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Risk of Hypospadias in Offspring of Women Using Loratadine during Pregnancy

A Systematic Review and Meta-Analysis

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Abstract

Background: Loratadine, a second-generation antihistamine, is commonly used to treat seasonal allergies. Some studies have suggested that use of loratadine by pregnant women increases the risk of hypospadias in male offspring.

Objective: This meta-analysis was designed to assess the strength of the association between loratadine and hypospadias.

Methods: To locate pertinent articles published in any language from January 1989 until August 2007, we searched electronic databases (MEDLINE, OVID, EMBASE, SCOPUS, TOXLINE Special, ReproTox, TERIS, CINAHL and others), conference proceedings and bibliographies. Studies were eligible for this analysis if they were cohort, case-control or case series studies that reported the incidence of hypospadias in the offspring of women who were or were not exposed to loratadine during pregnancy. Two authors independently extracted information on study design, participant characteristics, measures of outcome, control for potential confounding factors and risk estimates using a standardized data collection form. The Newcastle-Ottawa Scale was then used to assess the quality of each study. We used a random-effects meta-analysis model to combine the risk data.

Results: In 1402 potentially relevant titles, we found three case-control studies and seven cohort studies that reported the incidence of hypospadias or other congenital malformations in offspring of women who did or did not use loratadine during pregnancy. Together the studies in our meta-analysis provided information about 453 053 male births in Brazil, Canada, Denmark, Israel, Italy, Sweden, the UK and the US.

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Acknowledgements

This study was funded by grant K23 HD051585-01 from the National Institute of Child Health and Human Development (NICHD). The NICHD was not involved in study design; the collection, analysis and interpretation of data; or the writing of this report. We thank reference librarian Melissa Ratajeski for her guidance. No authors have any conflicts of interest to report.

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Authors and Affiliations

  1. Division of General Internal Medicine, Department of Medicine, Center for Research on Health Care, University of Pittsburgh, 230 McKee Place, Suite 600, Pittsburgh, Pennsylvania, 15213, USA

    Eleanor B. Schwarz (Assistant Professor of MedicineAssistant Professor of Medicine Obstetrics, Gynecology, and Reproductive Sciences) & Smita Nayak

  2. Motherisk Program, Division of Clinical Pharmacology/Toxicology, Hospital for Sick Children, Toronto, Ontario, Canada

    Myla E. Moretti & Gideon Koren

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  1. Eleanor B. Schwarz
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  2. Myla E. Moretti
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  3. Smita Nayak
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  4. Gideon Koren
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Correspondence to Eleanor B. Schwarz.

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Schwarz, E.B., Moretti, M.E., Nayak, S. et al. Risk of Hypospadias in Offspring of Women Using Loratadine during Pregnancy. Drug-Safety 31, 775–788 (2008). https://doi.org/10.2165/00002018-200831090-00006

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