Assessment of antihistamine use in early pregnancy and birth defects

J Allergy Clin Immunol Pract. 2013 Nov-Dec;1(6):666-74.e1. doi: 10.1016/j.jaip.2013.07.008. Epub 2013 Sep 12.


Background: Several studies have reported an association between use of specific antihistamines in early pregnancy and certain specific birth defects.

Objective: To test 16 previously hypothesized associations between specific antihistamines and specific birth defects, and to identify possible new associations.

Methods: We used 1998-2010 data from the Slone Epidemiology Center Birth Defects Study, a multicenter case-control surveillance program of birth defects in North America. Mothers were interviewed within 6 months of delivery about demographic, reproductive, medical, and behavioral factors, and details on the use of prescription and nonprescription medications. We compared first trimester exposure to specific antihistamines between 13,213 infants with specific malformations and 6982 nonmalformed controls by using conditional logistic regression to estimate odds ratios and 95% confidence intervals (CIs), with adjustment for potential confounders, including indication for use.

Results: Overall, 13.7% of controls were exposed to antihistamines during the first trimester. The most commonly used medications were diphenhydramine (4.2%), loratadine (3.1%), doxylamine (1.9%), and chlorpheniramine (1.7%). When estimates were stable, none supported the previously hypothesized associations. Among more than 100 exploratory comparisons of other specific antihistamine-defect pairs, 14 had odds ratios ≥1.5, of which 6 had 95% CI bounds excluding 1.0 before but not after adjustment for multiple comparisons.

Conclusion: Our findings do not provide meaningful support for previously posited associations between antihistamines and major congenital anomalies; at the same time, we identified associations that had not been previously suggested. We suspect that previous associations may be chance findings in the context of multiple comparisons, a situation that may also apply to our new findings.

Keywords: Antihistamines; Birth defects; First trimester; Maternal exposure.

Publication types

  • Multicenter Study
  • Research Support, N.I.H., Extramural

MeSH terms

  • Abnormalities, Drug-Induced / etiology*
  • Adolescent
  • Adult
  • Case-Control Studies
  • Female
  • Histamine Antagonists / adverse effects*
  • Humans
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Trimester, First
  • Risk Factors
  • Young Adult


  • Histamine Antagonists