Update on Supplemental Folic Acid During Later Pregnancy
One of our most popular posts looks at whether supplemental folic acid is worthwhile in the second and third trimesters of pregnancy. A group of researchers lead by Wang have now conducted a study that looks at supplemental folic acid use during pregnancy and risk of pre-eclampsia that provides more evidence in favor of continuing supplementation during pregnancy.
Using data from a large hospital in Gansu province in China, the researchers looked at the use of dietary supplements containing folic acid, dietary folic acid intake and pre-eclampsia risk in 10,041 pregnant women. This was a case-control study, and the researchers matched each case with two controls of the same age and approximate geographic location within the cohort. The rate of pre-eclampsia was 3.6% in this group, and the risk was higher for women who were older, had a higher BMI or greater pregnancy weight gain, had a lower income and educational status, and who were unemployed during pregnancy. Around three quarters of the women were users of folic acid supplements, either alone (78%) or as part of a multivitamin (22%).
The results showed that women using a supplement containing folic acid had about a 40% reduced risk of pre-eclampsia, and this risk did not change between use of the supplement before 12 weeks of pregnancy, or after 12 weeks of pregnancy. The results did not change whether women took folic acid alone or as part of a multivitamin. The risk was reduced for both mild and severe pre-eclampsia, although it was more markedly reduced in the mild pre-eclampsia group, and failed to reach statistical significance for women with severe pre-eclampsia.
When the authors estimated folic acid intakes from food, they did not find an association between the highest and lowest quartiles of intake and risk of pre-eclampsia. This may be due to the amount that the women consumed. Women in the lowest quartile of intake consumed less than 151.6 micrograms per day from food, while in the highest quartile, women consumed more than 274.4 micrograms per day. Many women in the highest quartile were therefore consuming less than the minimum recommended amount of 400 micrograms. Considering that the bioavailability of folate from food has been shown to be anywhere between 10% and 98% of the absorption from supplements, depending on the food matrix and measurement methodology, the contribution of food folate to folate status is highly unpredictable when compared to dietary supplements (see review from McNulty and Pentieva). Although the authors do not report the dose of folic acid supplements, a colleague let me know that a dose of 400 micrograms per day is recommended for pregnant women in China if women have not previously had a pregnancy affected by neural tube defects, and 800 micrograms are recommended for women with known folate deficiency or who have had a pregnancy with a neural tube defect. The dosage of folic acid in supplements from major brands is 400 micrograms. This is in line with international recommendations.
This study further supports the continued use of folic acid during the second and third trimesters of pregnancy. Pre-eclampsia is a serious condition that makes a significant contribution to maternal and child morbidity and mortality. Globally, 29,000 deaths in 2013 were attributable to eclampsia, the dangerous condition that develops from pre-eclampsia, and pre-eclampsia also increases risks to the baby from preterm birth. A simple intervention such as folic acid supplementation has the potential to reduce the incidence of pre-eclampsia and potentially to improve pregnancy outcomes for mother and child.
Wang Y, Zhao N, Qiu J, He X, Zhou M, Cui H, Lv L, Lin X, Zhang C, et al. Folic acid supplementation and dietary folate intake, and risk of preeclampsia. Eur J Clin Nutr 2015;69:1145-50. doi:10.1038/ejcn.2014.295
GBD 2013 Mortality and Causes of Death Collaborators. Global, regional, and national age-sex specific all-cause and cause-specific mortality for 240 causes of death, 1990-2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2015 Jan 10;385(9963):117-71. doi: 10.1016/S0140-6736(14)61682-2. Epub 2014 Dec 18. https://www.ncbi.nlm.nih.gov/pubmed/25530442
McNulty H, Pentieva K. Folate bioavailability. Proc Nutr Soc. 2004 Nov;63(4):529-36. http://www.ncbi.nlm.nih.gov/pubmed/15831124
World Health Organization. Daily iron and folic acid supplementation in pregnant women: Guideline. 2012, ISBN: 978 92 4 150199 6 http://www.who.int/nutrition/publications/micronutrients/guidelines/daily_ifa_supp_pregnant_women/en/
Acknowledgement: Thank you to my colleague Jing Shi, who provided information on folic acid supplement dosage in China for this blog post.