Research Article: Efficacy of vitamin D supplementation in gestational diabetes mellitus: Systematic review and meta-analysis of randomized trials

Date Published: March 22, 2019

Publisher: Public Library of Science

Author(s): Meline Rossetto Kron Rodrigues, Silvana Andréa Molina Lima, Glaucia Maria Ferreira da Silvia Mazeto, Iracema Mattos Paranhos Calderon, Claudia Garcia Magalhães, Guilherme Augusto Rago Ferraz, Ana Claúdia Molina, Roberto Antônio de Araújo Costa, Vania dos Santos Nunes Nogueira, Marilza Vieira Cunha Rudge, Diane Farrar.


Trials have examined on the benefits of vitamin D supplementation in pregnant women.

This review aimed to evaluate whether oral vitamin D supplements, when given to pregnant women with gestational diabetes mellitus (GDM), would improve maternal and neonatal outcomes, compared with no treatment or placebo.

We performed a systematic review following Cochrane methodology, and randomized trials were included where pregnant women with GDM received vitamin D supplementation versus placebo/no treatment or vitamin D and calcium versus placebo/no treatment. Primary outcomes were preeclampsia, preterm birth, cesarean delivery, gestational hypertension, and adverse events related to vitamin D supplementation. The search strategies were applied to the following databases: MEDLINE, Embase, LILACS, and CENTRAL. Similar outcomes in at least two trials were plotted using Review Manager 5.3 software. The quality of evidence was generated according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE).

The total of 1224 references were identified, eleven trials were potentially eligible, and six were included in this review (totaling 456 women). The meta-analysis of frequency of cesarean deliveries did not show significant differences between groups, none of the trials evaluated the remaining primary outcomes. For secondary outcomes, our results suggest that vitamin D supplementation in pregnant women with GDM may reduce newborn complications such as hyperbilirubinemia, polyhydramnios (RR: 0.40, 95% CI: 0.23 to 0.68; RR: 0.17, 95% CI: 0.03 to 0.89; respectively), and the need for maternal or infant hospitalization (RR: 0.13; 95% CI: 0.02 to 0.98; RR: 0.40, 95% CI: 0.23 to 0.69). However, the evidence was of low or very low quality.

We did not find moderate or high quality evidence indicating that vitamin D supplementation, when compared with placebo, improves glucose metabolism, adverse maternal and neonatal outcomes related to GDM in pregnant women.

Partial Text

GDM is associated with maternal and neonatal risks [1]. A large, multinational cohort study, Hyperglycemia and Adverse Pregnancy Outcome study [2], demonstrated that GDM or obesity alone, compared with normoglycemic pregnant controls, had significantly greater odds of low birth weight, newborn percent body fat, primary cesarean delivery, and preeclampsia. In addition, the risk of adverse maternal, fetal, and neonatal outcomes continuously increased as a function of maternal glycemia at 24–28 weeks, even within ranges previously considered normal [2]. In addition, a systematic review showed a positive association between maternal hyperglycemia and caesarean section, induction of labor, large for gestational age, macrosomia, and shoulder dystocia [3].

During pregnancy, maternal vitamin D deficiency has been associated with adverse maternal and fetal outcomes, such as increased incidence of preeclampsia, insulin resistance, diabetes mellitus, and increased frequency of cesarean delivery [12, 13, 28, 29].




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