EEG background activity, seizure burden and early childhood outcomes in neonatal encephalopathy in Uganda: a prospective feasibility cohort study.

Background: Intrapartum-related neonatal encephalopathy (NE) is a leading cause of childhood mortality and morbidity. Continuous electroencephalography (EEG) is gold standard for neonatal brain monitoring; however, low-income country data is lacking. We examined EEG in a Ugandan cohort with NE to describe feasibility, background activity, seizure prevalence and burden, and associations with clinical presentation and outcome. Methods: Neonates with NE were recruited from a single hospital referral centre in Kampala, Uganda (Oct 2019-Oct 2020) and underwent EEG monitoring. Feasibility was assessed as to whether EEG monitoring of diagnostic quality could be achieved from days 1-5. Evolution of clinical presentation was assessed by Sarnat classification and daily Thompson score was performed. EEG background severity was graded at 12, 24, 48 and 72 h after birth, and at time of Thompson score. Seizures were annotated remotely by experts and assessed for frequency, duration, burden, and status epilepticus. Early childhood outcome was assessed at follow up, and adverse outcome defined as death or neurodevelopmental impairment (NDI) at 18-24 months of age. Findings: In this prospective feasibility cohort study, diagnostic quality EEGs were recorded for 50 of 51 recruited neonates (median duration 71.4 h, IQR 52.4-72.2), indicating feasibility. Of 39 participants followed to 18-24 months, 13 died and 7 had NDI. Daily Thompson score and EEG background grade were strongly correlated across all timepoints (days 1-5). Thompson score of ≥7 was most predictive of moderate-severe EEG background abnormality (AUC 0.83). Prognostic accuracy of moderate-severe EEG background grade to predict NDI was high (AUC 0.74). Electrographic seizures were seen in 52% (26); median seizure burden was high at 264 min (IQR 27.8-523.7, range 1.3-1374.1); half (13) had status epilepticus. Interpretation: EEG monitoring was feasible as a research tool in this sub-Saharan Africa setting. EEG background activity correlated strongly with scored neurological assessment and predicted adverse early childhood outcome. Seizure prevalence and burden, including status epilepticus, were high in this uncooled cohort with important potential longer-term implications for survivors. Funding: Bill & Melinda Gates Foundation grant number OPP1210890; Wellcome Trust Innovator award (209325/Z/17/Z).