Brief Report: Risk of Adverse Fetal Outcomes Associated With Immunosuppressive Medications for Chronic Immune‐Mediated Diseases in Pregnancy

Abstract

Objective We assessed the risk of adverse fetal outcomes following exposure to individual immunosuppressive drugs in pregnant women with chronic immune mediated diseases. Methods We used health plan data from Tennessee Medicaid and Kaiser Permanente Northern California and Southern California linked with vital records and medical records. Women with inflammatory arthropathies, systemic lupus erythematosus, and inflammatory bowel disease who filled prescriptions for immunosuppressive treatments during pregnancy were included. Major congenital malformations, fetal deaths, and life-threatening neonatal complications were identified from electronic data and validated with medical record review. Results The cohort included 608 infants, including 437 with exposure during pregnancy (402 first trimester, 35 second and third trimester only) and 171 whose mothers filled prescriptions for immunosuppressives before, but not during, pregnancy. There were 25 pregnancies (4.1% of the cohort) with confirmed major congenital malformations, 10 fetal deaths (1.6%), 23 life-threatening neonatal complications among preterm infants (20.4%), and 10 (2.1%) life-threatening complications among term infants. Compared to the reference group (medication treatment before, but not during, pregnancy), the risk ratios for adverse fetal outcomes associated with immunosuppressive use during pregnancy by exposure category included: methotrexate [risk ratio 1.39 (95% confidence interval 0.43,4.53)], tumor necrosis factor inhibitors [0.98 (0.38,2.55)], hydroxychloroquine [1.33 (0.69,2.55)], and other immunosuppressives [0.98, (0.48,1.98)]. Conclusions We found no evidence of a large increase in risk of adverse fetal outcomes from first trimester exposure to immunosuppressive medications, though confidence intervals for risk ratios were wide. Further studies will be needed as use of these medications increases over time.

Reproductive outcomes following hydroxychloroquine use for autoimmune diseases: a systematic review and meta‐analysis

“…For craniofacial, cardiovascular and genitourinary malformations six studies were found eligible . Numbers of specific malformations were obtained through personal communication with the author for the study by Diav‐Citrin et al .…”

“…For the meta‐analysis of nervous system malformations, six studies were found eligible . However, ORs were not calculated for three of them since they reported zero events for the exposed and the control groups .…”

“…For stillbirth rates, six studies including a total of 571 exposed and 916 control pregnancies were included . The stillbirth rate in the exposed group was not significantly higher than the control group (OR 0.69, 95% CI 0.35, 1.34).…”

Editorial: Safety of Immunosuppressive Drugs in Pregnant Women With Systemic Inflammatory Diseases

“…The study by Cooper and colleagues(22) in this issue of Arthritis and Rheumatism investigated the risk of congenital malformations, fetal deaths, and serious neonatal complications in women exposed to immunosuppressive drugs for systemic inflammatory conditions during pregnancy. Using claims data from 3 U.S. health plans linked to vital records as well as medical records, they identified 608 pregnancies in 573 women with a wide range of immune-mediated diseases.…”

“…For the risk of major congenital malformations related to newer immunosuppressive drugs, some reassuring, albeit not definitive, data on TNFi from the results of Cooper et al and other previous reports is available. (21, 22) The effect of other biologic agents on fetal risks, however, remains uncertain. Comparative safety of immunosuppressive drugs on short- and long-term outcomes in mothers as well as offspring should be also studied.…”