There is emerging evidence suggesting that folate status during pregnancy may play a role in fetal programming of metabolic disease. Therefore, this systematic review aims to summarize and systematize the current evidence surrounding the relationship between maternal folate status during pregnancy and offspring metabolic programming, focusing on both animal and human studies. PubMed, Web of Science and Scopus databases were searched in order to identify studies conducted on pregnant women or in animals studying the association between maternal folate exposure and at least one metabolic syndrome outcome in offspring after birth (weight, blood pressure, glucose regulation parameters, triglycerides and high-density lipoprotein cholesterol (HDL-C) levels). The quality of included studies was assessed using SYRCLE Risk of Bias Tools for animal studies and NHLBI Study Quality Assessment Tools for observational studies and randomized controlled trials. Among the 10 "good" or "fair" studies that investigated excessive folate exposure during the perigestational period, 7 animal studies and 1 human study reported a positive association with development of metabolic outcomes in offspring. On the other hand, 6 of the 7 "good" or "fair" included human studies compared adequate versus low folate exposure, showing a lack of association (n = 3) or a protective effect (n = 3) regarding offspring's dysmetabolism. In conclusion, there is strong evidence from animal trials suggesting that excessive folate intake in early phases of development programs for metabolic dysfunction. While human evidence regarding excessive maternal folate exposure is currently scarce, human studies suggest that folate adequacy in pregnancy is not detrimental for metabolic function of the offspring.
Keywords: Fetal programming; Folate; Folic acid; Maternal nutrition; Metabolic syndrome; Offspring health; Pregnancy.
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