| Introduction:Encepha-lopathy of prematurity(EP)is a heterogeneous disease with limited diagnostic tools.Imaging studies do not reveal all injuries and some patients with mild Traumatic brain injury(TBI)and no visible lesions are left with permanent symptoms.Consequently,specific biochemical markers which would reveal even the mildest brain injury,help assessing its severity,improve existing outcome prediction models and monitor treatment efficacy are needed.S-100? has been a candidate biomarker but it has low sensitivity and lacks brain-specificity.Both glial fibrillary acidic protein(GFAP)and ubiquitin C-terminal hydrolase-L1(UCH-L1)are new promising biomarkers.GFAP is an intermediate filament protein of astroglial skeleton and represents glial injury.Neuronal UCH-L1 is involved in either adding or removing ubiquitin from proteins and represents neuronal injury.Increased UCH-L1 concentrations have been linked to injury severity and worse outcome after TBI.GFAP has been found to correlate with axonal injury,elevated intracranial pressure and mortality and has outperformed S-100? in detecting intracranial injuries.Biomarkers may also help identifying the injury types,as UCH-L1 seems to increase more in diffuse injuries and GFAP in mass lesions.Objective: In order to explore the predictive value of changes in umbilical cord blood GFAP and UCH-L1 levels in the early diagnosis of premature infant encephalopathy and whether the combined detection can be a biochemical indicator for predicting encephalopathy in premature infants,the levels of umbilical cord blood,serum in premature infants with encephalopathy group and the levels of glial fibrillary acidic protein(GFAP)and ubiquitin carboxy terminal hydrolases L1(UCH-L1)in the control group were detected in this study.Method:1.All patients in this researchThe study selected neonatal premature infants born in the obstetrics department of the Fourth Hospital of Hebei Medical University and the Fourth Hospital of Shijiazhuang City from March to October 2018,and who were transferred to neonatal intensive care unit(NICU)within 6 hours after birth.Exclusion of subjects: patients with congenital or hereditary metabolic diseases,nervous system infectious diseases,cerebral infarction,and cerebral hemorrhage or nervous system;less than 72 hours after admission Patients;cord blood,serum samples collected insufficiently or patients with specimen hemolysis.A total of 40 premature infants were included,and basic clinical information such as birth weight and gestational age of preterm infants was recorded.According to the results of cranial ultrasound or cranial MRI diagnosis,the preterm infants who were diagnosed with premature infant encephalopathy were preterm infant encephalopathy group(29 weeks ? GA < 37 weeks),and no correlation between imaging findings and abnormal neurological manifestations was control(31 weeks ? GA < 37 weeks).All enrolled preterm infants were diagnosed and changed by a professional neonatologist.The diagnosis of encephalopathy in premature infants is based on the consensus of the experts in the diagnosis and prevention of brain injury in premature infants in 2012.2.Retention and reparation of specimenAll preterm infants were given 2 ml of umbilical arterial blood after birth,and 2 ml of venous blood was taken within 72 hours after birth.All blood samples were centrifuged at 3000 r/min for 10 minutes before measuring GFAP and UCH-L1 levels.The supernatant was stored at-80 ?for cryopreservation.The head ultrasound was improved within 3 days after birth,and the MRI was performed before discharge and the results were recorded.3.Detection of specimen indicatorsAll blood samples were tested for the level of glial fibrillary acidic protein and ubiquitin carboxy terminal hydrolase L1 by double enzyme-linked immunosorbent assay(ELISA).4.Statistical analysisThis experiment uses SPSS21.0 software for analysis,and the quantitative data meets the normal distribution and the variance is expressed by the meanąstandard deviation.The t-test of independent samples was used for comparison between groups,the median(quartile)was used for non-satisfaction,and the non-parametric rank sum test was used for comparison between groups.Qualitative data is expressed as a percentage(%),and the chi-square test is used for comparison between groups,with a test level of 0.05.Result:1.Analysis of clinical characteristics of premature infants in EP group and control group: Statistical analysis of gestational age and maternal pregnancy history of premature infants in two groups indicated that there were differences(P < 0.05);other clinical characteristics had no statistical difference.2.Changes of umbilical cord blood GFAP and UCH-L1 levels in premature infants in EP group and control group:The levels of GFAP in cord blood of preterm infants in EP group and control group were 9.50(3.50,13.94)ng/ml,7.80(5.92,8.58)ng/ml.There was no significant difference by Mann-Whitney U test(P > 0.05).The levels of UCH-L1 in cord blood of preterm infants in EP group and control group were 2898.03(2044.14,3543.80)pg/ml,1045.86(851.21,1585.77)pg/ml.The difference was statistically significant by Mann-Whitney U test.Meaning(P < 0.05).3.Changes of umbilical cord blood GFAP and UCH-L1 levels in premature infants of different gestational ages:In EP group,the cord blood GFAP levels were 7.27(3.50,13.77)ng/ml,11.27(4.33,13.94)ng/ml in EP group at gestational age >32 weeks and <32 weeks,respectively.There was no significant difference by Mann-Whitney U test(P>0.05).Cord blood UCH-L1 levels were 2241.02(1783.37,3268.79)pg/ml and 3529.48(3046.14,4828.84)pg/ml at gestational age > 32 weeks and < 32 weeks.The difference was statistically significant by Mann-Whitney U test(P < 0.05).In the control group,the levels of GFAP and UCH-L1 in cord blood were 7.28(5.82,8.56)ng/ml,1065.63(851.02,1590.26)pg/ml,8.96(8.96,8.96)ng/ml and 964.54(964.54,964.54)pg/ml.There was no significant difference between the two groups by Mann-Whitney test(P > 0.05).4.Changes of cord blood GFAP and UCH-L1 levels between abnormal maternal pregnancy history and normal preterm infants:In EP group,the levels of GFAP and UCH-L1 in cord blood of preterm infants with and without abnormal maternal pregnancy history were 8.15(3.40,14.23)ng/ml,2630.42(1921.74,3515.17)pg/ml and 10.28(2.91,14.21)ng/ml,3443.32(2711.14,7721.28)pg/ml.There was no significant difference by Mann-Whitney U test(P > 0.05).Control group: The levels of GFAP and UCH-L1 in cord blood of preterm infants with and without abnormal maternal pregnancy history in control group were 7.71(6.22,7.71)ng/ml,1291.03(967.26,1291.03)pg/ml,7.28(5.73,8.58)ng/ml,1026.08(830.22,1581.29)pg/ml.There was no significant difference by Mann-Whitney U test(P > 0.05).5.Changes of serum GFAP and UCH-L1 levels in cord blood and 72 hours after birth in EP group:The levels of GFAP and UCH-L1 in cord blood and 72 hours after birth in EP group were 9.50(3.50,13.94)ng/ml,2898.03(2044.14,3543.80)pg/ml and 10.78(4.58,14.38)ng/ml,3087.33(2501.61,3812.94)pg/ml.There was no significant difference between them by Mann-Whitney U test(P > 0.05).6.Predictive value of cord blood GFAP and UCH-L1 in preterm infants with encephalopathy:The ROC curves of umbilical cord blood GFAP and UCH-L1 showed that the area under the two curves(AUC)were 0.558(95% CI 0.352-0.763)and 0.900(95% CI 0.801-0.999),respectively,suggesting that UCH-L1 of cord blood was more valuable for early prediction of premature infant encephalopathy.7.Correlation analysis of GFAP and UCH-L1 levels in premature infants: Spearman's correlation analysis showed that:The levels of GFAP and UCH-L1 in cord blood of control group were positively correlated(r=0.686,P=0.001).There was no significant correlation between cord blood and serum levels of GFAP and UCH-L1 in EP group.Conclusion:1.UCH-L1 in cord blood of premature infants has the value of early prediction of EP.2.The risk factors of EP were gestational age < 32 weeks and abnormal maternal pregnancy history.3.GFAP and UCH-L1 interact in normal physiological state of premature infants,but there is no significant relationship in EP. |
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