Time Until Recovery from Metabolic Acidemia: A Prognostic Marker for Perinatal Hypoxic-ischemic Encephalopathy (HIE)?

Background: Clinical, biochemical, electrophysiologic (EEG) and neuroradiologic (MRI) tools are used to assess outcomes of infants with HIE. The studies that correlated umbilical cord blood gas pH, bicarbonate (HCO3), base deficit (BD) and lactate concentrations with clinical outcomes have modest predictive accuracy. Metabolic acidemia in HIE gets corrected by acid-base buffers system. Time interval for correction (ToC) is variable in each infant and may serve as a marker for the degree of brain injury. There is no specific study that has explored ToC of acidemia with outcomes. The aim of the study was to correlate ToC from metabolic acidosis in HIE with short and long term outcomes.

Methods: This cohort study included infants with HIE treated with hypothermia from 2015-2020.Maternal and infant data were collected. ToC of metabolic acidemia on blood gas analysis (pH≥7.30, HCO3≥ 20 mmol/L, BD ≤ 4mEq/L & lactate <3 mmol/L) were noted. Infants were followed in the follow up clinic with Bayley scale of infant development (BSID) III at 12 months and 24 months. Composite scores for cognition (CCS), language (LCS) and motor (MCS) skills were obtained. P values were calculated with appropriate tests.

Results: Of the 82 infants included, 41% had mild or moderate HIE. Infants with severe HIE had lower Apgar score and required more chest compressions at birth (Table 1). They had longer time to reach full oral feeds, length of stay (LOS) and more seizures (p < 0.01). ToC of HCO3, BD and lactate were significantly longer across the severity of HIE (p < 0.05). Tables 2 and 3 show the outcomes for correction of parameters ≤24 hours compared to >24 hours. Seizures were significantly higher in infants who corrected their HCO3, BD and lactate ≤24 hours (p < 0.05). One and two-year follow up data were available on 45 and 33 infants respectively. Mean CCS, LCS and MCS at 8-14 months and 18-24 months were lower in infants with ToC >24 hours for all parameters. However, at 18-26 months, only MCS were significantly lower in infants who corrected their pH, BD and lactate at >24 hours (p < 0.05).

Conclusion: LOS, age at full oral feeds and seizures were higher in moderate and severe HIE. ToC of HCO3, BD and lactate were significantly longer across the severity of HIE. Seizures were higher in infants who corrected their HCO3, BD and lactate ≤24 hours. MCS on BSID at 18-26 months were significantly lower in infants who corrected their pH, BD and lactate at >24 hours. Further studies are needed to explore ToC of acidemia as a prognostic marker.