Vitamin A supplementation in extremely low-birth-weight infants: subgroup analysis in small-for-gestational-age infants

Abstract

Objective: Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD.

Study design: A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age-equivalent vitamin A-treated appropriate-for-gestational-age (AGA) infants.

Results: Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [-7.0, 68.8] versus 2.4 [-13.9, 55.1]; p < 0.001), no increases were noted in SGA ELBW infants.

Conclusions: Given the limited power of this analysis due to a low number of SGA infants, these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants.

Fig. 1

Relative risk of experiencing binary clinical outcomes for all study infants. A robust Poisson model assuming an interaction between treatment and gestational age group was used to obtain the p values and relative risk estimates. The model controlled for gestational age for all outcomes and also for center for the primary outcome. Abbreviations: AGA, average for gestational age; CLD, chronic lung disease; IVH, intraventricular hemorrhage; NEC, necrotizing enterocolitis; PDA, patent ductus arteriosus; PMA, postmenstrual age; PVL, periventricular leukomalacia; SGA, small for gestational age; Vit A, vitamin A.