Aggressive vs. Conservative Phototherapy for Infants with Extremely Low Birth Weight

Brenda H. Morris, M.D., William Oh, M.D., Jon E. Tyson, M.D., M.P.H., David K. Stevenson, M.D., Dale L. Phelps, M.D., T. Michael O'Shea, M.D., M.P.H., Georgia E. McDavid, R.N., Rebecca L. Perritt, M.S., Krisa P. Van Meurs, M.D., Betty R. Vohr, M.D., Cathy Grisby, B.S.N., Qing Yao, Ph.D., Claudia Pedroza, Ph.D., Abhik Das, Ph.D., W. Kenneth Poole, Ph.D., Waldemar A. Carlo, M.D., Shahnaz Duara, M.D., Abbot R. Laptook, M.D., Walid A. Salhab, M.D., Seetha Shankaran, M.D., Brenda B. Poindexter, M.D., Avroy A. Fanaroff, M.D., Michele C. Walsh, M.D., Maynard R. Rasmussen, M.D., Barbara J. Stoll, M.D., C. Michael Cotten, M.D., Edward F. Donovan, M.D., Richard A. Ehrenkranz, M.D., Ronnie Guillet, M.D., Ph.D., Rosemary D. Higgins, M.D., for the NICHD Neonatal Research Network

ABSTRACT

Background It is unclear whether aggressive phototherapy to prevent neurotoxic effects of bilirubin benefits or harms infants with extremely low birth weight (1000 g or less).

Methods We randomly assigned 1974 infants with extremely low birth weight at 12 to 36 hours of age to undergo either aggressive or conservative phototherapy. The primary outcome was a composite of death or neurodevelopmental impairment determined for 91% of the infants by investigators who were unaware of the treatment assignments.

Results Aggressive phototherapy, as compared with conservative phototherapy, significantly reduced the mean peak serum bilirubin level (7.0 vs. 9.8 mg per deciliter [120 vs. 168 µmol per liter], P<0.01)> (52% vs. 55%; relative risk, 0.94; 95% confidence interval [CI], 0.87 to 1.02; P=0.15). Aggressive phototherapy did reduce rates of neurodevelopmental impairment (26%, vs. 30% for conservative phototherapy; relative risk, 0.86; 95% CI, 0.74 to 0.99). Rates of death in the aggressive-phototherapy and conservative-phototherapy groups were 24% and 23%, respectively (relative risk, 1.05; 95% CI, 0.90 to 1.22). In preplanned subgroup analyses, the rates of death were 13% with aggressive phototherapy and 14% with conservative phototherapy for infants with a birth weight of 751 to 1000 g and 39% and 34%, respectively (relative risk, 1.13; 95% CI, 0.96 to 1.34), for infants with a birth weight of 501 to 750 g.

Conclusions Aggressive phototherapy did not significantly reduce the rate of death or neurodevelopmental impairment. The rate of neurodevelopmental impairment alone was significantly reduced with aggressive phototherapy. This reduction may be offset by an increase in mortality among infants weighing 501 to 750 g at birth. (ClinicalTrials.gov number, NCT00114543 [ClinicalTrials.gov] .)