Treatment with tumor necrosis factor inhibitor (TNF) increases birth weight in pregnant patients with rheumatoid arthritis (RA), independent of soluble Fms-like tyrosine kinase-1 (sFlt-1)/placental growth factor (PlGF). According to a study published in American Heart Association Journal.¹

PlGF and sFlt-1 are common biomarkers of placentation and placental function, and a high sFlt-1/PlGF ratio is associated with adverse pregnancy outcomes such as fetal growth restriction, preeclampsia, and low birth weight. It is considered.²

“A tight balance between pro-inflammatory substances (e.g. TNFα) [tumor necrosis factor α]), proper placentation requires interleukin (IL)-6 and anti-inflammatory (such as IL-10) cytokines, with anti-inflammatory cytokines predominating,” led by Cornelia H Quaak, MD the research team wrote. Department of Rheumatology, Erasmus Medical Center Rotterdam, Netherlands. “In rheumatoid arthritis, pro-inflammatory cytokines such as TNFα and IL-6 are increased. High levels of IL-6 are associated with reduced birth weight. It may be associated with poorer pregnancy outcomes, including lower body weight.”

Using data from the Prospective Preconception Counseling in Active Rheumatoid Arthritis (PreCARA) study conducted at the Erasmus Medical Center, a tertiary referral hospital in Rotterdam, the Netherlands, we investigated the We analyzed possible correlations with birth weight. T.N.F. sFlt-1 and PlGF were collected by blood samples from all gestational periods and compared according to TNF usage. Eligible patients visited the hospital regularly before pregnancy, visited the hospital every trimester during pregnancy, and were scheduled for regular follow-up until 26 weeks postpartum.

A total of 158 women were included in the analysis, of whom 52.5% (n = 83) received TNF during pregnancy. Forty-six women (29.1%) received treatment with their TNF throughout pregnancy. Relevant confounders include maternal age, diabetes, gestational age at delivery, and third trimester tender and swollen joint disease activity scores.

sFlt-1 and PlGF levels increased during pregnancy, but their ratio decreased. After accounting for relevant confounders and accounting for trimester-related variation in levels, the sFlt-1/PlGF ratio was similar between patients who received and did not receive TNF treatment (first trimester). sFlt-1/PlGF ratio in the 2nd period compared to the 1st period) semester: Estimated change 8.17 [95% confidence interval (CI), 2.54–26.29], P = .79; sFlt-1/PlGF ratio in late pregnancy compared to early pregnancy: estimated change 6.25 [95% CI, 1.73–22.50], P = .25).

Birth weight was significantly lower in women who were not treated with TNF (3180 g vs. 3302 g; P = .03). In these patients, sFlt-1 levels showed a negative correlation with birth weight (r = −.462, P <.001) and birth weight percentile (r = −.332, P = .008). These correlations were not present in patients who received their TNF during pregnancy.

This study was the first to investigate the correlation between sFlt, PlGF, and TNF treatment and included a large sample of women with a well-defined homogeneous disease. However, the researchers note limitations, including not being able to obtain test samples for all patients from all semesters. Additionally, it was not possible to determine the effect of TNF treatment by trimester, as patients who received TNF in one trimester were likely to use this treatment in other trimesters as well.

“TNF inhibitors may be considered as a therapeutic intervention for women with clinical conditions characterized by elevated sFlt-1 levels, such as pre-eclampsia,” the researchers concluded.

References

1. ^{Quack CH, Kleibers ACM, Burt SJ et al. Use of tumor necrosis factor inhibitors increases birth weight in pregnant women with rheumatoid arthritis independently of the soluble Fms-like tyrosine kinase-1/placental growth factor ratio. J. Am Heart Assoc. Published online March 27, 2024. doi:10.1161/JAHA.123.032655}
2. ^{Chen W, Wei Q, Liang Q, Song S, Li J. Diagnostic ability of sFlt-1/PlGF ratio in fetal growth restriction: a systematic review and meta-analysis. placenta. 2022;127:37–42. doi: 10.1016/j.placenta.2022.07.020}