Prevalence of survival without major morbidity and associated risk factors among very preterm infants: a systematic review and metaanalysis

XIANGTONG ZHANG¹Peiqin Wang¹Zhi Wan¹Ping Xiong²Dandan Rao³Zhangbin Yu^4*Genfeng Wu^1*

• ¹Department of Pediatrics, Shenzhen Longgang District Maternal and Child Health Care Hospital, Shenzhen, China
• ²Department of Neonatology, The Central Hospital of Enshi Tujia and Miao Autonomous Prefecture, Enshi, China
• ³Department of Neonatology, Shenzhen Luohu People's Hospital, Shenzhen, China
• ⁴Department of Neonatology, Shenzhen People's Hospital, The Second Clinical Medical College of Jinan University, First Affiliated Hospital of Southern University of Science and Technology, Shenzhen, China

Survival without major morbidity (SWMM) in very preterm infants represents a critical outcome measure in neonatal care. This systematic review evaluates both the prevalence of SWMM among infants born before 32 weeks' gestation and the associated risk factors.We conducted a comprehensive search of PubMed, Web of Science, Embase, Cochrane Library, Scopus, CNKI, CBM, and Wanfang databases from inception through February 4, 2025. Two independent reviewers performed study selection and data extraction. Study quality was assessed using the Agency for Healthcare Research and Quality (AHRQ) checklist for cross-sectional studies and the Newcastle-Ottawa Scale (NOS) for cohort studies. Pooled prevalence was calculated using a random-effects model. Heterogeneity was explored through subgroup analyses and metaregression, and publication bias was assessed via funnel plots and further evaluated with trim-and-fill analysis. Risk factors were evaluated using multivariate meta-analysis of adjusted odds ratios (ORs) with 95% confidence intervals (CIs).Results: From 1,606 screened articles, 35 studies spanning twelve countries met inclusion criteria. The pooled SWMM incidence was 47% (95% CI: 40-54%), with notable gestational age stratification: 67% (95% CI: 62-72%) for infants <32 weeks versus 44% (95% CI: 26-61%) for those <28 weeks. Meta-analysis identified gestational age maturity (OR 1.65; 95% CI: 1.50-1.81), antenatal corticosteroid administration (OR 1.46; 95% CI: 1.12-1.89), and higher 5-minute Apgar scores (OR 1.21; 95% CI: 1.06-1.37) as positive predictors of SWMM. Conversely, male sex (OR 0.62; 95% CI: 0.55-0.71) and hemodynamically significant patent ductus arteriosus (OR 0.51; 95% CI: 0.38-0.69) showed negative associations with SWMM.The review reports a 47% SWMM rate among very preterm infants, with higher rates observed in infants of later gestational age. Key predictors include gestational age, 5-minute Apgar score, and antenatal corticosteroids, while male sex and patent ductus arteriosus are associated with reduced SWMM. Limitations include heterogeneity in SWMM definitions and geographic variability. Future research should focus on standardizing outcome measures and validating risk factors through multinational studies.