title: Maternal high-dose folic acid during pregnancy and asthma medication in the offspring.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  We used data from the pregnancy database IADB.nl, 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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Unit of PharmacoEpidemiology and PharmacoEconomics, Department of Pharmacy, University of Groningen, Groningen, The Netherlands.
authors.forename: Priscilla A
authors.initials: PA
authors.lastname: Zetstra-van der Woude
authors.forename: Hermien E K
authors.initials: HE
authors.lastname: De Walle
authors.forename: Annemieke
authors.initials: A
authors.lastname: Hoek
authors.forename: H Jens
authors.initials: HJ
authors.lastname: Bos
authors.forename: H Marike
authors.initials: HM
authors.lastname: Boezen
authors.forename: Gerhard H
authors.initials: GH
authors.lastname: Koppelman
authors.forename: Lolkje T W
authors.initials: LT
authors.lastname: de Jong-van den Berg
authors.forename: Salome
authors.initials: S
authors.lastname: Scholtens
mesh_terms: D001249:Asthma / Q000139:chemically induced / Q000453:epidemiology*; D002648:Child; D016208:Databases, Factual; D004305:Dose-Response Relationship, Drug; D011307:Drug Prescriptions / Q000706:statistics & numerical data; D017723:Drug Utilization Review / Q000706:statistics & numerical data*; D005260:Female; D005492:Folic Acid / Q000008:administration & dosage* / Q000009:adverse effects* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D009426:Netherlands / Q000453:epidemiology; D010594:Pharmacies / Q000706:statistics & numerical data; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced / Q000453:epidemiology*; D015995:Prevalence
chemical_list: D005492:Folic Acid
keywords: childhood asthma; folic acid; guidelines; pharmacoepidemiology; pregnancy