TNFis Associated With Greater Birth Weight in Offspring of Patients With RA

Pregnant woman receiving ultra sound with female doctor
Pregnant woman receiving ultra sound with female doctor
Researchers assessed whether tumor necrosis factor inhibitor use affected birth outcomes in patients with rheumatoid arthritis.

Tumor necrosis factor inhibitor (TNFi) use during pregnancy is associated with increased birth weight, according to study results published in Annals of the Rheumatic Diseases.

Researchers extracted data from the Preconception Counseling in Active RA (PreCARA) study, an ongoing prospective cohort of rheumatic disease before and during pregnancy. Enrollment began in 2011; data up to May 2021 were used in the current analyses. Participants in the PreCARA cohort underwent a brief modified treat-to-target approach aimed at minimal disease activity. Follow-up visits were conducted in the first, second, and third trimesters of pregnancy, then at 6, 12, and 26 weeks postpartum.

Demographic and clinical data were extracted at baseline, including smoking status, body mass index, pregnancy history, and medication history. Disease activity was monitored at each visit using the Disease Activity Score in 28 joints and C-reactive protein level (DAS28-CRP). The primary outcome was birth weight. Multivariate linear regression analysis was used to identify variables associated with birth weight.

The study cohort included 188 patients with active RA, among whom 92 (48.9%) received a TNFi during pregnancy. Patients’ disease activity was low at every time point during pregnancy; mean DAS28-CRP score at the third trimester was 2.17±0.73. Patients who received TNFis during pregnancy had a higher age at delivery and more often tested positive for anticitrullinated protein antibodies (ACPA) compared with patients who did not receive a TNFi. Receiving TNFis did not appear to increase the risk for adverse pregnancy outcomes, including low birth weight, emergency caesarian section, hypertensive disorders, or congenital malformations.

During pregnancy, TNFi use was associated with greater offspring birth weight, as well as lower likelihood of being small-for-gestational age (P =.05). The absolute difference in mean birth weight between women who received a TNFi and those who did not was 173 g (3.344 kg vs 3.171 kg; P =.03). In multivariate models, TNFi use emerged as an independent correlate of greater birth weight (β, 0.20; 95% CI, 0.066-0.34; P =.004). Other factors associated with birth weight included maternal age (β, -0.023; 95% CI, -0.040 to -0.0065; P =.007), diabetes (β, 0.37; 95% CI, 0.12-0.63; P =.004), and gestational age (β, 0.18; 95% CI, 0.15-0.2; P <.001). Specifically, maternal age was inversely associated with birth weight, while diabetes and increasing gestational age predicted greater birth weight.

Limitations of the study include a study design that was not designed to detect congenital malformations, as correlates of this outcome were not collected. The risk for malformations with TNFi use also remains unclear.   

The study authors concluded, “Our results might pave the way towards new clinical indications for the use of TNFi during pregnancy such as intrauterine growth restriction. Future research should focus on understanding the underlying mechanism of TNF-inhibition on birth weight and the long-term consequences for the offspring.”


Smeele HTW, Röder E, Mulders AGMGJ, Steegers EAP, Dolhain RJEM. Tumour necrosis factor inhibitor use during pregnancy is associated with increased birth weight of rheumatoid arthritis patients’ offspring. Ann Rheum Dis. 2022 Jul 11:annrheumdis-2022-222679. doi:10.1136/ard-2022-222679