The effect of continued folic acid supplementation beyond the first trimester on unmetabolised folic acid in late gestation

Folic acid (FA) is the synthetic form of the vitamin folate. Pregnant women are advised to take FA supplements before conception and during the first three months of pregnancy to reduce their chances of having a neural tube defect (NTDs) affected pregnancy, severe birth such as spina bifida and anencephaly. However, NTDs occur in the first month of pregnancy, and after that, there is no known benefit of continuing FA. Current recommendations do not advise stopping FA, so most women continue to take FA throughout pregnancy. Concerns have been raised that excess FA, especially in later pregnancy, may lead to adverse maternal and child health outcomes. These include large for gestational age, gestational diabetes, autism spectrum disorders, and childhood allergy. Australian Health authorities could simply change recommendations to advise women to women to stop FA once pregnancy is confirmed. Policymakers warn that changing recommendations will confuse women and undermine three decades of successful public health efforts encouraging women to take FA to reduce NTDs. All harms are based on observational evidence, which is insufficient to change policy. Only a high-quality RCT can supply definitive proof. Circulating unmetabolised folic acid (UMFA) in serum is used as a biomarker of excess FA intake and has been associated with an increased risk of adverse outcomes in some studies. Before commencing a large RCT, we first wanted to determine whether removing FA from prenatal supplements after the first trimester reduces the amount of UMFA at 36 weeks gestation. We conducted a two-arm, parallel, double-blind RCT to address this question. Women with a singleton pregnancy 12-16 weeks (n=103) gestation were randomly assigned to a multi-micronutrient supplement without (intervention) or with 800 μg folic acid/day (control, current standard practice) from enrolment until 36 weeks gestation. We chose 800 μg/d because it is Australia's most commonly used FA dose. Of the 103 women randomised, 90 finished the study. The primary outcome was the difference in maternal serum UMFA concentration between the groups at 36 weeks. Only 12% of women had UMFA above the limit of quantification (LOQ); thus, we could not compare UMFA concentration. However, fewer women in the no folic acid (intervention) compared to the 800 μg folic acid/day (control) group (72% [n=33/46] vs 98% [n=43/44]; p = 0.001) had UMFA above the LOD. Removing FA from multi-micronutrient prenatal supplements after 12 weeks gestation reduced the number of women with detectable UMFA at 36 weeks gestation. However, differences in UMFA concentration between treatment groups were not quantifiable. Whether continued FA use beyond the first trimester increases the risk of adverse maternal and child health outcomes remains unclear. This can only be answered with adequately powered RCTs to determine if removing folic acid from supplements after the first trimester alters the rate of outcomes. Only after this trial is complete can an informed decision be made about the risks of continued FA supplementation after the first trimester.

Author dc:creator

• Sulistyoningrum, Dian Caturini

Advisors dc:contributor.advisor

• Green, Timothy J.
• Best, Karen
• Skubisz, Monika

• prenatal supplements, pregnancy vitamins, supplementation guidelines, antenatal, prenatal nutrition, unmetabolised folic acid, excess folic acid

Language dc:language.iso

en

Handle dc:identifier.uri

https://hdl.handle.net/2440/138271

OAI identifier oai:identifier

oai:digital.library.adelaide.edu.au:2440/138271