 2011 in Northern California. The mean follow-up time was 8.1 years, and the primary outcome was at least one seizure diagnosis plus at least one prescription for an antiepileptic drug.

As reported online September 24 in Pediatrics, the crude incidence rate per 1,000 person-years of the primary outcome was 1.24 among children who had phototherapy and 0.76 among those who didn't (rate ratio, 1.63). The adjusted hazard ratio was 1.22.

Boys were at higher risk of seizures overall (aHR, 1.18). The aHR for the primary outcome was statistically significant in boys (1.33) but not in girls (1.07).

The adjusted 10-year excess risks for seizures per 1,000 were 2.4 overall, 3.7 in boys, and 0.8 in girls.

Notably, febrile seizures were not significantly associated with phototherapy, nor was any type of epilepsy more strongly associated with phototherapy exposure. No seizure outcome was statistically significantly associated with phototherapy in girls.

The authors conclude, "Phototherapy in newborns is associated with a small increased risk of childhood seizures, even after adjusting for bilirubin values, and the risk is more significant in boys."

Dr. Newman notes that it is not clear why the increased risk only affects boys. "It is something we intend to study further."

Dr. Adwoa Osei, Assistant Clinical Professor of pediatrics at the University of California, Riverside, commented, "The study did not provide reliable data on the duration and intensity of phototherapy exposure in the cohort group. Thus, we are not sure what dose of phototherapy would actually be responsible for the association."

Further, she told Reuters Health by email, "The study did not include data on breastfeeding, which in some reports has been associated with decreased risk of epilepsy."

The small increased risk should not deter clinicians from using phototherapy in this population, she said. "However, the authors point to caution when using phototherapy in infants whose level of jaundice are below current treatment thresholds. In such cases, (they) indicate that the 'benefits are unlikely to exceed the potential harm.'"

Dr. Osei also cautions against prophylactic use of phototherapy. "Patients are better served when current treatment thresholds, guidelines and neonatal risk factors are all taken into consideration before the initiation of phototherapy," she concluded.

Dr. Jennifer Kurtz, Chief, Neonatal Medicine at Long Island Jewish in Forest Hills, New York, commented in an email to Reuters Health, "This is an important study for clinicians. Some prefer to initiate phototherapy at lower threshold total serum bilirubin levels, in hopes of avoiding longer lengths of hospital stays or readmissions. But this study shows us that we should consider raising the threshold to initiate phototherapy, something that many clinicians are already putting into practice."


Pediatrics 2018.