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European Journal of Pediatrics

, Volume 178, Issue 8, pp 1255–1265 | Cite as

Oral vitamin A supplementation in very low birth weight neonates: a randomized controlled trial

  • Sriparna BasuEmail author
  • Parul Khanna
  • Ragini Srivastava
  • Ashok Kumar
Original Article

Abstract

This randomized double-blind placebo-controlled trial evaluated the effects of early postnatal oral vitamin A supplementation (VAS) in 196 inborn very-low birth weight (VLBW) infants requiring respiratory support at 24 h of age. Eligible infants were randomized to receive aqueous syrup of vitamin A (10,000 IU of retinol/dose; n = 98) or placebo (n = 98) on alternate days for 28 days. Primary outcome variable was composite incidence of all-cause mortality and/or oxygen requirement for 28 days. Secondary outcome variables were safety/tolerability of VAS, serum retinol concentration at recruitment and day 28, duration of oxygen requirement and respiratory support and incidences of complications. On intention-to-treat analysis, composite incidence of all-cause mortality and oxygen requirement for 28 days was significantly lower in vitamin A group (relative risk (95% confidence interval), 0.440 (0.229–0.844); p < 0.05, number needed to benefit, 7). Requirement and duration of oxygen supplementation and non-invasive respiratory support, incidences of late-onset sepsis, patent ductus arteriosus, and duration of hospital stay were also significantly lower in vitamin A group. Serum retinol concentration improved significantly after VAS. No major adverse effect was observed.

Conclusions: Early postnatal oral VAS was associated with better composite outcome of all-cause mortality and oxygen requirement without any major adverse effects.

Clinical Trial Registration: Clinical Trials Registry of India (CTRI/2017/03/008131).

What is Known:

Postnatal intramuscular vitamin A supplementation improves the survival, respiratory outcome and other morbidities in very low birth weight neonates without major adverse effects.

Limited studies on oral vitamin A supplementation did not document substantial benefits.

What is New:

Early postnatal alternate-day oral vitamin A supplementation at the dose of 10,000 IU/dose for 28 days improves the composite outcome of death and oxygen requirement in very low birth weight neonates with respiratory distress

No major adverse effects were documented

Keywords

Neonate Oral Very low birth weight Vitamin A supplementation 

Abbreviations

BW

Birth weight

BPD

Bronchopulmonary dysplasia

CI

Confidence interval

CPAP

Continuous positive airway pressure

CTRI

Clinical Trial Registry of India

DDST

Denever Developmental Screening Test

EOS

Early-onset sepsis

HFNC

High flow nasal cannula

hs-PDA

Hemodynamically significant patent ductus arteriosus

IQR

Inter quartile range

IM

Intramuscular

IV

Intravenous

IVH

Intraventricular hemorrhage

LOS

Late-onset sepsis

LMIC

Low and middle income countries

MV

Mechanical ventilation

NICHD

National Institute of Child Health and Human Development

NEC

Necrotizing enterocolitis

NICU

Neonatal intensive care unit

NNTB

Number needed to treat for benefit

OGT

Orogastic tube

PVL

Periventricular leukomalacia

PMA

Post-menstrual age

RR

Relative risk

RDS

Respiratory distress syndrome

ROP

Retinopathy of prematurity

VLBW

Very low birth weight

VAS

Vitamin A supplementation

Notes

Acknowledgments

Vitamin A and placebo oral solutions were procured from the Apex Pharmaceuticals Private Limited, Chennai, India, though the manufacturer who did not have any control over study design or outcome.

Authors’ contributions

Prof Sriparna Basu and Prof Ashok Kumar conceptualized and designed the study, coordinated and supervised data collection, drafted the initial manuscript, and reviewed and revised the manuscript. Dr. Parul Khanna designed the data collection instruments, collected data, carried out the initial analyses, and reviewed and revised the manuscript. Dr. Ragini Srivastava supervised the data collection, did the biochemical analysis, reviewed and revised the manuscript. All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Compliance with ethical statements

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical approval

The trial was ethically approved by the Institute Ethics Committee of All India Institute of Medical Sciences, Rishikesh, India.

Informed consent

Informed consent was obtained from all individual participants included in the study.

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Neonatal Unit, Department of Pediatrics, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia
  2. 2.Department of NeonatologyAll India Institute of Medical SciencesRishikeshIndia
  3. 3.Department of Biochemistry, Institute of Medical SciencesBanaras Hindu UniversityVaranasiIndia

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