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.

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.