Investigation into biomarkers to predict preterm birth (INSIGHT): a longitudinal UK pregnancy cohort for spontaneous preterm birth research.

Abstract

Background: Spontaneous preterm birth (sPTB) remains a leading cause of perinatal morbidity and mortality worldwide. Progress in prediction and prevention has been limited by the biological heterogeneity of sPTB and a lack of longitudinal pregnancy cohorts integrating detailed clinical phenotyping with serial biological sampling. The INSIGHT study was established to enable mechanistic and biomarker-driven investigation of sPTB, with a focus on inflammatory pathways associated with cervical shortening.

Methods: INSIGHT is a prospective, multicentre UK pregnancy cohort that was active between 2013 and 2024 (recruitment finished in 2023). Pregnant women were recruited between 10 ^+ 0 and 28 ^+ 0 weeks' gestation and classified as high- or low-risk of preterm birth using predefined clinical criteria, including obstetric history, cervical length, prior cervical procedures, multiple pregnancy, and uterine anomalies. Serial clinical data were collected alongside longitudinal biological sampling, including maternal blood and cervicovaginal specimens, to support multiomic analyses. Pregnancy, delivery, and neonatal outcomes were ascertained through prospective data collection and routine clinical records.

Results: A total of 2,272 women were enrolled and completed the study, spanning a broad sociodemographic background and risk spectrum, with 1,317 (58%) classified as high-risk of preterm birth. The cohort captured a high incidence of sPTB in singleton pregnancies (n = 184/2,184, (8.4%)), alongside detailed treatment, delivery, and neonatal outcome data. Extensive biological material was collected longitudinally, enabling transcriptomic, microbiome, metabolomic, proteomic, and immune profiling across pregnancy. A total of 34,863 specimens were collected over 4,999 participant sampling visits. Descriptive characteristics of participants, risk factor distributions, pregnancy outcomes, and sample collection are presented.

Conclusion: INSIGHT provides a large, deeply phenotyped pregnancy cohort enriched for sPTB, integrating longitudinal clinical data with serial multiomic biological sampling. The study infrastructure supports discovery-driven and translational research into the mechanisms underlying sPTB and the development and independent validation of clinically scalable biomarker-based prediction strategies.