In Reply We appreciate the interest of Romigi and colleagues in our article recently published in JAMA Pediatrics. They clarify the effect of folic acid (FA) supplement doses higher than those recommended during pregnancy, particularly among women taking medical treatments for epilepsy.
The current FA recommended dose for the periconceptional period of between 400 μg/d and 1000 μg/d is based on solid evidence.1,2 In our study, 25.2% of women took more than 1000 μg/d of FA and a statistically significant detrimental effect was observed in the psychomotor development of children whose mothers took FA supplement doses higher than 5000 μg/d during pregnancy (3.5%). The effect was still evident after excluding women with medical conditions who were more likely to take an FA supplement dose higher than 5000 μg/d. This finding reinforces the hypothesis that taking very high doses of FA supplements during pregnancy may have a negative effect on infant development independent of treatments for medical reasons. However, along with others,3 we believe that consequences of long-term use of FA supplements throughout pregnancy have been insufficiently explored so far. More research is needed on this issue, with special focus on pregnant women with medical conditions, such as epilepsy or diabetes mellitus, who are more likely to be prescribed higher doses of FA.
Valera-Gran D, Navarrete-Muñoz EM, Vioque J. Folic Acid Supplements During Pregnancy in Specific Clinical Settings—Reply: What Do We Know About Epilepsy? JAMA Pediatr. 2015;169(5):506–507. doi:10.1001/jamapediatrics.2015.96
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