BACKGROUND: Despite efforts to improve neonatal care worldwide, neonatal mortality rates in sub-Saharan Africa remain high. Adequate space, equipment, and staff are vital to improving mortality rates through high-quality care. We evaluated the impact of a district-level neonatal special care nursery over seven years at Neno District Hospital, Malawi. METHODS: We conducted a retrospective cohort study to measure the neonatal outcomes in the neonatal special care nursery before nursery establishment (study period I, 2014-2015), following the establishment of a small nursery (study period II, 2016-2018), then with a transition to a larger nursery (study period III, 2019-2021). We extracted data from the neonatal registers and employed descriptive statistics and chi-square tests to compare the overall neonatal outcomes between study periods. We performed logistic regression to isolate factors associated with neonates alive at discharge. RESULTS: Of the 1366 neonates observed over the entire study period, the three primary admission diagnoses were birth asphyxia (30.1%), sepsis (29.0%), and prematurity (20.9%). The proportion of neonates discharged alive increased from 61.9% to 74.3% and then 87.6% in study periods I, II, and III, respectively. Neonates admitted during study periods II and III were over two and five times more likely to be discharged alive than neonates admitted during study period I in multivariate analysis controlling for sex (SPII aOR = 2.42
95% CI: 1.43-4.08
SPIII aOR = 5.32
95% CI: 3.13-8.98
p <
0.001). There was no difference in being discharged alive for neonates admitted with prematurity compared to birth asphyxia (aOR 0.87
95% CI: 0.51-.151) but neonates admitted with sepsis were over two times more likely to be discharged alive than birth asphyxia (aOR = 2.64
95% CI: 1.67-4.29). Neonates admitted with a birth weight of CONCLUSIONS: The establishment and systems strengthening of a neonatal nursery at Neno District Hospital resulted in a significant increase of neonates discharged alive from the neonatal special care nursery. A multidimensional approach to ensuring resource inputs and ongoing strengthening efforts in Malawi is critical to decreasing neonatal mortality within the special care nursery.