Value Of Serum GDF11 And VAP-1 Levels In Early Prediction And Disease Severity Assessment Of Bronchopulmonary Dysplasia In Premature Infants

Objective:The bronchopulmonary dysplasia（BPD）is the most common chronic lung disease in extreme/ultra-premature infants（VPI/EPI）.Its long-term complications include low lung function,repeated respiratory tract infection,asthma,pulmonary hypertension,poor growth and development of the nervous system and physique,which seriously reduce the quality of life of the children and cause a heavy burden on the family and society.With the release of the multi-child policy,the development of assisted reproductive technology,and the improvement of obstetrics and neonatal treatment technology,the birth rate of extremely/ultra-premature infants keeps rising,and the incidence of BPD increases year by year.Therefore,early diagnosis and timely intervention are very important to reduce the incidence of BPD in premature infants and improve their prognosis.Compared with traditional monitoring methods,serum biomarkers are objective,simple and feasible.Growth differentiation factor11（GDF11）is a secretory protein that is one of the key members of the transforming growth factor beta（TGF-β）superfamily.GDF11 induces pulmonary diseases through multiple signaling pathways such as Smad,PI3K/AKT,NF-κB,etc.,causing endothelial cell proliferation,angiogenesis and inflammatory response.Vascular adhesion protein-1（VAP-1）,a homodimer 170-k Da salivate glycoprotein,is expressed on the surface of endothelial cells,smooth muscle and adipose cells,and plays an important role as an amino urea sensitive amine oxidase and adhesion molecule in the exudation of leukocytes.It is closely related to the pathological process of lung disease.By studying the changes of serum GDF11 and VAP-1 levels in premature infants with BPD and non-BPD,the purpose of this study was to explore the clinical value of both for the early prediction and disease severity assessment of premature infants with BPD.Method:1.A total of 52 premature infants with gestational age<32 weeks admitted to Neonatology Department of Northern Jiangsu People’s Hospital from February 10th,2020 to January 10th,2023 were selected as research objects.According to the National Institute of Child Health and Human Development（NICHD）,the patients were divided into BPD group（20 cases）and non-BPD group（32 cases）.Preterm infants in the BPD group were divided into mild BPD group（12 cases）and moderate to severe BPD group（8 cases）.2.Clinical data of preterm infants in the two groups were collected:general information（gender,delivery mode,birth weight,gestational age,1min and 5min Apgar score）,mechanical ventilation duration during hospitalization,prenatal infection of mothers,etc.3.Biological serum samples were collected from two groups of premature infants:1ml peripheral blood was collected from the two groups of premature infants on day 1,day 7 and day 14 after birth and placed in an anticoagulant tube,centrifuged at3000r/min within 24 hours for 15min,and the supernatant was stored in a-80℃refrigerator and labeled for examination.enzyme-linked immunosorbent assay（ELISA）was used to determine the concentrations of GDF11 and VAP-1 in serum and record the data.4.Collate the data and use SPSS26.0 software for data analysis:The measurement data conforming to normal distribution were expressed as mean±standard deviation（x±s）.Independent sample t test was used for comparison between two groups,one-way analysis of variance was used for comparison at multiple time points within the group,and least significant difference（LSD-t）method was used for comparison at two time points of the same index within the group.Count data were compared by example（%）,and chi-square test was used for comparison between groups.The early predictive value of serum GDF11 and VAP-1 for BPD in premature infants was evaluated using receiver operating characteristic（ROC）.area under curve（AUC）,optimum cut-off value,sensitivity and specificity were used to represent the ROC curve.When AUC>0.7,the prediction accuracy is high.Pearson correlation analysis was used to determine the correlation between the serum GDF11 and VAP-1 levels and the severity of BPD in preterm infants.When P<0.05,the difference was statistically significant.Results:1.Comparison of clinical data of premature infants in BPD group and non-BPD groupThere were no significant differences in gender,delivery mode,birth weight,gestational age,1min and 5min Apgar scores between BPD group and non-BPD group（P>0.05）.The mechanical ventilation duration≥3d during hospitalization in the BPD group was higher than that in the non-BPD group,and the proportion of maternal prenatal infection was statistically significant（P<0.05）.2.Comparison of serum GDF11 levels of premature infants in BPD group and non-BPD group at different time points and at three time points within the group2.1 2.1 The serum GDF11 level of preterm infants in BPD group on day 7 and day14 after birth was lower than that in non-BPD group,and there was statistical significance in serum GDF11 level between the two groups on day 7 and day 14 after birth（P<0.05）;There was no significant difference in serum GDF11 level on day 1after birth between the two groups（P>0.05）.2.2 The serum GDF11 level of preterm infants in BPD group showed a decreasing trend with the extension of birth age,and the difference was statistically significant on7d,14d and 1d after birth（P<0.05）,and the difference was statistically significant on14d and 7d（P<0.05）.There was no significant change in serum GDF11 level on day 1,day 7 and day 14 after birth in the non-BPD group,and there was no statistical significance in intra-group comparison（P>0.05）.3.Comparison of serum VAP-1 levels of premature infants in BPD group and non-BPD group at different time points and at three time points within the group3.1 Serum VAP-1 level of preterm infants in BPD group was higher than that in non-BPD group on day 7 and day 14 after birth,and there was statistical difference in serum VAP-1 concentration between the two groups on day 7 and day 14 after birth（P<0.05）,while there was no statistical difference in serum VAP-1 concentration between the two groups on day 1 after birth（P>0.05）.3.2 The serum VAP-1 level of premature infants in BPD group increased gradually with the extension of birth age,and there was statistical difference between the 7d,14d and 1d after birth（P<0.05）,and the difference between the 14d and 7d was statistically significant（P<0.05）.There was no significant change in the serum VAP-1 level of preterm infants in the non-BPD group on day 1,day 7 and day 14 after birth,and there was no statistical significance in intra-group comparison（P>0.05）.4.Analysis of the efficacy of serum GDF11 and VAP-1 on day 1,day 7 and day 14in predicting the occurrence of BPD in preterm infantsThe 1d AUC=0.566,AUC=0.803,sensitivity=0.800,specificity=0.719,and optimal cut-off value=287.740 in serum GDF11 of preterm infants in BPD group.At the 14th day,AUC=0.848,sensitivity=0.900,specificity=0.656,and optimal cut-off value=287.925.Serum VAP-1 of preterm infants in BPD group was 0.525 at 1d AUC,0.780 at 7d,0.600 at sensitivity,0.844 at specificity,and 533.915 at optimal cut-off.At the 14th day,AUC=0.867,sensitivity=0.800,specificity=0.906,and optimal cut-off value=543.280.Serum GDF11 combined with VAP-1 had AUC=0.856,sensitivity=0.700,specificity=0.937 on day 7 after birth.At the 14th day,AUC=0.903,sensitivity=0.900,specificity=0.812.5.Comparison of serum GDF11 level of preterm infants in mild and moderate to severe BPD groups on day 1,day 7 and day 14 after birthThere was no significant difference in serum GDF11 level on day 1 after birth between mild BPD group and moderate to severe BPD group（P>0.05）.Serum GDF11level in mild BPD group was higher than that in moderate and severe BPD group on 7d and 14d after birth,with statistical significance（P<0.05）.6.Comparison of serum VAP-1 level on day 1,day 7 and day 14 after birth between preterm infants in mild and moderate to severe BPD groupsThere was no statistical significance in serum VAP-1 level between mild and moderate to severe BPD groups on day 1 after birth（P>0.05）.Serum VAP-1 level in mild BPD group was lower than that in moderate and severe BPD group on the 7th and14th day after birth,and the difference was statistically significant（P<0.05）.7.Correlation analysis of serum GDF11 and VAP-1 levels with the severity of BPD in preterm infantsSerum GDF11 levels were negatively correlated with the severity of BPD in preterm infants（r₁=-0.493,P<0.01）;Serum VAP-1 level was positively correlated with the severity of BPD in preterm infants（r₂=0.463,P<0.01）.Conclusion:1.GDF11 and VAP-1 may be involved in the occurrence and development of BPD in premature infants.2.Serum GDF11 and VAP-1 levels on the 7th and 14th day after birth had a certain predictive value for the occurrence of BPD in premature infants.The predictive efficacy of serum GDF11 combined with VAP-1 on the 7d and 14d after birth was higher than that of a single predictor,especially on the 14d after birth,with better sensitivity and specificity.3.Both GDF11 and VAP-1 levels can reflect the severity of BPD in premature infants.4.Both GDF11 and VAP-1 levels can be used as indicators for early prediction of BPD occurrence and disease assessment in premature infants.