This report describes an infant with multiple congenital anomalies born to a 20-year-old mother with juvenile rheumatoid arthritis who had been taking weekly low-dose methotrexate (MTX) during the first trimester of pregnancy. The abnormalities found were consistent with those associated with maternal ingestion of MTX at dosage levels used to induce abortions, i.e., the group of abnormalities referred to as the "aminopterin syndrome." Although weekly low-dose MTX has been associated with spontaneous abortions, this is, to our knowledge, the first case report describing multiple congenital abnormalities consistent with MTX embryopathy secondary to weekly low-dose MTX treatment.Methotrexate (MTX), a folic acid antagonist, is commonly used in the treatment of rheumatoid arthritis (RA) and severe juvenile rheumatoid arthritis (JRA), as well as other rheumatic conditions. MTX and aminopterin, another folic acid metabolism antagonist, have been used to induce abortions and are teratogenic (1). However, there have been no reports of congenital abnormalities associated with low-dose weekly MTX used in the treatment of arthritis in the mother. We report herein the case of a baby with multiple congenital abnormalities born to a mother with JRA who had taken low-dose MTX during the first trimester of pregnancy.
CASE REPORTThe mother was a 20-year-old woman who had been diagnosed as having polyarticular JRA at the age of Submitted for publication August 7, 1996; accepted in revised form November 19, 1996. 12. She was initially treated with nonsteroidal antiinflammatory drugs (NSAIDs) and injectable gold. MTX treatment was started at age 15, at doses between 10 mg and 12.5 mg per week with supplemental folic acid (1 mg per day).At age 20, the patient had an unplanned pregnancy, and stopped both MTX and naproxen after the second missed menses. It was estimated that the fetus was exposed to a total MTX dose of -100 mg over a period of 8 weeks. Although folic acid was one of the medications that the mother was listed as taking during this time, her level of compliance with folic acid supplementation treatment was unclear. She first saw an obstetrician when she was 4 months pregnant. The possible teratogenic effects of MTX were discussed by the obstetrician, a geneticist, and her rheumatologist, but the patient decided not to terminate the pregnancy. She received regular prenatal care during the remainder of the pregnancy. Amniocentesis was performed at 16 weeks gestation, and the karyotype was consistent with a chromosomally normal female (46,XX). Fetal echocardiography at 20 weeks gestation revealed a ventricular septa1 defect, probable double-outlet right ventricle, and suspected pulmonary artery stenosis since the great vessels were disproportionate in caliber.The patient gave birth to a 1.79-kg girl by vaginal delivery at 35 weeks gestation. Examination of the infant at birth revealed intrauterine growth retardation, skeletal abnormalities, and a heart murmur. Evaluation by the geneticist when the infant was 1 day old re...
