Effects of vitamin D supplementation during pregnancy on offspring health at birth: A meta-analysis of randomized controlled trails

Abstract

Background & aims: Vitamin D deficiency during pregnancy is common across the world. The effects of maternal vitamin D supplementation on offspring health were contradict from previous studies. This study was conducted to update the effects of vitamin D supplementation during pregnancy on offspring health with new evidence.

Methods: A systematic search of Medline, Embase, the Cochrane Database of Systematic Reviews, ClinicalTrials.gov and ChiCTR.org.cn through July 2021 were conducted. Studies were included if they reported randomized clinical trials comparing vitamin D supplementation with placebo, no supplementation (400 IU/day or less) during pregnancy, and included birth outcomes. Pooled analyses were performed using random-effects models.

Results: Forty-two RCTs recruiting 11,082 participants were included. Vitamin D supplementation during pregnancy was associated with a lower risk of intrauterine or neonatal death (RR, 0.69; 95% CI, 0.48-0.99) in 13 RCTs with 6238 participants. We also found prenatal vitamin D supplementation was associated with an increased offspring length at birth (MD, 0.27 cm; 95% CI, 0.02-0.51), increased neonatal vitamin D concentration (MD, 27.72 nmol/L; 95% CI, 20.51-34.92), and reduced risk of vitamin D insufficiency (RR of 0.51; 95% CI, 0.38-0.67), but not associated with birth weight (MD, 37.07 g; 95% CI, -9.67 to 83.80), head circumference (MD, 0.15 cm; 95% CI, -0.02 to 0.32), preterm birth (RR, 0.93; 95% CI, 0.79-1.09), or low birth weight (RR, 0.90; 95% CI, 0.66-1.24). Supplementation initiated before the 20th week of gestation was associated with a decreased risk of small for gestational age (RR, 0.46; 95% CI, 0.24-0.90).

Conclusions: Vitamin D supplementation during pregnancy was associated with improved offspring vitamin D sufficiency status, improved fetal linear growth, and reduced fetal or neonatal mortality. No effect was demonstrated for vitamin D supplementation on birth weight, risk of low birth weight, and risk of preterm birth.

Keywords: Birth outcome; Cholecalciferol; Neonatal health; Pregnancy; Vitamin D.