Few Adverse Outcomes Due to Exposure to Anti-Tumor Necrosis Factor-α and Thiopurine In Utero

A pregnant woman and her doctor are indoors in a medical center. The woman is holding her stomach while the doctor writes information on a clipboard.
Investigators assessed the health outcomes of children born to mothers with IBD and the effects of IBD medication use in utero on these children.

No evidence was found to suggest exposure to anti-tumor necrosis factor-α (anti-TNF-α) and/or thiopurine in utero had negative impacts on infection-related outcomes or growth in children born to mothers with inflammatory bowel disease (IBD). These results were published in Gut.

Patients (n=626) with IBD who had given birth at 20 hospitals in the Netherlands after 1999 were recruited. Disease characteristics, medication use during pregnancy, delivery factors, and child outcomes were assessed.

A total of 1000 babies were born during the study period. In utero, the babies were exposed to no medications (n=564), anti-TNF-α (n=136), thiopurine (n=240), and anti-TNF-α and thiopurine dual therapy (n=60).

Intrahepatic cholestasis of pregnancy was associated with thiopurine use (P <.01) while anti-TNF-α was associated with caesarean section (P <.01). Women who did not use medication during pregnancy were more likely to breastfeed (P <.01).

Preterm births (n=118) were associated with obstetric complications (P <.01), systemic corticosteroid use (P <.01), disease activity (P =.02), and endoscopy during pregnancy (P =.02).

Major congenital abnormalities occurred among 27 babies and were not associated with anti-TNF-α (odds ratio [OR], 1.85; 95% CI, 0.73-4.67; P =.19), thiopurine (OR, 1.34; 95% CI, 0.58-3.11; P =.49), or dual therapy exposure (OR, 2.25; 95% CI, 0.59-6.86; P =.27).

Cases of being small for their gestational age were observed among 34 babies and were not associated with anti-TNF-α (OR, 0.84; 95% CI, 0.29-2.41; P =.74), thiopurine (OR, 0.67; 95% CI, 0.27-1.63; P =.37), or dual therapy exposure (OR, 0.97; 95% CI, 0.23-4.17; P =.97).

During the 1000 person-year follow-up, 444 antibiotic courses were reported among the children. Antibiotic-treated infections were more likely to occur among babies born to mothers who smoked during pregnancy (adjusted incidence rate ratio [aIRR], 1.90; 95% CI, 1.19-3.04; P <.01) and were less likely among babies who were breast fed for >1 month (aIRR, 0.70; 95% CI, 0.54-0.90; P <.01).

Hospital admissions due to severe infection occurred among 107 children and 6 children were admitted twice. Hospital admissions were not associated with anti-TNF-α (aIRR, 1.66; 95% CI, 0.91-3.04; P =.10), thiopurine (aIRR, 1.35; 95% CI, 0.85-2.15; P =.20), dual therapy (aIRR, 1.65; 95% CI, 0.71-3.82; P =.24), or systemic corticosteroids exposure (aIRR, 1.52; 95% CI, 0.94-2.44; P =.09).

This study was limited by its retrospective design and lack of a non-IBD control group.

These data indicated in utero exposure to anti-TNF-α and/or thiopurine therapies were not associated with increased risk for congenital abnormalities, being small for their gestational age, antibiotic use, or hospital admission for infection. Risk for preterm birth was increased among women who used systemic corticosteroids and intrahepatic cholestasis of pregnancy was more likely among women who used thiopurine.

Disclosure: Multiple authors declared affiliations with industry. Please refer to the original article for a full list of disclosures.


Kanis SL, Modderman S, Escher JC, et al. Health outcomes of 1000 children born to mothers with inflammatory bowel disease in their first 5 years of life. Gut. 2021;70(7):1266-1274. doi:10.1136/gutjnl-2019-319129