Tumor necrosis factor-α inhibitor therapy and fetal risk: A systematic literature review

Abstract

Tumor necrosis factor-α inhibitors (anti-TNFs) are effective in the treatment of inflammatory bowel disease (IBD) recalcitrant to conventional medical therapy. As the peak incidence of IBD overlaps with the prime reproductive years, it is crucial to establish pharmacologic regimens for women of childbearing age that achieve effective disease control without posing significant fetal harm. A systematic literature review was performed to identify all human studies with birth outcomes data after maternal exposure to infliximab, adalimumab, or certolizumab pegol within 3 mo of conception or during any trimester of pregnancy. Live births, spontaneous abortions or stillbirths, preterm or premature births, low birth weight or small for gestational age infants, and congenital abnormalities were recorded. Fifty selected references identified 472 pregnancy exposures. The subsequent review includes general information regarding anti-TNF therapy in pregnancy followed by a summary of our findings. The benefits of biologic modalities in optimizing disease control during pregnancy must be weighed against the potential toxicity of drug exposure on the developing fetus. Although promising overall, there is insufficient evidence to prove absolute safety for use of anti-TNFs during pregnancy given the limitations of available data and lack of controlled trials.

Pregnancy Outcomes in Subjects Exposed to Certolizumab Pegol

“…The large majority of prospectively collected pregnancies resulted in positive outcomes with low rates of miscarriage, preterm birth, and congenital anomalies. Prior reports of anti-TNF medications have not found increased rates of congenital malformations following exposure during pregnancy 23,24,25,26,27 , although data from large cohorts are not yet available 7,8,9 . Reports based on small numbers of pregnancies or case studies have suggested that the use of anti-TNF, such as adalimumab (ADA), infliximab (IFX), and etanercept, do not increase the risk of adverse pregnancy outcomes, and the data in our large single anti-TNF study confirms these reports 24,28,29,30,31 .…”

“…Several updated reviews, including a systematic literature review, have investigated the safety of anti-TNF therapy use during pregnancy and breastfeeding 7,8,9 . These reports suggest that anti-TNF can be useful for controlling disease activity during pregnancy with no obvious effect on pregnancy outcomes to date, although treatment decisions need to be made on a case-by-case basis to evaluate potential toxic effects against the harm of high maternal disease activity on pregnancy outcomes.…”

Maternal obesity and inflammatory mediators: A controversial association

“…Tumour necrosis factor-alpha, one of the most studied cytokines, 71,72 is produced mostly by macrophages. It influences the immune response through its effect on the production of other cytokines, such as IL-6.…”

Intra-uterine experimental infection by Ureaplasma diversum induces TNF-α mediated womb inflammation in mice

“…Responses to infectious diseases endanger the health of the fetus, implantation, causing spontaneous abortion, fetal reabsorption or preterm births (Marenzoni et al 2013). It has been reported that elevated levels of pro-infl ammatory cytokines, including TNF-α, are present in most premature births (Marchioni and Lichtenstein 2013). Moreover, the effects of cytotoxic T cells and IFN-γ, TNF-α and IL -2 could lead to placental damage and fetal death mediated by destruction of syncytium-trophoblasts.…”