The Dichotomy of Preterm Birth Etiology: A Comprehensive Systematic Review of Risk Factors in High-Income versus Low- and Middle-Income Countries

Abstract

Introduction: Preterm birth (PTB), delivery before 37 completed weeks of gestation, is the leading cause of neonatal mortality globally. A profound disparity in PTB incidence and outcomes exists between high-income countries (HICs) and low- and middle-income countries (LMICs), suggesting divergent etiological pathways. This systematic review provides a comprehensive analysis and comparison of the dominant risk factors for PTB across these distinct socioeconomic settings.

Methods: A systematic search was conducted in PubMed, Google Scholar, Semantic Scholar, Springer, Wiley Online Library for observational studies (cohort, case-control, cross-sectional) published on the risk factors for singleton preterm birth. Studies were categorized based on their setting in HICs or LMICs according to the World Bank classification. Data were extracted using a standardized form, and the methodological quality of included studies was rigorously assessed using the Newcastle-Ottawa Scale (NOS). A detailed narrative synthesis was performed to compare and contrast the risk factor profiles.

Results: The synthesis reveals starkly different risk profiles. In LMICs, the etiology is dominated by factors rooted in poverty, systemic healthcare failures, endemic infectious diseases, and maternal malnutrition. The most potent predictors include inadequate or absent antenatal care (ANC) (AOR > 5.0), premature rupture of membranes (PROM) (AOR 5.90), urinary tract infections (UTI) (AOR 5.27), maternal anemia (AOR 4.58), and endemic infections such as malaria (AOR 3.08) and HIV (AOR 2.59). In contrast, risk factors in HICs are more frequently associated with advanced maternal age due to delayed childbearing, lifestyle-related comorbidities (e.g., obesity, hypertension), the use of assisted reproductive technologies, and persistent socioeconomic and racial disparities within well-resourced healthcare systems. While factors like a prior PTB and smoking are universal risks, their interplay with the surrounding environment and healthcare system differs significantly.

Discussion: The findings demonstrate that the etiology of PTB is profoundly shaped by the broader socioeconomic context, healthcare infrastructure, and endemic environmental factors. In LMICs, risk factors often cluster, creating a synergistic cycle of poverty, malnutrition, and infection. In HICs, the challenge lies in addressing chronic conditions, psychosocial stress, and systemic inequalities that lead to differential health outcomes.

Conclusion: Preterm birth is a complex syndrome with context-specific drivers, necessitating tailored prevention strategies. A "one-size-fits-all" global approach is unlikely to succeed. Prioritizing foundational healthcare, nutrition, and infection control is critical in LMICs, while HICs must focus on pre-conception health, mitigating social disparities, and providing robust psychosocial support.