title: Early pregnancy exposure to antihistamines and risk of congenital heart defects: results of two case-control studies.
abstract: We aimed to study the association between use of antihistamines in early pregnancy and congenital heart defects (CHD) in the offspring.
  
  
  METHODS
  Two case-control studies.
  
  
  METHODS
  HAVEN study, Erasmus MC, University Medical Centre, Rotterdam, and Eurocat Northern Netherlands (NNL), University Medical Center Groningen, Groningen, the Netherlands. We studied 361 children with CHD and 410 controls without congenital malformations from the HAVEN study and replicated the analyses in 445 children with CHD and 530 controls from the Eurocat NNL registry. Information about antihistamine use in early pregnancy and potential confounders was obtained from questionnaires postpartum. We calculated the association between antihistamines and CHD risk by multivariable logistic regression analysis.
  
  
  METHODS
  Odds ratios (OR) with 95% confidence intervals (CI). In the HAVEN study, 25 of 771 mothers used antihistamines that were associated with an increased CHD risk (OR 3.0, 95% CI 1.2-7.3), particularly atrioventricular septal defects (AVSD) (OR 5.1, 95 % CI 1.3-20.5) and perimembranous ventricular septal defects (pVSD) (OR 5.1, 95% CI 1.8-14.4). Mothers with severe nausea who did not use antihistamines had a reduced risk (OR 0.7, 95% CI 0.5-0.98), whereas nauseous mothers using antihistamines showed an almost fivefold increased risk of pVSD (OR 4.8, 95% CI 1.1-21.8). The association between antihistamines and AVSD was confirmed in the Eurocat cohort (OR 3.5, 95% CI 1.4-8.7), but we could not replicate the association with overall CHD risk. We found a positive association between antihistamine use in early pregnancy and CHD risk, particularly AVSD, which seemed to be independent of nausea/vomiting.
authors.affiliation: Department of Obstetrics and Gynaecology, Erasmus MC, University Medical Centre, Dr. Molewaterplein 40, Room Ee 2271a, 3015 GD, Rotterdam, The Netherlands.
authors.forename: Huberdina P M
authors.initials: HP
authors.lastname: Smedts
authors.forename: Linda
authors.initials: L
authors.lastname: de Jonge
authors.forename: Sarah J G
authors.initials: SJ
authors.lastname: Bandola
authors.forename: Marlies E
authors.initials: ME
authors.lastname: Baardman
authors.forename: Marian K
authors.initials: MK
authors.lastname: Bakker
authors.forename: Bruno H C
authors.initials: BH
authors.lastname: Stricker
authors.forename: Régine P M
authors.initials: RP
authors.lastname: Steegers-Theunissen
mesh_terms: D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D006330:Heart Defects, Congenital / Q000139:chemically induced* / Q000453:epidemiology; D006633:Histamine Antagonists / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D008297:Male; D048968:Morning Sickness / Q000188:drug therapy*; D009035:Mothers / Q000706:statistics & numerical data; D009426:Netherlands / Q000453:epidemiology; D016017:Odds Ratio; D011247:Pregnancy; D011295:Prenatal Care; D011297:Prenatal Exposure Delayed Effects; D012042:Registries; D012307:Risk Factors; D011795:Surveys and Questionnaires
chemical_list: D006633:Histamine Antagonists