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<p>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 term controls (AUROC: 0.7). Prominent features include enhanced immune cell responses to an adrenergic stimulus during the first and second trimesters, followed by increased production of pro-inflammatory cytokines in the third trimester&#xa0;in sPTB vs. term&#xa0;pregnancies. Transcriptome analysis of second trimester&#xa0;single-cell CD4<sup>+</sup> T cells reveals a Th17-skewed, neuroactive-protein responsive phenotype&#xa0;in sPTB pregnancies. 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.</p>

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Immunological maladaptation preceding spontaneous preterm birth in human pregnancies

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年7月27日

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  • Ina A. Stelzer,
  • Joshua Gillard,
  • Christopher Urbschat,
  • Kristin Thiele,
  • Dorien Feyaerts,
  • Mirja Pagenkemper,
  • Ann-Christin Tallarek,
  • Bettina Hollwitz,
  • Masaki Sato,
  • Edward Ganio,
  • Maïgane Diop,
  • Kazuo Ando,
  • Jakob Einhaus,
  • Nima Aghaeepour,
  • David K. Stevenson,
  • Nicola Gagliani,
  • Anna Woestemeier,
  • Stefan Bonn,
  • Anke Diemert,
  • Petra C. Arck,
  • Brice Gaudillière

摘要

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 term controls (AUROC: 0.7). Prominent features include enhanced immune cell responses to an adrenergic stimulus during the first and second trimesters, followed by increased production of pro-inflammatory cytokines in the third trimester in sPTB vs. term pregnancies. Transcriptome analysis of second trimester single-cell CD4+ T cells reveals a Th17-skewed, neuroactive-protein responsive phenotype in sPTB pregnancies. 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.