Incidence and risk factors for admissions among children attending the Sickle Cell Clinic at Mulago National Referral Hospital: A prospective cohort study nested in the SPARCO registry

Abstract

Background: Despite improvements in care, sickle cell disease (SCD) remains a major cause of childhood morbidity and mortality in sub-Saharan Africa, with high rates of hospitalization. This study aimed to determine the incidence of hospitalizations and identify associated risk factors among children attending the Mulago National Referral Hospital Sickle Cell Clinic in the hydroxyurea era. Methods: This prospective observational cohort study was nested within the Sickle PanAfrican Research Consortium (SPARCO) Uganda Registry. Children aged 6 months to 18 years enrolled in the registry between June 2025 and January 2026 were enrolled and followed for six months. Data on socio-demographic characteristics, clinical history, maintenance treatment (including hydroxyurea adherence), and prior hospital admissions collected at baseline, supplemented by data from the registry. Enrolled children were followed up for 6 months and assessed for ill health requiring hospitalization. Incidence density was calculated as admissions per 1,000 participant-years, while time to first admission was analysed using Kaplan-Meier survival curves. Risk factors were evaluated using multivariable Cox proportional hazards regression, with adjusted hazard ratios (aHR) and 95% confidence intervals (CI) reported. Statistical significance was set at p < 0.05. Results: A total of 405 children and the median age was 5.0 years (IQR 3.0-8.0), and 205 were male. Of the cohort, 316 (78.0%) were on hydroxyurea at baseline, however, only 57% had good adherence. Overall, a total of 142 occurred translating into an incidence density of 701 admissions per 1,000 participant-years (95% CI 592–828). A total of 142 (35.1%) had at least one hospitalization while 30 (21.1%) had two admissions during the study period. Vasoocclusive pain crises (69.0%: 98/142), severe anaemia (29.6%: 42/142), and acute chest syndrome (21.8%: 31/142) were the most common reasons for hospitalization. The probability of remaining admission-free was 78.2% at three months and 64.9% at six months. In multivariable analysis, younger age (<5 years) (aHR 1.78, 95% CI 1.24–2.56, p=0.002), lower caretaker education (aHR 1.45, 95% CI 1.10–1.92, p=0.009), greater distance to facility (>10 km) (aHR 1.62, 95% CI 1.18–2.23, p=0.003), and history of frequent crises (aHR 2.10, 95% CI 1.45–3.04, p<0.001) independently increased the risk of admission. Hydroxyurea use (aHR 0.52, 95% CI 0.34–0.79, p=0.002) and high baseline haemoglobin (aHR 0.78 per g/dL, 95% CI 0.68–0.90, p<0.001) were strongly protective. inadequate knowledge, persistent pain, poor communication, and drug stock-outs. Overall, 28 children (6.9%) were lost to follow-up and 2 died (both from acute chest syndrome). Conclusion: Despite widespread hydroxyurea utilisation, hospitalisation rates remain high among Ugandan children with SCD, driven primarily by vaso-occlusive crises and infections. Younger age and socioeconomic/access barriers increase risk, while hydroxyurea and better haemoglobin status are protective. Keywords: Sickle cell disease, hospitalisation, incidence, risk factors, hydroxyurea, Uganda, SPARCO registry