围生期常用治疗对新生儿神经发育的影响

新生儿大脑处于不断发育成熟的过程中,围生期的各种干预治疗措施都会直接或间接地影响脑发育过程,糖皮质激素、非甾体类抗炎药、硫酸镁、亚低温治疗、枸橼酸咖啡因、肺表面活性物质、一氧化氮、促红细胞生成素等是围生期的常见药物及治疗,与新生儿的神经发育预后有着密切的关系.该文综述围生期常用治疗是否会直接或间接地对新生儿的神经发育产生不利影响.     

影响足月小样儿神经行为发育的围生期因素分析

目的 探讨影响足月小样儿神经行为发育的围生期相关危险因素.方法 收集2008年4月至2010年4月于烟台毓璜顶医院产科分娩的111例足月小样儿的围生期相关资料,采用新生儿20项行为神经测定法(neonatal behavioral neurological assessment,NBNA)于生后3～7d对其进行评估,采用单因素及多因素Logistic回归分析考察影响足月小样儿神经行为发育的围生期危险因素.结果 足月小样儿行为能力、被动肌张力、主动肌张力及NBNA总分(分别为10.72±1.41,7.13±0.96,7.32±0.74,37.16±1.32)低于正常新生儿(分别为11.27±1.04,7.89±0.72,7.62±0.64,39.12±0.76),差异有统计学意义(P＜0.05).单因素Logistic回归分析提示影响足月小样儿神经行为的因素有分娩方式、胎盘异常、脐带异常、母亲围生期感染、妊娠高血压综合征、双胎妊娠、新生儿期高胆红素血症共7个因素.多因素Logistic回归分析提示母亲围生期感染(OR =2.175,95％CI1.981 ～2.408,P＜0.05)、双胎妊娠(OR=1.936,95％CI 1.517 ～2.368,P＜0.05)、高胆红素血症(OR=1.518,95％ CI1.072～2.149,P＜0.05)是影响足月小样儿NBNA评分的危险因素.结论 足月小样儿神经行为发育较正常新生儿差,母亲围生期感染、双胎妊娠、高胆红素血症是影响足月小样儿神经行为的危险因素.     

卵母细胞人工激活技术对子代近、远期发育的影响

卵胞浆内单精子注射(ICSI)技术是目前解决男性不育的重要手段, 但仍有少数患者由于精子不能激活卵母细胞而出现反复ICSI受精失败。卵母细胞人工激活(AOA)技术可提高受精率、妊娠率、活产率等, 但其对子代是否会带来近、远期影响尚未可知。现总结近年来有关AOA技术对子代围生期结局、遗传学、体格发育及神经发育等方面影响的相关文献, 为生殖医学工作者及儿科医师提供参考, 以期更好地服务于临床。     

亚低温治疗新生儿缺氧缺血性脑病临床研究进展

新生儿缺氧缺血性脑病(HIE)是世界范围内足月新生儿围生期死亡和后期神经发育异常的重要原因。目前临床上尚无明确有效的药物和特殊治疗方法。Gluckman和Eicher近期均报道了各中心随机对照中亚低温治疗新生儿HIE的临床安全性研究结果,研究表明,缺氧缺血后6h内给予持续48~72h亚低温治疗,神经保护作用显著,对振幅整合脑电图矫正病情后轻中度HIE疗效明显。     

孕妇甲状腺疾病对胎儿及新生儿的影响

妊娠甲状腺疾病是孕妇常见病,不论甲状腺功能亢进、甲状腺功能减低,还是亚临床型,对胎儿及新生儿均有不良影响,如死胎、流产、胎盘早剥、宫内发育迟缓及低出生体质量儿、早产儿发生率增加,少数还可引起新生儿甲状腺功能亢进或甲状腺功能减低,重者可危及生命或造成神经、心理、体格、智力发育异常.建议孕妇早期应检测甲状腺功能,发现异常即予积极治疗及监测,以降低对子代的影响.     

人类辅助生育技术子代生存质量的研究进展

人类辅助生殖技术(ARTs)对子代生存质量影响的研究目前主要集中在围生期结局及短期的跟踪研究。ARTs及其子代监测管理逐步全面和规范化。ARTs可导致较高的早产率、低出生体质量率及新生儿病死率,其原因除与多胎妊娠有关外,还与产妇的不孕因素有关。ARTs子代先天畸形的发生率也较高,但主要与孕妇和精子供体的因素有关。ARTs对子代智力发育有没有不良影响,是否会增加子代患脑性瘫痪的风险尚存争议。冻融胚胎技术及单精子卵细胞浆内显微注射技术对子代的安全性得到大多数学者的认可。     

妊娠期合并系统性红斑狼疮对子代影响及作用机制

系统性红斑狼疮(SLE)是一种严重的多系统自身免疫性疾病，绝大多数患者为育龄期女性。妊娠期合并SLE对胎儿、新生儿以及子代远期都会产生影响，包括死胎、流产、胎盘早剥、宫内发育迟缓及早产发生率升高等。少数还可引起新生儿狼疮(NL)，甚至对后代神经认知等方面产生影响。另外，SLE患者孕前及孕期需要口服药物控制疾病，其中多数会对子代产生影响。因此，建议SLE患者孕前和孕期严密监测，优化治疗，对其后代进行整体评估，以降低对子代的不利影响。文章利用文献调查分析妊娠期合并SLE对子代影响及其作用机制，同时阐述妊娠期使用SLE药物对后代影响。     

围生期性激素与神经行为发育的研究进展

性激素除传统的促性成熟作用外 ,对神经行为发育也有重要影响。围生期是小儿神经行为发育的关键时期 ,该时期影响性激素水平的因素多、变化范围大 ,并且具有性别差异。如何检测及干预围生期性激素水平以更好地促进小儿神经行为发育 ,尚待进一步研究     

髓鞘碱性蛋白在宫内感染早产大鼠脑中的表达及其意义

围生期脑损伤是影响新生儿生后生存质量最重要的因素.脑室周围白质软化(periventricular leu-komalacia,PVL)是早产儿脑损伤最主要的神经病理改变,是存活早产儿出现神经发育和行为障碍的主要原因[1].迄今对PVL的发病机制和神经生物学尚认知不多,对PVL尚无有效的治疗和预防方法.     

母亲妊娠期糖尿病对新生儿行为神经发育的影响

目的探讨母亲妊娠期糖尿病对围生期新生儿神经行为发育的影响。方法对57例妊娠糖尿病母亲所产新生儿及48例同期分娩的母亲孕期和出生时无异常的足月新生儿进行20项行为神经测定(NBNA),并行脑电图(EEG)和头颅B超检查。结果27.6%患儿生后7 d NBNA≤35分,观察组与对照组比较被动肌张力及主动肌张力有显著性差异(P<0.05),EEG检查也有显著差异(P<0.05)。结论NBNA测定和EEG检查能够早期发现母亲妊娠糖尿病对新生儿神经行为发育影响,可尽早对轻微脑损伤婴儿进行针对性干预。     

营养与早产儿神经发育结局

随着围产医学和新生儿医学发展,极低和超低出生体质量(VLBW/ELBW)早产儿存活率普遍提高,但这些早产儿可进一步发生神经系统发育不良。除与神经系统发育有关的疾病如脑损伤外,在大脑迅速生长和发育的时期,营养同样是影响神经系统发育及不良预后的重要因素。VLBW/ELBW早产儿发生生长发育迟缓的风险增高,主要与出生后营养摄入不足有关。目前的证据显示,VLBW/ELBW早产儿出生后生长发育迟缓与神经系统发育损害有关。此外某些特殊营养素,如长链多不饱和脂肪酸与早产儿神经发育有相关关系。     

Nutritional influences on brain development

There is increasing evidence from preclinical and human studies that nutrition in the late foetal and early neonatal period has a significant impact on neurodevelopment across the lifespan. Certain nutrients have particularly large effects in this time period, and their deficits cause greater long‐term risk. The mechanisms by which nutrients influence early brain growth and the sensitive periods for when certain nutrients should be provided are being elucidated. Assessments of nutritional status that index brain growth and predict long‐term development are important to assess the efficacy of early life nutritional therapies. Conclusion: Optimizing nutrition during foetal and early postnatal life is a golden opportunity to impact neurodevelopment and brain function across the lifespan.     

铁缺乏对早产儿神经发育影响的研究进展

铁缺乏是儿童最常见的微量营养素缺乏性疾病,早产儿出生时铁储备不足,加上生后快速的追赶性生长,缺铁的发生率更高。在脑发育关键期,铁缺乏通过改变铁依赖的神经代谢、神经化学、神经解剖以及基因/蛋白组分,影响中枢神经系统,最终导致神经认知和行为发育改变。婴幼儿期的铁剂补充无法恢复围产期缺铁对神经发育的负性影响。缺铁对神经系统发育的影响具有时间、区域特异性,对高危人群应该早期诊断,尽早给予适宜铁剂治疗,对于早产儿脑功能的恢复、生存质量的提高、远期预后的改善具有十分重要的意义。     

早产儿早期脑反应性与神经发育关系的研究

目的　研究早产儿早期脑对外界刺激的反应性与神经发育的关系 ,早期对早产儿进行脑功能的评价 ,为了解其神经发育水平、估价预后提供客观证据。方法　应用近红外光谱测定技术 ,对不同胎龄的早产儿进行脑氧合状态的监测 ,观察声刺激后脑反应性的变化 ;在纠正胎龄 4 0周时行新生儿神经行为评分 (NBNA) ,并进行神经发育随访 ,评价早产儿早期脑反应性与其后神经发育的关系。结果　本组早产儿生后对声刺激均显示出不同程度的反应 ,34周后的早产儿声刺激后最大反应值为 4 .1%± 1.4 % ,2 0例足月儿声刺激后最大反应值为 4 .2 %±1.4 % ,两者差异无显著性 ;小于 34w的早产儿声刺激后最大反应值为 3.1%± 1.4 % ,与足月儿相比差异有显著性(P <0 .0 5 )。有脑损伤早产儿声刺激后最大反应值为 2 .6 %± 1.8% ,无脑损伤早产儿声刺激后最大反应值为4 .4 %± 1.3% ,两者相比有统计学差异 (P <0 .0 5 )。纠正胎龄 4 0周的NBNA异常儿与正常儿比较 ,早期脑反应性有显著性差异 (P <0 .0 5 )。婴幼儿期随访 ,神经发育异常与正常儿比较 ,早期脑反应性也有显著性差异 (P <0 .0 5 )。结论　早产儿具备对声刺激后的脑反应性 ,成熟度越低 ,脑反应性越差。围产期脑损伤可影响脑的反应性。早期的脑反应性与神经发育水平有关。     

Ureaplasma and bronchopulmonary dysplasia

Advances in neonatal intensive care have greatly improved survival rates for children born in a very early stage of lung development (i.e. less than 26 weeks of gestation). In these premature babies, even low levels of oxygen and methods of minimally invasive ventilation may disrupt the growth of the distal airways, a condition described as “new” bronchopulmonary dysplasia (BPD).Ureaplasma infection can occur in utero or in the perinatal period in premature infants, in some of which the infection with these organisms triggers an important lung pro-inflammatory and pro-fibrotic response, and may increase the risk of developing BPD. The inflammation may be worsened by exposure to oxygen and mechanical ventilation. At present, clinical studies have not clarified the role of Ureaplasma in the pathogenesis of BPD and there is insufficient evidence to determine whether antibiotic treatment of Ureaplasma has influence on the development of BPD and its comorbidities.Future research in the context of well-designed and controlled clinical trials of adequate statistical power should focus on how to determine whether the treatment of Ureaplasma decreases lung inflammation, reduces rates of BPD, and improves long-term neurodevelopment.     

Current management of the infant who presents with neonatal encephalopathy

Neonatal encephalopathy after perinatal hypoxic-ischemic insult is a major contributor to global child mortality and morbidity. Brain injury in term infants in response to hypoxic-ischemic insult is a complex process evolving over hours to days, which provides a unique window of opportunity for neuroprotective treatment interventions. Advances in neuroimaging, brain monitoring techniques, and tissue biomarkers have improved the ability to diagnose, monitor, and care for newborn infants with neonatal encephalopathy as well as predict their outcome. However, challenges remain in early identification of infants at risk for neonatal encephalopathy, determination of timing and extent of hypoxic-ischemic brain injury, as well as optimal management and treatment duration. Therapeutic hypothermia is the most promising neuroprotective intervention to date for infants with moderate to severe neonatal encephalopathy after perinatal asphyxia and has currently been incorporated in many neonatal intensive care units in developed countries. However, only 1 in 6 babies with encephalopathy will benefit from hypothermia therapy; many infants still develop significant adverse outcomes. To enhance the outcome, specific diagnostic predictors are needed to identify patients likely to benefit from hypothermia treatment. Studies are needed to determine the efficacy of combined therapeutic strategies with hypothermia therapy to achieve maximal neuroprotective effect. This review focuses on important concepts in the pathophysiology, diagnosis, and management of infants with neonatal encephalopathy due to perinatal asphyxia, including an overview of recently introduced novel therapies.     

Pathophysiology of neonatal brain lesions: lessons from animal models of excitotoxicity

AIM: The pathophysiology of perinatal brain lesions is probably complex and multifactorial. The development and characterization of distinct yet complementary animal models should help to unravel the cellular and molecular mechanisms underlying perinatal brain lesions. This paper reviews experimental data obtained in animal models of neonatal excitotoxic brain lesions that closely mimic some of the lesions found in human cerebral palsy. CONCLUSION: Available data point to a key role for brain macrophages and oligodendrocytes in neonatal rodent excitotoxic brain lesions and underline the impact of cytokines on these lesions.     

Managing hypoxic ischaemic encephalopathy in term newborn infant

Hypoxic–ischaemic encephalopathy (HIE) is a brain dysfunction resulting from inadequate blood flow and oxygenation to the whole body during the perinatal period. It is a major cause of brain injury and is associated with mortality and significant disabilities in later life. Following HIE acute, secondary and tertiary phases of brain injury lasting from hours to years occurs. Therapeutic hypothermia reduces death and improves the neurodevelopment in infants with moderate to severe HIE. Passive cooling can be initiated soon after birth in infants that fulfil criteria for the treatment. Active cooling with appropriate intensive and supportive care including respiratory and cardiovascular support, maintaining normoglycaemia, sedation, and seizure management is essential for minimising the brain injury. In cooled infants likely to have a worse prognosis re-orientation of care is often considered in the infant's best interests. This short review aims to explain the underlying pathophysiological effects of HIE and its management.     

Genetic and epigenetic factors and early life inflammation as predictors of neurodevelopmental outcomes

Among individuals born very preterm, perinatal inflammation, particularly if sustained or recurring, is highly likely to contribute to adverse neurodevelopmental outcomes, including cerebral white matter damage, cerebral palsy, cognitive impairment, attention-deficit/hyperactivity disorder, and autism spectrum disorder. Antecedents and correlates of perinatal inflammation include socioeconomic disadvantage, maternal obesity, maternal infections, fetal growth restriction, neonatal sepsis, necrotizing enterocolitis, and prolonged mechanical ventilation. Genetic factors can modify susceptibility to perinatal inflammation and to neurodevelopmental disorders. Preliminary evidence supports a role of epigenetic markers as potential mediators of the presumed effects of preterm birth and/or its consequences on neurodevelopment later in life. Further study is needed of factors such as sex, psychosocial stressors, and environmental exposures that could modify the relationship of early life inflammation to later neurodevelopmental impairments. Also needed are pharmacological and non-pharmacological interventions to attenuate inflammation towards the goal of improving the neurodevelopment of individuals born very preterm.