Vitamin A Supplementation in Extremely Low-Birth-Weight Infants: Subgroup Analysis in Small-for-Gestational-Age Infants

Vedang A. Londhe; Tracy L. Nolen; Abhik Das; Rosemary D. Higgins; Jon E. Tyson; William Oh; Sherin U. Devaskar; for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

doi:10.1055/s-0032-1333410

American Journal of Perinatology, Table of Contents

Am J Perinatol 2013; 30(09): 771-780
DOI: 10.1055/s-0032-1333410

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Vitamin A Supplementation in Extremely Low-Birth-Weight Infants: Subgroup Analysis in Small-for-Gestational-Age Infants

Vedang A. Londhe

¹Division of Neonatology and Developmental Biology, Department of Pediatrics, Neonatal Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California

,

Tracy L. Nolen

²Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina

,

Abhik Das

²Statistics and Epidemiology Unit, RTI International, Research Triangle Park, North Carolina

,

Rosemary D. Higgins

³ Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bethesda, Maryland

,

Jon E. Tyson

⁴Department of Pediatrics, University of Texas Medical School at Houston, Houston, Texas

,

William Oh

⁵Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Islands

,

Sherin U. Devaskar

¹Division of Neonatology and Developmental Biology, Department of Pediatrics, Neonatal Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California

,

for the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network

› Author Affiliations

Abstract

Objective Preterm infants with intrauterine growth restriction are at increased risk of respiratory distress syndrome and bronchopulmonary dysplasia (BPD). A randomized clinical trial by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) Neonatal Research Network demonstrated that vitamin A supplementation in extremely low-birth-weight (ELBW) preterm infants requiring early respiratory support decreased the risk of developing BPD.

Study Design A subgroup analysis of small-for-gestational-age (SGA) infants from the original NICHD trial was performed to test the hypothesis that in infants requiring early respiratory support, vitamin A supplementation decreases the relative risk of BPD or death in premature SGA infants to a greater extent than in gestational age–equivalent vitamin A–treated appropriate-for-gestational-age (AGA) infants.

Results Although vitamin A supplementation significantly increased serum retinol concentrations in AGA ELBW infants (median [5th percentile, 95th percentile]: 16.3 [−7.0, 68.8] versus 2.4 [−13.9, 55.1]; p < 0.001), no increases were noted in SGA ELBW infants.

Conclusions Given the limited power of this analysis due to a low number of SGA infants, these data did not provide evidence to support the hypothesis that vitamin A supplementation in preterm SGA infants requiring early respiratory support decreases the relative risk of BPD or death as compared with preterm AGA infants.

Keywords

vitamin A - IUGR—intrauterine growth restriction - BPD—bronchopulmonary dysplasia - SGA—small for gestational age - AGA—appropriate for gestational age

Full Text

References

References
1 Rosenberg A. The IUGR newborn. Semin Perinatol 2008; 32: 219-224
2 McIntire DD, Bloom SL, Casey BM, Leveno KJ. Birth weight in relation to morbidity and mortality among newborn infants. N Engl J Med 1999; 340: 1234-1238
3 Greenough A, Yuksel B, Cheeseman P. Effect of in utero growth retardation on lung function at follow-up of prematurely born infants. Eur Respir J 2004; 24: 731-733
4 Tyson JE, Wright LL, Oh W , et al; National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A supplementation for extremely-low-birth-weight infants. N Engl J Med 1999; 340: 1962-1968
5 Ambalavanan N, Tyson JE, Kennedy KA , et al; National Institute of Child Health and Human Development Neonatal Research Network. Vitamin A supplementation for extremely low birth weight infants: outcome at 18 to 22 months. Pediatrics 2005; 115: e249-e254
6 Alexander GR, Himes JH, Kaufman RB, Mor J, Kogan M. A United States national reference for fetal growth. Obstet Gynecol 1996; 87: 163-168
7 Koch GGCG, Amara IA, Stokes ME, Uryniak TJ. Categorical data analysis. In: DA B, , ed. Statistical Methodology in the Pharmaceutical Sciences. New York, NY: Marcel Dekker; 1990: 389-473
8 Merritt TA, Deming DD, Boynton BR. The “new” bronchopulmonary dysplasia: challenges and commentary. Semin Fetal Neonatal Med 2009; 14: 345-357
9 Ambalavanan N, Kennedy K, Tyson J, Carlo WA. Survey of vitamin A supplementation for extremely-low-birth-weight infants: is clinical practice consistent with the evidence?. J Pediatr 2004; 145: 304-307
10 Kaplan HC, Tabangin ME, McClendon D, Meinzen-Derr J, Margolis PA, Donovan EF. Understanding variation in vitamin A supplementation among NICUs. Pediatrics 2010; 126: e367-e373
11 Aird FK, Greene SA, Ogston SA, Macdonald TM, Mukhopadhyay S. Vitamin A and lung function in CF. J Cyst Fibros 2006; 5: 129-131
12 Gilliland FD, Berhane KT, Li YF, Gauderman WJ, McConnell R, Peters J. Children's lung function and antioxidant vitamin, fruit, juice, and vegetable intake. Am J Epidemiol 2003; 158: 576-584
13 Checkley W, West Jr KP, Wise RA , et al. Maternal vitamin A supplementation and lung function in offspring. N Engl J Med 2010; 362: 1784-1794
14 Kayastha S, Tuladhar H. Study of low birth weight babies in Nepal Medical College. Nepal Med Coll J 2007; 9: 266-269
15 Stewart CP, Katz J, Khatry SK , et al. Preterm delivery but not intrauterine growth retardation is associated with young maternal age among primiparae in rural Nepal. Matern Child Nutr 2007; 3: 174-185
16 Hoo AF, Stocks J, Lum S , et al. Development of lung function in early life: influence of birth weight in infants of nonsmokers. Am J Respir Crit Care Med 2004; 170: 527-533
17 Dezateux C, Lum S, Hoo AF, Hawdon J, Costeloe K, Stocks J. Low birth weight for gestation and airway function in infancy: exploring the fetal origins hypothesis. Thorax 2004; 59: 60-66
18 Kotecha SJ, Watkins WJ, Heron J, Henderson J, Dunstan FD, Kotecha S. Spirometric lung function in school-age children: effect of intrauterine growth retardation and catch-up growth. Am J Respir Crit Care Med 2010; 181: 969-974
19 Massaro GD, Massaro D. Formation of pulmonary alveoli and gas-exchange surface area: quantitation and regulation. Annu Rev Physiol 1996; 58: 73-92
20 Londhe VA, Maisonet TM, Lopez B, Shin BC, Huynh JC, Devaskar SU. Retinoic acid rescues alveolar hypoplasia in the calorie-restricted developing rat lung. Am J Respir Cell Mol Biol 2012; , Oct 18; [E-pub ahead of print]
21 Kennedy KA, Stoll BJ, Ehrenkranz RA , et al. Vitamin 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