Language outcomes in preschool children with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia

Abstrakts

Objective To investigate language outcomes in preschool children with hypoxic–ischemic encephalopathy (HIE) treated with therapeutic hypothermia and without major neurodevelopmental disabilities, and to identify early developmental and neonatal factors associated with language disorder at preschool age (LD). Methods This prospective longitudinal cohort study included children with moderate-to-severe HIE treated with therapeutic hypothermia at a tertiary neonatal center and followed through preschool age. Children with cerebral palsy, intellectual disability (IQ <70), autism spectrum disorder, major genetic disorders, severe global developmental impairment, or other neurological conditions precluding reliable formal language assessment were excluded. Early developmental functioning was evaluated using the Griffiths Mental Development Scales at 24 months. Language skills were assessed between 30 and 76 months of age using standardized age-appropriate Italian instruments, and LD was identified on the basis of standardized assessment combined with clinical evaluation. Neonatal variables included cord blood pH, base excess, cerebral function monitoring, and brain magnetic resonance imaging (MRI). Results Seventy-five children completed language assessment. Nineteen children (25.3%) met criteria for LD. Difficulties were more frequent in expressive language domains, with naming deficits observed in 62.7% and articulation/repetition difficulties in 61.3% of participants. Children who subsequently developed LD had significantly lower Griffiths Hearing and Speech (Scale C) scores at 24 months compared with children without LD [median 75 [IQR 67–80] vs. 88 [81–95], p < 0.001]. In logistic regression, each 10-point decrease in Griffiths Scale C was associated with higher odds of later LD (unadjusted OR 3.85, 95% CI 1.84–8.06; p < 0.001; adjusted OR 3.78, 95% CI 1.78–8.02; p < 0.001). Severe neonatal acidosis was associated with poorer comprehension and articulation/repetition outcomes, whereas combined white and gray matter injury was associated mainly with poorer expressive language performance. Discussion Language difficulties are common among preschool survivors of neonatal HIE treated with therapeutic hypothermia, even in the absence of major neurological disabilities. Early language vulnerabilities are detectable at 24 months and may help identify children at increased risk of later LD, supporting the need for structured language surveillance within long-term follow-up programs.