Low Dose Methotrexate in the First Trimester of Pregnancy: Results of a French Collaborative Study

BÉNÉDICTE LEWDEN, THIERRY VIAL, ELISABETH ELEFANT, AGNÈS NELVA, PATRICK CARLIER, JACQUES DESCOTES, and the French Network of Regional Pharmacovigilance Centers

ABSTRACT.

Objective. To assess the risk of major malformations in pregnant women with chronic inflammatory disorders treated with low dose methotrexate (MTX) during the first trimester of pregnancy. Secondary outcomes included the rate of miscarriage, birth weight, and gestational age at delivery.

Methods. Data from the French network of 31 pharmacovigilance centers and 2 teratology information services were analyzed. The outcome of pregnancy was prospectively assessed in women exposed during the first trimester of pregnancy. Data on maternal history and drug exposure were collected at the initial inquiry, and on the outcome of pregnancy at followup.

Results. Twenty-eight cases were available for analysis. MTX exposure ended before 8 weeks of gestation in 26 patients. Miscarriages occurred in 4 patients and 5 had elective termination of pregnancy. There were 19 live births, among whom 3 were premature. Birth weights in full-term children were within the expected range. One child exposed until 8.5 weeks of gestation had only minor anomalies (metatarsus varus and eyelid angioma).

Conclusion. Although no definitive conclusion can be drawn, our results and the analysis of the literature support the conclusion that no strong teratogenic risk is associated with low dose MTX provided that the drug is discontinued as early as possible in pregnant women. (J Rheumatol 2004;31:2360-5)

Key Indexing Terms:

METHOTREXATE
PREGNANCY
TERATOGENICITY

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From the Centre Antipoison, Centre de Pharmacovigilance, Lyon; Centre de Renseignements sur les Agents Tératogènes, Hôpital Trousseau, Paris; Institut Européen des Génomutations, Lyon; and Centre de Pharmacovigilance, Hôpital Fernand Widal, Paris, France.

B. Lewden, PharmD; T. Vial, MD, Head, Centre Antipoison, Centre de Pharmacovigilance, Lyon; E. Elefant, MD, PhD, Head, Centre de Renseignements sur les Agents Tératogènes, Hôpital Trousseau; A. Nelva, MD, Institut Européen des Génomutations; P. Carlier, MD, Centre de Pharmacovigilance, Hôpital Fernand Widal; J. Descotes, MD, PharmD, PhD, Head, Centre Antipoison, Centre de Pharmacovigilance, Lyon.

Address reprint requests to Dr. T. Vial, Centre Antipoison, Centre de Pharmacovigilance, 162 avenue Lacassagne, 69424 Lyon Cedex 03, France.

Submitted October 1, 2003; revision accepted June 22, 2004.

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