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

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.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.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).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.