Safety of Anti-TNF-Alpha Therapy During Pregnancy on Long-term Outcome of Exposed Children: A Controlled, Multicenter Observation

Abstract

Background: Evidence of the impact of in utero exposure to anti-tumor necrosis factor (TNF)-alpha on long-term childhood development is limited. The aim was to assess the impact of in utero exposure to anti-TNF-alpha due to mothers' inflammatory bowel disease (IBD) on longterm postnatal development of exposed children. Methods: We included consecutive children (≥12 months of age) born to mothers with IBD (2007-2016) treated with anti-TNF-alpha during pregnancy in 3 centers in the Czech Republic. A control group was comprised of unexposed children of non-IBD mothers undergoing mandatory checkups at general pediatricians' offices. Data on perinatal period, psychomotor development, vaccination, infections, antibiotics, and allergy were collected by treating pediatricians using a predefined questionnaire. Results: Seventy-two exposed and 69 unexposed children were included (median age, 35 and 50 months, respectively). Exposed children had growth and psychomotor development similar to controls. There was no significant difference in infectious complications within the first year of life (23.9% vs 17.4%; P = 0.36) or during the whole follow-up between exposed infants and controls (P = 0.32). Concomitant immunosuppressants during pregnancy and anti-TNF-alpha levels in cord blood were not associated with elevated infection rate within the first year of life (P > 0.05). Over 95% of exposed children had adequate serologic response to vaccination, except for haemophilus and mumps vaccines. Clinically manifested allergy was similar between the groups (P = 0.98). Conclusions: Anti-TNF-alpha exposure in utero does not seem to have a negative impact on postnatal development of children with regard to infectious complications, allergy, growth, or psychomotor development when compared with unexposed children of non-IBD women.

Pregnancy outcomes in inflammatory bowel disease patients treated with vedolizumab, anti‐TNF or conventional therapy: results of the European CONCEIVE study

“…No adverse events after vaccination were reported. The rate of vaccination in our cohort is comparable to previous cohorts of TNFE children, though the administration rate of live attenuated vaccines was lower in our cohort …”

“…The rate of vaccination in our cohort is comparable to previous cohorts of TNFE children, though the administration rate of live attenuated vaccines was lower in our cohort. [20][21][22][23] Overall, the risk of adverse pregnancy outcome was similar within the three groups. Furthermore, the risk of congenital anomalies was low, and comparable among the three groups.…”

Intrauterine Exposure to Biologics in Inflammatory Autoimmune Diseases: A Systematic Review

“…The median ratio of infant to maternal drug concentration at birth was 1.97 (95% CI 1.50-2.43) in 44 patients (18 patients and 26 patients received last infusion before and after the 30th GW, respectively) [136]. In another study the median concentration was 7.8 μg/mL in patients who used infliximab until the 18th-36th weeks of gestation [51].…”

Editorial: safety of prenatal exposure to anti‐TNF therapy on postnatal infectious complications

“…The follow-up of children is one of the longest compared to previously published cohorts. [4][5][6][7][8][9] Although the study demonstrated slightly in- Somewhat conflicting, however, the impact of combined immunosuppressive treatment still remains. While two previous studies reported increased risk of infections in children exposed to combination of anti-TNF and thiopurines, others did not find any risk.…”

“…While two previous studies reported increased risk of infections in children exposed to combination of anti-TNF and thiopurines, others did not find any risk. [4][5][6][7][8][9] This discrepancy could be related to different definitions of infectious complication used or other confounders as discussed above.…”