Phenotypes of Preterm Birth: A Retrospective Cohort Study from a Tertiary Romanian Centre as a Framework for Future Genomic and Proteomic Research

Background/Objectives: Preterm birth (PTB) is a major global cause of neonatal morbidity and mortality, and its heterogeneous mechanisms limit the development of reliable prediction tools. Recent genomic and proteomic studies have highlighted molecular pathways involving inflammation, extracellular matrix dysfunction, and uterine activation, yet their clinical integration remains limited. Defining distinct clinical phenotypes may facilitate more targeted biomarker research. Methods: We performed a retrospective cohort study of singleton spontaneous preterm births (24–36 + 6 weeks) at Filantropia Clinical Hospital, Bucharest (2022–2024). Maternal and neonatal data were extracted from electronic records. Four phenotypes were defined by presentation (preterm premature rupture of membranes—PPROM vs. contractions) and maternal inflammatory status. Statistical comparisons used ANOVA or Kruskal–Wallis tests, Chi-square tests, and logistic regression adjusted for gestational age and birth weight to assess neonatal outcomes. Results: Of 585 preterm births, 318 spontaneous singleton cases met inclusion criteria. The cohort was predominantly late preterm, with 85.5% of deliveries occurring between 34 and 36 + 6 weeks’ gestation. Four phenotypes were identified: phenotype 1 inflammatory PPROM (22.3%), phenotype 2 structural PPROM (38.1%), phenotype 3 mixed inflammatory + uterine activation (11.9%), and phenotype 4 uterotonic/endocrine phenotype (19.2%). Conclusions: These clinical phenotypes exhibited distinct maternal and neonatal patterns and correspond to mechanisms increasingly supported by genomic and proteomic studies. They may provide a practical framework for integrating clinical and molecular approaches in future PTB research.