| Background:Hypoxic-ischemic encephalopathy（HIE）in neonates is the leading cause of death and disability in children,and therapeutic hypothermia（TH）is currently the only safe and effective neuroprotective treatment known to humans.In developed countries,TH has become a routine treatment method in the past decade.However,a national survey conducted in China in 2021 showed that the TH treatment rate for HIE patients in China was only 54%,and even less in high-altitude areas with relatively backward socio-economic conditions.In high-altitude areas,the incidence of HIE in newborns is much higher than in plains due to high altitude,low oxygen content in the air（only 16%in Dali,Yunnan）,relatively backward medical conditions,and lack of prenatal care for most pregnant women,resulting in more severe hypoxia after suffocation.Objective:To reduce neonatal mortality and disability,we implemented TH in the neonatal unit of the First Affiliated Hospital of Dali University（average altitude2100 m）to study the safety and efficacy of whole-body TH treatment for children with HIE born in the plateau area of northwest Yunnan Province,and to further explore the long-term effects of TH on children with HIE.The aim is to provide a theoretical basis for the implementation of TH for HIE in the plateau region.Methods:A retrospective controlled study method was used.Eighty-eight children with HIE who underwent whole-body TH treatment from December 2020 to December 2022 in our hospital were included in the study as the subcryogenic treatment group.To prevent more children from delaying treatment,50 children with HIE admitted from January 2019 to November 2020 were included as controls,and this group was the conventional treatment group.The conventional treatment group was given three symptomatic and three supportive treatments;the TH group was given whole-body TH on the basis of the conventional treatment group.Blood was collected on the day of birth and 7 days after birth for routine blood tests,coagulation function,electrolytes,liver and kidney function and cardiac enzymes,and the changes in vital organ function before and after treatment were compared between the conventional treatment group and the TH group.All children were clinically observed for complications such as hypotension,bradycardia,coagulation dysfunction,hypoglycemia,sclerosis,and sepsis.All children underwent a EEG within 6 hours after birth and cranial MRI after treatment（5～7 days after birth）.The children with HIE were also followed up and assessed with the Developmental Behavior Assessment Scale for Children 0～6 years old,by which the developmental quotient was calculated in order to understand the neuropsychological development of children.Results:1.In this study,after treatment,the average PLT level of children in the TH group was lower than that in the conventional treatment group（P=0.001）.However,only one case of PLT reduction occurred in each group,and the difference was not statistically significant（P>0.05）.Meanwhile,35 cases of neonatal anemia（39.80%）occurred in the TH group after treatment,which was significantly different from the 1 case（2.00%）in the conventional treatment group（P<0.01）.In terms of electrolytes,the average K+and Ca2+levels of the TH group were within the normal range and higher than those in the conventional treatment group,and the difference was statistically significant（P<0.05）.There were no cases of hypokalemia or hypocalcemia in the TH group,while the conventional treatment group had 3 cases of hypokalemia and 3 cases of hypocalcemia,and the difference was statistically significant（P<0.05）.In terms of liver biochemical indicators,the liver transaminases in the TH group decreased to normal levels and were significantly lower than those in the conventional treatment group（P<0.05）.However,both groups of children had a significant decrease in albumin levels after treatment（P<0.05）,and the incidence of hypoalbuminemia was 14.00%and 10.20%in the two groups,respectively,which increased compared with before treatment,but there was no statistical difference between the two groups（P>0.05）.In terms of coagulation function,the APTT in the TH group was significantly prolonged compared with that in the conventional treatment group（P<0.01）,but there was no difference between the two groups in the abnormal rate of APTT>45 seconds and other coagulation function indicators such as TT,PT,and FIB（P>0.05）.In terms of myocardial enzymes,the average levels and abnormal rates of CK-MB and LDH in the TH group were lower than those in the conventional treatment group,and the difference was statistically significant（P<0.05）.There was no difference between the two groups in terms of WBC,Na+,and renal function（P>0.05）.2.In the strength of association analysis,TH was significantly correlated with the incidence of neonatal anemia[OR=32.36,95%CI（4.27-245.24）,P=0.001];among the complications of TH,only bradycardia was correlated with TH[OR=4.20,95%CI（1.50-11.73）,P=0.006],and the rest of hypotension,Coagulation dysfunction,hypoglycemia,sepsis,and sclerosis were not correlated with TH（P>0.05）;in disease regression during hospitalization,the children in the 2 groups did not show any statistical difference in the mean duration of oxygen,hospitalization period and blue light exposure（P>0.05）,but TH increased the risk of>72 hours of oxygenation in children with HIE[OR=2.32,95%CI（1.14-4.47）,P=0.021].3.Cranial MRI results:after treatment,the difference in cranial MRI severity between the 2 groups of children was statistically significant（Z=2.497,P=0.013）.In the correlation strength analysis,TH showed significant efficacy in improving moderately severe abnormal cranial MRI findings in children with HIE[OR=0.42,95%CI（0.20-0.91）,P=0.026],while no difference was shown between the 2 treatment modalities in normal and mildly abnormal cranial MRI findings（P<0.05）.4.Follow-up results:In this study,there were no deaths in the TH group,while one child died in the conventional treatment group.Seven children had a developmental quotient（DQ）<70,manifested as varying degrees of language,motor,cognitive impairment,and seizures,with 3 cases（3.41%）in the TH group and 4 cases（8.00%）in the conventional treatment group.In the DQ level test results,there was no statistical difference between the conventional treatment group and the TH group in mild and severe HIE children（P>0.05）,while there was a significant difference in moderate HIE children（P<0.01）.In the correlation strength analysis,TH showed significant protection in children with DQ≥80[OR=3.61,95%CI（1.38-9.50）,P=0.007];at the same time,it also showed protective effect in children with critically low DQ（70-79）[OR=0.27,95%CI（0.08-0.85）,P=0.019];however,there was no statistically significant difference between the two treatment methods in children with intellectual disability（<70）（P>0.05）.Conclusion:1.TH showed some hepatic and myocardial protective effects and promoted the homeostasis of the internal environment,but TH can lead to prolonged APTT and bradycardia,during TH,attention should be paid to monitoring coagulation function and heart rate,after timely treatment,bradycardia and prolonged APTT can be improved;TH did not increase the complications of hypoglycemia,sepsis and sclerosis significantly;at the same time,TH did not prolong the risk of hospitalization,so sub-cold treatment in high altitude areas is safe and feasible;2.TH significantly improved the cranial imaging results of children with moderate and severe HIE and the long-term neurodevelopmental outcome of children with moderate HIE.Therefore,whole-body TH of moderate and severe neonatal HIE in the plateau area of northwest Yunnan is effective and should be promoted in clinical practice. |
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