Immunological Maladaptation as a Predictor of Spontaneous Preterm Birth in Human Pregnancies

This data set of single cell RNA sequencing was generated from maternal blood samples collected from pregnant women (n=10) in their first and second pregnancy, respectively, either experiencing a healthy term (n=10) or a spontaneous preterm birth (n=10).The analysis of this data set is part of the manuscript entitled "Immunological Maladaptation as a Predictor of Spontaneous Preterm Birth in Human Pregnancies" which is currently under consideration for publication with Nature Communications.Abstract:Dysregulated maternal immune adaptation during pregnancy plays a central role in the pathogenesis of spontaneous preterm birth (sPTB). However, predictive models of sPTB based on maternal immune features, ideally before clinical symptoms arise, remain limited. In a nested case-control study embedded within a population-based, low-risk pregnancy cohort, we decoded a pattern of abnormal immune response in mothers' blood that precedes sPTB by weeks to months. Prominent 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. CD4⁺ T cells exhibited gene expression patterns indicative of a Th17-skewed, neuroactive protein–responsive phenotype. Our study provides a multi-omics resource and a conceptual framework for identifying individuals at increased risk for sPTB with broad translational implications for advancing targeted preventive measures.