Background: Near-infrared spectroscopy (NIRS) has been applied for cerebral oxygen saturation (rSO2) monitoring in neonates. There is a paucity of data from low-middle income countries (LMIC) setting of cerebral rSO2 in neonates with encephalopathy of diverse etiologies. This study aimed to monitor cerebral rSO2 using NIRS in encephalopathic neonates aiming to maintain the rSO2 between 55 to 85%, in the first 72 hours of admission in order to improve short-term neurodevelopmental outcomes (NDO). Materials and Methods: This was a prospective cohort study enrolling encephalopathic neonates with hypoxic ischemic encephalopathy (HIE) and non-HIE etiologies into 8 clinical categories. Monitoring and targeting the cerebral rSO2 between 55 to 85% employing predefined actions and management alterations was done over 72 hours. The neurodevelopmental assessment was conducted at 3, 6 and 9-12 months corrected age. Motor and mental developmental quotients (MoDQ) (MeDQ) were recorded and compared to historical control. Results: A total of 120 neonates were enrolled and assessed for NDO. The MoDQ (mean ± SD) was 92.55 ± 14.85, 93.80 ± 13.20, 91.02 ± 12.69 and MeDQ (mean ± SD) was 91.80 ± 12.98, 91.80 ± 13.69, 88.41 ± 11.60 at 3, 6 and 9-12 months. The MoDQ and MeDQ scores of the historic cohort at 12 months were 86.35 ± 20.34 and 86.58 ± 18.27. The mean difference [MD (95%CI)] for MoDQ was - 4.670 (- 8.48 to - 0.85) (p=0.0165) and for MeDQ was - 1.83 (- 5.26 to 1.6) (p=0.29). There was a negative correlation between the composite developmental quotient (CoDQ) with mean rSO2 and a positive correlation with cerebral fractional tissue oxygen extraction (CFTOE). Neonates with HIE and neonatal encephalopathy (NE) (n=37/120) had the lowest motor and mental DQ on neurodevelopmental assessment. Clinical categories neonatal meningitis (NM) and intraventricular hemorrhage (IVH) showed improvement in DQ scores over the study period. Conclusion: In neonates with encephalopathy resulting from varied etiologies monitoring and maintaining cerebral rSO2 between 55-85% by appropriate management changes resulted in improved neurodevelopmental scores at 12 month follow-up.

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