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Pharmacoepidemiol Drug Saf. 2014 Oct;23(10):1059-65. doi: 10.1002/pds.3652. Epub 2014 Jun 14.

Maternal high-dose folic acid during pregnancy and asthma medication in the offspring.

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Unit of PharmacoEpidemiology and PharmacoEconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.



Low-dose folic acid supplementation (0.5 mg) taken during pregnancy has been associated with an increased risk for childhood asthma. The effect of high-dose folic acid (5 mg) advised to women at risk for having a child with neural tube defect has not been assessed so far. Our aim was to investigate the effect of dispensed high-dose folic acid during pregnancy and asthma medication in the offspring.


We used data from the pregnancy database, which contains pharmacy-dispensing data of mothers and children from community pharmacies in the Netherlands from 1994 until 2011. The dispension of asthma medication in children exposed in utero to high-dose folic acid was compared with children who were not exposed to this high dose. Incidence rate ratios (IRRs) with 95% confidence intervals (CIs) were calculated.


In 2.9% (N = 913) of the 39,602 pregnancies in the database, the mother was dispensed high-dose folic acid. Maternal high-dose folic acid was associated with an increased rate of asthma medication among children: recurrent asthma medication IRR = 1.14 (95%CI: 1.04-1.30) and recurrent inhaled corticosteroids IRR = 1.26 (95%CI: 1.07-1.47). Associations were clustered on the mother and adjusted for maternal age, maternal asthma medication, and dispension of benzodiazepines during pregnancy.


Almost 3% of the children were prenatally exposed to high-dose folic acid. This study suggests that supplementation of high-dose folic acid during pregnancy might increase the risk of childhood asthma.


childhood asthma; folic acid; guidelines; pharmacoepidemiology; pregnancy

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