BACKGROUND: Red blood cell transfusions (RBCTs) in preterm infants are associated with various adverse outcomes including transfusion-associated necrotizing enterocolitis (TANEC) and transfusion-related late-onset sepsis (TR-LOS). This study aimed to determine the adverse outcomes of RBCTs in very low birth weight infants (VLBWI) at a resource-restricted hospital in Cape Town, South Africa. STUDY DESIGN AND METHODS: A retrospective descriptive analysis of all VLBWI who received a RBCT in 2020 was performed. Univariate and multivariate logistic regression were performed to determine the association of adverse events after single, multiple, early, and late RBCTs. RESULTS: The study cohort included 178 VLBWI, representing a RBCT prevalence of 22.2%. The mean gestational age was 28 weeks and the mean birth weight was 0.99 kg. The first RBCT occurred at a mean of 27 days and at an Hb <
8 g/dL, differing significantly between single, multiple early, and late RBCT groups. After adjusting for confounders, multiple RBCTs showed a strong association with TR-LOS within 3 days (aOR 9.22, 95th CI 2.30
36.91, p = .002), TR-LOS within 7 days (aOR 8.39, 95th CI 2.72
25.89, p <
.002), any NEC ≥ Bell stage 2 (aOR 2.34, 95th CI 1.66
11.78, p = .026), BPD (aOR 3.62, 95th CI 1.37
9.54, p = .009) and mortality (aOR 3.58, 95th CI 1.39
9.22, p = .008). After adjusting for confounders, early RBCTs were strongly associated with mortality (aOR 2.47, 95th CI 1.28
8.90, p = .013). DISCUSSION: Multiple RBCTs may be associated with TR-related sepsis. This requires more research in resource-restricted areas with a high burden of disease.