Association between cerebral proton magnetic resonance spectroscopy and school-age neurodevelopment after perinatal asphyxia and therapeutic hypothermia: a cohort study

Objective To assess the association of early proton magnetic resonance spectroscopy (¹H-MRS) metabolite ratios with adverse outcomes at 5–8 years in infants with hypoxic-ischaemic encephalopathy (HIE) undergoing therapeutic hypothermia (TH) and to compare the association with outcome at 5–8 years versus outcome at 2 years. Design, setting and patients Single-centre, retrospective cohort study of 91 infants with moderate to severe HIE undergoing TH between 2011 and 2020, ¹H-MRS performed between day 4 and 6 after birth and outcome at 5–8 years. The subgroup with both 2-year and 5-year to 8-year outcomes (n=81) was used for comparative analyses. Adverse outcome at 5–8 years was defined as death or moderate-severe disability (total intelligence quotient score <85, Movement Assessment Battery for Children II <15th percentile, cerebral palsy and severe sensory impairment). Results Among 91 infants, 49 (54%) had adverse outcomes at 5–8 years, including 20 who died. The lactate/N-acetylaspartate (Lac/NAA) peak-area ratio was the strongest predictor of adverse outcome at school age (area under the curve (AUC) of 0.90 and OR 1.11 per 0.01 increase (95% CI 1.05 to 1.16)). The predictive performance of neonatal ¹H-MRS was slightly higher at 2 years, with Lac/NAA AUC 0.93 (OR 1.11, 95% CI 1.05 to 1.16) versus 0.89 (OR 1.09, 95% CI 1.04 to 1.15) at 5–8 years, with comparable effect sizes indicating preserved long-term association. Conclusions Neonatal ¹H-MRS biomarkers, especially Lac/NAA peak-area ratio, were associated with adverse outcomes at school age. Including ¹H-MRS in routine neonatal imaging could improve prognostication and guide early interventions.