早产儿脑白质损伤的发生、预后与病因探讨

目的：了解早产儿脑白质病变的类型、预后和发病的高危因素。方法：通过影像学检查，观察了64例早产儿脑室旁白质损伤的发生与转归，对这些患儿进行了远期智能发育水平的测评，并对可能导致早产儿脑或局部脑组织供氧供血障碍，造成脑室旁白质软化的围产期高危因素进行了分析，包括相关的母亲孕期合并症、新生儿早期疾病。结果：本组早产儿脑室旁白质病变程度不同：(1)脑室旁白质软化18例，其中多灶性病变6例，局灶性病变12例。(2)脑室旁白质持续存在强回声8例。(3)脑室旁白质一过性影像异常38例。46例随访结果显示，6例广泛性和6例局灶性脑室旁白质软化病例中，DQ≤75的发生率分别为100％和33％。经Logistic多元逐步回归分析，本组病例中颅内出血伴脑室扩大与脑室旁白质病变的发生关系更为密切，母亲孕期合并症存在与否，在早产儿脑室旁白质病变的发生中差异有显著性。结论：早产儿脑室旁白质损伤，尤其是脑室旁白质软化对小儿预后危害严重，多种围产期高危因素可导致发病，颅内出血伴脑室扩大是重要的发病因素。     

围产期脑白质损伤与后期神经纤维发育的关系

目的 应用影像学方法初步探讨围产期脑白质损伤与后期神经纤维发育的关系. 方法 对12例围产期有脑白质损伤的新生儿(早产儿8例,足月儿4例)早期应用超声,后期采用MRI弥散张量成像(DTI)技术进行白质三维重建,并进行部分各向异性(FA)值测定,同时结合临床资料,分析围产期脑白质损伤对后期神经纤维发育的影响及其与临床的对应关系. 结果 早期超声显示脑白质损伤程度重者后期DTI三维重建图像显示神经纤维数量减少明显,向皮层投射减少.定量分析表明,半卵圆中心、额叶白质、枕叶白质、内囊前肢、内囊后肢的FA值在重度脑损伤的患儿分别为0.32±0.08,0.24±0.16,0.27±0.18,0.32±0.06,0.47±0.14,同一部位均较同期正常者(分别为0.46±0.03,0.39±0.02,0.45±0.05,0.50±0.05,0.65±0.02)和轻度脑损伤的患儿(分别为0.43±0.07,0.36±0.09,0.37±0.17,0.39±0.11,0.61±0.05)低(P<0.05);轻度脑损伤患儿的FA值除内囊前肢外多与同期正常者相近(P>0.05).不同部位的脑损伤影像表现随临床症状轻重有不同,且神经系统体征定位与影像定位有一致性. 结论 DTI结果与早期白质损伤程度相符,与临床神经定位一致,该技术对于围产期脑白质损伤的早期诊断和后期神经纤维发育的评价有重要意义.     

早产儿生后早期头颅磁共振成像表现与智力及心理运动发育预后的关系

目的 探讨早产儿生后早期头颅磁共振成像异常表现(脑白质损伤、脑室扩大及脑室出血)与其12月龄时智力及心理运动发育预后的关系. 方法 2007年3月15日至2011年4月12日,在解放军第二○二医院住院治疗的早产儿122例在出生8～14 d行头颅磁共振成像检查.患儿12月龄时成功随访其中的115例,采用智力发育指数和心理运动发育指数评估其神经发育预后,智力发育指数＜70分为智力发育障碍,～84分为边缘障碍,～114分为正常;心理运动发育指数＜70分为心理运动发育障碍,～84分为边缘障碍,～114分为正常.采用方差分析、LSD两两检验及Kruskal-Wallis H检验进行统计学分析. 结果 122例早产儿中男69例,女53例,中位胎龄32周(28～36周),中位出生体重2050 g(1270～3110 g).完成随访的115例早产儿中,智力发育障碍者24例,边缘障碍32例,另59例正常;心理运动发育障碍者20例,边缘障碍33例,另62例正常.24例智力发育障碍早产儿平均胎龄[(28.7±1.7)周]、出生体重[(1520.1±44.8)g]和1 min Apgar评分[(5.5±0.8)分]均显著小于智力发育正常的早产儿[n=59,(33.5±2.2)周、(2240.4±47.1)g和(7.1±o.8)分],而平均机械通气时间显著延长[(20.4±5.8)d与(5.6±2.7)d],差异均有统计学意义(t分别为2.37、2.49、2.13和2.44,P均＜0.05).20例心理运动发育障碍早产儿平均胎龄[(27.9±1.4)周]、出生体重[(1515.6±43.7)g]、1 min Apgar评分[(5.6±0.5)分]均显著小于心理运动发育正常的早产儿[n=62,(33.2±2.4)周、(2264.3±42.5)g和(7.2±0.6)分],而平均机械通气时间显著延长[(18.2±4.7)d与(5.3±2.2)d],差异均有统计学意义(t分别为2.28、2.52、2.09和2.38,P均＜0.05).13例脑白质重度损伤的患儿中11例发生智力发育障碍,9例发生心理运动发育障碍;11例中/重度脑室扩大的患儿中7例发生智力发育障碍,6例发生心理运动发育障碍.脑白质损伤程度和脑室扩大程度越重,智力发育障碍的发生率越高(H分别为16.23和14.33,P均＜0.05),心理运动发育障碍的发生率也越高(H分别为18.63和12.69,P均＜0.05). 结论 脑白质损伤在早产儿中较为常见,早产儿脑白质损伤及脑室扩大程度越重,其智力及心理运动发育预后越差.     

早产儿脑白质损伤MRI 诊断及其神经发育结局

脑白质损伤（white matter damage,WMD）是指胎龄24～35周的早产未成熟儿,由于血管损伤或炎症反应等多种因素导致的大脑白质损伤。受累部分主要分布于脑室旁白质,包括深层脑白质的局灶坏死和中央脑白质的弥漫性病变。WMD是早产儿脑损伤的最常见形式,而脑室周围白质软化（periventricular leukomalacia,PVL）则为WMD的最严重表现。近年来,极低出生体重儿（VLBWI）和超低出生体重儿（ELBWI）成活率日益提高,脑瘫的发生率并没有按预想的减少,反而随着存活患儿胎龄的减少而增加。在美国,存活的VLBWI,约10%出现脑瘫,25%～50%伴有认知障碍、行为缺陷及轻度运动障碍,而在该类患儿中,MRI对不同程度WMD的患儿诊断率高达50%。由此可见,WMD已成为影响低出生体重儿远期神经发育结局的主要疾病。但在出生早期,由于早产儿WMD缺乏特异的神经系统症状及体征,甚至没有任何临床表现,故其诊断必需依赖于影像学检查。     

404例早产儿头颅B超检查结果及临床分析

目的调查新疆医科大学第一临床学院住院早产儿脑损伤发生率及影响因素。 方法对2003 08—2005 10新生儿科收治的404例早产儿应用ABR4000S/L B超诊断仪在生后3~7d内常规进行床边头颅B超检查。 结果150例早产儿存在脑损伤，平均胎龄为(33.27±1.99)周；平均出生体重(1992.9±505.2)g。总的脑室内出血(IVH)发生率为35.1%(142/404)，脑室周围白质软化(PVL)的发生率为3.5%(14/404)，轻度和重度脑损伤发生率分别为23.5%(95/404)、13.6%(55/404)。胎龄越小，体重越低，脑损伤发生率越高，但与颅内出血程度无关。窒息程度与脑损伤程度密切相关。并发症肺透明膜病、呼吸暂停、呼吸衰竭、肺出血、低血糖、多器官功能损害及贫血与脑损伤程度有关。母妊高征、胆汁淤积、胎膜早破、胎龄小、出生体重低及HFOV治疗可使早产儿脑损伤发生率增高。 结论早产儿脑损伤的发生及严重程度与多因素有关，头颅B超可对早产儿脑损伤作出早期诊断，为早期干预提供依据。     

早产儿脑白质损伤的研究进展

随着新生儿医学的发展,早产儿的救治成功率明显提高,而神经系统后遗症的发生率却居高不下.早产儿脑损伤以脑白质损伤(white matter damage,WMD)为主.早产儿少突胶质细胞对损伤的易感性及各种内、外损伤因素共同作用是早产儿WMD的主要原因之一[1].早产儿WMD分为脑室周围白质软化(periventricular leukomalacia,PVL)和弥漫性脑白质损伤(diffuse white matter damage)[2].现就早产儿WMD的病因、发病机制、早期诊断方法及防治策略的研究进展进行综述.     

振幅整合脑电图评分系统评价新生儿脑发育的临床价值

随着新生儿重症监护技术的提高,新生儿特别是早产儿存活率显著提高,但在住院期间发生颅内出血、脑室周围白质软化(periventricular leucomalacia,PVL)、缺氧缺血性脑病(hypoxic-ischcmic encephalopathy,HIE)、惊厥,脑膜炎等并发症的危险性也显著增加,最终导致脑性瘫痪和神经发育异常.因此,在这一关键时期连续监测新生儿脑功能有助于识别发生脑损伤的高危儿和高危因素,防止脑损伤发生.     

孕母子(癎)前期、子(癎)对新生儿脑损伤及神经发育的影响

目的 研究孕母妊娠期合并子痫前期、子痫对新生儿脑损伤及远期神经发育的影响。方法 通过临床观察和动态颅脑影像学检查，观察子痫前期、子痫母亲所生265例新生儿脑损伤的情况，并对神经系统发育情况进行随访。结果 新生儿脑损伤发生率为63．0％。损伤类型主要是脑室旁白质损伤和缺氧缺血性脑病。母亲子痫前期、子痫的病情越重新生儿重度脑损伤的发生率越高，早发型重度子痫前期孕母的新生儿重度脑损伤的发生率（38．5％）明显高于晚发型（19．4％）（P〈0．05）。214例随访患儿中有56．1％出现了神经发育异常：严重神经发育异常发生率为3．3％；轻度神经发育异常发生率为17．3％；一过性神经发育异常发生率为35．5％。母亲子痫前期、子痫的病情越重小儿神经发育异常的发生率越高，重度脑损伤小儿神经发育异常的发生率（93．5％）明显高于轻度脑损伤者（66．7％）（χ^2=82．5，P〈0．01）。小儿神经发育异常的危险因素是孕母重度子痂前期（OR=4．37，95％CI1．67～8．35）和新生儿期重度脑损伤（OR=9．66，95％CI3．73～21．16）。结论 母亲子痫前期、子痫程度越重，其新生儿脑损伤和生长过程中神经发育异常发生率越高，早发型重度子痫前期孕母的新生儿重度脑损伤的发生率高于晚发型，重度子痫前期和重度脑损伤是小儿神经发育异常的危险因素。因此，对于子痫和子痫前期孕母所生新生儿要加强监测，早诊断、早干预以改善预后。     

超声灰度值测定诊断围产期脑白质损伤的作用

目的 探讨超声灰度值测定在围产期脑白质损伤早期定量评价中的价值。方法 对生后7d内超声诊断为脑白质病变的新生儿104例及对照组48例新生儿在生后早期进行常规颅脑超声检查，在超声影像定性判断基础上，应用医学图像分析软件测定侧脑室后角三角区脑白质的超声灰度值。病例组新生儿生后1个月内复查颅脑超声，记录白质回声强弱及有无囊腔；出院后3～6月龄时再次复查颅脑超声，记录白质容积改变、侧脑室的形态及囊腔变化；1.5～2岁时采用Gesell评分定量评价神经功能，分为正常和异常2类。采用受试者上作特性曲线分析新生儿期脑白质灰度值与后期神经系统发育的关系。 结果新生儿期重度损伤组脑白质平均灰度值为131.72±2.40，高于轻度损伤组(116.61±2.48)，轻度损伤组高于对照组（100.50±1.66），差异均有统计学意义（q分别=4.521和4.492，P均＜0.05）。受试者工作特性曲线分析显示，新生儿期脑白质灰度值＞114.37有助于诊断白质损伤，其敏感性0.721，特异性0.854;灰度值＞119.80有助于诊断重度脑白质损伤，其敏感性0.716，特异性0.776。随灰度值的增加，损伤后期出现脑白质容积减少及侧脑室扩大的比例增加，其中灰度值＞130者更易发生白质软化。新生儿期脑白质灰度值＜110的患儿在2岁前遗留神经系统发育异常的比例为5.0％，在灰度值110～120的患儿中比例为27.8％，在灰度值＞120的患儿为47.8％。 结论超声定量分析脑白质灰度值在围产期脑白质损伤的早期诊断中具有重要的实用意义，有助于早期判断白质损伤的结局和远期神经发育预后。     

炎症反应在早产儿脑室周围白质软化发病中的作用

早产儿脑室周围白质软化(periventricular leukomalacia,PVL)的病理牛理学涉及多种因素,其中可能包括遗传、血流动力学、代谢、营养、内分泌、毒物以及感染等机制.目前公认的主要有以下3种:(1)缺氧缺血性损伤;(2)由于脑血管不成熟以及局部血流自身调节功能发育缺陷而引起的脑灌注不足;(3)宫内感染及胎儿炎症反应.     

Can electronic fetal monitoring identify preterm neonates with cerebral white matter injury?

OBJECTIVE: Although preterm delivery occurs in only 10% of all births, these infants are at high risk for cerebral white matter injury and constitute a third of all cerebral palsy cases. Our objective was to estimate if electronic monitoring can identify preterm fetuses diagnosed with brain injury during the neonatal period. METHODS: In this case-control study, 150 consecutive neonates with ultrasonography-diagnosed cerebral white matter injury were matched by gestational age within 7 days to 150 controls with normal head ultrasonograms. Tracings were retrieved for 125 cases (83%) and 121 controls (81%) and reviewed by 3 perinatologists blinded to outcome. Vaginal (64 cases, 72 controls) and cesarean deliveries (61 cases, 49 controls) were analyzed separately. RESULTS: There was no difference in baseline heart rate, tachycardia, bradycardia, short-term variability, accelerations, reactivity, number or types of decelerations, or bradycardic episodes between cases and controls in either the vaginal or cesarean delivery groups. For the 6 neonates with metabolic acidosis severe enough to increase the risk for long-term neurologic morbidity, there was a significant increase in baseline amplitude range less than 5 beats per minute; however, its positive predictive value in predicting severe metabolic acidosis was only 7.7%. Increasing late decelerations were associated with decreasing umbilical arterial pH and base excess, but were not significantly different in the acidosis and control groups (1.0 +/- 1.8, 0.55 +/- 1.23 late decelerations per hour, P = .39). CONCLUSION: Although decreased short-term variability and increased late decelerations are associated with decreasing umbilical arterial pH and base excess, electronic fetal monitoring is unable to identify preterm neonates with cerebral white matter injury.     

Brain growth in preterm infants is affected by the degree of growth restriction at birth

Abstract

Objective: Documentation of examination of brain structural development by magnetic resonance imaging (MRI) beyond the neonatal period is scarce for both preterm and small for gestational age (SGA) infants.

Aim: To investigate structural brain development during infancy in preterm children born SGA by MRI.

Methods: A total of 205 preterm infants, 139 appropriate for gestational age (AGA) and 66 SGA, of which 33 had birth weight (BW)?<?3rd percentile and 33 had BW 3rd–10th percentile, were examined prospectively by brain MRI at the corrected age of 5 months. The total volume of the brain, ventricles and cerebellum, the area of vermis and corpus callosum, and the height of the pituitary, mesencephalon and pons were estimated on MRI.

Results: Brain volume was smaller in the SGA?<?3rd percentile infants, independent of other perinatal factors. Chronic lung disease was an independent predictor of low brain volume. Pituitary height was greater in SGA?<?3rd percentile than in AGA infants. The corpus callosum area was less in SGA?<?3rd percentile than in SGA of 3rd–10th percentile infants.

Conclusions: Preterm infants born SGA with BW?<?3rd percentile had differences in brain structural measurements at the corrected age of 5 months, compared with preterm AGA infants, which could have implications for their neurocognitive development.     

新生儿重症监护病房早产儿脑损伤危险因素分析

目的 调查新生儿重症监护病房(NlCU)早产儿脑损伤的发生情况并分析其高危因素.方法将2006年2月1日至2007年1月31日入住复旦大学附属儿科医院NICU的胎龄≤34周或出生体重≤2000 g的早产儿纳入研究.应用超声诊断仪对早产儿进行系列床边头颅B超检查.同时收集临床资料,分析早产儿脑损伤的发生率,用Logistic回归模型分析其危险因素. 结果 (1)328例早产儿完成系列头颅B超检查,141例(43.0%)发生脑室内出血(IVH),其中轻度101例,重度40例.9.8%的患儿(32/328)发生脑白质损伤(WMD).13.4%的患儿(44/328)发生持续脑室扩大.10.7%的患儿(35/328)在生后初次头颅B超筛查时即发现有颅内囊肿形成.(2)IVH组和WMD组患儿的出生体重和胎龄较未发病组低,差异有统计学意义(P<0.05).(3)Logistic回归分析提示出生体重、感染、小于胎龄儿、机械通气是IVH的独立危险因素.出生体重是WMD的独立危险因素. 结论 NICU早产儿脑损伤发生率较高.出生体重、感染、小于胎龄儿、机械通气是IVH的独立危险因素.出生体重是WMD的独立危险因素.     

Diffuse white matter injury and neurologic outcomes of infants born very preterm in the 1990s

Neurocognitive outcomes of infants born very preterm (less than 32 weeks gestation) remain a major concern in perinatal practice. Very preterm birth rates have increased, with enhanced survival since 1990. As focal brain lesions become less common, diffuse injury to both gray and white matter is now the primary focus for improving neurologic outcomes in survivors. Recent evidence supports preoligodendrocytes as the principal cellular target of diffuse white matter injury due to their susceptibility to hypoxic-ischemic and inflammatory insults. An understanding of their development and vulnerability can inform acute nursing care of very preterm infants.     

The near-term (late preterm) human brain and risk for periventricular leukomalacia: a review

Historically the major focus in neonatal neurology has been on brain injury in premature infants born less than 30 gestational weeks. This focus reflects the urgent need to improve the widely recognized poor neurological outcomes that occur in these infants. The most common underlying substrate of cerebral palsy in these premature infants is periventricular leukomalacia (PVL). Nevertheless, PVL also occurs in near-term (late preterm), as well as term, infants, as documented by neuroimaging and autopsy studies. In both very preterm and late preterm infants, gray matter injury is associated with PVL. In this review, we discuss the cellular pathology of PVL and the developmental parameters in oligodendrocytes and neurons that put the late preterm brain at risk in the broader context of brain development and injury close to term. Further research is needed about the clinical and pathologic aspects of brain injury in general and PVL in particular in late preterm infants to optimize management and prevent adverse neurological outcomes in these infants that, however subtle, may be currently underestimated.     

不同胎龄和日龄早产儿心功能变化

目的 探讨不同胎龄早产儿出生后心功能的变化特点及影响因素.方法 早产儿111例,根据胎龄分为28～31+6、32～33+6和34～36+6周组.以足月儿作为对照组(n=50),胎龄为37～41+6周.在生后1周内,平均(4.8±1.4)d,应用SonoSite 180 PLUS彩色多普勒超声仪测定心功能,测量指标包括主动脉瓣峰流速、肺动脉瓣峰流速、心输出量、每搏输出量、左室舒张末期容积、左室收缩末期容积、二、三尖瓣口舒张早期与舒张晚期血流充盈速度比(二尖瓣E/A、三尖瓣E/A)和心率,比较不同胎龄新生儿心功能的变化.另外162例早产儿根据心功能检查日龄分为12 h～,24 h～,72 h～和1周～28 d组,比较不同日龄早产儿心功能变化.采用多元线性回归分析探讨影响心功能的因素.结果 (1)不同胎龄新生儿心功能变化:主动脉瓣峰流速、肺动脉瓣峰流速、左室舒张末期容积、左室收缩末期容积、每搏输出量和心输出量随胎龄增加而增加;在28～31+6、32～33+6和34～36+6周组,二尖瓣E/A分别为1.13±0.17、1.14±0.18和1.13±0.18,三尖瓣E/A分别为0.90±0.16、0.90±0.13和0.90±0.15,均高于胎龄37～41+6周的足月儿(分别为1.28±0.17和1.04±0.20),差异均有统计学意义(P均＜0.05).(2)不同日龄早产儿心功能变化:72 h～和1周～28 d组肺动脉瓣峰流速分别为(79.60±11.22)cm/s和(78.86±13.64)cm/s,高于12 h～组[(72.61±8.56)cm/s];1周～28 d组心率快于其他3组,差异均有统计学意义(P均＜0.05).(3)影响心功能的因素:心输出量与体重和胎龄正相关,r分别=0.55和0.36,P均＜0.05.每搏输出量与体重和胎龄正相关,r分别=0.61和0.52,P均＜0.05.结论 早产儿随胎龄增大,左心室泵功能渐增强,左右心室舒张功能无明显变化.出生72 h后,肺动脉瓣血流速度显著加快.体重和胎龄是影响早产儿心功能的主要因素.

Abstract：

Objective To investigate the features and influence factors of cardiac function in preterm infants.Methods One hundred and eleven preterm infants were divided into three groups according to the gestational age which was 28-31+6,32-33+6 and 34-36+6 weeks respectively.Fifty term-birth infants at gestational age of 37-41+6 weeks were taken as control group.The cardiac function was examined by SonoSite 180 PLUS color Doppler ultrasonic diagnostic apparatus.The parameters of cardiac function included heart rate,peak flow rate of aorta valve orifice (AV),peak flow rate of pulmonary artery valve orifice (PV),cardiac output (CO),stroke volume (SV),left ventricular end diastolic volume (LVEDV),left ventricular end systolic volume (LVESV),the ratio of early (E) and late (A) diastolic velocities of mitral and tricuspid valves (MVE/A,TVE/A).Within one week after delivery,the cardiac function was examined,and the cardiac function of preterm infants with different gestational age were compared.Another 162 preterm infants were divided into four groups according to the time at examination as 12 h-,24 h-,72 h-and 1 week-28 d.The influence factors of cardiac function were determined by multi-factor linear regression analysis.Results The AV,PV,CO,LVEDV,LVESV and SV increased with the increasing of gestational age.MVE/A (1.13±0.17,1.14±0.18,1.13±0.18) and TVE/A (0.90±0.16,0.90±0.13,0.90±0.15) of 28-31+6,32-33+6 and 34-36+6 weeks group were higher than those of control group (1.28±0.17 and 1.04±0.20),respectively (P＜0.05).PV of 72 h-group and 1 week-28 d group were higher than that of 12 h-group [(79.60±11.22) cm/s and (78.86±13.64) cm/s vs (72.61±8.56) cm/s](P＜0.05).The heart rate of 1 week-28 d group was higher than that of other three groups (P＜0.05).Both CO and SV were positively related to body weight and gestational age (r=0.55 and 0.36,0.61and 0.52,respectively,P＜0.05).Conclusions The left ventricular pump function increases with the increasing of gestational age,while the diastolic function of left and right ventricle of preterm infants does not change significantly in the first month of life.The PV of preterm infants significantly increases 72 h after delivery.The body weight and gestational age are important influence factors of cardiac function in preterm infants.     

Neonatal porencephaly in very low birth weight infants: ultrasound timing of asphyxial injury and neurodevelopmental outcome at two years of age.

OBJECTIVE: To investigate and diagnose the timing of asphyxial injury leading to cerebral cavitation with subsequent developing of neonatal porencephaly in the preterm VLBW infant. All newborns underwent careful neurodevelopmental outcome at 2 years of corrected age. METHODS: 250 consecutive VLBW infants (mean gestational age of 28 weeks and mean birthweight of 1150 g) have been study by means of weekly neonatal transfontanellae ultrasonography. Periventricular white matter necrosis was diagnosed when echolucencies were visible after day 3 from birth. RESULTS: Twelve cases of neonatal porencephaly were diagnosed by ultrasound. The timing of asphyxial insult leading to cerebral cavitation seems to have occurred in 33% of neonates during the antepartum period, in 42% during the peripartum period (antepartum + neonatal period) and 25% in the remaining neonatal period. Periventricular-intraventricular hemorrhage (PVH-IVH) was found in all cases and in 50% a severe IVH (grade III-IV) was diagnosed within 7 days neonatal period. Nine infants had evidence of cerebral palsy at 2 years neurological outcome. CONCLUSIONS: The ultrasound criteria of cerebral cavitation have been priorly selected in order to assure that the damage may have occurred before delivery. A comprehensive prenatal study of fetal brain, integrating ultrasound with high-velocity MRI, is also advocate. This will lead to a more detailed understanding of the underlying cerebral condition that is of critical importance for the clinician in planning the time and mode of delivery and have great deal with further medico-legal consideration.