Inadequate Folic Acid Intake Among Women Taking Antiepileptic Drugs During Pregnancy in Japan: A Cross-Sectional Study

Abstract

This study aimed to assess characteristics of pregnant women taking antiepileptic drugs with inadequate folic acid intake. This cross-sectional study examined pregnant women taking antiepileptic drugs who were registered in the Japanese Drug Information Institute in Pregnancy (JDIIP) database between October 2005 and December 2016. Participants were classified into two groups according to when they started folic acid supplementation (before pregnancy: ‘adequate’, after pregnancy or never: ‘inadequate’). Logistic regression analysis was performed to investigate factors associated with inadequate folic acid intake. Of 12,794 registrants, 468 pregnant women were taking antiepileptics during the first trimester. Of these, we analysed data from 456 women who had no missing data. As a result, inadequate folic acid intake was noted among 83.3% of them, suggesting that the current level of folic acid intake is insufficient overall. Younger age, smoking, alcohol drinking, multiparity, unplanned pregnancy, and being prescribed AEDs by paediatric or psychiatric departments were independent factors associated with inadequate folic acid intake. As unplanned pregnancy was the strongest factor, healthcare professionals should ensure that childbearing women taking antiepileptics are informed of the importance of planned pregnancy. In addition, healthcare professionals must gain a better understanding of folic acid intake, as the prevalence of adequate intake differed according to which departments prescribed antiepileptic drugs.

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

“…Another cross‐sectional study reported that out of 456 pregnant women who were registered in the Japanese Drug Information Institute in Pregnancy database and taking AED during the first trimester, 83.3% presented with inadequate FA intake as they either started FA supplementation after pregnancy or never took it in the first place. These findings suggest that the current level of FA intake is insufficient overall (Ikeda‐Sakai et al, 2019); this previous study included both prescribed FA and OTC FA supplements. However, the conclusion regarding insufficient FA intake was consistent with that of our study.…”

“…The present study suggested that the prevalence of FA prescription was low especially before pregnancy and the situation in Japan resembled that of European countries (Charlton et al, 2015). Younger age, smoking, alcohol consumption, multiparity, unplanned pregnancy, and AED prescription by pediatricians or psychiatrists were independent factors associated with inadequate FA intake (Ikeda‐Sakai et al, 2019). In the present study, the average age of the women with FA prescriptions before pregnancy was younger than that for the women without FA prescriptions before pregnancy.…”

“…In contrast, the guidelines of certain other countries recommend that women receiving AED therapy should be administered up to 5 mg/day of FA (Asadi‐Pooya, 2015; National Institute for Health and Care Excellence, 2020). Few registry and cohort studies have reported the prevalence of prenatal women who are administered AED and FA concurrently in Japan (Ikeda‐Sakai et al, 2019; Ishikawa, Obara, Nishigori, et al, 2020; Ohtani et al, 2016); however, they reported varying results.…”

Excessive folic acid intake combined with undernutrition during gestation alters offspring behavior and brain monoamine profiles

“…Thus, proper folic acid fortification during pregnancy can prevent impairments in neural function. However, some women exceed the tolerable upper limit of intake for folic acid (1000 μg/day), 10,11 and, in some cases, a highdose of folic acid (4000 μg or more/day) has been given to the patient, who took antiepileptic drug to reduce the incidence of NTD 12 . However, excess folic acid supplementation between 1 week prior to mating and the lactation period was found to cause anxiety‐like behavior in male rat offspring 13 .…”

“…However, some women exceed the tolerable upper limit of intake for folic acid (1000 μg/day), 10,11 and, in some cases, a highdose of folic acid (4000 μg or more/day) has been given to the patient, who took antiepileptic drug to reduce the incidence of NTD. 12 However, excess folic acid supplementation between 1 week prior to mating and the lactation period was found to cause anxiety-like behavior in male rat offspring. 13 In addition, a prospective US birth cohort study recently suggested that a high folic acid intake is linked to an increased risk of ASD.…”