Anti‐TNF treatment during pregnancy and birth outcomes: A population‐based study from Denmark, Finland, and Sweden

Abstract

Purpose To study the risk of preterm birth, caesarean section, and small for gestational age after anti‐tumor necrosis factor agent treatment (anti‐TNF) in pregnancy. Methods Population‐based study including women with inflammatory bowel disease, rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, and psoriasis, and their infants born 2006 to 2013 from the national health registers in Denmark, Finland, and Sweden. Women treated with anti‐TNF were compared with women with nonbiologic systemic treatment. Adalimumab, etanercept, and infliximab were compared pairwise. Continuation of treatment in early pregnancy was compared with discontinuation. Odds ratios with 95% confidence intervals were calculated in logistic regression models adjusted for country and maternal characteristics. Results Among 1 633 909 births, 1027 infants were to women treated with anti‐TNF and 9399 to women with nonbiologic systemic treatment. Compared with non‐biologic systemic treatment, women with anti‐TNF treatment had a higher risk of preterm birth, odds ratio 1.61 (1.29‐2.02) and caesarean section, 1.57 (1.35‐1.82). The odds ratio for small for gestational age was 1.36 (0.96‐1.92). In pairwise comparisons, infliximab was associated with a higher risk of severely small for gestational age for inflammatory joint and skin diseases but not for inflammatory bowel disease. Discontinuation of anti‐TNF had opposite effects on preterm birth for inflammatory bowel disease and inflammatory joint and skin diseases. Conclusions Anti‐TNF agents were associated with increased risks of preterm birth, caesarean section, and small for gestational age. However, the diverse findings across disease groups may indicate an association related to the underlying disease activity, rather than to agent‐specific effects.

Benefits and Risks of IgG Transplacental Transfer

“…The current data show that pregnancies exposed to anti-TNFα are not associated with an increased risk of fetal malformations, preterm delivery or pregnancy loss [ 128 , 129 , 130 ]. One of the main concerns, when the fetus is exposed in utero to biological therapy, is the risk of neonatal infections, particularly in the first year of life [ 131 ].…”

Infliximab clearance decreases in the second and third trimesters of pregnancy in inflammatory bowel disease

“…As a result, IFX concentrations in infants, whose mothers have been exposed to IFX during pregnancy, are often supramaternal and IFX can be detected for up to 1 year postpartum 6,7 . IFX exposure of the fetus and newborn have not been associated with severe adverse outcomes for the child, and reported associations with lower birth weight, shorter gestational term, and increased risk of delivery by cesarean section may have been attributable to confounding by disease activity 8–12 . However, pharmacological use during pregnancy is often done carefully and with extra safety precautions.…”

“…6,7 IFX exposure of the fetus and newborn have not been associated with severe adverse outcomes for the child, and reported associations with lower birth weight, shorter gestational term, and increased risk of delivery by cesarean section may have been attributable to confounding by disease activity. [8][9][10][11][12] However, pharmacological use during pregnancy is often done carefully and with extra safety precautions. Current European guidelines advocate pausing IFX in the third trimester whereas North American guidelines recommend pausing in the last 6-10 weeks prior to delivery.…”

IL-6 but Not TNFα Levels Are Associated With Time to Pregnancy in Female Rheumatoid Arthritis Patients With a Wish to Conceive

“…Potential effects of TNFi on pregnancy outcomes should be considered. Increased risks associated with TNFi of preterm birth, caesarean section and small for gestational age children have been previously reported (Bröms et al, 2020). However, given the study design and the fact that high disease activity is known to negatively influence pregnancy outcomes (Smeele and Dolhain, 2019), these effects might not be drug-derived, but due to confounding by indication.…”