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.

The authors have declared no competing interest.

The GARBH-Ini cohort study was funded by the Department of Biotechnology, Government of India (BT/PR9983/MED/97/194/2013). The ultrasound repository was partly supported by the Grand Challenges India-All Children Thriving Program, Biotechnology Industry Research Assistance Council, Department of Biotechnology, Government of India (BIRAC/GCI/0115/03/14-ACT). The research reported in this publication was made possible by a grant (BT/kiData0394/06/18) from the Grand Challenges India at Biotechnology Industry Research Assistance Council (BIRAC), an operating division jointly supported by DBT-BMGF-BIRAC. An alum endowment from Prakash Arunachalam (BIO/18-19/304/ALUM/KARH) and Data Science and AI Consortium grant by the Ministry of Education, Government of India (SB/22-23/1256/CSETWO/008156) partly funded this study at the Centre for Integrative Biology and Systems Medicine, Wadhwani School of Data Science and AI, IIT Madras.

I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained.

Yes

The details of the IRB/oversight body that provided approval or exemption for the research described are given below:

Ethics approvals were obtained from the Institutional Ethics Committees of Translational Health Science and Technology Institute; District Civil Hospital, Gurugram; Safdarjung Hospital, New Delhi (ETHICS/GHG/2014/1.43); Indian Institute of Technology Madras (IEC/2019-03/HS/01/07). Written informed consent was obtained from all study participants enrolled in the GARBH-Ini cohort. All the methods were performed following the relevant guidelines and regulations.

I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals.

Yes

I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance).

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I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable.

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The datasets used and analysed in the current study are available upon reasonable request from the corresponding author after approval of the DBT Steering Committee of GARBH-Ini.