Aim: We performed a meta-analysis of randomized controlled trials (RCT) and observational studies to answer the two following questions: (i) whether low maternal circulating 25 hydroxyvitamin D (25-OHD) is associated with an increased risk of preterm birth (PTB) or spontaneous PTB (sPTB); and (ii) whether vitamin D supplementation alone during pregnancy can reduce the risk of PTB. Methods: Literature search was carried out using Pubmed, Web of Science and Embase databases up to June 2016. Pooled OR or relative risk (RR) with 95%CI were computed using fixed or random effects models depending on the size of heterogeneity. Subgroup analysis was used to explore potential sources of between-study heterogeneity. Publication bias was evaluated using Egger's test and Begg's test. Results: Twenty-four articles (six RCT and 18 observational studies) were identified. Maternal circulating 25-OHD deficiency (pooled OR, 1.25; 95%CI: 1.13-1.38) rather than insufficiency (pooled OR, 1.09; 95%CI: 0.89-1.35) was associated with an increased risk of PTB, and vitamin D supplementation alone during pregnancy could reduce the risk of PTB (pooled RR, 0.57; 95%CI: 0.36-0.91). This was also the case for the sPTB subgroup (circulating 25-OHD <50 vs >50 nmol/L; pooled OR, 1.45; 95%CI: 1.20-1.75). Conclusions: Maternal circulating 25-OHD deficiency could increase PTB risk and vitamin D supplementation alone during pregnancy could reduce PTB risk. Extrapolation of the results, however, must be done with caution, and there is urgent need for larger, better-designed RCT to confirm this effect.

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Supplementation with folic acid (FA) was proven to prevent neural tube defects (NTDs) and was recommended worldwide before and during early pregnancy. However, much less is known regarding the role of FA after the 12th gestational week (GW). This study aimed to investigate the related effects of continued FA supplementation after the first trimester of pregnancy on fetal growth. The study subjects came from the Ma’anshan-Anhui Birth Cohort Study (MABC) that recruited 3474 pregnant women from the city of Ma’anshan in Anhui Province in China during the period of May 2013 to September 2014. The information on use of vitamin and mineral supplements was recorded in different periods (the first/second/third trimester of pregnancy). Small-for-gestational-age (SGA) births were live-born infants that were <10th percentile of birth weight, and large-for-gestational-age (LGA) births were live-born infants that were ≥90th percentile of birth weight according to nomograms based on gender and gestational age from the latest standards. We used multivariable logistic regression to evaluate the effects of FA supplement consumption in the second/third trimester of pregnancy on the risk of LGA and SGA. In addition, propensity score analysis was also performed to examine the effects. In this prospective birth cohort study conducted in Chinese women who had taken FA in the first trimester of pregnancy, we found that continued FA supplementation with 400 micrograms/day in the second and third trimesters of pregnancy significantly increased the risk of LGA (RR = 1.98 (1.29, 3.04)). This relation was strong or monotonic after adjusting for maternal age, newborn’s gender, maternal pre-pregnancy BMI, maternal education level, smoking, alcohol consumption and calcium supplementation. We did not observe that continuing FA supplementation after the first trimester of pregnancy remarkably decreased the risk of SGA. The propensity score analysis showed similar results. To confirm these findings, additional investigations or trials with a large sample and the tracking of folate status throughout pregnancy are recommended.

ObjectiveTo determine whether maternal vitamin D deficiency during pregnancy is associated with small for gestational age (SGA).MethodsA comprehensive literature search of PubMed, the Cochrane Library, Embase, and the Elsevier ScienceDirect library was conducted to identify relevant articles reporting prospective cohort studies in English, with the last report included published in February 2017. Pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were used to evaluate the correlation in a random effects model.ResultsA total of 13 cohort studies were included in this meta-analysis with a sample of 28 285 individuals from seven countries. The pooled overall OR for babies born SGA was 1.588 (95% CI 1.138 to 2.216; p<0.01) for women with vitamin D deficiency. The prevalence of vitamin D deficiency during pregnancy varied from 13.2% to 77.3%. Subgroup analyses identified no significant differences in the association between vitamin D deficiency and SGA based on study quality, gestational week during which blood sampling was performed, cut-off vitamin D levels, sample size, adjustment for critical confounders and method for measuring vitamin D.ConclusionThis meta-analysis suggests that vitamin D deficiency is associated with an increased risk of SGA.