The Effect Of Early Application Of Recombinant Human Erythropoietin On White Matter Development And Neurological Prognosis In Preterm Infants

Background and ObjectiveThere is a higher incidence of preterm births,foreign data show that global preterm birth accounts for 5% to 15% of the total number of births,multicenter studies show that the incidence of premature labor in China is 8%.With the development of perinatal medicine and the improvement of neonatal intensive care level increased,the survival rate of the preterm infants significantly improved.But the survival of preterm infants,especially very early and extrmetely early preterm infants often leave different degrees of neurological sequelae,such as audio-visual disorders,learning and behavioral disorders,cerebral palsy and so on,which make the quality of survival in preterm infants reduced.The main manifestations of brain injury in premature infants are intracranial hemorrhage and cerebral white matter damage.At present,there is no effective neuroprotective therapy for brain injury in premature infants except for symptomatic support treatment.The prevention and treatment of brain injury in premature infants is increasingly becoming a hot topic in clinical research.Erythropoietin(EPO),as a hematopoietic cell factor,was initially widely used to prevent anemia in preterm infants.Later,many experimental studies have confirmed that EPO has a neuroprotective effect on the brain.In recent years,clinical trials have confirmed that recombinant human erythropoieti(rhEPO)has been used in the treatment of hypoxic ischemic encephalopathy(HIE)in term infants and early intervention for very early preterm infants.It has the effect of improving the long-term neural prognosis,and the clinical application is safe.At present,the effect of EPO on the brain development of preterm infants is not yet evaluated from the perspective of morphology.Diffusion tensor imaging(DTI)is a new imaging method developed based on diffusion weighted imaging(DWI)in recent years to study the molecular diffusion characteristics,which can describe the direction and development of white matter noninvasively.DTI commonly used fractional anisotropy(FA)is positively correlated with the fiber compactness,integrity and parallelism of myelin sheath,and can quantitatively assess myelin sheath development and injury in white matter fibers.In this study,repeated low dose rhEPO was used to intervene early preterm infants,and the FA value of DTI was used to quantitatively evaluate the myelination of white matter and gray matter in preterm infants,and to investigate the effect of rhEPO on white matter development of preterm infants.The preterm infants included in the study were followed up to further study the effect of rhEPO on neuroprognosis of preterm infants.MethodsA total of 120 preterm infants with a gestational age of ?32 weeks and a birth weight of <1500g and within 24 hours after birth were selected as research objects.All these infants were hospitalized in the NICU of the Third Affiliated Hospital of Zhengzhou University during the period from August 2016 to August 2017.These objects were divided into rhEPO group and the control group by random number table method,81 cases were included in the study.Among them,42 cases were administered with rhEPO during their hospital stays as rhEPO group.The treatment started within 72 hours after birth(500IU/kg by intravenous injection,every other day and last 2 weeks).39 cases were administered with the same volume of saline injection(same course and usage as rhEPO group)as the control group.The two groups of the preterm infants were performed head MRI,DWI and DTI at the corrected gestational age of about 35-37 weeks.Fractional anisotropy(FA)were measured at the same regions of interest in the two groups.The two groups of surviving preterm infants were performed neonates behavioral nerve assessment(NBNA)at the corrected gestational age of 40 weeks,and performed children's development center of China(CDCC)at the corrected gestational age of 3 months and 6 months.Results1.Head routine MRI sequence and DWI sequence:the rhEPO group with 6 cases of intracranial hemorrhage(ICH),1 cases of periventricular leukomalacia(PVL),5 cases of focal cerebral white matter damage(CDWD),2 cases of extensive CDWD;the control group with 7 cases of ICH,2 cases of PVL,6 cases of focal CDWD,2 cases of extensive CDWD;there was no difference in the incidence of various types of brain damage between the two groups preterm infants(P > 0.05).2.DTI sequence:compared with the control group,the rhEPO group showed higher FA values at the site of the posterior limb of the internal capsule,frontal white matter,the splenium of corpus callosum,and occipital white matter(P < 0.05),and there was no significant difference in FA values at the parietal white matter,thalamus,lenticular nucleus and caudate nucleus between the two groups(P > 0.05).3.NBNA score:the rhEPO group NBNA scores were higher than that of control group at the corrected gestational age of 40 weeks(P < 0.05).4.CDCC score:the scores of mental development index(MDI)and psychomotor development index(PDI)in rhEPO group were higher than those in control group at the corrected gestational age of 3 months and 6 months.ConclusionsThe early application of recombinant human erythropoietin has neuroprotective effect on white matter development in preterm infants,and can improve the neurological prognosis in preterm infants.