DOI: 10.3390/jcm15218434 ISSN: 2077-0383

The Effect of Vitamins During Pregnancy on Pregnancy and Assisted Reproduction Outcomes: An Umbrella Review

Yuzhu Zhang, Huimin Liu, Lang Qin, Rui Gao

Background: Vitamin deficiency is associated with multiple adverse maternal and fetal outcomes. Objective: To summarize systematic reviews and meta-analyses, and to evaluate the impact of vitamin deficiency and vitamin supplementation during pregnancy on maternal and fetal outcomes, including outcomes of assisted reproductive technology (ART). Methods: Prior to conducting this umbrella review, we registered the protocol in PROSPERO (CRD420251026875). We searched PubMed, Embase and the Cochrane Library for all systematic reviews and meta-analyses concerning vitamin status assessment and supplementation during pregnancy up to April 2025, and extracted all relevant pregnancy outcomes associated with prenatal vitamins. Screening, data extraction, and quality assessment (AMSTAR 2) were completed by two independent reviewers. Data were quantitatively synthesized, and odds ratios (OR) with 95% confidence intervals (95%CI) were mainly reported. Results: A total of 33 eligible systematic reviews and meta-analyses covering 679 primary studies were included, which explored 29 maternal–fetal outcomes related to six vitamins from the perspectives of vitamin insufficiency/deficiency and supplementation. Vitamin B12, folate, vitamin C and D deficiencies were linked to higher risks of gestational diabetes mellitus (GDM), pre-eclampsia, low birth weight, recurrent spontaneous abortion (RSA), preterm birth and other adverse outcomes. Low vitamin D also correlated with poorer assisted reproductive outcomes including reduced clinical pregnancy and live birth rates. Appropriate supplementation of folate, vitamin C and D may lower the risks of megaloblastic anemia, premature rupture of membranes, GDM and stillbirth, and improved neonatal growth. Vitamin A exerted no notable influence on pregnancy outcomes. Conclusions: Insufficiency or deficiency in vitamin B12, folic acid, vitamin C, and vitamin D is more likely to result in adverse pregnancy outcomes. Supplementation with folic acid, vitamin C and vitamin D during pregnancy can improve the incidence of maternal and fetal outcomes to some extent.

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