Effects of Vitamin D Supplementation During Pregnancy on Birth Size: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Abstract

During pregnancy, vitamin D supplementation may be a feasible strategy to help prevent low birthweight (LBW) and small for gestational age (SGA) births. However, evidence from randomized controlled trials (RCTs) is inconclusive, probably due to heterogeneity in study design and type of intervention. A systematic literature search in the PubMed-Medline, EMBASE, and Cochrane Central Register of Controlled Trials databases was carried out to evaluate the effects of oral vitamin D supplementation during pregnancy on birthweight, birth length, head circumference, LBW, and SGA. The fixed-effects or random-effects models were used to calculate mean difference (MD), risk ratio (RR), and 95% Confidence Interval (CI). On a total of 13 RCTs, maternal vitamin D supplementation had a positive effect on birthweight (12 RCTs; MD = 103.17 g, 95% CI 62.29⁻144.04 g), length (6 RCTs; MD = 0.22 cm, 95% CI 0.11⁻0.33 cm), and head circumference (6 RCTs; MD:0.19 cm, 95% CI 0.13⁻0.24 cm). In line with these findings, we also demonstrated that maternal vitamin D supplementation reduced the risk of LBW (3 RCTs; RR = 0.40, 95% CI 0.22⁻0.74) and SGA (5 RCTS; RR = 0.69, 95% CI 0.51⁻0.92). The present systematic review and meta-analysis confirmed the well-established effect of maternal vitamin D supplementation on birth size. However, further research is required to better define risks and benefits associated with such interventions and the potential implications for public health.

Keywords: birth length; birthweight; diet; gestational age; head circumference; nutrition; pregnancy outcomes; vitamin D.

Figure 1

PRISMA flow diagram of study selection.

Figure 2

Forest plot of the effect of vitamin D intervention alone or in combination with micronutrients on birthweight (g), based on the fixed-effects model. Charandabi 2015 (a): Vit D + Ca (1000 IU/day); Charandabi 2015 (b): Vit D (1000 IU/day); Goldring 2013 (a): Vit D2 (800 IU/day); Goldring 2013 (b): Vit D3 (single dose of 200000 IU); Hollis 2011 (a): Vit D3 + micronutrients (1600 IU/day); Hollis 2011 (b): Vit D3 + micronutrients (3600 IU/day).

Figure 3

Forest plot of the effect of vitamin D intervention alone or in combination with micronutrients on birth length (cm), based on the fixed-effects model. Charandabi 2015 (a): Vit D + Ca (1000 IU/day); Charandabi 2015 (b): Vit D (1000 IU/day).

Figure 4

Forest plot of the effect of vitamin D intervention alone or in combination with micronutrients on head circumference (cm), based on the fixed-effects model. Charandabi 2015 (a): Vit D + Ca (1000 IU/day); Charandabi 2015 (b): Vit D (1000 IU/day).

Figure 5

Forest plot of the effect of vitamin D intervention on the risk of low birthweight, based on the fixed-effects model. Yu 2009 (a): Vit D2 (800 IU/day); Yu 2009 (b): Vit D2 (single dose of 200000 IU).

Figure 6

Forest plot of the effect of vitamin D intervention on the risk of small for gestational age, based on the fixed-effects model. Yu 2009 (a): Vit D2 (800 IU/day); Yu 2009 (b): Vit D2 (single dose of 200000 IU).

Figure 7

Risk-of-bias assessment of randomized controlled trials included in the meta-analysis. Risk-of-bias summary (A) and graph (B), according to the Cochrane’s Collaboration tool for assessing risk of bias in randomized trials.

Figure 8

Funnel plot with estimated 95% confidence intervals for meta-analysis of the effect of vitamin D intervention on birthweight.