The Risk of Adverse Pregnancy Outcome After First Trimester Exposure to H1 Antihistamines: A Systematic Review and Meta-Analysis

Drug Saf. 2017 Feb;40(2):121-132. doi: 10.1007/s40264-016-0479-9.


Introduction: H1 antihistamines are used for the treatment of nausea and vomiting during pregnancy as well as the symptomatic relief of asthma, urticaria, allergy, and the common cold. Although they are overall felt to be safe during pregnancy, recently several studies have challenged this assumption, as millions of women are exposed to them in the first trimester.

Methods: Following the guidelines of PRISMA, a systematic review was performed to retrieve all published articles involving H1-antihistamine exposure during pregnancy. Electronic databases including PubMed and EMBASE were searched for possibly relevant articles published in any language up to December 2015.

Results: After removing duplicate publications, and excluding animal studies and studies on drug effectiveness, 342 articles were reviewed in detail and 37 studies fulfilled the inclusion criteria for the meta-analysis. In cohort studies, the risk of major malformation in the offspring of women exposed to H1 antihistamines was not higher than that of the control population (OR 1.07; 95% CI 0.98-1.16). The Q-statistic for heterogeneity of effects was not significant (p > 0.05, I 2 < 25%) and there was no evidence of publication bias. Similar results were achieved with case-control studies (OR 1.05; 95% CI 0.90-1.23). Similarly, H1 antihistamines were not associated with more spontaneous abortions (OR 1.00; 95% CI 0.83-1.20), prematurity (OR 0.96; 95% CI 0.76-1.20), stillbirth (OR 1.23; 95% CI 0.48-3.18) or low birth weight (OR 1.20; 95% CI 0.63-2.29).

Conclusions: Based on our meta-analyses, which included a large number of studies, H1 antihistamines are not associated with an increased risk of major malformation or other adverse fetal outcomes. This study provides important information to both pregnant women and their healthcare providers regarding the safety and risk of H1 antihistamine use during this sensitive time.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Abnormalities, Drug-Induced / epidemiology
  • Abnormalities, Drug-Induced / etiology
  • Female
  • Histamine H1 Antagonists / administration & dosage
  • Histamine H1 Antagonists / adverse effects*
  • Humans
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Pregnancy Outcome*
  • Pregnancy Trimester, First
  • Risk


  • Histamine H1 Antagonists