Early Postnatal Additional High-Dose Oral Vitamin A Supplementation versus Placebo for 28 Days for Preventing Bronchopulmonary Dysplasia or Death in Extremely Low Birth Weight Infants

Abstract

Background: Prematurity and the associated risk for bronchopulmonary dysplasia (BPD) remain a significant threat to extremely low birth weight (ELBW) infants. Vitamin A has been considered a therapeutic alternative in reducing the rate of BPD and mortality. Objectives: To investigate whether early postnatal, additional high-dose oral vitamin A supplementation for 28 days is more efficient in reducing BPD or death in ELBW infants than placebo treatment. Methods: This is a multicenter, double-blind RCT comparing postnatal high-dose oral vitamin A supplementation (5,000 IU vitamin A/kg/day vs. placebo) for 28 days in ELBW neonates requiring mechanical ventilation, noninvasive ventilatory support or supplemental oxygen at 24 h of age. The primary end point is the proportion of children who died before 36 weeks' gestational age or developed moderate or severe BPD. BPD is defined as the need for supplemental oxygen to maintain SaO₂ of ≥92% at rest at 36 weeks' postmenstrual age (PMA). Clinical secondary end points include the following: BPD (including mild form), intraventricular hemorrhage, periventricular leukomalacia, retinopathy of prematurity, necrotizing enterocolitis, total number of days of mechanical ventilation and oxygen supplementation, and safety and tolerability of high-dose vitamin A supplementation. Results and Conclusions: The results of the NeoVitaA trial will provide robust data with regard to the efficacy of high-dose oral vitamin A supplementation in reducing the incidence of BPD or death at 36 weeks' PMA in ELBW infants.

Developing a better and practical definition of bronchopulmonary dysplasia

“…The synopsis by Hines et al reports various definitions of bronchopulmonary dysplasia (BPD) (1). We agree there is a need to harmonise the definition of BPD, and our definition (2) was adapted from the National Institute of Child Health and Human Development network definition by Jobe and Bancalari (3) It incorporates important aspects that have evolved over time, such as the use of high-flow nasal cannulas, and takes into account differences between clinical centres, including different target oxygen saturations. Our definition covers two aspects: evolving BPD measured in days and the assessment of definite BPD at a postmenstrual age of 36 weeks.…”

Parenteral Nutrition in Premature Infants

“…Most pediatric vitamin formulations that are currently used in neonatal units are not designed for VLBW infants. Recent data suggest that additional intakes of fat-soluble vitamins A and E may provide some value for VLBW infants [106][107][108][109]. For premature infants, vitamin deficiencies are usually defined as below 200 µg/L for vitamin A and below 1 mg/dL for vitamin E, but for vitamin E a ratio below 0.8 mg/g of total lipid is usually preferred.…”

Impaired Pulmonary Vascular Development in Bronchopulmonary Dysplasia

“…However, a recent retrospective analysis of one of these trials suggested that combining iNO with enteral vitamin A supplementation may improve outcomes in certain preterm infants [110]. A prospective randomized clinical trial is now underway to determine whether 28 days of high-dose vitamin A supplementation reduces BPD and death in preterm infants [111]. …”