| ObjectiveNeonatal hypoxic-ischemic brain damage(HIBD)is one of the most common acute and critical diseases leading to neonatal death and disability.The early symptoms and signs of some patients are often atypical and lack of high sensitivity and specificity,which often leads to misdiagnosis,missed diagnosis and missing the best time for treatment.Hepcidin(Hepc)is an antimicrobial peptide hormone composed of 25 amino acids(AA),which is the main regulator of iron absorption and distribution by tissues.In recent years,it has been reported that Hepc mRNA and serum Hepc levels are up-regulated in adult ischemic stroke patients.Serum ferritin(SF)is a commonly used indicator of iron deficiency anemia and liver disease,and related studies also found that SF is significantly increased in adult acute cerebral infarction.In this paper,we compared the expression changes of serum Hepc and SF levels at different time points and between HIHD group and non-HIBD group,and analyzed the correlation between serum Hepc and SF levels and disease severity in HIBD newborns.It aimed to evaluate the value of serum Hepc and SF level for early prediction and evaluation of neonatal HIBD.MethodsSixty neonates admitted to the NICU from January 2021 to January 2023 were selected as the study subjects,and were divided into mild HIBD(13 cases),moderate HIBD(10 cases),severe HIBD(8 cases),and non-HIBD(29 cases)according to the diagnosis and grading criteria of neonatal HIBD.All neonates underwent head MRI within 7 days after birth,and 2ml of venous blood was collected in the 1st d,3rd d and 7th d afther birth and placed in the anticoagulant tube,sent to the laboratory and centrifuged at 3000 r/min in the centrifuge for 10min.The supernatant was kept in minus 80 degrees celsius refrigerator and labeled for testing,and serum Hepc and SF levels were detected by enzyme-linked immunosorbent assay(ELISA)and chemiluminescence immunization method respectively.Using SPSS 22.0 software for data statistics,the normal distribution of measurement data as mean ± standard deviation(x±s)and the mean between two groups using independent sample t test.Means were compared between multiple groups using analysis of variance(F test)and pair-wise comparison using LSD-t test.Count data were expressed as rate(%)and analysed by chi-square(χ2)test.Using receiver operating characteristic(ROC)curves to assess the predictive value of serum Hepc and SF expression levels for neonatal HIBD(AUC>0.7,indicating predictive value).The relationship between serum Hepc and SF expression levels and the disease severity of neonatal HIBD disease was analyzed by Pearson correlation.Statistical significance is indicated atp<0.05.Results1.Comparison of general data between HIBD and non-HIBD groups:There was no significant difference in sex,gestational age,birth weight and delivery mode of newborns between the two groups(p>0.05).2.Comparison of neonatal serum Hepc and SF levels in HIBD and non-HIBD groups:Hepc and SF levels were higher in the 1d,3d and 7d HIBD groups than in the non-HIBD group,which were significant(p<0.05).3.Comparison of serum Hepc and SF levels in the HIBD group at different time points:Serum Hepc and SF levels in the HIBD group gradually increased in the 1d and 3d,and decreased in the 7d after birth.The difference were significant compared the pairwise time points(p<0.05).4.ROC curve analysis of serum Hepc and SF levels at 1d,3d and 7d after birth for predicting HIBD in neonates:Serum Hepc AUC at 1d was 0.786(95%CI 0.673-0.900),the maximum YouDen index was 0.475,the best diagnostic threshold was 89.68,sensitivity of 0.613,speciality 0.862;Serum Hepc AUC at 3d was 0.815(95%CI 0.807-0.932),the maximum YouDen index was 0.795,the best diagnostic threshold was 102.45,sensitivity of 0.839,speciality 0.956;Serum Hepc AUC at 7d was 0.674(95%CI 0.535-0.812),the maximum YouDen index was 0.410,the best diagnostic threshold was 91.87,sensitivity of 0.548,specific degree of 0.862.SF AUC at 1d was 0.805(95%CI 0.703-0.928),the maximum YouDen index was 0.483,the best diagnostic threshold was 160.73,sensitivity of 0.618,speciality 0.865;The 3d SF AUC was 0.908(95%CI was 0.858-0.996),the maximum YouDen index value was 0.826,the best diagnostic threshold was 297.54,sensitivity of 0.871,speciality 0.955;SF AUC at 7d was 0.684(95%CI 0.550-0.818),the maximum YouDen index value was 0.318,the best diagnostic threshold was 170.75,Sensitivity of 0.387,specific degree of 0.931,Serum Hepc combined with SF 1d AUC=0.874(95%CI 0.779-0.968),YouDen index maximum 0.619,sensitivity=0.726,specificity=0.893;3d AUC=0.920(95%CI 0.863-0.998),YouDen index maximum 0.874,sensitivity=0.896,specificity=0.978.5.Comparison of serum Hepc levels in HIBD newborns in mild,moderate and severe groups:Serum Hepc levels gradually increased with the severity of the disease,statistically significant difference between different groups(F=37.349,p<0.001;F=12.091,p<0.001;F=41.475,p=0.016),and the pairwise comparisons between the groups,and the differences were also statistically significant(p<0.05);Comparison of the different time points within the same group,gradually higher serum Hepc after birth at 1d and 3d,a decreasing trend to the 7th d,statistically significant difference(F=43.862,p=0.009;F=38.725,p<0.001;F=46.513,p<0.001).And compare the pairwise time points within the group,the differences were also statistically significant(p<0.05).6.Comparison of SF levels in HIBD between mild,moderate and severe groups:SF level gradually increased with the severity of illness,and showed statistically significant differences between different groups(F=48.674,p<0.001;F=62.358,p<0.001;F=45.254,p<0.001).And the pairwise comparisons between the groups,the differences were also statistically significant(p<0.05);Comparison of the different time points within the same group,the serum SF gradually increased on 1d and 3d,a decreasing trend to the 7th d,Statistically significant difference(F=49.854,p<0.001;F=53.128,p<0.001;F=62.346,p<0.001).And compare the pairwise time points within the group,the differences were also statistically significant(p<0.05).7.Results of serum Hepc,SF levels and neonatal HIBD disease severity were assessed by Pearson correlation analysis:Serum Hepc were positively correlated with the severity of HIBD(r1=0.435,p<0.05);SF was also positively associated with the severity of HIBD(r2=0.462,p<0.05).Conclusions1.Serum Hepc and SF may be involved in the occurrence and development of neonatal HIBD,and both of them can reflect the occurrence of HIBD.2.The serum Hepc and SF in 1d and 3d have certain predictive value for neonatal HIBD,among which the 3d has the higher efficacy of serum Hepc and SF in 1d and 3d are higher than the single index,and the efficacy of the 3d is higher,so that the serum Hepc and SF levels can be used as the sensitive and specific index for early prediction of neonatal HIBD.3.The changes in serum Hepc and SF levels in the 1st d,3rd d and 7th d HIBD can reflect the disease outcome.4.Serum Hepc and SF levels were positively correlated with neonatal disease severity in HIBD and can be used as a reference index to assess the disease severity in HIBD.5.Serum Hepc and SF can be used as potential biological markers of neonatal HIBD for early disease prediction,disease outcome and severity assessment,and have certain clinical application value. |
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