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Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis

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An Erratum to this article was published on 17 May 2017

Abstract

Introduction

Lamotrigine is used in pregnancy to control epilepsy and mood disorders. The reproductive safety of this widely used drug remains undefined and may represent a significant public health concern.

Objective

We aimed to perform a systematic review and meta-analysis of existing knowledge related to malformation rates and maternal–neonatal outcomes after in utero exposure to monotherapy with lamotrigine.

Methods

Relevant studies were identified through systematic searches conducted in MEDLINE (Ovid), Embase (Ovid), CENTRAL (Ovid), and Web of Science (Thomson Reuters) from database inception to July 2016; no language or date restrictions were applied. All publications of clinically relevant outcomes of pregnancies following in utero exposure to lamotrigine were included in this systematic review and meta-analysis.

Results

A total of 21 studies describing immediate pregnancy outcomes and rates of congenital malformations fulfilled the inclusion criteria. Compared with disease-matched controls (n = 1412, total number of patients) and healthy controls (n = 774,571, total number of patients), in utero exposure to lamotrigine monotherapy was found to be associated with significantly decreased rates of inborn defects (odds ratio [OR] 1.15; 95% confidence interval [CI] 0.62–2.16 and OR 1.25; 95% CI 0.89–1.74, respectively). Rates of miscarriages, stillbirths, preterm deliveries, and small for gestational age (SGA) neonates were not found to have been increased after in-utero exposure to LTG compared to the general population. Similarly, in utero exposure to lamotrigine monotherapy was not found to be associated with increased rates of inborn defects compared with in utero exposure to carbamazepine, and lamotrigine was found to be statistically significantly less teratogenic than valproic acid (n = 12,958 and 10,748; OR 0.84; 95% CI 0.68–1.03 and OR 0.32; 95% CI 0.26–0.39, respectively).

Conclusion

No association was found between prenatal lamotrigine monotherapy and increased rates of birth defects and other explored variables related to adverse pregnancy outcomes.

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Authors and Affiliations

  1. Division of Clinical Pharmacology and Toxicology, The Hospital for Sick Children, University of Toronto, 555 University Avenue, Toronto, ON, M5G 1X8, Canada

    Gali Pariente, Tom Leibson, Talya Shulman & Irena Nulman

  2. Hospital Library, The Hospital for Sick Children, Toronto, ON, Canada

    Thomasin Adams-Webber

  3. Department of Obstetrics and Gynecology, Chaim Sheba Medical Center, Tel Hashomer, Affiliated with the Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel

    Eran Barzilay

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  1. Gali Pariente
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  2. Tom Leibson
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Correspondence to Gali Pariente.

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Gali Pariente, Tom Leibson, Talya Shulman, Thomasin Adams-Webber, Eran Barzilay, and Irena Nulman have no conflicts of interest.

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An erratum to this article is available at http://dx.doi.org/10.1007/s40263-017-0439-7.

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Pariente, G., Leibson, T., Shulman, T. et al. Pregnancy Outcomes Following In Utero Exposure to Lamotrigine: A Systematic Review and Meta-Analysis. CNS Drugs 31, 439–450 (2017). https://doi.org/10.1007/s40263-017-0433-0

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