Burden of neurological and neurocognitive impairment in pediatric sickle cell anemia in Uganda (BRAIN SAFE): a cross-sectional study

Table 3 Uni- and multi-variate analyses for study variables assessed for each of the three primary tests performed: neurocognitive dysfunction, abnormal TCD and prior stroke^a

	Unadjusted			Adjusted*
	OR	95%CI	p-value	OR	95%CI
Neurocognitive Dysfunction (N = 246)
Age (years)	1.44	1.23–1.68	< 0.0001	1.50	1.26–1.79	< 0.0001
Sex (male)	1.01	0.45–2.24	0.98	–	–	–
Hemoglobin (grams/dl)	1.09	0.74–1.62	0.65	–	–	–
Malnutrition (z-score)⁺	0.80	0.62–1.04	0.09	0.83	0.59–1.17	0.29
Abnormal TCD⁺⁺	2.82	1.06–7.50	0.04	–	–	–
Prior stroke	6.67	2.16–20.6	0.001	6.88	1.95–24.3	0.003
Abnormal TCD (N = 252)
Age	0.92	0.81–1.04	0.19	0.90	0.77–1.05	0.18
Sex	0.90	0.45–1.82	0.77	–	–	–
Hemoglobin (grams/dl)	0.93	0.64–1.34	0.69	–	–	–
Malnutrition	1.37	1.01–1.86	0.04	1.36	0.99–1.85	0.05
Neurocognitive Dysfunction	2.82	1.06–7.50	0.04	4.37	1.30–14.7	0.02
Prior stroke	0.69	0.08–5.72	0.74	–	–	–
Prior stroke (N = 264)
Age	1.12	0.94–1.34	0.20	1.01	0.84–1.23	0.86
Female Sex	0.96	0.34–2.74	0.94	–	–	–
Hemoglobin (grams/dl)	1.19	0.73–1.95	0.48	–	–	–
Malnutrition⁺	0.81	0.58–1.13	0.21	–	–	–
Abnormal TCD	0.69	0.08–5.72	0.73	–	–	–
Neurocognitive Dysfunction	6.67	2.16–20.6	0.0010	6.27	1.79–22.0	0.004

*For each outcome, adjusted models were constructed using each of risk factors collected (sex, age, hemoglobin and malnutrition) and other outcome(s) identified as associated in the univariable analyses. Hemoglobin and age were kept as continuous variables in the model
⁺Defined per World Health Organization standards, by age and sex, for children 1–4 years and ages 5–12 years, as z-score of ≤ − 2 (ref. 28)
⁺⁺TCD data refer to abnormal velocities, including those in the “conditional” and “abnormal” ranges for pediatric SCA (ref. 43)
Individual and potentially overlapping associated risk factors collected were assessed separately for each of the three abnormal primary test results. Only neurocognitive dysfunction was significantly related to age and to abnormal results in each of the other tests. Malnutrition was associated with elevated TCD and showed a trend to neurocognitive dysfunction, while hemoglobin and age were not associated with any of the three primary results. Overall, the most significant predictor of poor outcome was other poor outcomes, holding age and malnutrition constant. Prior stroke was most strongly associated neurocognitive dysfunction. In contrast, prior stroke was not associated elevated TCD

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