Bronchopulmonary dysplasia (BPD) is a common complication of premature birth and is associated with significant morbidity. Vitamin A supplementation has been suggested as a potential preventative measure against BPD due to its role in lung maturation and because preterm infants are particularly predisposed to vitamin A deficiency. The aim of this review was to determine whether vitamin A supplementation reduces BPD risk among preterm infants. PubMed, CINAHL, and Web of Science databases were searched with the keywords “bronchopulmonary dysplasia,” “vitamin A,” and “preterm infants” and with the time frame of 2006–2016, and 4 studies were selected for review per the inclusion criteria. Only 1 study found a significant reduction in BPD risk associated with vitamin A supplementation; however, 2 studies indicated a nonsignificant benefit and may have been underpowered to show statistical significance. One study revealed an increased risk of sepsis associated with vitamin A supplementation (for infants weighing >1000 g at birth), but no risk was seen with vitamin A supplementation in the other studies. Because intramuscular vitamin A has shown benefit with minimal risk, continued supplementation for preterm infants is warranted. Future studies aimed at assessing infant groups that are most likely to benefit from supplementation (based on birth weight or other conditions), as well as determining the optimal dosing while minimizing injections, would be beneficial.
American Lung Association. Respiratory distress syndrome and bronchopulmonary dysplasia (RDS & BPD). http://www.lungusa.org. Published 2008. Accessed March 2016.
2.
LemonsJABauerCROhWVery-low-birth-weight outcomes of the NICHD Neonatal Research Network, January 1995 through December 1996. Pediatrics. 2001;107(1):E1.
3.
Zysman-ColmanZTremblayGMBandealiSLandryJS. Bronchopulmonary dysplasia: trends over three decades. Paediatr Child Health. 2013;18:86-90.
4.
D’AngioCTManiscalcoWM. Bronchopulmonary dysplasia in preterm infants: pathophysiology and management strategies. Pediatr Drugs. 2004;6:303-330.
NorthwayWHJrRosanRCPorterDY. Pulmonary disease following respiratory therapy of hyaline-membrane disease: bronchopulmonary dysplasia. N Eng J Med. 1967;276:357-368.
7.
ShimaYKumasakaSMigitaM. Perinatal risk factors for adverse long-term pulmonary outcome in premature infants: comparison of different definitions of bronchopulmonary dysplasia/chronic lung disease. Pediatr Intern. 2013;55:578-581.
8.
JobeAHBancalariE. Bronchopulmonary dysplasia: NICHD/NHLBI/ORD workshop summary. Am J Resp Crit Care Med. 2001;163:1723-1729.
9.
EhrenkranzRAWalshMCVohrBRValidation of the National Institutes of Health consensus definition of bronchopulmonary dysplasia. Pediatrics. 2005;116:1353-1360.
10.
SimpsonSJHallGLWilsonAC. Lung function following very preterm birth in the era of “new” bronchopulmonary dysplasia. Respirology. 2015;20:535-540.
11.
CockMHannaMSozoFPulmonary function and structure following mild preterm birth in lambs. Pediatr Pulmonol. 2005;40:336-348.
12.
SimpsonSJFlecknoeSJClugstonRDGreerJJHooperSBFrappellPB. Structural and functional development of the respiratory system in a newborn marsupial with cutaneous gas exchange. Physiol Biochem Zool. 2011;84:634-649.
13.
BancalariEHWalshMC. Bronchopulmonary dysplasia in the neonate. In: MartinRJFanaroffAAWalshMC eds. Fanaroff & Martin’s Neonatal-Perinatal Medicine. Philadelphia, PA: Saunders; 2015:1157-1169.
WardleSPHughesAChenSShawNJ. Randomised controlled trial of oral vitamin A supplementation in preterm infants to prevent chronic lung disease. Arch Dis Childhood. 2001;84:F9-F13.
16.
ShenaiJPChytilFStahlmanMT. Vitamin A status of neonates with bronchopulmonary dysplasia. Pediatr Res. 1985;19:185-188.
17.
GreeneHLPhillipsBLFranckLPersistently low blood retinol levels during and after parenteral administration of very low birth weight infants: examination of losses into intravenous administration sets and a method of prevention by addition to a lipid emulsion. Pediatrics. 1987;79:894-900.
18.
ChabraSMayockDEZerzanJBittnerRNeufeldMDGleasonCA. Vitamin A status after prophylactic intramuscular vitamin A supplementation in extremely low birth weight infants. Nutr Clin Pract. 2013;28:381-386.
19.
DarlowBAGrahamPJ. Vitamin A supplementation to prevent mortality and short- and long-term morbidity in very low birth weight infants. Cochrane Database Syst Rev. 2011;(10):CD000501.
20.
ChabraSArnoldJDLeslieGIBowenJREarlJWoodF. Vitamin A status in preterm neonates with and without chronic lung disease. J Paediatr Child Health. 1994;30:432-435.
21.
BrandtRBMuellerDBSchroederJRSerum vitamin A in premature and term neonates. J Pediatr. 1978;92:101-104.
22.
MactierHWeaverLT. Vitamin A and preterm infants: what we know, what we don’t know, and what we need to know. Arch Dis Child Fetal Neonatal Ed. 2005;90:F103-F108.
23.
MassaroGDMassaroD. Postnatal treatment with retinoic acid increases the number of pulmonary alveoli in rats. Am J Physiol. 1996;270:L305-L310.
24.
TsangRCLucasAUauyR, eds. Nutritional Needs of the Preterm Infant: Scientific Basis and Practical Guidelines. Baltimore, MD: Williams & Wilkins; 1993.
25.
ChytilF. The lungs and vitamin A. Am J Physiol. 1992;262:L517-L527.
26.
HusteadVA. Relationship of vitamin A (retinol) status to lung disease in the preterm infant. J Pediatr. 1984;105:610-615.
27.
VermaRP. Vitamin A deficiency and severe bronchopulmonary dysplasia in very low birthweight infants. Am J Perinatol. 1996;13:389-393.
28.
TysonJEWrightLLOhWVitamin A supplementation for extremely low birth weight infants. N Eng J Med. 1999;340:1962-1968.
29.
JensenEAFogliaEESchmidtB. Evidence-based pharmacologic therapies for prevention of bronchopulmonary dysplasia. Clinics Perinatol. 2015;42:755-779.
30.
WardleSPHughesAChenSShawNJ. Randomised controlled trial of oral vitamin A supplementation to prevent chronic lung disease. Pediatric Research. 1999;45:914.
31.
ToliaVNMurthyKMcKinleyPSBennettMMClarkRH. The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants. JAMA Pediatr. 2014;168:1039-1044.
32.
AmbalavananNKennedyKTysonJCarloWA. Survey of vitamin A supplementation for extremely-low-birth-weight infants: is clinical practice consistent with the evidence?J Pediatr. 2004;145:304-307.
33.
KiatchoosakunPJirapraditthaJPanthongviriyakulMCVitamin A supplementation for prevention of bronchopulmonary dysplasia in very-low-birth-weight premature Thai infants: a randomized trial. J Med Assoc Thai. 2014;97:S82-S88.
34.
GadhiaMMCutterGRAbmanSHKinsellaJP. Effects of early inhaled nitric oxide therapy and vitamin A supplementation on the risk for bronchopulmonary dysplasia in premature newborns with respiratory failure. J Pediatr. 2014;164:744-748.
35.
KinsellaJPCutterGRWalshWF. Early inhaled nitric oxide therapy in premature newborns with respiratory failure. N Engl J Med. 2006;355:354-364.
36.
UberosJMiras-BaldoMJerez-CaleroANarbona-LopezE. Effectiveness of vitamin A in the prevention of complications of prematurity. Pediatr Neonatol. 2014;55:358-362.
37.
KennedyKAStollBJEhrenkranzRAVitamin A to prevent bronchopulmonary dysplasia in very low birth weight infants: has the dose been too low? The NICHD Neonatal Research Network. Early Hum Dev. 1997;49:19-31.
38.
MoreiraACaskeyMFonsecaRMalloyMGearyC. Impact of providing vitamin A to the routine pulmonary care of extremely low birth weight infants. J Matern Fetal Neonatal Med. 2012;25:84-88.
39.
FeldmanMHSchlezingerNS. Benign intracranial hypertension associated with hypervitaminosis A. Arch Neurol. 1970;22:1-7.
40.
RestakRM. Pseudo tumor cerebri, psychosis, and hypervitaminosis A. J Nerv Ment Dis. 1995;155:72-76.
41.
MorriceGHaevnerWHKapentanskyF. Vitamin A intoxication as a cause of pseudotumor cerebri. JAMA. 1960;173:1802-1805.
42.
IliffPJHumphreyJHMahomvaAITolerance of large doses of vitamin A given to mothers and their babies shortly after delivery. Nutr Res. 1999;19:1437-1446.
43.
MadduxGWFoltzFMNelsonSR. Effect of vitamin A intoxication on intracranial pressure and brain water in rats. J Nutr. 1974;104:478-482.
44.
MeyerSGortnerL. NeoVitA Trial Investigators. 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. Neonatology. 2014;105:182-188.
45.
WestKPJrKhatrySKLeClerqSCTolerance of young infants to a single, large dose of vitamin A: a randomized community trial in Nepal. Bull World Health Organ. 1992;70:733-739.
46.
AgoestinaTHumphreyJHTaylorGASafety of one 52-μmol (50,000 IU) oral dose of vitamin A administered to neonates. Bull World Health Organ. 1994;72:859-868.
47.
CoutsoudisAAdhikariMPillayKEffect of vitamin A supplementation on morbidity of low-birthweight infants. S Afr Med J. 2000;90:730-736.
48.
AmbalavananNWuTJTysonJEKennedyKARoaneCCarloWA. A comparison of three vitamin A dosing regimens in extremely low birth weight infants. J Pediatr. 2003;142:1A-3A.
49.
SonnevilleKDugganC, eds. Manual of Pediatric Nutrition. 5th ed.Shelton, CT: People’s Medical Publishing House; 2014.
50.
LondheVANolenTLDasAVitamin A supplementation in extremely low-birth-weight infants: subgroup analysis in small-for-gestational-age infants. Am J Perinatol. 2013;30:771-780.
51.
ToliaVNMurthyKMcKinleyPSBennettMMClarkRH. The effect of the national shortage of vitamin A on death or chronic lung disease in extremely low-birth-weight infants. JAMA Pediatr. 2014;168:1039-1044.
52.
SUPPORT Study Group of the Eunice Kennedy Shriver NICHD Neonatal Research Network. Target ranges of oxygen saturation in extremely preterm infants. NEJM. 2010;362:1959-1969.
53.
WaiKCKohnMABallardRA. Early cumulative supplemental oxygen predicts bronchopulmonary dysplasia in high risk extremely low gestational age newborns [published online July 25, 2016]. J Pediatr.
