Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia

doi:10.1016/S0022-3476(05)81800-1

The Journal of Pediatrics

Volume 121, Issue 3, September 1992, Pages 420-427

https://doi.org/10.1016/S0022-3476(05)81800-1 Get rights and content

We performed a randomized, double-blind, controlled triat to determine whether vitamin A supplementation in a group of very low birth weight infants would reduce the incidence of bronchopulmonary dysplasia. Forty-nine infants (birth weight 700 to 1100 gm) requiring mechanical ventilation and supplemental oxygen at 96 hours age were randomly assigned to recelve either 2000 IU retinyl palmitate (n=27) or saline placebo (n=22) intramuscularly every other day for up to 14 doses. There were no differences between treatment groups in the incidences of bronchopulmonary dysplasia at 31 days of postnatal age (vitamin A group 48% placebo group 55%; p=0.776), supplemental oxygen requirement at 34 weeks of postconceptional age, or other complications of prematurity. The vitamin A group had higher mean plasma vitamin A concentrations than the placebo group, but mean plasma vitamin A concentrations were greater than 20 μg/dl (suggesting sufficiency) in both groups after the first study week. By study day 28, only one fourth of the infants in either group had plasma vitamin A concentrations less than 20 μg/dl. In contrast to an earlier report, we found no change in the incidence of BPD with vitamin A supplementation. Our findings may reflect a low baseline, incidence of vitamin A deficiency in the study population and recent changes in the respiratory care of very low birth weight infants. The latter may have lessened the potential impact of vitamin A deficiency on lung disease.

References (16)

BrandtRB et al.
Serum vitamin A in premature and term neonates
J Pediatr
(1978)
ShenaiJP et al.
Plasma vitamin A and retinol-binding protein in premature and term neonates
J Pediatr
(1981)
HusteadVA et al.
Relationship of vitamin A (retinol) status to lung disease in the preterm infant
J Pediatr
(1984)
ShenaiJP et al.
Clinical trial of vitamin A supplementation in infants susceptible to bronchopulmonary dysplasia
J Pediatr
(1987)
EdwardsDK
Radiology of hyaline membrane disease, transient tachypnea of the newborn, and bronchopulmonary dysplasia
ThompsonJN et al.
Fluorometric determinations of vitamin A in human blood and liver
Biochem Med
(1971)
ShenaiJP et al.
Plasma retinol-binding protein response to vitamin A administration in infants susceptible to bronchopulmonary dysplasia
J Pediatr
(1990)
WoodruffCW et al.
Vitamin A status of preterm infants: correlation between plasma retinol, concentration and retinol dose response
Am J Clin Nutr
(1987)

There are more references available in the full text version of this article.

Cited by (124)

Vitamin A supplementation in very-preterm or very-low-birth-weight infants to prevent morbidity and mortality: A systematic review and meta-Analysis of randomized trials
2021, American Journal of Clinical Nutrition
A previous systematic review showed that intramuscular vitamin A supplementation reduced the risk of bronchopulmonary dysplasia (BPD) in very-low-birth-weight (VLBW) infants. However, more recent studies have questioned this finding.
Our objective was to synthesize current evidence on vitamin A supplementation in very-preterm (<32 wk gestational age) or VLBW infants and investigate the factors that may modify its efficacy.
A systematic review was conducted using the Cochrane systematic review methodology. We included randomized controlled trials investigating vitamin A supplementation for reducing morbidity and mortality in very-preterm or VLBW infants. Certainty of evidence was assessed using Grading of Recommendations, Assessment, Development and Evaluation (GRADE) recommendations. Prespecified subgroup analyses assessed factors that may modify the effects of vitamin A supplementation.
We included 17 studies (n = 2471) in the qualitative and 15 studies (n = 2248) in the quantitative synthesis. Moderate-certainty evidence suggested a beneficial effect of vitamin A for decreasing the risk of BPD at 36 wk postmenstrual age (RR: 0.83; 95% CI: 0.74, 0.93; numbers needed to treat for an additional beneficial outcome: 16; 95% CI: 9, 53; 9 studies, n = 1752; P = 0.002). Subgroup analysis suggested that the beneficial effect was limited to infants with baseline vitamin A intake <1500 IU · kg⁻¹ · d⁻¹. Both enteral and parenteral routes were effective. Vitamin A supplementation did not have adverse effects and did not alter mortality before discharge (12 studies, n = 1917) or neurodevelopmental outcomes at 18–22 mo (1 study, n = 538).
The benefit of vitamin A supplementation for reducing BPD is likely to be limited to infants with baseline vitamin A intake <1500 IU · kg⁻¹ · d⁻¹ and is not affected by the route of administration.
Serum retinol levels and neonatal outcomes in preterm infants
2017, Journal of the Formosan Medical Association
Citation Excerpt :
Furthermore, the retinol carrier protein is lower in premature infants than in term infants, which affects delivery of retinol to the liver for storage.6 Some studies have shown that BPD and chronic lung disease in premature infants cannot be prevented by the intramuscular administration of retinol15,16; these studies vary, however, in their methods and timing of retinol-concentration measurement. In addition, there are various and complicated factors that affect the development of BPD and chronic lung disease and that affect retinol levels in premature infants.
Glucocorticoids are frequently administered to preterm infants, both antenatally and postnatally; however, the effect on serum retinol levels has not been determined. The risk of bronchopulmonary dysplasia is increased in premature infants with low retinol concentrations.
Our purpose was to determine the effect of glucocorticoid administration on serum retinol levels in preterm infants.
All infants <1250 g or <29 weeks' gestation admitted to the neonatal intensive care unit within 48 h of birth were eligible for inclusion. A retinol concentration <20 μg/dL during the first 48 h of birth was defined as low serum retinol, and a level <10 μg/dL as retinol deficiency.
Data from 115 premature infants were collected during a 7-year period, from 2005 to 2012. Neither antenatal nor postnatal steroid administration affected retinol concentrations. Retinol deficiency was associated with an increased risk for severe respiratory distress syndrome and adverse pulmonary outcome (death during the first 28 days of life and long-term oxygen dependence >90 days); low retinol levels conferred an increased risk for bronchopulmonary dysplasia. Prolonged duration of total parenteral nutrition (>21 days) was associated with serum retinol deficiency during hospitalization (P < 0.05). Retinol deficiency was associated with an increased risk for delayed neurological development in 1-year-old and 2-year-old children.
Glucocorticoids do not affect retinol levels in premature infants, but retinol concentrations are correlated with respiratory and neurological outcomes.
Impaired Lung Growth After Injury in Premature Lung
2017, Fetal and Neonatal Physiology, 2-Volume Set
Evidence-Based Pharmacologic Therapies for Prevention of Bronchopulmonary Dysplasia: Application of the Grading of Recommendations Assessment, Development, and Evaluation Methodology
2015, Clinics in Perinatology
Citation Excerpt :
Although vitamin A is potentially toxic when administered in high doses, the published RCTs did not demonstrate increased rates of any adverse events among vitamin A treated infants.78 One RCT reported that IM vitamin A injections appeared to be painful.84 When considering risks and benefits, the GRADE system recommends that the costs of a therapy may also be considered.18
Impact of Nutrition on Bronchopulmonary Dysplasia
2015, Clinics in Perinatology
Citation Excerpt :
Very few randomized trials have demonstrated efficacy of drugs or nutritional interventions for the prevention or treatment of BPD.19 One intervention shown to be efficacious is vitamin A. Two randomized clinical trials have evaluated the use of vitamin A for the prevention of BPD in 856 extremely premature infants,20,21 although some have questioned whether a higher dose of vitamin A supplementation is necessary to reduce the risk of BPD.22 There is no evidence that vitamin A supplementation reduces hospitalizations or pulmonary morbidity after hospital discharge.23
Pulmonary Consequences of Preterm Birth
2014, The Lung: Development, Aging and the Environment: Second Edition
Preterm birth is an environmental stress that disrupts lung development during the second half of gestation. Structural and functional immaturity of the preterm infant’s lungs necessitates use of antenatal steroids, perinatal surfactant replacement therapy, ventilation support with oxygen-rich gas, nutritional support, and other supportive measures. Many supported preterm infants develop acute lung injury that requires prolonged invasive mechanical ventilation with oxygen-rich gas, leading to neonatal chronic lung disease. Challenges remain to understand how invasive mechanical ventilation with oxygen-rich gas dysregulates molecular pathways and thereby disrupts the trajectory of lung development during the canalicular stage through to the alveolar stage of lung development. Results of new mechanistic studies suggest that invasive mechanical ventilation with oxygen-rich gas may dysregulate epigenetic determinants of regulation of gene expression.

View all citing articles on Scopus

^*: Supported by the North Carolina Chapter of the American Lung Association.

View full text

Trial of vitamin A supplementation in very low birth weight infants at risk for bronchopulmonary dysplasia*

J Pediatr

J Pediatr

J Pediatr

J Pediatr

Biochem Med

J Pediatr

Am J Clin Nutr