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Immunological maladaptation preceding spontaneous preterm birth in human pregnancies

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Jun 11, 2026 version files 29.19 GB

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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 is currently 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 shows 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.