A 2-week prospective observational study highlights the need to consider neonatal mortality risk factors, even in pregnant women without prior medical history

Background Existing research on neonatal mortality risk factors mainly emphasizes maternal preconception risks and severe antenatal comorbidities, leaving a significant gap in understanding the risk factors among uncomplicated pregnancies.This cohort study aims to identify the key risk factors for neonatal mortality within the first two weeks of birth among healthy mothers.​ Methods A cohort study was conducted, collecting data on delivery, labor complications, neonatal variables, and transfers. Multivariate logistic regression, weighted restricted cubic spline (RCS) curves, threshold effect, and interaction analyses were employed to explore the associations between these factors and neonatal mortality risk.​ Results Multivariate logistic regression analysis revealed that higher gestational age (P < 0.001) and birth weight (P < 0.001) were protective factors against neonatal mortality. Conversely, threatened abortion (P = 0.006), history of perinatal asphyxia (P = 0.014), intraventricular hemorrhage (P = 0.016), neonatal shock (P = 0.014), teratogenesis (P < 0.001), and seizures (P = 0.010) significantly increased the risk of neonatal mortality. RCS modeling demonstrated a non-linear inverted J-shaped relationship between gestational age, birth weight, and mortality, with elevated risk observed when gestational age was < 33 weeks and birth weight was < 1,530 g. No significant interaction was detected between gestational age and birth weight (P > 0.05).​ Conclusion Neonates with a gestational age < 33 weeks, birth weight < 1,530 g, and co-existing conditions face a substantially higher mortality risk. Clinicians should exercise enhanced vigilance and prioritize targeted interventions for these high-risk neonates in clinical practice. Trial registration This cohort study have been registered in the Chinese Clinical Trial Registry (Registration No. ChiCTR2500096024,Registration Date 2025-01-16).