Clinical Research Of Umbilical Cord Blood HIF-1a, VEGF Determination And Its Relationship With Brain Injury In Premature Infants

Objective: Brain injury in premature infants is a common complication,preterm survivors often suffer from severe neurodevelopmental disorders,such as cognitive deficits and movement disorders. With the increase ofpremature infant survival rate, the incidence rate of brain injury also increases,which makes it extremely significant on how to compolish the early diagnosisof brain injury in premature infants and reduce the neurological sequelafterwards.The common causes of brain injury in premature infants includeperinatal hypoxia or ischemia as well as intrauterine infection andinflammation, but perinatal hypoxia or ischemia is the most common. Todaydiagnosis mainly relies on the clinical manifestations and imagingexaminations such as ultrasound and magnetic resonance imaging (MRI), andthere are no objective biochemical diagnostic indicators to reflect thepathogenetic conditions.Umbilical cord blood HIF-1a (Hypoxia induciblefactor1a, HIF-1a) is the global regulatory factor of hypoxia. It widelyparticipates in specific response induced by hypoxia in mammalian cells andplays a pivotal role in gene expression regulation induced by hypoxia.Theexpression of HIF-1a increased in1hour and peaked in48-72hours underconditions of hypoxia or ischemia in mice’ brain tissues. The subordinateVEGF (vascular endothelial growth factor, VEGF) is the main regulator ofpromoting the formation of new blood vessels and the activation of thesetarget genes protects the hypoxic tissues. Animal experiments have confirmedthat the hypoxia or ischemia in brain tissues of newborn mice can make theVEGF protein significantly increase in6~24hours which shows VEGF playsa role in the expandation of tubes and formation of small blood vessels.To further expounds HIF-1a possible mechanism in the premature infant braininjury incidence, HIF-1a, VEGF synergy and protection mechanism of VEGFfor the damaged central nervous system as well as to provide experimentalbasis for clinical diagnosis and treatment, by examining PH value, HIF-1a andthe content of VEGF in umbilical cord blood of104premature infants withperinatal hypoxia related risk factors, we want to explore:(1) The relationshipbetween perinatal hypoxia related high risk factors and the premature infantbrain injury.(2) The relationship between Umbilical cord blood PH andasphyxia and brain injury in preterm neonates.(3) The relationship betweenchange of Umbilical cord blood HIF-1a, VEGF level and occurrence and itsdegree of the brain injury.Methods: Choose104cases of premature infants with perinatal hypoxiarelated risk factors that are born from March2012to December2012in theFourth Hospital, Hebei Medical University. Perinatal hypoxia related riskfactors include pregnancy-induced hypertension syndrome, maternal anemia,abnormal placenta, umbilical cord abnormality and intrauterine distress.According to clinical manifestations and ultrasound, the diagnosis and gradingare:70cases with no brain injury and34cases with brain injury among whichthere are23cases with mild brain injury and11cases with moderately severebrain injury. The premature infants’ gender, gestational age, weight, etc arerecorded to compare and analyze along with the relevant clinical data. Beforenewborn breathes on their own, immediately draw1ml of umbilical arterialblood with heparin anticoagulation syringe to do blood gas analysis, andrecord Apgar score within1minute. In addition, draw3ml of subject’sumbilical arterial blood and centrifuge (4℃,3000r/min,15min); draw1mlof serum and store it under-80℃in refrigerator to detect the levels of HIF-laand VEGF by enzyme linked immunosorbent method. Use software SPSS16.0to statistically analyze experimental data and record measurement databy mean plus or minus standard deviation. Use one-way ANOVA forone-to-one comparison, and further significant difference, LSD for pair wisecomparison and Dunnett’s method for comparison of unequal various means. Count data by chi-square test. Use bilateral inspection to do statisticalprocessing and take α=0.05, P <0.05as the difference of statisticalsignificance.Results:1The relationship between hypoxia related risk factors and brain injury inpremuture infantsPremature perinatal hypoxic brain injury related high-risk factors analysisshows the rate of pregnancy hypertension syndrome and fetal intrauterinedistress increases significantly that shows a statistical significance (P <0.05)in comparison with the premature group without brain injury. And there is nosignificant difference on the rate of abnormal umbilical cord, placentalabnormalities and maternal anemia incidence which shows no statisticalsignificance after statistics analysis.2The relationship between gestational age and birth weight and brain injury inpremuture infants2.1Early preterm group has a significantly higher brain injury incidence rate40.98%than20.93%of late preterm group. By chi-square test, the differencewas statistically significant (P <0.05).2.2Low birth weight group has a significantly higher brain injury incidencerate40.68%than18.46%of very low birth weight group. By the chi-squaretest, the difference was statistically significant (P <0.05).3The Relationship between Umbilical cord blood PH and PrematureAsphyxia and Brain InjuryUmbilical cord blood PH of asphyxia group is (7.13±0.03）which issignificantly lower than （7.30±0.04）of group wi他hout asphyxia. The PH ofbrain injury group is（7.05±0.06）which is also much lower than（7.30±0.05）of group without brain injury. By the T test analysis, the difference wasstatistically significant (P <0.05).4The Relationship between Umbilical cord blood HIF-1a, VEGF andPremature Brain Injury and Its DegreeUmbilical cord blood HIF-1a (54.25±19.15) and VEGF (201.63±31.86) of brain injury group are significantly higher than no brain injury group. By Ttest, difference is significant (P <0.05). And as the degree of brain injuryaggravates, the level of HIF-1a increases accordingly. The rate is (42.96±9.57)in mild brain injury group and (77.85±10.13) in moderately severe brain injurygroup which are significantly higher than that in no brain injury group(P <0.05); the expression of HIF-1a in moderately severe brain injury group isobviously higher than mild brain injury group (P <0.05); And with the degreeof brain injury aggravates, the level of VEGF significantly decreases as theexpression of VEGF (167.95±8.74) in moderately severe brain injury group issignificantly lower than the mild brain injury group (217.73±25.49)(P <0.05).5Comparison between Umbilical cord blood PH and Serum HIF-1a, VEGF inPremature Brain Injury EvaluationUse ROC (Receiver operating characteristic curve, the ROC) curve tocompare sensitivity and specificity of levels of umbilical cord blood PH andserum HIF-1a, VEGF in premature infant brain injury group.Unit area under ROC curve: PH> HIF-1a>VEGF;Sensitivity: VEGF> HIF-1a> PH;Specificity: PH> HIF-1a> VEGF.Conclusion:1The incidence rate of pregnancy-induced hypertension syndrome andfetal intrauterine distress in premature brain injury group is obviously higherthan that of group without brain injury. Pregnancy-induced hypertensionsyndrome and fetal intrauterine distress is absolute high risk factors of and areclosely related with premature infant brain injury.2Umbilical cord blood PH decreases significantly in the prematureinfant brain injury group which prompts umbilical cord blood PH value can bea diagnosis index of premature infant brain injury.3HIF-1a level in premature brain injury group is obviously higher thanthat in group without brain injury and the degree changes consistently with thebrain injury degree. HIF-1a level in moderately severe brain injury group is significantly higher than that in mild group which prompts HIF-1a levelmeasurement is of a certain value in predicting preterm brain injury, injurydegree and the prognosis.4VEGF level in premuture brain injury group increases significantly andthe degree doesn’t change consistently with the brain injury degree. VEGFlevel in moderately severe brain injury is lower than that in the mild braininjury group which prompts VEGF may be involved in the repair of prematureinfant brain injury and it can be used as a judgement index of brain injurydegree and prognosis.