Neurodevelopmental outcomes of mild neonatal encephalopathy treated with therapeutic hypothermia

Background Recent clinical practice has increasingly applied therapeutic hypothermia (TH) to mild neonatal encephalopathy (NE) to avoid missing the optimal treatment window. This study evaluates the efficacy and safety of TH for improving neurodevelopmental outcomes in infants with mild NE. Methods This study comprised a retrospective cohort (2020-2022) and a prospective cohort (2022-2023). Neonates with mild NE were divided into TH and non-TH groups. The general condition, short-term and 2-year neurodevelopmental outcomes, incidence of adverse events, and hospitalization costs of the two groups were compared. Results This study included 220 patients with mild NE: 147 in TH group and 73 in non-TH group. Compared with the non-TH group, TH group exhibited higher rates of vaginal delivery and lower umbilical cord blood pH (both P<0.05). The TH group experienced delayed first feeding, higher rates of arrhythmia or circulatory instability requiring inotropes/vasopressor support and greater hospitalization costs (all P<0.05). As for the neurodevelopmental outcomes, compared with the non-TH group, the TH group exhibited a higher proportion of abnormal aEEG within 24 hours (P=0.011) but no significant differences emerged at 24-48 hours of age (P=0.064), 48-72 hours (P=1.000) or 4-7 days of age (P=0.340). There were no statistical significant differences in total MRI scores within 1-2 weeks of age (1 (0, 3) vs. 1.5 (0, 6), P=0.362), test of infant motor performance (TIMP) scores within 1-2 weeks (-1.00 (-1.36, -0.72) vs. -1.20 (-1.46, -0.86), P=0.197) or at 4 months of age (-0.63 (-1.00, -0.31) vs. -0.63 (-0.90, -0.50), P=0.917), or 2-year-old Griffith scores between the TH and non-TH groups (all P>0.05). In telephone scripted interviews at 2-year-old, a total of 46 (20.9%) mild NE had abnormal outcomes: 25 (17.0%) in TH group, 21 (28.8%) in non-TH group (P=0.053). Logistic regression analysis revealed no independent association between TH and MRI abnormalities (OR=0.71, 95%CI: 0.25-1.86, P=0.493). Conclusion Mild NE may leave neurological sequelae. TH did not significantly improve neurodevelopmental outcomes in mild NE cases, and may introduce adverse effects and increase hospitalization costs. Clinicians should exercise caution in applying TH for mild NE until robust evidence confirms its efficacy. Trial registration: Chinese clinical trial registry, ChiCTR2200065304. Registered 1 November 2022 - Retrospectively registered, https://www.chictr.org.cn/index.html