J Perinat Med. 2025 Nov 17. doi: 10.1515/jpm-2025-0231. Online ahead of print.
ABSTRACT
OBJECTIVES: Preterm birth (PTB), defined as delivery before 37 weeks of gestation, is a leading cause of neonatal mortality and long-term developmental impairment. Its complex etiology, spanning environmental, genetic, psychosocial, and socio-economic domains, limits effective prediction and prevention. We systematically synthesized evidence on how environmental exposures influence PTB risk through multi-omic disruptions within a fetal exposome framework.
METHODS: A comprehensive literature search was conducted in major biomedical databases, following PRISMA guidelines. Ninety-five human studies published through May 2025 were included, encompassing exposures such as ambient air pollution, endocrine-disrupting chemicals, maternal stress, nutrition, occupational hazards, climate variability, and microbiome alterations. Two reviewers independently extracted data (exposure type, omics platform, biospecimen, PTB subtype) with inter-rater reliability assessment, and study quality was evaluated using the Newcastle-Ottawa Scale. Findings were narratively stratified by exposure category, study design, and spontaneous vs. indicated PTB.
RESULTS: Environmental exposures were consistently associated with disruptions in oxidative stress, inflammation, immune regulation, hormonal signaling, placental aging, and microbial ecology, mediated by multi-omic signatures in maternal, placental, and fetal tissues. Candidate biomarkers show promise for early risk stratification but lack validation and population-level predictive performance due to heterogeneous exposure assessment and study design.
CONCLUSIONS: Integrating fetal exposome concepts with multi-omics enhances mechanistic insight into PTB risk and may support biomarker discovery and precision-guided prenatal interventions. Clinical translation requires standardized exposure measurement, biomarker validation, and equity-focused implementation.
PMID:41242981 | DOI:10.1515/jpm-2025-0231
