Immunological Maladaptation preceding Spontaneous Preterm Birth in Human Pregnancies - Immunome and Proteome data set

Abstract

The majority of spontaneous preterm births (sPTB) occurs without identifiable clinical indications or apparent risk factors. A dysregulated maternal immune adaptation at delivery has been associated with sPTB. Yet, a precise understanding of maternal immune dynamics preceding sPTB remains lacking.

Here we show, in a nested case-control study within a low-risk, population-based pregnancy cohort, that an abnormal immune adaptation in mothers' blood precedes sPTB by weeks to months and discriminates sPTB cases from full-term controls (AUROC: 0.7). Prominent immunoproteome features include heightened sensitivity to adrenergic signals within myeloid and T cell populations in early pregnancy, followed by increased production of pro-inflammatory cytokines in the third trimester.

Transcriptome analysis of single-cell CD4 + T cells reveals a Th17-skewed, neuroactive-protein responsive phenotype. Our study provides a multi-omics resource and a conceptual framework for early identification of individuals at increased risk for sPTB with broad translational implications for advancing targeted preventive measures.