Immunological maladaptation preceding spontaneous preterm birth in human pregnancies
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 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.
Authors
- Jakob Einhaus (ORCID: https://orcid.org/0000-0002-3450-4325)
- Joshua Gillard (ORCID: https://orcid.org/0000-0001-8509-2212)
- Maïgane Diop (ORCID: https://orcid.org/0000-0003-2580-8084)
- Kazuo Ando (ORCID: https://orcid.org/0000-0003-1778-1344)
- Anke Diemert (ORCID: https://orcid.org/0000-0003-2546-5464)
- Mirja Pagenkemper
- Stefan Bonn (ORCID: https://orcid.org/0000-0003-4366-5662)
- Anna Woestemeier (ORCID: https://orcid.org/0000-0003-0577-0576)
- Christopher Urbschat (ORCID: https://orcid.org/0000-0002-8866-9133)
- Kristin Thiele (ORCID: https://orcid.org/0000-0002-9343-9834)
- Nima Aghaeepour (ORCID: https://orcid.org/0000-0002-6117-8764)
- M Sato (ORCID: https://orcid.org/0000-0001-6724-7786)
- Brice Gaudillière (ORCID: https://orcid.org/0000-0002-3475-5706)
- Nicola Gagliani (ORCID: https://orcid.org/0000-0001-8514-1395)
- Edward Ganio
- Petra Arck (ORCID: https://orcid.org/0000-0002-2932-926X)
- Dorien Feyaerts (ORCID: https://orcid.org/0000-0002-0795-6625)
- Ina A. Stelzer (ORCID: https://orcid.org/0000-0002-9974-4661)
- David K. Stevenson (ORCID: https://orcid.org/0000-0002-7127-0281)
- Bettina Hollwitz
- A Tallarek
Institutions
- Universität Hamburg (DE)
- University Hospital Bonn (DE)
- German Climate Computing Centre (DE)
- University of California San Diego (US)
- German Center for Pediatric and Adolescent Rheumatology (DE)
- University Medical Center Hamburg-Eppendorf (DE)
- Stanford Medicine (US)
- Stanford University (US)
Publication Details
- Journal
- Nature Communications
- Published
- 2026-07-27
- DOI
- https://doi.org/10.1038/s41467-026-75605-5
- Primary Topic
- Preterm Birth and Chorioamnionitis
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- March of Dimes Foundation
- Robertson Foundation
- Deutsche Forschungsgemeinschaft
- Universität Hamburg
- National Institutes of Health
- Universitätsklinikum Hamburg-Eppendorf
- Stanford Maternal and Child Health Research Institute