Anna Pupco

Pregnancy Outcome After Methotrexate Treatment for Rheumatic Disease Prior to or During Early Pregnancy: A Prospective Multicenter Cohort Study

High‐dose methotrexate (MTX) exposure during pregnancy is associated with embryopathy. The teratogenic potential of MTX at dosages typically used in the treatment of rheumatic diseases remains uncertain. The aim of this study was to evaluate the risk of spontaneous abortion, major birth defects, elective termination of pregnancy, shortened gestational age at delivery, and reduced birth weight in women exposed to MTX.

Safety of infliximab use during pregnancy

Infliximab is a chimeric IgG1 monoclonal antibody to tumor necrosis factor alpha (TNF)-α used in the treatment of inflammatory bowel disease and rheumatoid arthritis. Infliximab does not actively cross the placenta during the first trimester, but undergoes efficient placental transfer during the late second and third trimesters and is detectable in the infants serum for several months after birth. This raises concerns about immunological risks of infection and response to vaccines. Available evidence from registry studies and case reports involving more than 300 pregnancy outcomes suggest that infliximab carries low fetal risk and is compatible with use during conception and the first two trimesters of pregnancy. The long-term effects of infliximab exposure on the developing immune system are yet unknown. Based on limited data from several case reports, infants born with detectable levels of infliximab do not seem to have an increased risk of infections in their first year of life and have normal responses to nonlive vaccines. However, a fatal case of disseminated mycobacterial infection has been reported in an infant who received BCG vaccine at 3 months of age, to a mother who had been treated with infliximab throughout her pregnancy. Vaccination with live viruses should be postponed in infants exposed to infliximab in utero, until serum levels are undetectable which may require more than 6 months. Discontinuing infliximab early in the third trimester should be considered in order to minimize late fetal exposure.

MOTHERISK ROUNDS: The Fetal Safety of Fluoxetine: A Systematic Review and Meta-Analysis

OBJECTIVE Fluoxetine is the selective serotonin reuptake inhibitor (SSRI) with the longest clinical use. Published reports regarding its fetal safety are contradictory. We aimed to establish the fetal safety of the drug. METHODS We performed a systematic review of the literature, searching PubMed, Medline, and Embase from inception to August 31, 2012, for cohort and case-control studies in which women were exposed to fluoxetine during the first trimester and compared outcomes with those of unexposed control subjects. RESULTS Twenty-one studies met the inclusion criteria. The odds ratio for major malformations associated with maternal fluoxetine use in cohort studies was 1.12 (95% CI 0.98 to 1.28). The studies included were homogeneous. Fifteen cohort studies evaluated cardiac malformations and yielded an overall odds ratio of 1.6 (95% CI 1.31 to 1.95). These studies also were homogeneous. In contrast, two case-control studies assessing cardiac malformations yielded a combined odds ratio of 0.63 (95% CI 0.39 to 1.03). CONCLUSION The apparent increased risk of fetal cardiac malformations associated with maternal use of fluoxetine has recently been shown also in depressed women who deferred SSRI therapy in pregnancy, and therefore most probably reflects an ascertainment bias. Overall, women who are treated with fluoxetine during the first trimester of pregnancy do not appear to have an increased risk of major fetal malformations.

Drug exposure in pregnancy and heart defects.

Being the most common group of congenital malformations, congenital heart defects have often been investigated to rule out teratogenic effects by medicinal drugs and chemicals. Yet, the use of rigorous epidemiological methods has rejected such claims in many cases. We critically evaluate drugs believed to be associated with an increased risk of causing congenital heart defects, highlighting the debate and the practical implications of such associations.