First-trimester circulating immune mediator profiles in pregnancies subsequently complicated by preeclampsia: an exploratory nested case–control study

Abstract

Immune dysregulation is increasingly recognised as a contributor to the pathogenesis of preeclampsia (PE), but it is unclear whether circulating immune mediator profiles differ before clinical disease. This pilot study explored circulating immune mediators during the late first trimester in pregnancies that subsequently developed PE. In this exploratory nested case–control study, maternal serum samples collected at 11–14 weeks of gestation from women who later developed PE ( n = 7) and normotensive controls ( n = 7) were analysed using an 80-plex immune mediator panel, and placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1) were measured by enzyme-linked immunosorbent assay. Analytes measurable in most samples of both groups were compared quantitatively, with false discovery rate correction; detection frequency was compared for the remaining analytes. Sensitivity analyses addressed maternal BMI, pre-analytical variation and differential replication, and principal component analysis was used to describe multivariate structure. Of the 80 analytes, 42 were measurable in most samples of both groups and were compared quantitatively. Four mediators (eotaxin, granzyme A, CCL25 and TWEAK) showed nominally lower concentrations in women who subsequently developed PE, but none remained significant after false discovery rate correction at the prespecified threshold of Q = 0.10. These differences were not attenuated by adjustment for maternal BMI. IL-20 was detected less frequently in PE samples, but this difference also did not survive correction for multiple testing. PlGF, sFlt-1 and the sFlt-1/PlGF ratio did not differ between groups. This pilot study identified nominal differences in a small number of circulating immune mediators in the late first trimester of pregnancies that subsequently developed PE, in the absence of differences in angiogenic markers. None survived correction for multiple testing, and confounding by maternal BMI, baseline blood pressure and pre-analytical factors cannot be excluded. These observations are hypothesis-generating and require confirmation in larger, independent cohorts. Not applicable.

The authors' abstract, as published at the source. BMC Pregnancy and Childbirth, 2026 · DOI ↗