TOPLINE:

Additional early postnatal high-dose enteral fat-soluble vitamin A supplementations did not show any benefit over placebo for pulmonary or neurodevelopmental outcomes in infants with extremely low birth weight (ELBW) who received standard vitamin A supplementation during the first 2 years of life.

METHODOLOGY:

• Researchers conducted a follow-up study of a trial to assess long-term effects of early postnatal high-dose enteral fat-soluble vitamin A supplementation on lung development in premature infants receiving recommended basic vitamin A supplementation.
• They followed 759 infants with ELBW between September 2019 and June 2024, of whom 372 received additional high-dose vitamin A supplementation (5000 international units [IU]/kg body weight/d) for 28 days and the remaining 387 received placebo.
• All infants received the recommended basic enteral vitamin A supplementation of 1000 IU/kg body weight/d prior to randomisation.
• Pulmonary outcomes were measured in terms of the number of antibiotic treatment and hospital admissions required at 12 and 24 months of corrected age, and neurodevelopmental outcomes were measured using composite scores of the Bayley Scales of Infant and Toddler Development, Second (Bayley-II) or Third Edition (Bayley-III).

TAKEAWAY:

• High-dose vitamin A had no effect on the total number of antibiotic courses required for pulmonary infections or on hospital admissions for pulmonary infections at 12 and 24 months of corrected age.
• Rates of recurrent wheeze did not differ significantly between high-dose vitamin A and placebo groups at 12 and 24 months of corrected age.
• Mental and Psychomotor Development Index scores for Bayley-II were not significantly different between infants receiving additional high-dose vitamin A supplementation and those receiving placebo.
• Among infants with Bayley-III scores, the median cognitive composite score and motor score did not differ significantly between the two groups.

IN PRACTICE:

"Although high dose vitamin A may be considered safe, as no adverse effects were noted, higher dosages than those proposed by the ESPGHAN [European Society for Paediatric Gastroenterology Hepatology and Nutrition] are not generally recommended in ELBW infants," the authors wrote.

SOURCE:

This study was led by Martin Poryo, Saarland University Medical Center, Department of Paediatric Cardiology, Kirrberger Straße, Homburg, Germany. It was published online on September 15, 2025, in eClinicalMedicine.

LIMITATIONS:

The study findings may not be generalisable to premature infants of other ethnic backgrounds and geographic regions because most of them were Caucasian and NICUs were located in Austria and Germany. Data on serial serum retinol concentrations were not obtained due to regulatory and ethical concerns. This study lacked data on the cohort's immunisation status or respiratory syncytial virus prophylaxis and specific respiratory infections.

DISCLOSURES:

The NeoVitaA trial was funded by the Deutsche Forschungsgemeinschaft ME 3827/1-1/2 and European Clinical Research Infrastructures Network. Two authors reported receiving grants or contracts, consulting fees, and/or payment or honoraria from various organisations.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.