2 Neuro-Developmental Outcomes at 18 Months Corrected Age in Infants Weighing

Abstract

The “safe” level of serum bilirubin in infants <1500 grams is controversial, but recent retrospective reviews show direct correlation between peak bilirubin level and adverse neuro-developmental outcome. Our recent randomized study showed that infants <1000 grams who received conservative phototherapy had higher peak bilirubin levels and that infants <1500 grams who received conservative phototherapy reached peak bilirubin levels earlier than those treated with aggressive phototherapy. The purpose of this study was to examine the 18 month neuro-developmental outcomes in infants <1500 grams who had been enrolled in our randomized trial of aggressive versus conservative phototherapy. This follow-up phase of an unmasked, randomized study included infants with birth weight <1500 grams who had no evidence of major anomaly or iso-immunization and for whom parental consent was obtained. Aggressive phototherapy was started by 12 hours of post-natal age, while conservative phototherapy was started when the serum bilirubin level exceeded 8.8 mg/dL (150 μmol/L). All surviving infants were enrolled in a comprehensive neuro-developmental follow-up program at 4, 8, 12, 18, 14 and 36-months corrected age. At each visit, a full neuro-developmental assessment was performed and information on growth, hospital readmission, interval health and medication use was collected. All children had hearing screens at the 12-month visit, regular vision screening, and Bayley Scales of Infant Development (BSID-III) at the 18 and 36 month visits, if cooperative. Of 95 patients enrolled in the original study, 87 (92%) survived until hospital discharge, of whom 82 (94% of survivors) attended for comprehensive neuro-developmental assessment until 12 months corrected age and 75 (86% of survivors) attended until 18 months corrected age. The incidence of cerebral palsy was higher in the conservative phototherapy group 7/41 (17%) vs 2/41 (5%), p=0.15, OR 4.01 [0.69, 41.50]. The combined outcome of CP/death was also higher in the conservative group at 12/46 (26%) vs 5/44 (11%), p=0.04, OR 3.44 [0.92, 15.82]. Two-thirds of the infants with CP were in the <1000 grams subgroup. An MDI <84 on 18-month corrected age BSID-III testing did not differ between the two groups being 6/38 (16%) in the conservative group and 8/37 (22%) in the aggressive group, p=0.52, OR 0.68 [0.17, 2.56]. Although the numbers in this study are too small to draw definitive conclusions, there is a worrisome trend for poor neuro-developmental outcome for infants receiving conservative phototherapy, particularly in the <1000 grams group. Further studies with long-term neuro-developmental outcome as the primary outcome are urgently required.