Nearly every very surviving low birth-weight infant admitted to a neonatal intensive care unit receives phototherapy for hyperbilirubinemia. In these small babies, very little is known about what level of bilirubin in the blood is harmful, or when phototherapy should be initiated to protect the neonate from neurodevelopmental injury as a consequence of hyperbilirubinemia.

In a large, multicenter clinical trial sponsored by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, nearly 2000 extremely low birth-weight (ELBW) infants were randomized to receive either aggressive or conservative phototherapy. Infants randomized to aggressive phototherapy were started on phototherapy at enrollment (before 24 hours of age). In the conservative group, phototherapy was started when the infant's total serum bilirubin reached 8.0 mg/dL in infants weighing 501 to 750 g and 10.0 in infants weighing 751 to 1000 g. Infants were followed until death or neurodevelopmental testing at 18 to 22 months.

Data analysis revealed that aggressive phototherapy, compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs 9.8 mg/dL, P < .01) and reduced the rate of neurodevelopmental impairment such as cerebral palsy, deafness, and physical or mental disability. In the smallest babies, the reduction in profound impairment was offset by a small increase in mortality in this birth-weight group. It is not known if this increased mortality is related to oxidative injury to cell membranes in these immature infants whose gelatinous skin more readily transmits light, or if the higher bilirubin levels in the conservative group conferred an antioxidant benefit. The study was published in the New England Journal of Medicine.1

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