Anti-TNF-α therapy has been used in Denmark since 1999 to treat moderate to severe inflammatory bowel disease (IBD). It is not infrequently continued during pregnancy to maintain remission and to treat disease flares. The safety of anti-TNF-α therapy during the third trimester of pregnancy is debated and GI society recommendations differ as to whether anti-TNF-α treatment should be continued in late pregnancy. There is concern among clinicians regarding rapidly increasing levels of anti-TNF-α in the foetus during the third trimester, but birth outcomes have yet to be fully investigated. This study aimed to examine the impact of anti-TNF-α therapy used during the third trimester on the risk of preterm birth and low birth weight (LBW). We compared birth outcomes of children whose mothers received anti-TNF-α treatment during the third trimester to birth outcomes of children whose mothers discontinued anti-TNF-α therapy before the third trimester.Methods:
We reviewed all medical records of a nationwide unselected cohort of Danish women with IBD who (from 2005 through 2014) were treated with anti-TNF-α therapy at some time during pregnancy or 3 months before conception (N = 219 women). We included retrospectively collected disease activity indices, demographics, and clinical details. The exposed cohort included pregnancies (N = 113) treated with anti-TNF-α therapy in the third trimester. The unexposed cohort included women who did not receive anti-TNF-α therapy in the third trimester (N = 106). Analyses were stratified according to women with (N = 144) and without (N = 75) disease activity during the pregnancy. Logistic regression analyses, with adjustment for multiple confounders (parity, mother's age, medications other than anti-TNF-α therapy, Charlson comorbidity score, and smoking), were used to examine the effect on LBW (birthweight = <2500 g) and preterm birth (<37 weeks of gestation).Results:
In pregnancies where women had disease activity during the pregnancy, the adjusted odds ratio (aOR) for preterm birth was 2.20 (95% CI, 0.79–6.13) and for LBW 1.18 (95% CI, 0.26–5.31) among those treated with anti-TNF-α therapy. In pregnancies by women without disease activity during pregnancy, the aOR for preterm birth and LBW was 3.36 (95% CI, 0.31–36.46) and 0.86 (95% CI, 0.05–14.95) respectively, among those treated with anti-TNF-α therapy during third trimester.Conclusions:
This is by far the largest study examining pregnant women with moderate to severe IBD, who have been treated with anti-TNF-α therapy during third trimester. Our results confirm the previously published results that treatment with anti-TNF-α therapy during third trimester was not associated with an increased risk of preterm birth or LBW. These results are very reassuring.