Maternal-placental timing profiles of hypoxic-ischemic insult and association with prognosis in neonatal encephalopathy.

OBJECTIVES

To determine whether temporal profiles of hypoxic-ischemic insult in neonatal encephalopathy (NE) were associated with outcomes, and to assess their prognostic value.

STUDY

DESIGN

Infants with mild, moderate and severe NE treated with hypothermia were included. Placental histopathology, maternal risk factors, and neonatal clinical, biochemical, electrographic, and neuroimaging data were used to classify infants into proximal, distal, and proximal-on-distal profiles. Neurodevelopmental outcomes were assessed at 18 months.

RESULTS

Ninety-eight infants were included (34 distal, 43 proximal, 21 proximal-on-distal). Mortality and composite adverse outcomes were similar between distal-predominant and proximal-predominant groups. Timing of insult profiles was not associated with adverse outcome, whereas the deep gray matter injury subscore independently predicted adverse outcome (aOR 1.36, 95% CI 1.15-1.59; p < 0.001) with an area under the curve of 0.89.

CONCLUSION

Perinatal timing of insult profiles did not demonstrate prognostic significance after accounting for NE severity, while MRI-defined injury burden provided the strongest prognostic value.

IMPACT: Integrating placental pathology with neonatal neuroimaging provides valuable mechanistic insight but limited prognostic value for outcome prediction across the full spectrum of neonatal encephalopathy due to presumed hypoxic-ischemic encephalopathy. Once neonatal encephalopathy occurs, outcomes are primarily driven by the severity of the hypoxic-ischemic insult. Timing of insult (proximal versus distal) was not associated with mortality, brain injury severity, or neurodevelopmental outcomes in infants with neonatal encephalopathy treated with therapeutic hypothermia.