Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy.

BACKGROUND & AIMS: Safety data on anti-tumor necrosis factor (anti-TNF) treatment during pregnancy are limited. We studied the risk of birth defects after anti-TNF treatment in early pregnancy.

METHODS: We collected data on 1,272,424 live-born infants identified from the Danish (2004-2012) and Swedish (2006-2012) population-based health registers. We determined the prevalence of birth defects among infants born to women with chronic inflammatory disease (inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis), with (n = 683) and without (n = 21,549) anti-TNF treatment during early pregnancy, and in the general population. We compared the risk of any major birth defect and birth defect by organ system for infants born to women with chronic inflammatory disease, with and without anti-TNF treatment. Risks were presented as odds ratios (ORs) with 95% confidence intervals (CIs). We adjusted for maternal age, parity, smoking, body mass index, multiple gestation, country, and chronic inflammatory diagnosis.

RESULTS: Birth defects were more prevalent among infants born to women with chronic inflammatory disease, regardless of anti-TNF treatment status, than in the general population (4.8% vs 4.2%). Birth defects occurred in 43 of the infants born to the 683 women who received anti-TNF treatment (6.3%), and 1019 of the infants born to women with chronic inflammatory disease (4.7%). The OR for any defect in women receiving anti-TNF therapy was 1.32 (95% CI, 0.93-1.82); the OR for a cardiovascular defect was 1.60 (95% CI, 0.93-2.58), and the OR for a urinary defect was 2.22 (95% CI, 0.86-4.71).

CONCLUSIONS: Based on an analysis of data from the health registries in Denmark and Sweden, women who received anti-TNF agents during pregnancy had a slightly (but not significantly) higher risk of having children with birth defects. Although larger studies are needed, the heterogeneity of the observed birth defects did not indicate a common etiology.