Effect of hypothermia on the expression level of serum ubiquitin carboxy-terminal hydrolase- L1 and hypoxia-induced factor-1α and neurodevelopmental outcomes in neonatal hypoxicischemic encephalopathy
Lyu Hongyan, Yin Xiaojuan, Liu Fang, et al
(1.Department of Neonatology, Handan Maternal and Child Health CareHospital, Hebei, Handan 056002, China; 2. Beijing Key Laboratory of Pediatric Organ Failure, NationalEngineering Laboratory for Birth Defects Prevention and Control of Key Technology, Institute of Pediatrics,the Seventh Medical Center of PLA General Hospital, Faculty of Pediatrics, the Chinese PLA GeneralHospital, Beijing 100700, China; 3. Department of Pediatrics, the 980th Hospital of the PLA Joint LogisticsSupport Force, Hebei, Shijiazhuang 050082, China; 4. Department of Pediatrics, Xingtai City the NinthHospital, Hebei, Xingtai 055250, China)
Abstract: 【Abstract】 Objective To explore the effect of hypothermia treatment on the expression levels of serum ubiquitin carboxy-terminal hydrolase- L1 (UCH-L1) and hypoxia-induced factor-1α(HIF-1α) and neurodevelopmental outcomes in neonatal hypoxic-ischemic encephalopathy (HIE). Method From August 2015 to August 2022, 110 children with moderate to severe HIE admitted in the neonatal intensive care unit (NICU) of Handan Maternal and Child Health Hospital were selected. According to whether family members agreed to receive mild hypothermia treatment，the cases were divided into hypothermia treatment group (n=70) and traditional treatment group (n=40). The hypothermia treatment group was given selective head cooling (SHC) treatment from 0 to 6 hours after birth in addition to conventional treatment. The children in the traditional treatment group were given conventional treatment. The expression levels of UCH-L1 and HIF-1α in all children were detected by enzyme-linked immunosorbent assay double anti-sandwich assay before treatment and on the 3rd day after treatment. Neurodevelopmental outcomes were followed up 12 to 15 months after birth. The Independent sample t-test, paired sample t-test, χ2 test or Fisher exact probability method were used for statistical analysis. Result The expression levels of serum UCH-L1 [ (1.9±0.4) vs(3.1±0.3) μg/L, t=16.495, P<0.001 ] and HIF-1α [(1.40±0.22) vs (2.75±0.19) μg/L, t=32.486, P<0.001)]in mild hypothermia treatment group were significantly lower than those in traditional treatment group after treatment. The expression level of serum UCH-L1 in mild hypothermia group after treatment was lower than before treatment [(1.9±0.4) vs (3.3±0.5) μg/L, t=18.293, P<0.01]. The expression level of serum HIF-1α in both groups were higher than those before treatment [(1.40±0.22) vs (1.23±0.29) μg/L, t'=3.907, P<0.001] and [(2.75±0.19) vs (1.27±0.35) μg/L, t'=23.504, P<0.001], but the results of mild hypothermia treatment inhibition of serum HIF-1α increase were significantly better than those of traditional treatment. Followup results showed that the proportion of normal neurodevelopment in mild hypothermia treatment group was higher than that in traditional treatment group [68.6% (48/70) vs 32.5% (13/40), χ2=13.408, P<0.001]. Theproportion of neurodevelopmental retardation in mild hypothermia treatment group was lower than that intraditional treatment group [11.4% (8/70) vs 37.5% (15/40), χ2=10.462, P<0.001]. Conclusion The serum UCH-L1 level of children with moderate to severe HIE could be significantly decreased in mild hypothermia treatment group. Moreover, the effect of mild hypothermia treatment on the elevation of serum HIF-1α level is significantly better than that of the traditional treatment group, which may be one of the neuroprotective mechanisms of hypothermia level.
2024, Vol. 12 
