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

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Abstract

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.

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, Health Sciences Addition Room 222, London, ON, N6A 5C1, Canada

    Fatma Etwel, Lauren H. Faught, Michael J. Rieder & Gideon Koren

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  1. Fatma Etwel
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  2. Lauren H. Faught
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  3. Michael J. Rieder
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  4. Gideon Koren
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Correspondence to Gideon Koren.

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This systematic review of published manuscripts meets the criteria for ethical standards.

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No sources of funding were used to assist in the preparation of this study.

Conflict of interest

Fatma Etwel, Lauren H. Faught, Michael J. Rieder and Gideon Koren have no conflicts of interest that are directly relevant to the content of this study.

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Etwel, F., Faught, L.H., Rieder, M.J. et al. The Risk of Adverse Pregnancy Outcome After First Trimester Exposure to H1 Antihistamines: A Systematic Review and Meta-Analysis. Drug Saf 40, 121–132 (2017). https://doi.org/10.1007/s40264-016-0479-9

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