Safety of TNF-α inhibitors during IBD pregnancy: a systematic review

Abstract

BackgroundTumor necrosis factor (TNF)-α inhibitors are increasingly being used in inflammatory bowel disease (IBD). Because this chronic intestinal disorder often affects women of fertile age, it is essential to assess the effect of biologics on pregnancy outcome.MethodsWe performed a systematic review of the English-language literature to investigate if treatment with TNF-α blockers during pregnancy in women with IBD increases the risk of spontaneous abortions, preterm delivery, stillbirth, low birth weight, congenital malformations, or risk of infections in the offspring. Of 552 articles and abstracts reviewed, 58 articles or abstracts with unique content were identified and included in this systematic review. However, most presentations were case reports or case series supplied by a limited number of observational studies. No randomized controlled studies were available.ResultsTNF-α inhibitors do not seem to affect either outcome of pregnancy in mothers with IBD, or the outcome in the offspring (congenital malformations and immunosuppression). Further, recent data have not identified any increased risk of infections in the first year of life in the offspring of mothers who received biologics, even in combination with immunomodulators (thiopurines).ConclusionsFrom the present systematic review, no association was found between administration of TNF inhibitors for IBD during pregnancy and adverse pregnancy outcome or congenital abnormalities. Further, no increased relative risk of infections has been reported in the first year of life in offspring of mothers who received biologics. Biologics should be discontinued during pregnancy solely if the IBD is in remission using the same stopping criteria as for patients with IBD in general, as uncontrolled activity of IBD may expose the mother and child to a risk greater than those only potentially coming from the use of TNF-α inhibitors. In such cases, inoculation of the offspring with live vaccines is contraindicated until the biologic agent is no longer detectable in the child’s circulation.

Inflammatory Bowel Disease Increases Risk of Adverse Pregnancy Outcomes: A Meta-Analysis

“…Since that publication, several large population-based studies have been published that have examined this issue and medical management of the disease has continued to evolve. Data support the safety of thiopurines and biological medications in pregnancy [4,5], and patients have been counseled to delay conception based on disease activity to improve outcomes [6]. In addition, over the same time period, obstetricians have become increasingly more reluctant to deliver prior to 39 weeks secondary to a growing awareness of the adverse impact of late-preterm and early-term delivery [7,8].…”

Challenges and treatment options for rheumatoid arthritis during pregnancy

“…In contrast to one of the first studies, reporting a high rate of congenital malformations, including the VACTERL association (Vertebral defects, Anal atresia, Cardiac defects, Tracheoesophageal abnormalities, Renal and Radial anomalies and Limb defects) in foetuses exposed to TNFi, data subsequently collected from the experience in different diseases have not shown an increased risk of congenital abnormalities or a recurrent pattern of defects in a very large number of TNFi exposed pregnancies [2,[77][78][79][80][81][82][83]. Nevertheless, in 2015 Weber-Schoendorfer et al reported a significantly increased risk for major defects in 495 TNFi exposed pregnancies during the first trimester compared to 1542 controls (5% vs 1.5% -adjusted Odds Ratio 2.2, 95% CI 1.01, 4.8), without any correlation with VACTERL spectrum [84].…”

Medical problems in pregnancy

“…The effect on the neonate is unclear and there are theoretical concerns about neonatal immunosuppression. However, data from the PIANO registry 26 are reassuring: third trimester anti-TNFα use had no effect on infant growth, development and immune development in the first year of life and a systematic review 27 found no increased risk of infections up to 1 year of age. There has been a single isolated case of fatal disseminated Bacillus Calmett-Guerin (BCG) in an infliximab-exposed infant who received the vaccine at 3 months of age.…”