Periconceptional folic acid and risk for neural tube defects among higher risk pregnancies

Abstract

Background: Women with a previous neural tube defect (NTD)-affected pregnancy are recommended to consume 4,000 μg daily folic acid (FA) for prevention (10 times the general-population recommendation). Protection from doses between 400 and 4,000 μg for this and other higher risk groups is unclear. Methods: In the case-control Slone Birth Defects Study , we examined the associations between periconceptional FA doses and NTDs among four higher risk groups: NTD family history, periconceptional antiepileptic drug exposure (AED), pregestational diabetes, and prepregnancy obesity. Mothers completed standardized interviews about pregnancy events and exposures. FA categorizations were based on (a) supplements only and (b) supplements and diet ("total folate").We estimated odds ratios (ORs) and 95% confidence intervals (CIs) (adjusted for age and study center) using logistic regression. Results: Cases and controls included: 45 and 119 with family history, 25 and 108 with AED exposure, 12 and 63 with pregestational diabetes, 111 and 1,243 with obesity. Daily FA supplementation was associated with lower NTD risk compared to no supplementation (adjusted ORs were 0.33 [95% CI 0.13, 0.76] for family history, 0.31 [0.09, 0.95] for AED exposure, 0.25 [0.04, 1.05] for pregestational diabetes, 0.65 [0.40, 1.04] for obesity). Though estimates were imprecise, as total folate increased stronger point estimates were observed, notably among family history. No mothers with a prior NTD-affected pregnancy supplemented with 4,000 μg. Conclusions: Our findings reinforce that all women of childbearing potential should consume at least 400 μg FA/day to protect against NTDs. Higher risk groups may benefit from higher doses.

Management of prepregnancy, pregnancy, and postpartum obesity from the FIGO Pregnancy and Non‐Communicable Diseases Committee: A FIGO (International Federation of Gynecology and Obstetrics) guideline

“…While there are some differences within published guidelines, FIGO’s advice is that all women of childbearing age should consume at least 0.4 mg (400 μg) supplementary folic acid a day for at least 1 month before conception, continuing until at least the end of the first trimester of pregnancy, to reduce the risk of neutral tube defects 33,44,59 . Consideration should be given to the potential use of a higher dose (5 mg/d) for women with obesity, for example in those who may have other additional risk factors for neural tube defects, for example pregestational diabetes or family history, in line with local and national guidelines and resources 37,60,61 .…”

Maternal folic acid and multivitamin supplementation: International clinical evidence with considerations for the prevention of folate-sensitive birth defects

“…An obese cohort, using daily FA supplementation (at least 400 μg), was associated with a lower NTD risk (aOR 0.65(0.40,1.04) NS) compared with no supplementation ( Petersen et al, 2019 ). In a pre-food fortification cohort, assessment of maternal pre-pregnancy weight and NTD risk reduction using ≥400 μg FA daily reduced the risk for women < 70 Kg by 40% but there was no reduction for women > 70 Kg ( Kose et al, 2019 ).…”

“…A pregestational diabetes cohort reported that daily FA supplementation (≥400 μg) was associated with a lower NTD risk (0.25 (0.04, 1.05) NS) compared to no supplementation ( Petersen et al, 2019 ).…”

“…Although the preconception-pregnancy duration of FA supplementation and the joint effects of FA and vitamin B12 imbalance (higher folate/vitamin B12 ratio) has reported a higher pregnancy risk for the development of gestational diabetes (GDM) ( Cheng et al, 2019 , Huang et al, 2019 , Li et al, 2019 , Petersen et al, 2019 ). GDM may alter the concentrations of serum folate, plasma betaine and trimethylamine N-oxide (TMAO) in fetal cord blood with a possible impact on fetal epigenetic programming and later adult health ( Barzilay et al, 2018 ).…”

Folic acid prescribed to prenatal and postpartum women who are also prescribed antiepileptic drugs in Japan: Data from a health administrative database

“…FA supplementation and dietary fortification before conception may prevent NTDs (Kancherla, Wagh, Johnson, & Oakley, 2018 ; Petersen et al, 2019 ; United States Preventive Services Task Force, 2017) and mitigate the risks of other congenital malformations (Yerby, 2003). Other reported beneficial pediatric effects of FA supplementation included reduced risks of severe language delay (Roth et al, 2011) and autistic disorders (Surén et al, 2013).…”