Vitamin D supplementation to improve pregnancy and perinatal outcomes: an overview of 42 systematic reviews

Objective: To review the evidence to assess effectiveness of vitamin D supplementation during pregnancy and associations of serum vitamin D levels with perinatal outcomes.

Design: Overview of systematic reviews (SRs).

Data sources: Searches conducted in January 2019: Ovid Medline (1946-), Cochrane Library databases.

Eligibility criteria for selecting studies: Two reviewers independently screened titles and abstracts, and full texts using predefined inclusion criteria: SRs evaluating vitamin D supplementation in pregnant women and/or examining the association between serum vitamin D levels reporting at least one predefined perinatal outcome. Only SRs with high AMSTAR scores were analysed.

Data extraction and synthesis: Data were extracted independently by one reviewer and checked by a second. Results were assessed for quality independently by two reviewers using GRADE criteria.

Results: Thirteen SRs were included, synthesising evidence from 204 unique primary studies. SRs of randomised controlled trials (RCTs) with the highest level of evidence showed no significant benefit from vitamin D in terms of preterm birth (RR 1.00 (95% CI 0.77, 1.30); high quality), pre-eclampsia (RR 0.91 (0.45, 1.86); low quality), gestational diabetes (RR 0.65 (0.39, 1.08); very low quality), stillbirth (RR 0.75 (0.50, 1.12); high quality), low birth weight (RR 0.74 (0.47, 1.16); low quality), caesarean section (RR 1.02 (0.93, 1.12); high quality). A significant difference was found for small for gestational age (RR 0.72 (0.52, 0.99); low quality). SRs of observational studies showed associations between vitamin D levels and preterm birth (RR 1.19 (1.08, 1.31); moderate quality), pre-eclampsia (RR 1.57 (1.21, 2.03) for 25-hydroxy vitamin D (25 (OH)D)<50 nmol/L subgroup; low quality), gestational diabetes (RR 1.12 (1.02, 1.22) for 25 (OH)D<50 nmol/L and RR 1.09 (1.03, 1.15)<75 nmol/L; moderate quality) and small for gestational age (RR 1.35 (1.18, 1.54)<50 nmol/L; low quality). SRs showed mixed results for associations between vitamin D and low birth weight (very low quality) and caesarean section (very low quality).

Conclusion: There is some evidence from SRs of observational studies for associations between vitamin D serum levels and some outcomes; however SRs examining effectiveness from RCTs showed no effect of vitamin D supplementation in pregnancy with the exception of one predefined outcome, which had low quality evidence. Credibility of the evidence in this field is compromised by study limitations (in particular, the possibility of confounding among observational studies), inconsistency, imprecision and potential for reporting and publication biases.