Pregnancy outcome after TNF‐α inhibitor therapy during the first trimester: a prospective multicentre cohort study

Abstract

Aims TNF‐α inhibitors are considered relatively safe in pregnancy but experience is still limited. The aim of this study was to evaluate the risk of major birth defects, spontaneous abortion, preterm birth and reduced birth weight after first trimester exposure to TNF‐α inhibitors. Methods Pregnancy outcomes of women on adalimumab, infliximab, etanercept, certolizumab pegol or golimumab were evaluated in a prospective observational cohort study and compared with outcomes of a non‐exposed random sample. The samples were drawn from pregnancies identified by institutes collaborating in the European Network of Teratology Information Services. Results In total, 495 exposed and 1532 comparison pregnancies were contributed from nine countries. The risk of major birth defects was increased in the exposed (5.0%) compared with the non‐exposed group (1.5%; adjusted odds ratio (ORadj) 2.2, 95% CI 1.0, 4.8). The risk of preterm birth was increased (17.6%; ORadj 1.69, 95% CI 1.1, 2.5), but not the risk of spontaneous abortion (16.2%; adjusted hazard ratio [HRadj] 1.06, 95% CI 0.7, 1.7). Birth weights adjusted for gestational age and sex were significantly lower in the exposed group compared to the non‐exposed cohort (P = 0.02). As a diseased comparison group was not possible to ascertain, the influence of disease and treatment on birth weight and preterm birth could not be differentiated. Conclusions TNF‐α inhibitors may carry a risk of adverse pregnancy outcome of moderate clinical relevance. Considering the impact of insufficiently controlled autoimmune disease on the mother and the unborn child, TNF‐α inhibitors may nevertheless be a treatment option in women with severe disease refractory to established immunomodulatory drugs.

Pregnancy and rheumatoid arthritis

“…These results are not easy to interpret since no distinct pattern of malformations could be identified which would be expected for typical teratogens. In addition, the rate of 1.5% major birth defects in the comparison cohort is lower than the prevalence of all non-chromosomal anomalies of 2.2% recorded by EUROCAT [97]. TNF inhibitors that contain an Fc part of an IgG molecule are actively transported from the maternal to the fetal circulation starting at around week 18 of gestation [98].…”

Pregnancy Outcomes of Patients Exposed to Adalimumab in Japan

“…The risk of miscarriage was not increased in the exposed cohort (9.3 vs. 7.9%). The authors concluded that the use of TNF-α inhibitors during pregnancy may carry a risk of adverse pregnancy outcomes of moderate clinical relevance (major birth defects and preterm birth: adalimumab [6%, 17.4%]; infliximab [4.5%, 16%]; etanercept [5.4%, 17.9%], respectively) [24]. In contrast, in the current study, no fetal or neonatal congenital abnormalities and 4 (8.2%) miscarriages were observed in 49 pregnancies exposed to adalimumab during the first trimester.…”

Inflammatory and glandular skin disease in pregnancy

“…defects, preterm birth, and low birth weights than control, 19 however, most of the women in this study were on TNF-α inhibitors for inflammatory bowel disease or rheumatoid arthritis, which can independently result in preterm birth and low birth weights. Psoriasis and psoriatic arthritis patients accounted for only 8% of the pregnancies in this study, making it unclear whether the poorer fetal outcomes in the exposed group were a result of the underlying severe disease or of TNF-α inhibitors exposure.…”

“…5, 16, 17 TNF-α biologics cannot cross the placenta until after 20 weeks" gestation, when most organogenesis is complete. 17,19 A recent prospective cohort study found that women exposed to TNF-α inhibitors during pregnancy had a higher risk of birth…”