Tanzania is amongst the countries with high neonatal mortality in Sub-Saharan Africa (SSA), and estimates vary widely among regions. Various interventions are being implemented at Muhimbili National Hospital (MNH), a tertiary and teaching facility, to contribute towards the reduction of neonatal mortality. This study aimed to detail the magnitude, trends and factors associated with neonatal mortality at MNH. A hospital-based retrospective cohort study was conducted from January 2018 to December 2020. Records of all neonates admitted during the study period were extracted from neonatal registers and the electronic medical record system and recorded in a pretested data collection form. Data cleaning and analysis were done using SPSS version 23. Poisson regression was used to determine adjusted relative risk (aRR) with a 95% confidence interval (CI) to test association. A p-value of <0.05 was considered significant. Of the 17,021 neonates admitted, 11,552 (67.9%) were inborn. During the three years reviewed, 1,814 (10.7%) neonates died. The mortality rates were 5.9% for inborn neonates, 24.1% for outborn neonates, and 4.8% for readmitted neonates. Mortality trends declined quarterly at an average of 0.15%. Factors associated with neonatal mortality included; birth weight < 2500g [{aRR = 1.14; 95% CI (1.01-1.29)}], GA < 37 weeks[{aRR = 1.17; 95% CI (1.03-1.33)}], fifth-minute Apgar score <7[{aRR = 2.53; 95% CI (2.32-2.77)}], vaginal delivery[{aRR = 1.39; 95% CI (1.24-1.55)}], out-born[{aRR = 2.85; 95% CI (2.58-3.14)}], positive maternal HIV status[{aRR = 1.18; 95% CI (1.02-1.36)}] and maternal age ≥35years [{aRR = 1.12; 95% CI (1.01-1.25)}]. Despite a declining trend, in-hospital neonatal mortality at MNH is still high. Ongoing quality improvement strategies should prioritize the identification of neonates with risk factors for poor outcomes. Specifically, the high proportion of mortality among out-born neonates requires more attention and further investigation.
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