Two-year outcomes after early postnatal high-dose fat-soluble enteral vitamin A supplementation in extremely low birth weight infants: follow-up of the NeoVitaA randomized controlled trial

Abstract

Background The longer-term effects of early high-dose vitamin A to support lung development in preterm infants remain to be clarified. The aim of the NeoVitaA follow-up study was to assess the effects of early postnatal additional high-dose fat-soluble enteral vitamin A supplementation (HD-VitA) vs. placebo (control) for 28 days on respiratory complications and neurodevelopmental outcome in ELBW infants receiving recommended basic vitamin A supplementation, specified as secondary outcome parameters in the NeoVitaA trial. Methods The trial was approved by the ethics committee of Saarland, Saarbruecken, Germany (file number: 70/2011) as well as by all local ethics committees and the Bundesinstitut für Arzneimittel und Medizinprodukte (BfArM, Bonn, Germany). The NeoVitaA trial was registered with EudraCT (2013-001998-24) and DRKS (DRKS00006541). This follow-up covers secondary endpoints at 12 and 24 months as mentioned in the registration. Follow-up took place between September 2019 and June 2024. Follow-up assessment at 12 and 24 months’ corrected age (CA) of infants enrolled in the NeoVitaA-trial included anthropometric data, number of antibiotic treatments, antibiotic treatments for pulmonary infections, hospital admissions, and hospital admissions for pulmonary infections, composite scores of the Bayley Scale of Infant and Toddler Development, second (Bayley-II) or third edition (Baley-III), other medical diagnoses and medical treatments. Findings Follow-up examinations were available for 759 infants (83.0%). HD-VitA had no effect on number of antibiotics needed for pulmonary infections or number of hospital admissions for pulmonary infections at 12 or 24 months' CA. At 24 months’ CA, the median number of antibiotic courses for pulmonary infections was one for both the HD-VitA and control group; the median number of hospital admissions for pulmonary infections per patient was 0 (HD-VitA) and 1 (control). Successful Bayley assessment was completed in 618/759 infants (92 Bayley-II, 526 Bayley-III). The median Mental Development Index score for Bayley-II was 95 vs. 97 (median difference −5.0, 95%-CI [−12.0, 2.0]) and Psychomotor Development Index 96 vs. 92 (median difference 3.0, 95%-CI [−4.0, 8.0]), with intervention and placebo, respectively. The median cognitive composite score for Bayley-III was 95 vs. 95 (median difference 0.0, 95%-CI [−5.0, 0.0]) and motor score was 92 vs. 92 (median difference 0.0, 95%-CI [−4.0, 3.0]), respectively. Interpretation Early postnatal high-dose enteral fat-soluble vitamin A supplementation in ELBW infants did not affect pulmonary or developmental outcomes at 24 months’ CA. Funding The NeoVitaA trial was funded by the Deutsche Forschungsgemeinschaft ME 3827/1-1/2 and European Clinical Research Infrastructures Network.