A long-term follow-up study of pediatric patients treated with therapeutic hypothermia for neonatal encephalopathy found that neurodevelopmental issues—particularly involving motor skills, cognition, and behavior—often emerged or worsened by age 8 to 10 years, even when early assessments appeared normal.
Researchers followed 77 children treated at two Dutch neonatal intensive care units between 2008 and 2015. All patients had received cooling therapy after experiencing oxygen deprivation at birth. They underwent standardized neurodevelopmental evaluations at 18 to 24 months, 5 to 6 years, and 8 to 10 years. While early outcomes were often within normal limits, later assessments revealed meaningful declines in several domains.
Motor Skills
Motor performance declined nonlinearly over time. At age 2, 9% of patients had motor delays or mild cerebral palsy. This figure more than doubled to 20% by age 10. Children with deep gray matter (DGM) injury on neonatal MRI and those with lower IQ scores at age 10 were significantly more likely to have motor impairments.
Cognitive Function
Cognitive outcomes were stable in most children, but those with mammillary body injury on neonatal MRI experienced a clear decline. At 18 to 24 months, only 7% had cognitive delays, but this rose to 38% at age 6 and remained high (33%) at age 10. Lower gestational age and lower socioeconomic status were also linked to lower cognitive scores.
Behavioral Health
Behavioral issues, especially internalizing symptoms such as anxiety and withdrawal, became more prominent with age. Just one patient met clinical thresholds at age 2, compared with 13 by age 10. These behavioral outcomes were not associated with sex, MRI findings, or socioeconomic background, suggesting a broader vulnerability in this population.
Other Late-Onset Conditions
Additional diagnoses included epilepsy in four children and moderate-to-severe hearing impairment in five. Neurodevelopmental disorders, such as attention-deficit/hyperactivity disorder and autism spectrum disorder, were also identified in several cases during later follow-up visits.
Predictive Value of Early Assessments
Importantly, early developmental testing did not reliably predict later difficulties. Among eight children who had isolated mammillary body injury on neonatal MRI, all showed normal results at age 2—but seven developed cognitive or behavioral issues by age 10.
Assessment Methods and Tools
At each visit, researchers used standardized instruments including the Bayley Scales, Wechsler Intelligence Scales, Movement Assessment Battery for Children, and Child Behavior Checklist. Linear mixed modeling was used to evaluate outcome trajectories and contributing risk factors.
Overall, the proportion of patients with an adverse outcome increased from 14% at age 2 to 60% at age 6, then slightly declined to 51% by age 10. The findings reinforce that while therapeutic hypothermia mitigates some immediate injury, many children continue to face evolving neurodevelopmental challenges over time.
The authors emphasized the importance of sustained follow-up, even for children who appear developmentally typical in early life. Ongoing monitoring can help identify emerging concerns early and allow for timely intervention and support.
Full disclosures can be found in the original study.
Source: The Journal of Pediatrics