Use of antihistamine medications during early pregnancy and isolated major malformations

Birth Defects Res A Clin Mol Teratol. 2009 Feb;85(2):137-50. doi: 10.1002/bdra.20513.


Background: Antihistamines are commonly used during pregnancy. There is little evidence that they have teratogenic effects, but there are knowledge gaps with respect to newer products, as well as the relationship between specific antihistamines and specific birth defects.

Methods: Using the National Birth Defects Prevention Study (1997-2003), the authors examined associations between maternal use of 14 antihistamines during early pregnancy and 26 isolated major birth defects. A Bayesian analysis incorporating prior knowledge about the relationships between antihistamines, birth defects, and measured covariates was conducted.

Results: Of the 364 associations investigated, 24 had 95% posterior intervals excluding 1.0. All 24 associations were positive; 23 associations were of weak to moderate magnitude (posterior OR < 3.0) and one was strong (OR > 6.0) but very imprecise. Of the 24 associations, 20 were with noncardiac defects. Eight associations involved the antihistamine diphenhydramine.

Conclusions: The results of this study generally were consistent with no association between birth defects and antihistamine use during early pregnancy. Several of the findings might warrant further investigation, although the observed elevated associations should be interpreted in the context of the number of associations investigated and the analysis of retrospective, self-reported data.

Publication types

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

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology*
  • Case-Control Studies
  • Female
  • Histamine Antagonists / adverse effects*
  • Histamine Antagonists / therapeutic use*
  • Humans
  • Hypersensitivity / drug therapy
  • Hypersensitivity / epidemiology
  • Infant, Newborn
  • Pregnancy
  • Pregnancy Complications / drug therapy
  • Pregnancy Trimester, First* / drug effects
  • Prenatal Exposure Delayed Effects / chemically induced
  • Prenatal Exposure Delayed Effects / epidemiology*
  • Retrospective Studies


  • Histamine Antagonists