Maternal exposure to methotrexate and birth defects: A population‐based study

Abstract

Methotrexate is an anti-folate medication that is associated with increased risk of multiple birth defects. Using data from the National Birth Defects Prevention Study, a case-control study of major birth defects in the United States, we examined mothers exposed to methotrexate. The study population included mothers of live-born infants without major birth defects (controls) and mothers of fetuses or infants with a major birth defect (cases), with expected dates of delivery between October 1997 and December 2009. Mothers of cases and controls were asked detailed questions concerning pregnancy history, demographic information, and exposures in a telephone interview. Approximately 0.06% (n=16/27,623) of case and 0.04% (n=4/10,113) of control mothers reported exposure to methotrexate between three months prior to conception through the end of pregnancy. Of the 16 case infants, 11 (68.8%) had a congenital heart defect (CHD). The observed CHDs included atrial septal defects, tetralogy of Fallot, valvar pulmonary stenosis, ventricular septal defects (VSDs), and total anomalous pulmonary venous return. One case infant had microtia in addition to a VSD and another had VACTER association. Exposed cases without a CHD had one of the following birth defects: cleft palate, hypospadias, congenital diaphragmatic hernia, or craniosynostosis. Based on a limited number of methotrexate-exposed mothers, our findings support recent case reports suggesting an association between early pregnancy exposure to methotrexate and CHDs. Because of the rarity of maternal periconceptional exposure to methotrexate, long-term, population-based case-control studies are needed to confirm these findings and better evaluate the association between methotrexate and birth defects.

The Effect of Liman Leaves Extract on Fetal Rat Development

“…These compounds had ability to inhibit proliferation of the growth of cancer cells [9][10][11][12]. The other studies revealed that medicine which has inhibitory effects in proliferation such as methotrexate also gave similar abnormalities of intrauterine growth and significant weight loss in both human and animal experiments [19,20]. Besides external abnormalities, fetal bleeding was also found, which was hematoma (Fig.…”

In response to “In utero exposure to methotrexate and risk of congenital malformations”

“…We thank Dr. Damkier and Dr. Kaplan [Damkier and Kaplan, this issue] for their interest in our recent manuscript [Dawson et al, ], and their comments on our presentation of data regarding birth defects in the children of mothers who reported preconceptional or prenatal exposure to methotrexate in the National Birth Defects Prevention Study.…”

Outcomes of conception subsequent to methotrexate treatment for an unruptured ectopic pregnancy

“…A low dose of the folic acid antagonist methotrexate is being increasingly used for the treatment of ectopic pregnancy . Methotrexate is teratogenic for embryos of various species and has been associated with congenital defects . Because methotrexate can be detected in the kidney and liver months after exposure concern has been raised regarding the effects of treatment with high‐dose methotrexate for ectopic pregnancy on subsequent pregnancies.…”