The Effect Of The Recombinant Human Erythropoietin On Long-term Neurological Outcomes In Very Preterm Infants With Intraventricular Hemorrhage

Intraventricular hemorrhage(IVH)is one of the most common complications in preterm infants,which occurs inversely according to birth weight and gestational age.The incidence of IVH in preterm infants with a gestational age <32 weeks or birth weight <1500g is up to 40%~50%.Around 90% of the PVH-IVH occurres within 72 hours after birth(50% within 24 hours,25% between 34 and 48hours)and 20%~40% of the PVH-IVH deteriorated within one week after birth.With the development of medical technology and nursing concept,the last few decades has witnessed an increase of survival rate.However,the incidence of complications related with intracranial hemorrhage has not been decreased.It was reported that 2.9% of the premature infants were diagnosed with severe intracranial hemorrhage.Nearly 60% of preterm infants with III-IV IVH develop severe neurodevelopmental outcomes.However,no specific treatment or drug for IVH infants has been approved efficently.Intracranial pressure,blood flow of cerebral infarction and maturity of the embryo germinal matrix microvessel were risk factors that accounting for the occurrence of IVH.Hypoxia/Ischemia induces hypoxemia and hypercapnia in newborns and thus leads to brain blood vessel dilatation,which induces the capillary fracture and intracerebral hemorrhage.All the factors that may cause fetal or neonatal hypoxic ischemia during prenatal,labor and postpartum may lead to severe IVH in the newborn.Therefore,to explore the risk factors of severe IVH in very premature infants and take corresponding preventive measures in time can effectively reduce the incidence of severe IVH.Erythropoietin(EPO),which is commonly used for anemia in preterm infants,is a promising drug with neuroprotective effect.Animal experiments showed that EPO could play neuroprotective effects in preterm infants.EPO can improve neurodevelopmental outcomes in preterm infants with III-IV IVH in a few clinical trials.However,it is still controversial with regard to its effect in preterm infants with I-II IVH.The dose and course of EPO is still uncertain.Part I:Recombinant Human Erythropoietin Improves Neurological Outcomes in Very Preterm Infants with Intraventricular HemorrhageObjectiveTo evaluate the long-term neuroprotective effect of repeated low-dose rh EPO in very preterm infants with IVH.MethodsBetween July 2014 and April 2016,preterm infants ≤32 weeks gestational age who were diagnosed with IVH within 72 hours after birth in NICU were included in our study.Preterm infants were randomly assigned to receive rh EPO(500IU/kg)or placebo(equivalent volume of saline)intravenously within 24 h after diagnosis and then once every other day for 2 weeks.The primary outcome was death or neurological disability assessed at 18 months of corrected age.ResultsA total of 319 subjects were included in the study,with 155 in rh EPO group and 164 in placebo group.At 18 months of corrected age,neurological disability occurred in 32 of 130 very preterm infants(24.6%)in the placebo group and in 20 of 137 very preterm infants(14.6%)in the rh EPO group(OR = 0.52,95% CI [0.28–0.97],p =0.039).The rate of MDI<70 was reduced in the rh EPO group compared to the placebo group(8.8% vs 20.8%,OR = 0.37,95% CI [0.18–0.76],p=0.005).The mortality rate of preterm infants was of no significant difference between the two groups.Subgroup analyses showed that rh EPO improved long-term neurological outcomes for infants in boys and girls,and in gestational age of 28-296/7.ConclusionRepeated low-dose rh EPO treatment decreases the risk of long-term neurological disability in very preterm infants with IVH with no obvious adverse effects.Part II: Analysis of Risk Factors for Severe Intraventricular Hemorrhage in Extremely Premature InfantsObjectiveTo explore the main risk factors of severe intraventricular hemorrhage(IVH)in extremely premature infants and provide evidence for clinical prevention.MethodsFrom July 2014 to October 2016,1049 premature infants were treated at NICU in Third Affiliated Hospital of Zheng Zhou University and underwent cranial ultrasound examination within 72 hours after birth were analyzed retrospectively.The possible high risk factors of severe IVH were analyzed by univariate and multivariate logistic regression analysis,then showed the risk factors of severe IVH in extremely preterm infants(EPI).ResultsIn univariate Logistic analysis of severe IVH in EPI,there were 7 factors had statistical significance,including gestational age,birth weight,boys,mechanical ventilation,severe asphyxia,III-IV RDS,cesarean section.In multivariate univariate logistic analysis,there were four factors that had statistical significance,including boys,severe asphyxia,mechanical ventilation,cesarean section.Subgroup analysis showed that severe asphyxia was significantly in subgroup of <28 weeks of gestational age and birth weight <1000g,while mechanical ventilation was statistically significant in girl,older gestational ages and larger birth weight.ConclusionsSevere asphyxia was the independent risk factor of severe IVH in boys,gestational age < 28 weeks and birth weight <1000g,while in girls and older gestational ages and larger birth weight,the main independent risk factor was mechanical ventilation.According to different gestational age,body weight,sex with different risk factors and taking preventive measures to reduce the incidence of severe IVH.