【作者】 李冰；

【导师】 张茜；

【作者基本信息】 郑州大学 ， 儿科学， 2015， 硕士

【摘要】 背景及目的颅内出血(intracranial hemorrhage,ICH)为新生儿期常见的一种引起颅脑损伤的疾病,往往多见于早产儿,并且与胎龄有关,胎龄愈小,发病率愈高,严重者通常遗留有神经系统并发症及后遗症,如脑积水、脑性瘫痪、癫痫、视听障碍、智力运动发育落后等。急剧恶化性出血患儿可在短时间内死亡。近几年来,围产新生儿医学技术不断发展,并逐步提高,但因早产儿、极低或超低出生体质量儿的增加,使ICH的发生率有增无减,其发生与这一阶段早产儿胚胎生发基质的组织解剖结构特点和多种围产期高危因素有关。出血后继发脑积水是新生儿ICH后的一个严重并发症,发生率为25%~35%,主要发生在Ⅲ级或Ⅳ级ICH,表现为双侧侧脑室及第三、第四脑室的进行性增宽。脑积水通常发生在出血后2~3周,临床上常表现为头围进行性增大、前囟增大或隆起、颅缝分离,严重的颅内高压可出现双眼“落日征”等,诊断主要依靠超声、CT、MRI等影像学检查,而头颅超声以其特有的优点,成为新生儿脑积水的主要诊断方法。目前脑积水的治疗以手术治疗为主,但疗效欠佳,预后较差,存活下来的大部分脑积水患儿存在不良的神经系统预后,严重影响了我国的整体人口质量。早产儿颅内出血后继发脑积水的发生与多种影响因素有关,并且常常由多个致病因素共同作用而引起。本研究通过搜集整理入住郑州大学第一附属医院新生儿科、床旁头颅超声示存在ICH的早产儿的临床资料,探讨早产儿颅内出血后继发脑积水的相关影响因素,并对脑室增宽程度进行动态监测,为预防或治疗出血后继发脑积水提供较多的临床经验。材料和方法1研究对象与分组选取2012年6月至2014年9月期间,入住郑州大学第一附属医院新生儿科床旁头颅超声示存在ICH的新生儿病例,并对ICH进行分级。将入选的新生儿按出血后是否继发脑积水分为两组,即脑积水组和非脑积水组。2临床资料收集记录入选患儿的基本信息、围生期因素、实验室检查结果,包括性别、胎龄(GA)、出生体质量(BW)、Apgar评分(1分钟、5分钟)、孕母妊娠期合并症(妊娠合并高血压、糖尿病)、新生儿呼吸窘迫综合征(RDS)、心力衰竭(HF)、动脉导管未闭(PDA)、新生儿感染、心衰标志物(血浆NT-Pro BNP)测定、血气分析、凝血功能、血小板、颅内出血分级、测量脑室大小的各项指标(侧脑室前角宽度、体部最宽纵径、后角斜径、后角比值、第三、第四脑室宽度)。3统计学分析用Excel软件建立数据库,应用SPSS 17.0统计学软件进行数据分析。符合正态分布的计量资料以均数±标准差(x±s)表示,两组间比较采用两独立样本t检验,多组间比较采用单因素方差分析;计数资料以百分比和率来表示,组间比较采用c2检验。多因素分析采用二分类Logistic回归分析。结果1一般情况共统计病例资料1052例,符合本次纳入标准的研究对象共244例(其中Ⅲ级出血212例,Ⅳ级出血32例)。脑积水组59例,男43例、女16例,胎龄(29.6±2.4)周(范围:25.4~34.0周),出生体质量(1230±550)g(范围:560~3100g);非脑积水组185例,男112例、女73例,胎龄(32.0±1.6)周(范围:27.0~34.0周),出生体质量(1650±409)g(范围:760~3000g)。两组间性别比的差异无统计学意义(c2=2.94,P=0.086);两组间胎龄(t=8.806,P<0.001)和出生体质量(t=6.275,P<0.001)的差异均有统计学意义。2早产儿出血后继发脑积水相关因素单因素分析经单因素分析,结果显示,胎龄<32周、出生体质量<1500g、重度窒息、RDS、新生儿感染、HF(血浆NT-Pro BNP≧35000pg/ml)、PDA、酸中毒(PH值<7.2或BE值<-6)、血小板减少(<100×109/L)、凝血功能异常(PT、APTT延长或FIB降低)、Ⅲ级或Ⅳ级颅内出血11个因素,在脑积水组与非脑积水组之间的差异有统计学意义(P<0.05),而性别(男)、孕母妊娠合并症2个因素与早产儿继发脑积水的发生无相关性(P>0.05)。3早产儿出血后脑积水相关因素多因素Logistic回归分析将单因素分析中具有统计学意义的变量引入多因素Logistic回归分析,结果显示,胎龄<32周、酸中毒(PH值<7.2或BE值<-6)、Ⅳ级颅内出血、Ⅲ级颅内出血、重度窒息、凝血功能异常(PT、APTT延长或FIB降低)、血小板减少(<100×109/L)为早产儿出血后继发脑积水的高危因素(P<0.05),其OR值分别为20.462、11.686、10.004、6.914、5.803、3.379、1.758。4两组患儿侧脑室增宽程度比较(以后角比值为例)脑积水组侧脑室的增宽程度在出血后第2~3周时达到高限,而非脑积水组的侧脑室增宽程度随时间变化的趋势不明显。双侧侧脑室进行性增宽与脑积水的发生紧密相关。结论1胎龄<32周、出生体质量<1500g、重度窒息、RDS、新生儿感染、HF、PDA、酸中毒、血小板减少、凝血功能异常、Ⅲ级或Ⅳ级颅内出血与早产儿颅内出血后继发脑积水具有相关性。2胎龄<32周、酸中毒、重度颅内出血(Ⅳ级或Ⅲ级)、重度窒息、凝血功能异常、血小板减少为早产儿颅内出血后继发脑积水的高危因素。更多还原

【Abstract】 Background and ObjectiveIntracranial hemorrhage(ICH) is a common kind of disease which can caused serious brain damage in neonates,It is more common in premature infants,the smaller the gestational age,the higher the incidence rate.Those survivors often had different types and levels of neurologic sequelaes,such as Hydrocephalus,Cerebral palsy,Epilepsy,vision or audition disorder,Mental and Motor retardation,and so on.The sharply deterioration can result in death in a short period of time.In recent years,along with the development and improvement of medicine technology of Perinatal,But,As a result,the incidence of intracranial hemorrhage continued unabated,because of the increased prematurity of very low birth weight or extremely low birth weight infants,The incidence rate of intracranial hemorrhage was associated with the anatomic characteristics of Nervous system and physiological features in premature infants and a variety of perinatal high risk factors. Hydrocephalus after intracranial hemorrhage was the most common and serious complication in neonates,especially in premature infants with intracranial hemorrhage,the incidence rate was 25%~35%,which mainly occured in the grade III or IV intracranial hemorrhage,it showed that the bilateral lateral ventricle,the third ventricle and the fourth ventricle were more and more broadened.The hydrocephalus was usually occurred in 2 ~ 3 weeks after intracranial hemorrhage in neonates,The primaryly clinical manifestations were:the increasingly enlargement of head circumference,the enlargement or bulge of bregmatic fontanel,the separation of cranial sutures and seriously increased intracranial pressure could caused sunset syndrome in patients’ both eyes,and so on.Diagnosis mainly depend on imaging examination,such as Ultrasound,CT,MRI,and so on,Ultrasound with its peculiarly advantages was becomed the main diagnostic method in neonatal hydrocephalus.At present,the treatment for hydrocephalus still remained very difficult,and the total efficacy was poor,Therefore,the neurodevelopmental prognosis was poor too,they often remained different types and levels of neurologic sequelaes who had survived in the end,which was a grievous hidden trouble to influence on the quality of the whole population in our country.The process of the occurrence of hydrocephalus after intracranial hemorrhage in premature infants may be associated with various affected factors.By collecting the clinical datas of the neonates who were admitted to the Neonatology after birth were enrolled of the First Affiliated Hospital of Zhengzhou University of Neonatology,and bedside cranial ultrasound showed the presence of intracranial hemorrhage in premature infants in this study,The purpose is to analysis the factors which related to intracranial hemorrhage secondary to hydrocephalus in preterm infants,And measure the ventricle size of grade Ⅲ or Ⅳintracranial hemorrhage for dynamic analysis,so that providing more clinical experiences for the prevention or treatment of intracranial hemorrhage secondary to hydrocephalus. Materials and methods 1 The research objects and groupingThe present study was conducted during the period of 2012 June to 2014 Sep,the premature infants who were admitted to the Neonatal Intensive Care Unit(NICU) of the First Affiliated Hospital of Zhengzhou University after birth were enrolled and Bedside cranial ultrasound showed intracranial hemorrhage.Intracranial hemorrhage were divided into 4 levels.They were divided into two groups according to whether secondary to hydrocephalus after intracranial hemorrhage,Preterm infants with hydrocephalus were enrolled as hydrocephalus group,and preterm infants without hydrocephalus were simultaneously enrolled as non-hydrocephalus group. 2 Clinical data collectionRecording the relevant clinical data of the patient with intracranial hemorrhage as basic information,perinatal factors,and laboratory test results of the patients who were selected,including gender,gestational age(GA),birth weight(BW),the Apgar score,pregnancy complication(hypertension and diabetes mellitus),respiratory distress syndrome(RDS),heart failure(HF),patent ductus arteriosus(PDA),neonatal infection,the biomarker of HF(the plasma N-terminal pro-brain natriuretic peptide,NT-pro BNP),blood gas analysis,blood coagulation function,platelet,grade of intracranial hemorrhage,the indicators of ventricular size(anterior horn of lateral ventricle width,ventricular body diameter,posterior horn of lateral ventricle oblique diameter,the ratio of cornu posterius ventriculi lateralis,the third ventricle and the fourth ventricle).Those neonates with incomplete data of clinical and/or accessory tests were excluded at last.3 Statistical analysisThe establishment of a data base with Excel software,Applying the statistical software of SPSS version 17.0 for data analysis.The quantitative data accord with normal distribution can be expressed with mean and standard deviation(x±s),using independent samples t test for the gestational age and birth weight comparation between the two groups,the one-way analysis of variance(ANOVA) was performed in multiple groups,the count data expressed as percentage and rate,comparison among groups used Chi-square test,Single factor analysis and multivariate Logistic regression analysis were used to analysis the relevant factors for secondary to hydrocephalus after intracranial hemorrhage in neonates. Result1 General resultA total of 1052 cases were collected in this study,the total of premature infants which conformed to the inclusion criteria was 244 cases(Among of the 244 cases,grade III of ICH was 212,32 cases were grade IV of ICH).The cases of hydrocephalus group was 59(43 males and 16 females),The mean of gestational age was(29.6 ± 2.4) weeks(range 25.4 to 34.0weeks),the mean of Birth weight was(1230 ±550) g(range 560 to 3100g).185 cases were included in the non-hydrocephalus group,(112 males and 73 females),The mean of gestational age was(32.0 ±1.6) weeks(range 27.0 to 34.0 weeks),the mean of birth weight was(1650 ±409) g(range 760 to 3000g).The difference of sex ratio between the hydrocephalus and non-hydrocephalus groups had no statistical significant(c2=2.94,P=0.086),the difference of gestational age(t=8.806,P<0.001)and birth weight between(t=6.275,P<0.001)the two groups had statistical significant. 2 Single factor analysis of the related factors of hydrocephalus after hemorrhage in premature infantsIn this study,Single factor analysis showed that 11 factors were related with hydrocephalus after intracranial hemorrhage in premature infants,including gestational age<32 weeks,birth weight <1500g,severe asphyxia,RDS,neonatal infection,heart failure,PDA,acidosis(PH<7.2or BE<-6),thrombocytopenia(<100×109/L),coagulation abnormalities(PT or APTT prolonged or FIB decreased),grade Ⅲ or Ⅳ of intracranial hemorrhage,the difference of those factors between the two groups had statistical significant(all P <0.05,c2=6.59 ~ 106.16).but gender(male) and pregnancy complication(hypertension and diabetes mellitus),the two factors had nothing to do with the occurrence of hydrocephalus in premature infants(all P >0.05).3 Multivariate Logistic regression analysis of the related factors of hydrocephalus after hemorrhage in premature infantsMultivariate Logistic regression analysis indicated that gestational age <32.0 weeks,acidosis(PH<7.2 or BE<-6),grade Ⅳ of ICH,grade Ⅲof ICH,severe Resultasphyxia,coagulation abnormalities(PT or APTT prolonged or FIB decreased),thrombocytopenia(<100×109/L) were its risk factors for hydrocephalus after intracranial hemorrhage in premature infants(all P <0.05) and the odds ratio(OR) values were 20.462,11.686,10. 004,6.914,5.803,3.379,1.758.4 the comparison of lateral ventriculomegaly degree of two groups(the ratio of cornu posterius ventriculi lateralis)According to the grade Ⅲ or Ⅳ of intracranial hemorrhage,the ventricle size of hydrocephalus group was higher than the non-hydrocephalus group and the broadening of lateral ventricle had achieved the high limit in the first 2~3 weeks, Rather than the non-hydrocephalus,the variation tendency along with the time had no obviously changed,its difference has statistical significance.The Bilateral ventricles became wide progressively was closely related to the occurrence of hydrocephalus. Conclusion1 gestational age<32 weeks,birth weight <1500g,severe asphyxia,cesarean section,RDS,neonatal infection,heart failure,PDA,acidosis,thrombocytopenia, coagulation abnormalities,grade Ⅲ or Ⅳ of intracranial hemorrhage were related to hydrocephalus after intracranial hemorrhage in premature infants.2 gestational age <32.0 weeks,acidosis,severe intracranial hemorrhage(grade Ⅲor Ⅳ),severe asphyxia,coagulation abnormalities,thrombocytopenia were its highly risk factors for hydrocephalus after intracranial hemorrhage in premature infants.更多还原