Ensuring a mother has adequate amounts of folate during pregnancy is clearly beneficial for fetal development, although there may be adverse effects if taken beyond recommended dosages. Additionally, folate exposure during pregnancy may impact the infants' epigenome (gene expression), potentially influencing health in the long term.[1]
In the 1990s several large randomized controlled trials (RCTs) conducted in various countries found that folic acid supplementation was effective at lowering the risk of fetal NTDs when taken before conception.[2][3][4] In response, folic acid supplementation is now routinely recommended to women who are pregnant or trying to conceive. Because of the clear benefits of folic acid supplementation, it’s no longer ethical to perform RCTs where one group of pregnant women is given folic acid and the other is not. As a result, much of the research we have today is from decades-old RCTs or observational studies, providing an overall weaker evidence base.
Limited data from RCTs suggests that folic acid supplementation likely reduces the rate of pregnancy termination due to NTDs and may increase birth weight, although research is mixed on the latter.[5][6][7] Unfortunately, folic acid has not been found to protect against other types of congenital disorders, such as cleft lip, cleft palate, or congenital heart defects.[7].
Observational research suggests that folic acid supplementation during pregnancy may be associated with a reduced risk of certain types of childhood cancers,[8][9] and a reduced risk of autism and attention deficit hyperactivity disorder (ADHD) traits.[10]
References
- ^Dominguez-Salas P, Cox SE, Prentice AM, Hennig BJ, Moore SEMaternal nutritional status, C(1) metabolism and offspring DNA methylation: a review of current evidence in human subjects.Proc Nutr Soc.(2012-Feb)
- ^Czeizel AE, Dudás I, Métneki JPregnancy outcomes in a randomised controlled trial of periconceptional multivitamin supplementation. Final report.Arch Gynecol Obstet.(1994)
- ^A E Czeizel, I DudásPrevention of the first occurrence of neural-tube defects by periconceptional vitamin supplementationN Engl J Med.(1992 Dec 24)
- ^Prevention of neural tube defects: results of the Medical Research Council Vitamin Study. MRC Vitamin Study Research Group.Lancet.(1991 Jul 20)
- ^Saccone G, Berghella VFolic acid supplementation in pregnancy to prevent preterm birth: a systematic review and meta-analysis of randomized controlled trials.Eur J Obstet Gynecol Reprod Biol.(2016-Apr)
- ^Fekete K, Berti C, Trovato M, Lohner S, Dullemeijer C, Souverein OW, Cetin I, Decsi TEffect of folate intake on health outcomes in pregnancy: a systematic review and meta-analysis on birth weight, placental weight and length of gestation.Nutr J.(2012-Sep-19)
- ^De-Regil LM, Peña-Rosas JP, Fernández-Gaxiola AC, Rayco-Solon PEffects and safety of periconceptional oral folate supplementation for preventing birth defects.Cochrane Database Syst Rev.(2015-Dec-14)
- ^Wan Ismail WR, Abdul Rahman R, Rahman NAA, Atil A, Nawi AMThe Protective Effect of Maternal Folic Acid Supplementation on Childhood Cancer: A Systematic Review and Meta-analysis of Case-control Studies.J Prev Med Public Health.(2019-Jul)
- ^Chiavarini M, Naldini G, Fabiani RMaternal Folate Intake and Risk of Childhood Brain and Spinal Cord Tumors: A Systematic Review and Meta-Analysis.Neuroepidemiology.(2018)
- ^Chen H, Qin L, Gao R, Jin X, Cheng K, Zhang S, Hu X, Xu W, Wang HNeurodevelopmental effects of maternal folic acid supplementation: a systematic review and meta-analysis.Crit Rev Food Sci Nutr.(2023)