No Significant Increased Risk of Birth Defects in Offspring of Women on Anti-TNF Agents

HealthDay News – Birth defects are not significantly more prevalent among women receiving anti-tumor necrosis factor (TNF) agents during pregnancy, according to a study published in the February issue of Clinical Gastroenterology and Hepatology.1

Gabriella Bröms, MD, from the Karolinska Institutet in Stockholm, and colleagues collected data on 1,272,424 live-born infants identified from the Danish and Swedish population-based health registers. They examined the prevalence of birth defects among infants born to women with chronic inflammatory disease and in the general population. Chronic inflammatory disease was defined in this study as inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, or psoriasis.

The researchers found that the prevalence of birth defects was higher among infants born to women with chronic inflammatory disease than in the general population (4.8% versus 4.2%), irrespective of anti-TNF treatment status. Birth defects occurred in 6.3% of infants born to women who received anti-TNF treatment versus 4.7% of infants born to women with chronic inflammatory disease who received no treatment. 

In women receiving anti-TNF treatment, the odds ratios were 1.32 (95% confidence interval [CI], 0.93 to 1.82) for any defect; 1.60 (95% CI, 0.93 to 2.58) for a cardiovascular defect; and 2.22 (95% CI, 0.86 to 4.71) for a urinary defect.

“Women who received anti-TNF agents during pregnancy had a slightly (but not significantly) higher risk of having children with birth defects,” the authors write.

The authors’ institutions have received financial support from pharmaceutical companies. The study was developed independently from a post-authorization safety study commissioned via Janssen Biotech.

Summary and Clinical Applicability

In this data set from Denmark and Sweden, women who received anti-TNF agents during pregnancy did not have a statistically significant higher risk of having children with birth defects.1 

Biologics are effective and increasingly used in the treatment of inflammatory arthritis. Most biologic agents are classified as ‘category B’ drugs by the US Food and Drugs Administration (FDA),2 meaning that animal reproduction studies have not shown any risk to the fetus, but there are no adequate and well-controlled studies in pregnant women. 

The transplacental transfer of IgG begins around week 20, and increases thereafter.3 For this reason, some physicians advocate the discontinuation of biologic medication after week 20 of gestation, minimizing the break from biologic treatment. It is thought that this may decrease the risk of immunogenicity (the risk of hypersensitivity reactions or loss of response once the biologic is reintroduced postpartum). 

The data presented here suggest that the rates of congenital malformations are similar to the rates in the background population of pregnant women with inflammatory disease. This suggests that, with respect to the risk of birth defects, biologics may not have to be discontinued during pregnancy (even after 20 weeks of gestation). 

Because of immunosupression, it should be noted that the use of live vaccines in the newborn is contraindicated until the biologic is no longer detectable in the newborn’s circulation, due to the increased risk of fatal infections.4

Summary and clinical applicability statement by Corinna Panlilio Sison, MD


1. Bröms G, Granath F, Ekbom A, et al. Low Risk of Birth Defects for Infants Whose Mothers Are Treated With Anti-Tumor Necrosis Factor Agents During Pregnancy. Clin Gastroenterol Hepatol. 2016;14(2):234-241.e5.

2. Krause ML, Amin S, Makol A. Use of DMARDs and biologics during pregnancy and lactation in rheumatoid arthritis: what the rheumatologist needs to know. Ther Adv Musculoskelet Dis. 2014;6(5):169-84.

3. Chaparro M, Gisbert JP: Transplacental transfer of immunosuppressants and biologics used for the treatment of inflammatory bowel disease. Curr Pharm Biotechnol 2011;12:765–773.

4. Succi RC, Farhat CK. Vaccination in special situations. J Pediatr (Rio J). 2006;82(3 Suppl):S91-100.