No Significant Increased Risk with TNF Inhibitors During Pregnancy Save

A population-based study of 1,272,424 live-born infants from Denmark and Sweden examined the prevalence of birth defects among infants born to 683 women with chronic inflammatory disease (inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis) treated with TNF inhibitors (TNFi).

Women were exposed to TNFi treatment during early pregnancy and compared to normal controls (n = 21,549). 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, were presented as odds ratios (ORs) and were adjusted for maternal age, parity, smoking, body mass index, multiple gestation, country, and chronic inflammatory diagnosis.

Birth defects were slightly more prevalent among infants born to women with chronic inflammatory disease (regardless of anti-TNF treatment status), when compared to the general population (4.8% vs. 4.2%). Birth defects occurred in 43/683 women who received anti-TNF treatment (6.3%), and 4.7% in women with chronic inflammatory disease not taking TNFi.

A nonsignificant trend was seen for any defect while on anti-TNF therapy (OR 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).

This study is limited by a) mixing disorders (RA, PsA, IBD, AS) with highly variable risks for disease activity during pregnancy and differential rates of pregnancy related complications; and b) no adjustment for disease activity (largely because such administrative registry data does not include measures of disease activity).

Nevertheless, this is one of the largest TNFi exposed pregnancy cohorts and does not show a significantly higher risk of having children with birth defects. Some may view this slight trend for higher numbers as cautionary evidence. But, most of the evidence thus far published concur with the lack of data to indicate a serious risk for major birth defects. Larger studies are needed and would be ideal in the future.