A comparison of mortality for neonates aged 35 versus 36 weeks gestational age with hypoxic-ischemic encephalopathy treated with therapeutic hypothermia in the National Inpatient Sample.

Objectives: Using a nationally representative database of U.S. hospitalizations, we aimed to (1) characterize contemporary trends in hypoxic-ischemic encephalopathy (HIE) prevalence by severity, therapeutic hypothermia (TH) utilization, and associated in-hospital mortality; and (2) examine the association between TH and mortality by HIE severity and gestational age (GA), focusing on 35- and 36-weeks GA. Methods: We analyzed newborn hospitalizations from the National Inpatient Sample, 2016-2023. Unspecified, mild, moderate, and severe HIE were identified using ICD-10-CM diagnosis codes P91.60-P91.63; and 35- and 36-weeks GA using codes P07.38-P07.39. TH was identified using ICD-10-PCS codes 6A4Z0ZZ and 6A4Z1ZZ. Survey-weighted multivariable generalized linear models with marginal standardization were used to estimate adjusted mortality risk differences (RD) with surprisal (S) values, and assess whether associations between TH and mortality differed by HIE severity across GA strata. Results: Among 29,767,238 hospital discharges, HIE was identified in 66,535 neonates (2.24 per 1,000), and TH used in 19.2% of HIE cases. In-hospital mortality was 9.74% among all HIE cases and 6.65% among TH-treated neonates. From 2016-23, HIE prevalence nearly doubled (1.58 to 3.01 per 1,000; p-for-trend <0.001) and TH utilization more than doubled (0.33 to 0.74 per 1,000; p-for-trend <0.001), while TH use as a proportion of HIE remained stable (17.8%-20.8%; p-for-trend=0.39). HIE severity distribution was: mild (15%), moderate (29.4%), severe (18.3%), and unspecified (37.3%), with moderate HIE increasing over time (22.3%-33.5%). Crude mortality was consistently highest for severe HIE (range: 33.65%-35.25%). Among infants with severe HIE, TH was associated with reduced mortality overall (RD -10.12%; 95% CI -14.86, -5.39; p<0.001; S=15.12), and specifically at 36-weeks GA (RD -21.98%; 95% CI -35.85, -8.12; p=0.002; S=9.06), but not at 35-weeks (RD -1.83%; 95% CI -21.2, 17.55; p=0.86; S=0.22). Conclusions: TH was associated with mortality reduction in severe HIE overall and at 36-weeks GA, but this benefit remains uncertain at 35-weeks GA.