引言
神经发育结局受损是一种与早产相关的重要远期并发症。胎龄(gestational age, GA)越小，发生神经发育损害及心理和行为问题的风险越高。
本专题将总结早产存活者婴儿期之后的远期神经发育、行为、心理和功能结局。早产儿的后续神经发育管理参见其他专题。(参见“早产儿远期神经发育结局的管理”)
此外，早产的发生率及早产儿的生存率、出院后医学管理及短期并发症的概述参见其他专题。(参见“早产儿的发生率和死亡率”和“早产儿的短期并发症”和“新生儿转出重症监护病房后的管理”)
定义
早产 — 早产程度通常由出生体重(birth weight, BW)或胎龄来定义，在本专题中使用以下定义(表 1)。
按BW分类如下：
低出生体重儿(low birth weight, LBW)–BW小于2000g
极低出生体重儿(very low birth weight, VLBW)–BW小于1500g
超低出生体重儿(extremely low birth weight, ELBW)–BW小于1000g
按GA分类如下：
晚期早产–GA介于34至36+6周。
中度早产–GA介于32至33+6周。
早期早产(very preterm, VPT)–GA介于28至31+6周。
极早早产(extremely preterm, EPT)–GA不足28周。
现已确定了相应GA的BW百分位数(表 2A-B)。
神经发育结局 — 神经发育结局是一个复合术语，通常指认知、神经系统和/或感觉发育的结局。
传统上在结局研究中，神经发育损害被定义为存在一个或多个以下问题：
认知迟缓，判断依据是标准化认知测试得分低于均值2个标准差(standard deviations, SD)。例如，这相当于贝利婴儿发育量表(Bayley Scales of Infant Development, BSID)智力发育指数(Mental Developmental Index, MDI)得分小于等于70。
中到重度脑性瘫痪(cerebral palsy, CP)，定义为大运动功能分级系统(Gross Motor Function Classification System, GMFCS)评分大于等于2。
需要助听装置的双耳听力缺陷/损失。
严重视力障碍，视力较好一侧眼睛的最佳常规矫正视力小于等于20/200(即法定盲的定义)。
此外，行为、心理及功能结局也逐渐被认为是重要的远期神经发育结局，也会在本文中讨论。
解读结局资料的困难
由于临床实践(例如，生存力极限)和研究设计(研究人群、评估工具和结局定义)的差异以及围生期保健随时间的变化，新生儿结局文献的解读较难。因此，在比较各研究或试图将文献结果应用于临床时，需要考虑到这些因素。
临床实践的差异：生存力极限 — 在发达国家，对于处于生存力阈值的婴儿(可确保有较大宫外存活机会的胎儿成熟期)，提供的初始管理水平有全球性和地区性差异[1-3]。临床实践中的这些差异会影响在妊娠22-25周出生的婴儿的生存率(表 3)，可能还会影响神经发育结局(表 4)。因此，很难比较采用不同复苏方法的研究中EPT婴儿的生存率及神经发育结局，也很难基于个体患者解读这些数据。(参见“Periviable birth (Limit of viability)”, section on ‘Impact of initial management’)
处于生存力极限的早产儿的相关数据解读参见其他专题。(参见“Periviable birth (Limit of viability)”, section on ‘Interpreting the data’)
研究设计因素
研究人群–界定研究人群的差异使得比较不同研究的数据存在困难。
•例如，用出生体重而非胎龄来分类可能存在问题，因为一个出生体重分类中可能包括相对较成熟的宫内发育迟缓(intrauterine growth retardation, IUGR)婴儿。如果有较多的IUGR患儿，可能会影响结局，因为IUGR婴儿发生新生儿并发症和较差结局的风险高于相应的适于胎龄儿(appropriate for gestational age, AGA)，但其结局通常优于同等出生体重的更早产婴儿[4](参见“胎儿期(宫内)生长受限的婴儿”)。随着确定胎龄的技术得到改善，按GA分类已成为主导。尽管GA分类法可能在同一组中纳入大于胎龄儿和小于胎龄儿，但相比于BW分类法，该方法所确定的分组更有可能纳入相似胚胎/胎儿发育阶段的婴儿。因此，胎龄分类更常用于报告早产儿的远期结局。
•转运婴儿 vs 非转运婴儿–与不需要转运的婴儿相比，在没有三级新生儿重症监护病房(neonatal intensive care unit, NICU)、需要新生儿转运的中心出生的早产儿，并发症发生率和死亡率似乎更高[5,6]。因此，研究之间非转运和转运婴儿的混合分析可能会影响生存率和远期结局。
结局测量指标的定义–不同的结局定义，特别是重度神经发育损害(neurodevelopmental impairment, NDI)的定义，会改变结果。例如，对加拿大新生儿随访网络(Canadian Neonatal Follow-up Network)早产儿(胎龄23-28周)数据库的一项分析显示，根据不同的定义，重度NDI的发生率为3.5%-14.9%[7]。NDI通常定义为至少有以下一种情况：认知或运动测试得分低于均值2个标准差以上；助听装置无效的双耳听力损失；双眼法定盲；以及中度、重度或深度脑瘫。
评估方法–不同研究中用于评估结局的工具不同，因此结果可能无法直接比较。例如，一些研究显示，第3版贝利标准(BSID Ⅲ，2006)测定的认知评分高于第2版(BSID Ⅱ，1992)[8-11]。BSID Ⅲ是高估了认知表现还是可以比BSID Ⅱ更准确地评估认知功能，目前还不明确。2019年9月发布了第4版贝利标准(BSID Ⅳ)，但目前还没有研究比较BSID Ⅳ与之前版本对早产存活者的评估。
后续混杂因素–可能影响神经发育和入学准备度的后续因素包括社会人口学因素(例如，母亲的教育程度)、家庭收入(例如，Medicaid保险是贫困的标志)、持续存在的健康问题及是否参与早期干预项目。这些因素的存在情况可能各异，因此很难比较不同研究的结果。(参见“School readiness for children in the United States”, section on ‘Factors related to a child's ability to learn’)
生存率随时间的变化 — 围生期医疗的进步提高了存活率[12]，因此，更难准确判断临床实践的变化对改善神经发育结局的影响，因为生存率提高的速度已经超过了伴随的远期神经发育后遗症发生率降低的速度。
随着围生期医疗的进步，关于早产儿的神经发育结局是否随存活情况一并得到改善，相关数据不一致。虽然世界各发达国家的一些大型或人群研究表明，早产儿的神经发育结局和生存率均有所改善[13-19]，但也有例外[20,21]。结果不一致的原因可能是不同胎龄或出生年份的结局改善有差异。以下研究强调了在比较结局时考虑胎龄的重要性：
法国的一项对早产儿的人群研究[Etude épidémiologique sur les petits âges gestationnels(EPIPAGE)和EPIPAGE-2]报道，从1997年至2011年，妊娠25-26周出生的婴儿和妊娠27-31周出生的婴儿中，不伴重度或中度神经运动或运动感觉障碍的生存率增加，分别为45.5% vs 62.3%和82.1% vs 90.3%[22]。然而，在妊娠24周出生的婴儿或妊娠32-34周出生的婴儿中，两个队列的不伴重大残疾生存率没有差异，分别为29% vs 25.8%和95.7% vs 96.8%。此外，在2011年的队列中仅有1例在妊娠22-23周出生的婴儿存活。
在美国国立儿童健康与人类发展研究所(National Institute of Child Health and Human Development, NICHD)网络的一份报告中，1995-2010年间出生于胎龄25周、26周、27周和28周的婴儿中，不伴重大新生儿并发症的生存率有所改善，但在胎龄23周和24周出生的婴儿中没有变化[12]。
在随后对EPT婴儿(胎龄<28周)的一项NICHD研究中，2011-2014年，重度脑瘫的发病率下降了43%，轻度脑瘫的发病率上升了13%[18]。
临床实践的改变 — 现认为，观察到的一些随时间而发生的临床实践改变是新生儿存活率提高的主要原因，也可能是神经发育结局改善的主要原因[13-16]。因此，对不同时代出生队列之间的比较应慎重解读。这在与较近期出生队列比较早产儿成人期结局时尤为重要，因为随着临床实践改变，2015年出生的EPT婴儿(胎龄<28周)所接受的治疗干预不同于1993年出生的婴儿，因此，其远期结局风险可能也不同。例如，美国NICHD的一项研究显示，随着临床实践的一些改变(例如，产前皮质类固醇应用增加，以及产后皮质类固醇使用率和产房插管率降低)，新生儿生存率提高，特定并发症发生率降低[例如，重度脑室内出血(intraventricular hemorrhage, IVH)和晚发型脓毒症][12]。但该研究未评估神经发育结局。另一项meta分析发现，在使用产前类固醇和表面活性物质时代出生的早产儿(胎龄<37周)到5岁或5岁以上时，神经发育结局仍然不如足月出生者，包括学习成绩方面的严重困难[23]。
预防性干预措施 — 过去数十年，围生期保健中出现的下列变化/干预可能直接或间接[通过减少相关并发症，如脑室周围-脑室内出血(periventricular-intraventricular hemorrhage, PIVH)]改善神经发育结局。
产前皮质类固醇治疗，可降低死亡率和神经发育损害发生率、减少中度至重度脑瘫的发病率、缩短机械通气时间，以及降低发生重度PIVH的风险[24,25]。(参见下文‘相关病况’和“产前皮质类固醇治疗以减少早产导致的新生儿呼吸系统并发症发病率和死亡率”)
避免出生后早期使用皮质类固醇治疗，因其与发生脑瘫的风险增加有关。关于出生后使用皮质类固醇治疗的远期影响详见其他专题[26-28]。(参见“支气管肺发育不良的预防：出生后使用糖皮质激素”)
新生儿通气的进步，包括采取无创通气方法[如持续气道正压(continuous positive airway pressure, cPAP)]和改进机械通气策略(例如，容量目标和同步化通气)，提高了生存率并降低了并发症发生率[如，支气管肺发育不良(bronchopulmonary dysplasia, BPD)、重度PIVH和肺气漏]，这可能影响神经发育结局。(参见下文‘相关病况’和“新生儿机械通气”和“支气管肺发育不良婴儿的结局”，关于‘神经发育结局’一节和“新生儿生发基质-脑室内出血的预防、管理和并发症”，关于‘远期结局’一节和“新生儿肺气漏”)
表面活性物质，其与生存率增加相关，特别是对EPT婴儿。然而，表面活性物质治疗与神经发育结局改善没有直接关系。(参见“早产儿呼吸窘迫综合征的预防和治疗”)
产前使用硫酸镁，这与脑瘫和重度运动功能障碍风险降低相关。临床试验显示，母亲使用硫酸镁的早产儿发生脑瘫和重度运动功能障碍的风险低于无宫内暴露者。(参见“硫酸镁对胎儿的神经保护作用”，关于‘随机试验和meta分析的疗效证据’一节)
无效的预防措施 — 既往观察数据表明，预防性使用重组红细胞生成素(recombinant erythropoietin, EPO)具有神经保护作用，然而，一项对941例EPT婴儿进行的多中心试验报道，EPO对改善神经发育结局没有益处[29]。矫正胎龄22-26个月时，EPO组和安慰剂组的主要结局发生率相近(26% vs 26%，RR 1.03，95%CI 0.81-1.32)。主要结局指的是死亡或重度神经发育损害，后者定义为重度脑瘫，或使用BSID Ⅲ得到的运动或认知综合评分低于70[29]。在该试验中，受试者在出生后24小时内接受安慰剂或EPO(剂量为1000U/kg)，每48小时1次，共6次。EPO组和安慰剂组的早产儿视网膜病变(retinopathy of prematurity, ROP)、颅内出血、BPD、坏死性小肠结肠炎(necrotizing enterocolitis, NEC)、死亡或严重不良反应发生率相近。因此，不应预防性地使用EPO作为神经保护剂。
神经发育残疾和学业成绩
结局研究表明，GA和BW越小，神经发育残疾的风险越高[24,30-36]。下文根据胎龄分类总结了存活者的结局数据。(参见上文‘早产’)
EPT婴儿
患病率和严重程度 — 一些研究显示，在EPT和/或ELBW婴儿中，存在神经发育损害的ELBW存活者的比例较高，且通常会随胎龄增加而降低(表 4)。EPT存活者常发生认知障碍以及运动和感觉神经障碍，且通常较严重，会持续到学龄期和成人期。
基于现有文献，我们与EPT婴儿的父母及看护人员讨论以下临床结局指标的风险。如上所述，综合这些信息存在困难，因为研究设计不同(例如，结局评估的年龄和重大残疾的定义)，并且结局数据与较新的出生队列不同。(参见上文‘解读结局资料的困难’)
重大残疾–重大残疾是指标准化认知和运动测试得分低于均值2个标准差以上和/或存在脑瘫、盲和需要助听装置的听力损失。
•1995-2007年出生队列的6-10岁学龄儿童–人群研究报道，出生时为EPT的儿童中，17%-46%有重大残疾[37-40]。据报道，1995年出生、胎龄<25周的患儿风险最高[38]。
•2008-2011年出生、矫正月龄为18-24个月的幼儿出生队列–根据认知测试分数或存在脑瘫、盲和需要助听器的听力损失，在较近的出生队列中，约一半EPT出生的儿童有重大残疾[22,41]。
18-24个月时的重大残疾可能在整个儿童时期持续存在。
学习障碍及需要专门的教育干预和服务–EPT出生的儿童更有可能在阅读和数学方面有学习困难，并且教师评分较低[42-45]。这些儿童常需要额外的教育干预和特殊服务[43,46]。
成人结局–仅有1995年的一个出生队列的成人结局数据，该队列显示，约60%的个体在19岁时有至少1种认知功能和视觉运动能力损害，1/3有4类或更多缺陷[47]。45%的EPT出生成人存在认知障碍，而对照组只有3%。
危险因素 — EPT出生者神经发育损害的危险因素还包括[33,48,49]：
母亲因素–受教育水平较低、无商业保险、非白人种族、未婚和肥胖。出院后需要儿童保护服务监管的婴儿在2岁时认知发育延迟的风险增加[50]。
婴儿因素–宫内生长障碍[4]、男性[37,51]、多胎生产、非白人，以及伴随重大新生儿并发症(重度IVH、脑室周围白质软化和接受大手术)。[39,52]
医疗保健因素–未进行产前保健或产前未使用皮质类固醇，以及阴道分娩。
早期早产儿 — 虽然VPT(胎龄28周至<32周)或VLBW(出生体重<1500g)婴儿出现神经发育障碍的风险低于EPT或ELBW存活儿，但仍有相当数量存在神经发育缺陷[46,53-60]。对VLBW婴儿的研究也可能包含ELBW，这可能不成比例地促进不良结局。因此，由于这些研究中ELBW患者的相对百分比不同，结局数据可能存在差异。(参见上文‘研究设计因素’)
研究者在一个包含2901例1997年出生早产儿的前瞻性队列中说明了VPT婴儿的风险程度[46]。该研究显示，在29-32周出生者的早产儿中，在5岁时36%有神经发育障碍，30%使用了特殊的医疗资源(例如，物理治疗、言语治疗、技能训练、心理学治疗和精神科治疗)。即使出院时没有中度或重度神经障碍的儿童，与足月对照者相比，仍有可能出现全面发育迟缓和学习成绩差异[53,54]。出现不良结局的危险因素包括：出生胎龄较小、影像学检查发现脑病变、宫内生长障碍、未母乳喂养，以及父母社会经济地位低。在2011年出生的婴儿队列中，妊娠27-31周出生的婴儿2岁时有4.2%出现脑瘫，41%出现发育迟缓[22]
其他研究报道，与足月出生的儿童相比，VPT学龄儿童的记忆力评分较差，并且更有可能出现学习困难[59,61]。
在一项文献系统评价中，5岁以下早期早产儿发生认知发育不良的可能危险因素包括男性、低GA和父母教育水平低[60]。然而，在年长儿中唯一持续存在的危险因素是父母教育水平低下。
其他研究报道，与足月出生的儿童相比，VPT学龄儿童的记忆力评分较差，并且更有可能出现学习困难[59,61]。
中度至晚期早产儿 — 中度(胎龄在32-33+6周)和晚期(胎龄在34周至＜37周)早产儿存在远期神经发育损害的可能性大于足月儿。对世界各地中度至晚期早产儿的纵向国际性研究基于评估年龄报道了以下神经发育损害[62-70]：
2岁–认知测试结果差，神经心理功能和感觉神经损害。[62,70,71]
学龄前–据家长报告，学龄前发育迟缓。[64]
学龄期–认知测试差，需要特殊教育服务，学业测试或教师评估成绩低于预期年级水平[63,66,67,72,73]
晚期早产儿(胎龄为34-36周)的远期神经发育结局详见其他专题。(参见“晚期早产儿”，关于‘神经发育结局’一节)
结构性脑损伤 — 重度新生儿脑损伤(即头部超声检测到异常)的早产存活者有最严重的神经发育损害[例如，需要额外的学校服务，以及伴运动、认知或感觉神经损害的重大残疾(如，脑瘫)][74-77]。新生儿脑损伤也可能与青春期精神障碍[例如，重性抑郁和强迫症(obsessive-compulsive disorder, OCD)]风险增高相关[78]。
MRI证实早产儿在学龄期、青春期和成人期存在大脑结构改变，包括胼胝体变薄、脑室容积增加、脑发育期灰质和白质的相对体积减少，以及总脑容积减少[79-88]。
言语和语言结局 — 早产存活儿中常见言语和语言障碍，其风险和严重度与GA成反比。表达性和/或感受性语言的习得及发音清晰度方面可能存在迟缓[9,89-92]。有证据表明，与足月对照组相比，早产儿的言语功能出现部分性追赶，并随着母亲受教育水平等环境因素而增加[92,93]。语言结局与认知功能、听觉、产前和产后社会经济地位、环境、族群以及既往插管相关喉水平结构改变有关[91,94-96]。
行为和心理影响
早产儿(尤其是EPT或VPT)在儿童期出现特定行为和心理问题的可能性高于足月出生者。
极早早产和早期早产儿 — EPT或VPT出生的儿童比足月出生的儿童更可能发生行为和心理问题。对NICHD新生儿研究网络中2008-2012年出生的EPT婴儿(胎龄<27周)进行的一项研究报道，在矫正月龄为18-22个月时，1/3的婴儿存在行为问题，1/4存在社会情绪能力缺陷[97]。社会人口学因素(例如，母亲受教育程度在高中以下、母亲年龄较小)及认知和语言功能缺陷会增加早产儿发生行为和社会情绪能力问题的风险。然而，与足月儿相比，早产儿在青春期和成年早期倾向于采取风险较低的行为，且更腼腆[98-102]。
与足月出生的同龄人相比，以下行为问题和心理问题在EPT或VPT出生的儿童和青少年中更常见。
注意力集中困难[98,102-111]
同伴互动不良[99,105-107,111,112]
多动[102-106,108-110,113]
情绪和品行问题，包括焦虑、抑郁、退缩和躯体主诉[98,102,103,105-107,109,110,114,115]
孤独症谱系障碍[109,116,117]
精神障碍[114,118,119]
中度至晚期早产儿 — 虽然数据有限，但根据父母的评估，中度至晚期早产儿在学龄前存在行为和情绪问题的风险高于足月出生的同龄人[120-122]。另外，一项报告显示，中度至晚期早产儿在2岁时孤独症筛查测试阳性的可能性高于足月出生儿[123]。
功能残疾
与足月出生的同龄人相比，EPT或VPT出生的学龄儿童更可能发生影响其完成日常活动和生活质量的功能障碍，可能为轻微缺陷，包括运动协调(发育性运动协调障碍，也称为非脑瘫性运动障碍)[124,125]、社交技能和执行功能(工作记忆、解决问题、规划和组织)方面的问题[56,72,111,126-130]。胎龄越小，发生功能障碍的风险越高，据报道，在妊娠26周前出生的儿童有40%会出现功能障碍[42,56]。在一些儿童中，这些缺陷可能影响学业、运动和行为结局。(参见“发育性协调障碍：临床特征和诊断”)
环境对潜在神经功能改善的影响
尽管早产和脑损伤与神经发育障碍之间的关联已经很清楚，但我们对环境和经验在调节这些关联中的作用却知之甚少。几项研究报道了环境因素对认知和言语-语言功能的有益影响，包括较高的母亲受教育水平、父母干预、高质量的家庭环境和日间看护资源[92,93,131-134]。然而，较高的母亲受教育水平对运动结局不存在有益影响[135]。
成人结局
残疾 — 在既往为早产的个体中，GA越小，成人期医学和社会残疾的风险越高。
一些研究报道，早产存活儿成年后的教育成就、独立生活的比例、净收入和终生雇佣率低于足月出生者[136-141]。这些结果很可能由以下两个原因造成：认知技能差导致学习能力受损，特别是出生体重低于1500g或胎龄低于32周的成人；发生医学残疾(脑瘫、精神和行为障碍，以及躯体残疾)的风险增加[136,142-144]。较高的社会经济地位似乎可减轻GA对认知功能测试评分的影响[142]。
而其他研究显示，虽然早产儿出现神经发育障碍的风险较高，但其在成人期可能会克服这些困难，成为功能正常的年轻成人的比例与足月出生者相当，包括高中毕业、接受高等教育、就业、独立生活、婚姻和养育子女方面[145,146]。这些研究的结局差异归因于研究人群的社会经济地位较高、教育支持增加或来自国家医疗保健体系的获益[147]。
生活质量 — 早产年轻成人及其父母报告的功能限制患病率及复杂程度均高于足月出生对照者及其父母所报告的[148]。纵向研究报道，根据健康效用指数标记-3问卷的评估结果，早期早产个体的健康相关生命质量更低[148-150]。对该文献的一项系统评价显示，早产儿成年后建立恋爱关系、性关系及养育子女的可能性较小[151]。但在一些研究中，早产成人及其家人所报告的满意生活质量与足月出生者相似[152-156]。
此外，早产患者及其父母所感受到的生活质量优于医护人员所判断的[157]。因此，医护人员须认识到这种差异，以便不仅重点关注患者的神经发育残疾，而且拓宽对结局的考虑，将成人存活者凭着对生活质量的积极自我感知从而克服自身限制的能力也考虑在内[145,158,159]。
相关病况
与神经发育结局不良风险增加有关的早产相关新生儿病况包括：
BPD[41,160,161]。(参见“支气管肺发育不良婴儿的结局”，关于‘神经发育结局’一节)
此外，出生后应用糖皮质激素治疗BPD与脑瘫风险增加有关。(参见“支气管肺发育不良的预防：出生后使用糖皮质激素”)
围生期感染，包括[41,162,163]：
•坏死性小肠结肠炎(necrotizing enterocolitis, NEC)(参见“新生儿坏死性小肠结肠炎：治疗”，关于‘生长发育’一节)
•脓毒症(参见“早产儿(胎龄小于34周)细菌性脓毒症的治疗和预防”，关于‘并发症’一节)
•脑膜炎(参见“新生儿细菌性脑膜炎：治疗和结局”，关于‘结局’一节)
ROP。(参见“早产儿视网膜病变的发病机制、流行病学、分类和筛查”)
IVH。(参见“新生儿生发基质-脑室内出血的预防、管理和并发症”，关于‘结局’一节)
生长不良：
•胎儿生长受限–胎儿生长受限会增加早产儿发生神经发育结局受损的风险。(参见“胎儿期(宫内)生长受限的婴儿”，关于‘神经发育’一节)
•出生后生长–在VPT婴儿中，生长障碍，包括头部生长不良，会造成认知和运动功能受损[164-166]。美国NICHD新生儿研究网的一项报告表明生长改善与神经发育结局改善相关，该研究在矫正年龄为18-22个月时对ELBW儿进行评估，发现其在新生儿重症监护病房(neonatal intensive care unit, NICU)住院期间的体重增长越多，则CP发病率越低，认知测试评分越好，神经系统检查异常或神经发育障碍的可能性越低，再住院需求亦越少[167]。
先天性异常–有先天性异常的早产存活者更可能发生认知损害及运动和感觉神经缺陷[168]。
双胎妊娠的ELBW儿[169]。目前尚无三胎或以上妊娠的类似数据。
出生住院期间接受外科手术[170]。
总结与推荐
由于临床实践、研究设计(研究人群、评估工具和结局定义)方面的差异，以及围生期保健的变化，解读新生儿远期神经发育结局相关文献的难度较大(参见上文‘解读结局资料的困难’)。因此，当回顾文献数据以便应用于临床时，需考虑到这些因素。尽管存在这些局限性，但结局资料仍充分支持下列有关早产儿神经发育结局的观察结果：
早产儿出现神经发育结局损害的风险高于足月儿，这些损害包括：认知异常、运动障碍(轻度、精细和/或大运动发育迟缓)、脑性瘫痪(CP)以及视力和听力损失。出生胎龄(GA)越小，发生损害的风险越高。(参见上文‘神经发育残疾和学业成绩’)
早产出生者比足月出生者更可能出现心理和行为问题，包括注意缺陷/多动障碍(ADHD)、同伴交往困难、广泛性焦虑和抑郁，以及孤独症谱系障碍。(参见上文‘行为和心理影响’)
与足月出生的儿童相比，早产儿在学龄期更可能出现影响其完成日常活动的功能障碍(运动协调、社交技能和执行功能方面的问题)。(参见上文‘功能残疾’)
与足月儿相比，早产儿成年后更可能出现医学和社会残疾。然而，相当数量的早产儿在成年后自诉有与足月出生者相似的满意生活质量。(参见上文‘成人结局’)
有些新生儿并发症与神经发育结局不良的风险增加有关，这些并发症包括：支气管肺发育不良(BPD)、坏死性小肠结肠炎(NEC)、早产儿视网膜病(ROP)、脑室内出血(IVH)、生长不良和存在先天异常。其他导致神经发育结局不良的因素包括母亲因素(例如，母亲的教育背景)，以及婴儿因素(性别和多胎生产)；但围生期保健的进步(如，产前使用皮质类固醇激素)会改善结局。(参见上文‘相关病况’和‘危险因素’)
致谢
UpToDate的编辑人员感谢对这一专题的早期版本做出贡献的Yvette Johnson, MD, MPH。
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