Phenotypic characteristics associated with preterm births in the Indian population

ABSTRACT Background Preterm birth (PTB), defined as the birth of infants before 37 weeks of gestation, poses significant health risks, including increased mortality and long-term disabilities. India stands as a major contributor to global PTB-related mortality, primarily due to its substantial prevalence. The complex temporal relationship among multiple etiological factors makes predicting PTB occurrence challenging. This is further complicated by the diverse PTB phenotypic categories, namely maternal, foetal, placental, parturition, and pathway-to-delivery features affecting birth outcomes. Methods Our study focused on PTB in the Indian population using a comprehensive dataset from the GARBH-Ini cohort. We analysed 21 variables across maternal, foetal, placental, parturition-related, and other phenotypic categories in the context of Phenotype I (PTB/Non-PTB) and Phenotype II, which classifies PTB based on the pathway to delivery as either Spontaneous Onset of Labour (SOL) or Caregiver-Initiated (CGI). We assessed the prevalence of these phenotypic variables using the complete dataset and applied hierarchical clustering to identify key PTB-associated phenotypic patterns and their impact on neonatal outcomes, including NICU admissions and early neonatal mortality. Additionally, we used one-year follow-up data to examine infant-related phenotypic variables and their distribution across PTB and non-PTB cases. Results We identified key phenotypic variables across maternal, foetal, placental, and parturition categories that significantly influenced PTB outcomes. In SOL cases, foetal (perinatal sepsis, polyhydramnios) and parturition-related (PROM, short cervix, peripartum bleeding) features were significantly associated. In contrast, CGI cases were predominantly associated with maternal complications like pre-eclampsia. Placental abnormalities, such as placenta previa, in combination with PROM and short cervix, were notably prevalent in PTB cases, impacting neonatal mortality, NICU admissions, and infant health. Conclusions The study underscores the complexity of PTB as a time-based, multifaceted syndrome driven by diverse etiological factors. India’s prominence in global PTB-related mortality necessitates tailored preventive strategies. Our findings emphasise the significance of monitoring specific phenotype class and their associated features, facilitating the development of targeted interventions to reduce PTB occurrences in the Indian population. These relationships among features could assist in prioritising cases for personalised care and improve understanding of how PTB phenotypes affect infant health.