Rheumatology Advance Access originally published online on March 29, 2005
Rheumatology 2005 44(5):698; doi:10.1093/rheumatology/keh611
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LETTER TO THE EDITOR |
Methotrexate in pregnancy: reply
Rheumatology, Leicester Royal Infirmary, Leicester and 1 Schering Plough, Welwyn Garden City, Hertfordshire, UK
Correspondence to: A. J. Kinder. E-mail: alisonkinder{at}dsl.pipex.com
We would like to thank Lloyd and colleagues for their interest in our recent case report. We would certainly agree that any patient exposed to any dose of methotrexate during pregnancy or in the 6 months prior to conception is at risk of fetal abnormality. Our advice to all patients is certainly to avoid methotrexate for at least 6 months prior to conception and during pregnancy.
From the literature, there is a suggestion by Donnenfeld et al. [1] and Feldcamp et al. [2] that the threshold dose of methotrexate required to produce defects is 10 mg weekly and the vulnerable period of gestation is between 6 and 8 weeks. Given the small number of available case reports and the limited details on the timing of methotrexate, we would agree with Lloyd and colleagues that these suggestions should be considered speculative. We thank Lloyd and colleagues for highlighting a case report of a single 7.5 mg dose of methotrexate producing fetal abnormalities. There is a further case report of a lady being exposed to 7.5 mg of methotrexate orally for 2 days at 3.5 weeks of conception. Multiple anomalies were noted on ultrasound at 18 weeks consistent with methotrexate embryopathy that was confirmed on fetopsy [3].
A recent survey of 600 members of the American College of Rheumatology, of whom 175 replied, showed 39 patients exposed to methotrexate during pregnancy; 21 pregnancies resulted in full-term healthy infants, eight patients had elective abortions and seven had a spontaneous abortion (with one fetus having congenital malformation), and three pregnancies resulted in congenital malformations [4]. However, no further information is provided on the nature of the abnormalities and whether they were manifestations of the methotrexate syndrome. There is also no information on the doses of methotrexate used and the period of exposure during pregnancy. Chakravarty et al. assumed none of these cases had previously been published and produced a combined rate of reported congenital malformation in infants with known outcomes who were exposed to methotrexate in utero as 17%.
When there is inadvertent ingestion of methotrexate during pregnancy or the preconception period, we would agree with the recommendation by Lloyd and colleagues that these cases should be discussed with the National Tetralogy Information Service. The patient and her partner should be informed about available data from the literature. There is a further case report of methotrexate embryopathy being identified prenatally at 26 weeks by ultrasound, and the ultrasound findings were confirmed at autopsy [5]. A normal ultrasound in this setting certainly does not guarantee that a fetus is free of teratogenic effects from methotrexate.
J.E. works as a Remicare liaison nurse for Ashfield Health Care. She is seconded to Schering Plough in a non-promotional role. The other authors have declared no conflicts of interest.
References
- Donnenfeld AE, Pastuszak A, Noah JS, Schick B, Rose NC, Koren G. Methotrexate exposure prior to and during pregnancy. Teratology 1994;49:79–81.[CrossRef][Web of Science][Medline]
- Feldcamp M, Carey JC. Clinical teratology counseling and consultation case report: low dose methotrexate exposure in the early weeks of pregnancy. Teratology 1993;47:533–9.[CrossRef][Web of Science][Medline]
- Nguyen C, Duhl AJ, Escallon CS, Blakemore KJ. Multiple anomalies in a fetus exposed to low dose methotrexate in the first trimester. Obstet Gynecol 2002;99:599–602.[CrossRef][Web of Science][Medline]
- Chakravarty EF, Sanchez-Yamamoto D, Bush TM. The use of disease modifying antirheumatic drugs in women with rheumatoid arthritis of childbearing age: a survey of practice patterns and pregnancy outcomes. J Rheumatol 2003;30:241–6.
[Abstract/Free Full Text] - Chapa JB, Hibbard JU, Weber EM, Abramowicz JS, Verp MS. Prenatal diagnosis of methotrexate embryopathy. Obstet Gynecol 2003;101:1104–7.[Medline]
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