Cumulative secondary systemic metabolic cerebral insults are associated with disease severity and mortality in neonatal hypoxic–ischaemic encephalopathy: a retrospective study

Background Secondary systemic cerebral metabolic insults (mSSCI), including abnormalities of glucose, sodium, and carbon dioxide, may exacerbate brain injury in neonatal hypoxic–ischaemic encephalopathy (HIE). Their burden and prognostic value remain poorly described. We aimed to assess the frequency of mSSCI and their association with disease severity and mortality. Methods This single-centre observational study included all newborns admitted for HIE between 2018 and 2020. mSSCI were defined as at least one abnormal blood glucose, sodium, or carbon dioxide value measured from routine samples during the first three days of life. A cumulative mSSCI score was calculated as the sum of the six possible abnormalities. Associations between mSSCI burden, markers of perinatal asphyxia, resuscitation characteristics, and mortality were explored using univariate analyses. Results Among the 109 newborns, 106 received therapeutic hypothermia within 6 h of birth; 12 developed neonatal seizures, 32 had brain lesions on MRI, and 10 died. 22% experienced no mSSCI, 35% had one, 28% had two, and 15% had three or more. Increasing cumulative mSSCI was significantly associated ( p < 0.01) with greater HIE severity (8.3% of newborns without mSSCI to 53.8% with ≥3 mSSCI were Sarnat III stage), higher lactate levels at birth and lower 5-minute Apgar scores ( p < 0.01). The cumulative number of mSSCI was significantly associated with the severity of individual metabolic disturbances. Mortality increased significantly with cumulative mSSCI, from 0/24 in newborns without mSSCI to 5/16 (31.3%) in those with ≥3 mSSCI. Conclusions Most newborns with HIE experienced metabolic systemic insults. Accumulation of mSSCI was associated with encephalopathy severity and mortality. Further studies are needed to determine whether mSSCI are markers of illness severity or modifiable targets for neuroprotective strategies.