Methods
anomaly, Sarnat, seizures, seizure, congenital malformations, HIE, disability
MAY, SECONDARY
This randomized clinical trial was carried out at neonatal intensive care units (NICU), pediatric departments of Tanta University and Kafrelsheikh University Hospitals during the period from May 2019 to December 2021 on eighty neonates suffering from moderate to severe HIE. Institutional ethical committee approval was obtained and written consent was taken from the guardians of all included neonates. The study was registered at ClinicalTrials.gov (NCT03949049).Inclusion criteria: neonates with moderate to severe HIE according to Sarnat classifications [Neonates with HIE who underwent therapeutic cooling, gestational age less than 34 weeks, major congenital malformations, or the presence of a known lethal chromosomal anomaly were excluded.All children meeting the inclusion criteria were randomly assigned to one of the two groups:The citicoline treatment group: included 40 neonates with HIE who received citicoline 10 mg /kg /12 h IV within 6 h of admission for 4 weeks plus other supportive measures (including mechanical ventilation, inotropic support, and phenoparbitone for management of seizures if needed) in the NICU [The control group: included 40 neonates with HIE who were managed with placebo and the same supportive measures as indicated.The random number list was generated by computer software. Allocation concealment was performed by sequentially numbered sealed opaque envelopes. Once the written consent was signed, the sealed opaque envelope was opened and the neonate was enrolled into the respective group by the doctor on duty who was not a part of the study. The outcome assessors and investigators were blinded to the treatment groups.All patients enrolled in this study were evaluated for postnatal age, gestational age, Sarnat staging, capillary blood gases, duration of resuscitation, and urinary lactate /creatine ratio [Conventional electroencephalogram (EEG) was performed for all included neonates by Nicolet EEG V32 and recording was done using caps including electrodes. Cranial ultrasounds and brain magnetic resonance images (MRI) were performed for all included neonates after 4 weeks of treatment. Images were blindly reviewed by a specialized pediatric neuroradiologist.All the included neonates were followed up for 1 year to assess the developmental progress and the occurrence of seizures. Assessment of the development was performed at 3 months, 6 m, 9 m, and at 1 year using Griffiths mental development scales (GMDS) by a pediatric neurologist. Vital signs were monitored during the period of citicoline treatment and any side effects were also recorded. Griffiths mental development scales (GMDS): are used for the neurodevelopmental assessment of the included infants. Scores are estimated for each subscale, and an overall general quotient (GQ) score is then calculated. A GQ of ≥ 90 was considered normal, 80–89 was mild disability, 70–79 was moderate disability, and < 70 was severe disability [The primary outcome was to evaluate the improvement of GMDS after citicoline treatment. The secondary outcomes were to evaluate the effect of citicoline on duration of NICU stay, duration of MV, duration of inotropes, seizure frequency and duration, and to assess side effects of citicoline.