引言

神經(jīng)發(fā)育結(jié)局受損是一種與早產(chǎn)相關(guān)的重要遠(yuǎn)期并發(fā)癥吭服。胎齡(gestational age, GA)越小，發(fā)生神經(jīng)發(fā)育損害及心理和行為問(wèn)題的風(fēng)險(xiǎn)越高假勿。

本專題將總結(jié)早產(chǎn)存活者嬰兒期之后的遠(yuǎn)期神經(jīng)發(fā)育、行為、心理和功能結(jié)局耘纱。早產(chǎn)兒的后續(xù)神經(jīng)發(fā)育管理參見(jiàn)其他專題。(參見(jiàn)“早產(chǎn)兒遠(yuǎn)期神經(jīng)發(fā)育結(jié)局的管理”)

此外毕荐，早產(chǎn)的發(fā)生率及早產(chǎn)兒的生存率束析、出院后醫(yī)學(xué)管理及短期并發(fā)癥的概述參見(jiàn)其他專題。(參見(jiàn)“早產(chǎn)兒的發(fā)生率和死亡率”和“早產(chǎn)兒的短期并發(fā)癥”和“新生兒轉(zhuǎn)出重癥監(jiān)護(hù)病房后的管理”)

定義

早產(chǎn) — 早產(chǎn)程度通常由出生體重(birth weight, BW)或胎齡來(lái)定義憎亚，在本專題中使用以下定義(表 1)员寇。

按BW分類如下：

低出生體重兒(low birth weight, LBW)–BW小于2000g

極低出生體重兒(very low birth weight, VLBW)–BW小于1500g

超低出生體重兒(extremely low birth weight, ELBW)–BW小于1000g

按GA分類如下：

晚期早產(chǎn)–GA介于34至36+6周弄慰。

中度早產(chǎn)–GA介于32至33+6周。

早期早產(chǎn)(very preterm, VPT)–GA介于28至31+6周蝶锋。

極早早產(chǎn)(extremely preterm, EPT)–GA不足28周陆爽。

現(xiàn)已確定了相應(yīng)GA的BW百分位數(shù)(表 2A-B)。

神經(jīng)發(fā)育結(jié)局 — 神經(jīng)發(fā)育結(jié)局是一個(gè)復(fù)合術(shù)語(yǔ)扳缕，通常指認(rèn)知慌闭、神經(jīng)系統(tǒng)和/或感覺(jué)發(fā)育的結(jié)局。

傳統(tǒng)上在結(jié)局研究中躯舔，神經(jīng)發(fā)育損害被定義為存在一個(gè)或多個(gè)以下問(wèn)題：

認(rèn)知遲緩驴剔，判斷依據(jù)是標(biāo)準(zhǔn)化認(rèn)知測(cè)試得分低于均值2個(gè)標(biāo)準(zhǔn)差(standard deviations, SD)。例如粥庄，這相當(dāng)于貝利嬰兒發(fā)育量表(Bayley Scales of Infant Development, BSID)智力發(fā)育指數(shù)(Mental Developmental Index, MDI)得分小于等于70丧失。

中到重度腦性癱瘓(cerebral palsy, CP)，定義為大運(yùn)動(dòng)功能分級(jí)系統(tǒng)(Gross Motor Function Classification System, GMFCS)評(píng)分大于等于2惜互。

需要助聽(tīng)裝置的雙耳聽(tīng)力缺陷/損失布讹。

嚴(yán)重視力障礙，視力較好一側(cè)眼睛的最佳常規(guī)矯正視力小于等于20/200(即法定盲的定義)训堆。

此外描验，行為、心理及功能結(jié)局也逐漸被認(rèn)為是重要的遠(yuǎn)期神經(jīng)發(fā)育結(jié)局坑鱼，也會(huì)在本文中討論挠乳。

解讀結(jié)局資料的困難

由于臨床實(shí)踐(例如，生存力極限)和研究設(shè)計(jì)(研究人群姑躲、評(píng)估工具和結(jié)局定義)的差異以及圍生期保健隨時(shí)間的變化睡扬，新生兒結(jié)局文獻(xiàn)的解讀較難。因此黍析，在比較各研究或試圖將文獻(xiàn)結(jié)果應(yīng)用于臨床時(shí)卖怜，需要考慮到這些因素。

臨床實(shí)踐的差異：生存力極限 — 在發(fā)達(dá)國(guó)家阐枣，對(duì)于處于生存力閾值的嬰兒(可確保有較大宮外存活機(jī)會(huì)的胎兒成熟期)马靠，提供的初始管理水平有全球性和地區(qū)性差異[1-3]。臨床實(shí)踐中的這些差異會(huì)影響在妊娠22-25周出生的嬰兒的生存率(表 3)蔼两，可能還會(huì)影響神經(jīng)發(fā)育結(jié)局(表 4)甩鳄。因此，很難比較采用不同復(fù)蘇方法的研究中EPT嬰兒的生存率及神經(jīng)發(fā)育結(jié)局额划，也很難基于個(gè)體患者解讀這些數(shù)據(jù)妙啃。(參見(jiàn)“Periviable birth (Limit of viability)”, section on ‘Impact of initial management’)

處于生存力極限的早產(chǎn)兒的相關(guān)數(shù)據(jù)解讀參見(jiàn)其他專題。(參見(jiàn)“Periviable birth (Limit of viability)”, section on ‘Interpreting the data’)

研究設(shè)計(jì)因素

研究人群–界定研究人群的差異使得比較不同研究的數(shù)據(jù)存在困難。

?例如揖赴，用出生體重而非胎齡來(lái)分類可能存在問(wèn)題馆匿，因?yàn)橐粋€(gè)出生體重分類中可能包括相對(duì)較成熟的宮內(nèi)發(fā)育遲緩(intrauterine growth retardation, IUGR)嬰兒。如果有較多的IUGR患兒燥滑，可能會(huì)影響結(jié)局渐北，因?yàn)镮UGR嬰兒發(fā)生新生兒并發(fā)癥和較差結(jié)局的風(fēng)險(xiǎn)高于相應(yīng)的適于胎齡兒(appropriate for gestational age, AGA)，但其結(jié)局通常優(yōu)于同等出生體重的更早產(chǎn)嬰兒[4](參見(jiàn)“胎兒期(宮內(nèi))生長(zhǎng)受限的嬰兒”)铭拧。隨著確定胎齡的技術(shù)得到改善赃蛛，按GA分類已成為主導(dǎo)。盡管GA分類法可能在同一組中納入大于胎齡兒和小于胎齡兒搀菩，但相比于BW分類法呕臂，該方法所確定的分組更有可能納入相似胚胎/胎兒發(fā)育階段的嬰兒。因此秕磷，胎齡分類更常用于報(bào)告早產(chǎn)兒的遠(yuǎn)期結(jié)局。

?轉(zhuǎn)運(yùn)嬰兒 vs 非轉(zhuǎn)運(yùn)嬰兒–與不需要轉(zhuǎn)運(yùn)的嬰兒相比炼团，在沒(méi)有三級(jí)新生兒重癥監(jiān)護(hù)病房(neonatal intensive care unit, NICU)澎嚣、需要新生兒轉(zhuǎn)運(yùn)的中心出生的早產(chǎn)兒，并發(fā)癥發(fā)生率和死亡率似乎更高[5,6]瘟芝。因此易桃，研究之間非轉(zhuǎn)運(yùn)和轉(zhuǎn)運(yùn)嬰兒的混合分析可能會(huì)影響生存率和遠(yuǎn)期結(jié)局。

結(jié)局測(cè)量指標(biāo)的定義–不同的結(jié)局定義锌俱，特別是重度神經(jīng)發(fā)育損害(neurodevelopmental impairment, NDI)的定義晤郑，會(huì)改變結(jié)果。例如贸宏，對(duì)加拿大新生兒隨訪網(wǎng)絡(luò)(Canadian Neonatal Follow-up Network)早產(chǎn)兒(胎齡23-28周)數(shù)據(jù)庫(kù)的一項(xiàng)分析顯示造寝，根據(jù)不同的定義，重度NDI的發(fā)生率為3.5%-14.9%[7]吭练。NDI通常定義為至少有以下一種情況：認(rèn)知或運(yùn)動(dòng)測(cè)試得分低于均值2個(gè)標(biāo)準(zhǔn)差以上诫龙；助聽(tīng)裝置無(wú)效的雙耳聽(tīng)力損失；雙眼法定盲鲫咽；以及中度签赃、重度或深度腦癱。

評(píng)估方法–不同研究中用于評(píng)估結(jié)局的工具不同分尸，因此結(jié)果可能無(wú)法直接比較锦聊。例如，一些研究顯示箩绍，第3版貝利標(biāo)準(zhǔn)(BSID Ⅲ孔庭，2006)測(cè)定的認(rèn)知評(píng)分高于第2版(BSID Ⅱ，1992)[8-11]材蛛。BSID Ⅲ是高估了認(rèn)知表現(xiàn)還是可以比BSID Ⅱ更準(zhǔn)確地評(píng)估認(rèn)知功能史飞，目前還不明確尖昏。2019年9月發(fā)布了第4版貝利標(biāo)準(zhǔn)(BSID Ⅳ)，但目前還沒(méi)有研究比較BSID Ⅳ與之前版本對(duì)早產(chǎn)存活者的評(píng)估构资。

后續(xù)混雜因素–可能影響神經(jīng)發(fā)育和入學(xué)準(zhǔn)備度的后續(xù)因素包括社會(huì)人口學(xué)因素(例如抽诉，母親的教育程度)、家庭收入(例如吐绵，Medicaid保險(xiǎn)是貧困的標(biāo)志)迹淌、持續(xù)存在的健康問(wèn)題及是否參與早期干預(yù)項(xiàng)目。這些因素的存在情況可能各異己单，因此很難比較不同研究的結(jié)果乌妒。(參見(jiàn)“School readiness for children in the United States”, section on ‘Factors related to a child's ability to learn’)

生存率隨時(shí)間的變化 — 圍生期醫(yī)療的進(jìn)步提高了存活率[12]凿傅，因此，更難準(zhǔn)確判斷臨床實(shí)踐的變化對(duì)改善神經(jīng)發(fā)育結(jié)局的影響，因?yàn)樯媛侍岣叩乃俣纫呀?jīng)超過(guò)了伴隨的遠(yuǎn)期神經(jīng)發(fā)育后遺癥發(fā)生率降低的速度庞萍。

隨著圍生期醫(yī)療的進(jìn)步，關(guān)于早產(chǎn)兒的神經(jīng)發(fā)育結(jié)局是否隨存活情況一并得到改善套耕，相關(guān)數(shù)據(jù)不一致构灸。雖然世界各發(fā)達(dá)國(guó)家的一些大型或人群研究表明，早產(chǎn)兒的神經(jīng)發(fā)育結(jié)局和生存率均有所改善[13-19]笋额，但也有例外[20,21]元暴。結(jié)果不一致的原因可能是不同胎齡或出生年份的結(jié)局改善有差異。以下研究強(qiáng)調(diào)了在比較結(jié)局時(shí)考慮胎齡的重要性：

法國(guó)的一項(xiàng)對(duì)早產(chǎn)兒的人群研究[Etude épidémiologique sur les petits ages gestationnels(EPIPAGE)和EPIPAGE-2]報(bào)道兄猩，從1997年至2011年茉盏，妊娠25-26周出生的嬰兒和妊娠27-31周出生的嬰兒中，不伴重度或中度神經(jīng)運(yùn)動(dòng)或運(yùn)動(dòng)感覺(jué)障礙的生存率增加枢冤，分別為45.5% vs 62.3%和82.1% vs 90.3%[22]鸠姨。然而，在妊娠24周出生的嬰兒或妊娠32-34周出生的嬰兒中淹真，兩個(gè)隊(duì)列的不伴重大殘疾生存率沒(méi)有差異享怀，分別為29% vs 25.8%和95.7% vs 96.8%。此外趟咆，在2011年的隊(duì)列中僅有1例在妊娠22-23周出生的嬰兒存活添瓷。

在美國(guó)國(guó)立兒童健康與人類發(fā)展研究所(National Institute of Child Health and Human Development, NICHD)網(wǎng)絡(luò)的一份報(bào)告中，1995-2010年間出生于胎齡25周值纱、26周鳞贷、27周和28周的嬰兒中，不伴重大新生兒并發(fā)癥的生存率有所改善虐唠，但在胎齡23周和24周出生的嬰兒中沒(méi)有變化[12]搀愧。

在隨后對(duì)EPT嬰兒(胎齡<28周)的一項(xiàng)NICHD研究中，2011-2014年，重度腦癱的發(fā)病率下降了43%咱筛，輕度腦癱的發(fā)病率上升了13%[18]搓幌。

臨床實(shí)踐的改變 — 現(xiàn)認(rèn)為，觀察到的一些隨時(shí)間而發(fā)生的臨床實(shí)踐改變是新生兒存活率提高的主要原因迅箩，也可能是神經(jīng)發(fā)育結(jié)局改善的主要原因[13-16]溉愁。因此，對(duì)不同時(shí)代出生隊(duì)列之間的比較應(yīng)慎重解讀饲趋。這在與較近期出生隊(duì)列比較早產(chǎn)兒成人期結(jié)局時(shí)尤為重要拐揭，因?yàn)殡S著臨床實(shí)踐改變，2015年出生的EPT嬰兒(胎齡<28周)所接受的治療干預(yù)不同于1993年出生的嬰兒奕塑，因此堂污，其遠(yuǎn)期結(jié)局風(fēng)險(xiǎn)可能也不同。例如龄砰，美國(guó)NICHD的一項(xiàng)研究顯示盟猖，隨著臨床實(shí)踐的一些改變(例如，產(chǎn)前皮質(zhì)類固醇應(yīng)用增加换棚，以及產(chǎn)后皮質(zhì)類固醇使用率和產(chǎn)房插管率降低)式镐，新生兒生存率提高，特定并發(fā)癥發(fā)生率降低[例如圃泡，重度腦室內(nèi)出血(intraventricular hemorrhage, IVH)和晚發(fā)型膿毒癥][12]碟案。但該研究未評(píng)估神經(jīng)發(fā)育結(jié)局愿险。另一項(xiàng)meta分析發(fā)現(xiàn)颇蜡，在使用產(chǎn)前類固醇和表面活性物質(zhì)時(shí)代出生的早產(chǎn)兒(胎齡<37周)到5歲或5歲以上時(shí)，神經(jīng)發(fā)育結(jié)局仍然不如足月出生者辆亏，包括學(xué)習(xí)成績(jī)方面的嚴(yán)重困難[23]风秤。

預(yù)防性干預(yù)措施 — 過(guò)去數(shù)十年，圍生期保健中出現(xiàn)的下列變化/干預(yù)可能直接或間接[通過(guò)減少相關(guān)并發(fā)癥扮叨，如腦室周圍-腦室內(nèi)出血(periventricular-intraventricular hemorrhage, PIVH)]改善神經(jīng)發(fā)育結(jié)局缤弦。

產(chǎn)前皮質(zhì)類固醇治療，可降低死亡率和神經(jīng)發(fā)育損害發(fā)生率彻磁、減少中度至重度腦癱的發(fā)病率碍沐、縮短機(jī)械通氣時(shí)間，以及降低發(fā)生重度PIVH的風(fēng)險(xiǎn)[24,25]衷蜓。(參見(jiàn)下文‘相關(guān)病況’和“產(chǎn)前皮質(zhì)類固醇治療以減少早產(chǎn)導(dǎo)致的新生兒呼吸系統(tǒng)并發(fā)癥發(fā)病率和死亡率”)

避免出生后早期使用皮質(zhì)類固醇治療累提，因其與發(fā)生腦癱的風(fēng)險(xiǎn)增加有關(guān)。關(guān)于出生后使用皮質(zhì)類固醇治療的遠(yuǎn)期影響詳見(jiàn)其他專題[26-28]磁浇。(參見(jiàn)“支氣管肺發(fā)育不良的預(yù)防：出生后使用糖皮質(zhì)激素”)

新生兒通氣的進(jìn)步斋陪，包括采取無(wú)創(chuàng)通氣方法[如持續(xù)氣道正壓(continuous positive airway pressure, cPAP)]和改進(jìn)機(jī)械通氣策略(例如，容量目標(biāo)和同步化通氣)，提高了生存率并降低了并發(fā)癥發(fā)生率[如无虚，支氣管肺發(fā)育不良(bronchopulmonary dysplasia, BPD)缔赠、重度PIVH和肺氣漏]，這可能影響神經(jīng)發(fā)育結(jié)局友题。(參見(jiàn)下文‘相關(guān)病況’和“新生兒機(jī)械通氣”和“支氣管肺發(fā)育不良嬰兒的結(jié)局”嗤堰，關(guān)于‘神經(jīng)發(fā)育結(jié)局’一節(jié)和“新生兒生發(fā)基質(zhì)-腦室內(nèi)出血的預(yù)防、管理和并發(fā)癥”咆爽，關(guān)于‘遠(yuǎn)期結(jié)局’一節(jié)和“新生兒肺氣漏”)

表面活性物質(zhì)梁棠，其與生存率增加相關(guān)，特別是對(duì)EPT嬰兒斗埂。然而符糊，表面活性物質(zhì)治療與神經(jīng)發(fā)育結(jié)局改善沒(méi)有直接關(guān)系。(參見(jiàn)“早產(chǎn)兒呼吸窘迫綜合征的預(yù)防和治療”)

產(chǎn)前使用硫酸鎂呛凶，這與腦癱和重度運(yùn)動(dòng)功能障礙風(fēng)險(xiǎn)降低相關(guān)男娄。臨床試驗(yàn)顯示，母親使用硫酸鎂的早產(chǎn)兒發(fā)生腦癱和重度運(yùn)動(dòng)功能障礙的風(fēng)險(xiǎn)低于無(wú)宮內(nèi)暴露者漾稀。(參見(jiàn)“硫酸鎂對(duì)胎兒的神經(jīng)保護(hù)作用”模闲，關(guān)于‘隨機(jī)試驗(yàn)和meta分析的療效證據(jù)’一節(jié))

無(wú)效的預(yù)防措施 — 既往觀察數(shù)據(jù)表明，預(yù)防性使用重組紅細(xì)胞生成素(recombinant erythropoietin, EPO)具有神經(jīng)保護(hù)作用崭捍，然而尸折，一項(xiàng)對(duì)941例EPT嬰兒進(jìn)行的多中心試驗(yàn)報(bào)道，EPO對(duì)改善神經(jīng)發(fā)育結(jié)局沒(méi)有益處[29]殷蛇。矯正胎齡22-26個(gè)月時(shí)实夹，EPO組和安慰劑組的主要結(jié)局發(fā)生率相近(26% vs 26%，RR 1.03粒梦，95%CI 0.81-1.32)亮航。主要結(jié)局指的是死亡或重度神經(jīng)發(fā)育損害，后者定義為重度腦癱匀们，或使用BSID Ⅲ得到的運(yùn)動(dòng)或認(rèn)知綜合評(píng)分低于70[29]缴淋。在該試驗(yàn)中，受試者在出生后24小時(shí)內(nèi)接受安慰劑或EPO(劑量為1000U/kg)泄朴，每48小時(shí)1次重抖，共6次。EPO組和安慰劑組的早產(chǎn)兒視網(wǎng)膜病變(retinopathy of prematurity, ROP)祖灰、顱內(nèi)出血钟沛、BPD、壞死性小腸結(jié)腸炎(necrotizing enterocolitis, NEC)夫植、死亡或嚴(yán)重不良反應(yīng)發(fā)生率相近讹剔。因此油讯，不應(yīng)預(yù)防性地使用EPO作為神經(jīng)保護(hù)劑。

神經(jīng)發(fā)育殘疾和學(xué)業(yè)成績(jī)

結(jié)局研究表明延欠，GA和BW越小陌兑，神經(jīng)發(fā)育殘疾的風(fēng)險(xiǎn)越高[24,30-36]。下文根據(jù)胎齡分類總結(jié)了存活者的結(jié)局?jǐn)?shù)據(jù)由捎。(參見(jiàn)上文‘早產(chǎn)’)

EPT嬰兒

患病率和嚴(yán)重程度 — 一些研究顯示兔综，在EPT和/或ELBW嬰兒中，存在神經(jīng)發(fā)育損害的ELBW存活者的比例較高狞玛，且通常會(huì)隨胎齡增加而降低(表 4)软驰。EPT存活者常發(fā)生認(rèn)知障礙以及運(yùn)動(dòng)和感覺(jué)神經(jīng)障礙，且通常較嚴(yán)重心肪，會(huì)持續(xù)到學(xué)齡期和成人期锭亏。

基于現(xiàn)有文獻(xiàn)，我們與EPT嬰兒的父母及看護(hù)人員討論以下臨床結(jié)局指標(biāo)的風(fēng)險(xiǎn)硬鞍。如上所述慧瘤，綜合這些信息存在困難，因?yàn)檠芯吭O(shè)計(jì)不同(例如固该，結(jié)局評(píng)估的年齡和重大殘疾的定義)锅减，并且結(jié)局?jǐn)?shù)據(jù)與較新的出生隊(duì)列不同。(參見(jiàn)上文‘解讀結(jié)局資料的困難’)

重大殘疾–重大殘疾是指標(biāo)準(zhǔn)化認(rèn)知和運(yùn)動(dòng)測(cè)試得分低于均值2個(gè)標(biāo)準(zhǔn)差以上和/或存在腦癱伐坏、盲和需要助聽(tīng)裝置的聽(tīng)力損失怔匣。

?1995-2007年出生隊(duì)列的6-10歲學(xué)齡兒童–人群研究報(bào)道，出生時(shí)為EPT的兒童中桦沉，17%-46%有重大殘疾[37-40]每瞒。據(jù)報(bào)道，1995年出生永部、胎齡<25周的患兒風(fēng)險(xiǎn)最高[38]独泞。

?2008-2011年出生呐矾、矯正月齡為18-24個(gè)月的幼兒出生隊(duì)列–根據(jù)認(rèn)知測(cè)試分?jǐn)?shù)或存在腦癱苔埋、盲和需要助聽(tīng)器的聽(tīng)力損失，在較近的出生隊(duì)列中蜒犯，約一半EPT出生的兒童有重大殘疾[22,41]组橄。

18-24個(gè)月時(shí)的重大殘疾可能在整個(gè)兒童時(shí)期持續(xù)存在。

學(xué)習(xí)障礙及需要專門的教育干預(yù)和服務(wù)–EPT出生的兒童更有可能在閱讀和數(shù)學(xué)方面有學(xué)習(xí)困難罚随，并且教師評(píng)分較低[42-45]玉工。這些兒童常需要額外的教育干預(yù)和特殊服務(wù)[43,46]。

成人結(jié)局–僅有1995年的一個(gè)出生隊(duì)列的成人結(jié)局?jǐn)?shù)據(jù)淘菩，該隊(duì)列顯示遵班，約60%的個(gè)體在19歲時(shí)有至少1種認(rèn)知功能和視覺(jué)運(yùn)動(dòng)能力損害屠升，1/3有4類或更多缺陷[47]。45%的EPT出生成人存在認(rèn)知障礙狭郑，而對(duì)照組只有3%腹暖。

危險(xiǎn)因素 — EPT出生者神經(jīng)發(fā)育損害的危險(xiǎn)因素還包括[33,48,49]：

母親因素–受教育水平較低、無(wú)商業(yè)保險(xiǎn)翰萨、非白人種族脏答、未婚和肥胖。出院后需要兒童保護(hù)服務(wù)監(jiān)管的嬰兒在2歲時(shí)認(rèn)知發(fā)育延遲的風(fēng)險(xiǎn)增加[50]亩鬼。

嬰兒因素–宮內(nèi)生長(zhǎng)障礙[4]殖告、男性[37,51]、多胎生產(chǎn)雳锋、非白人黄绩，以及伴隨重大新生兒并發(fā)癥(重度IVH、腦室周圍白質(zhì)軟化和接受大手術(shù))玷过。[39,52]

醫(yī)療保健因素–未進(jìn)行產(chǎn)前保健或產(chǎn)前未使用皮質(zhì)類固醇宝与，以及陰道分娩。

早期早產(chǎn)兒 — 雖然VPT(胎齡28周至<32周)或VLBW(出生體重<1500g)嬰兒出現(xiàn)神經(jīng)發(fā)育障礙的風(fēng)險(xiǎn)低于EPT或ELBW存活兒冶匹，但仍有相當(dāng)數(shù)量存在神經(jīng)發(fā)育缺陷[46,53-60]习劫。對(duì)VLBW嬰兒的研究也可能包含ELBW，這可能不成比例地促進(jìn)不良結(jié)局嚼隘。因此诽里，由于這些研究中ELBW患者的相對(duì)百分比不同，結(jié)局?jǐn)?shù)據(jù)可能存在差異飞蛹。(參見(jiàn)上文‘研究設(shè)計(jì)因素’)

研究者在一個(gè)包含2901例1997年出生早產(chǎn)兒的前瞻性隊(duì)列中說(shuō)明了VPT嬰兒的風(fēng)險(xiǎn)程度[46]谤狡。該研究顯示，在29-32周出生者的早產(chǎn)兒中卧檐，在5歲時(shí)36%有神經(jīng)發(fā)育障礙墓懂，30%使用了特殊的醫(yī)療資源(例如，物理治療霉囚、言語(yǔ)治療捕仔、技能訓(xùn)練、心理學(xué)治療和精神科治療)盈罐。即使出院時(shí)沒(méi)有中度或重度神經(jīng)障礙的兒童榜跌，與足月對(duì)照者相比，仍有可能出現(xiàn)全面發(fā)育遲緩和學(xué)習(xí)成績(jī)差異[53,54]盅粪。出現(xiàn)不良結(jié)局的危險(xiǎn)因素包括：出生胎齡較小钓葫、影像學(xué)檢查發(fā)現(xiàn)腦病變、宮內(nèi)生長(zhǎng)障礙票顾、未母乳喂養(yǎng)础浮，以及父母社會(huì)經(jīng)濟(jì)地位低帆调。在2011年出生的嬰兒隊(duì)列中，妊娠27-31周出生的嬰兒2歲時(shí)有4.2%出現(xiàn)腦癱豆同，41%出現(xiàn)發(fā)育遲緩[22]

其他研究報(bào)道贷帮，與足月出生的兒童相比，VPT學(xué)齡兒童的記憶力評(píng)分較差诱告，并且更有可能出現(xiàn)學(xué)習(xí)困難[59,61]撵枢。?

在一項(xiàng)文獻(xiàn)系統(tǒng)評(píng)價(jià)中，5歲以下早期早產(chǎn)兒發(fā)生認(rèn)知發(fā)育不良的可能危險(xiǎn)因素包括男性精居、低GA和父母教育水平低[60]锄禽。然而，在年長(zhǎng)兒中唯一持續(xù)存在的危險(xiǎn)因素是父母教育水平低下靴姿。

其他研究報(bào)道沃但，與足月出生的兒童相比，VPT學(xué)齡兒童的記憶力評(píng)分較差佛吓，并且更有可能出現(xiàn)學(xué)習(xí)困難[59,61]宵晚。?

中度至晚期早產(chǎn)兒 — 中度(胎齡在32-33+6周)和晚期(胎齡在34周至＜37周)早產(chǎn)兒存在遠(yuǎn)期神經(jīng)發(fā)育損害的可能性大于足月兒。對(duì)世界各地中度至晚期早產(chǎn)兒的縱向國(guó)際性研究基于評(píng)估年齡報(bào)道了以下神經(jīng)發(fā)育損害[62-70]：

2歲–認(rèn)知測(cè)試結(jié)果差维雇，神經(jīng)心理功能和感覺(jué)神經(jīng)損害淤刃。[62,70,71]

學(xué)齡前–據(jù)家長(zhǎng)報(bào)告，學(xué)齡前發(fā)育遲緩吱型。[64]

學(xué)齡期–認(rèn)知測(cè)試差逸贾，需要特殊教育服務(wù)，學(xué)業(yè)測(cè)試或教師評(píng)估成績(jī)低于預(yù)期年級(jí)水平[63,66,67,72,73]

晚期早產(chǎn)兒(胎齡為34-36周)的遠(yuǎn)期神經(jīng)發(fā)育結(jié)局詳見(jiàn)其他專題津滞。(參見(jiàn)“晚期早產(chǎn)兒”铝侵，關(guān)于‘神經(jīng)發(fā)育結(jié)局’一節(jié))

結(jié)構(gòu)性腦損傷 — 重度新生兒腦損傷(即頭部超聲檢測(cè)到異常)的早產(chǎn)存活者有最嚴(yán)重的神經(jīng)發(fā)育損害[例如，需要額外的學(xué)校服務(wù)触徐，以及伴運(yùn)動(dòng)咪鲜、認(rèn)知或感覺(jué)神經(jīng)損害的重大殘疾(如，腦癱)][74-77]撞鹉。新生兒腦損傷也可能與青春期精神障礙[例如疟丙，重性抑郁和強(qiáng)迫癥(obsessive-compulsive disorder, OCD)]風(fēng)險(xiǎn)增高相關(guān)[78]。

MRI證實(shí)早產(chǎn)兒在學(xué)齡期孔祸、青春期和成人期存在大腦結(jié)構(gòu)改變隆敢，包括胼胝體變薄发皿、腦室容積增加崔慧、腦發(fā)育期灰質(zhì)和白質(zhì)的相對(duì)體積減少，以及總腦容積減少[79-88]穴墅。

言語(yǔ)和語(yǔ)言結(jié)局 — 早產(chǎn)存活兒中常見(jiàn)言語(yǔ)和語(yǔ)言障礙惶室，其風(fēng)險(xiǎn)和嚴(yán)重度與GA成反比温自。表達(dá)性和/或感受性語(yǔ)言的習(xí)得及發(fā)音清晰度方面可能存在遲緩[9,89-92]。有證據(jù)表明皇钞，與足月對(duì)照組相比悼泌，早產(chǎn)兒的言語(yǔ)功能出現(xiàn)部分性追趕，并隨著母親受教育水平等環(huán)境因素而增加[92,93]夹界。語(yǔ)言結(jié)局與認(rèn)知功能馆里、聽(tīng)覺(jué)、產(chǎn)前和產(chǎn)后社會(huì)經(jīng)濟(jì)地位可柿、環(huán)境鸠踪、族群以及既往插管相關(guān)喉水平結(jié)構(gòu)改變有關(guān)[91,94-96]。

行為和心理影響

早產(chǎn)兒(尤其是EPT或VPT)在兒童期出現(xiàn)特定行為和心理問(wèn)題的可能性高于足月出生者复斥。

極早早產(chǎn)和早期早產(chǎn)兒 — EPT或VPT出生的兒童比足月出生的兒童更可能發(fā)生行為和心理問(wèn)題营密。對(duì)NICHD新生兒研究網(wǎng)絡(luò)中2008-2012年出生的EPT嬰兒(胎齡<27周)進(jìn)行的一項(xiàng)研究報(bào)道，在矯正月齡為18-22個(gè)月時(shí)目锭，1/3的嬰兒存在行為問(wèn)題评汰，1/4存在社會(huì)情緒能力缺陷[97]。社會(huì)人口學(xué)因素(例如痢虹，母親受教育程度在高中以下被去、母親年齡較小)及認(rèn)知和語(yǔ)言功能缺陷會(huì)增加早產(chǎn)兒發(fā)生行為和社會(huì)情緒能力問(wèn)題的風(fēng)險(xiǎn)。然而奖唯，與足月兒相比编振，早產(chǎn)兒在青春期和成年早期傾向于采取風(fēng)險(xiǎn)較低的行為，且更靦腆[98-102]臭埋。

與足月出生的同齡人相比踪央，以下行為問(wèn)題和心理問(wèn)題在EPT或VPT出生的兒童和青少年中更常見(jiàn)。

注意力集中困難[98,102-111]

同伴互動(dòng)不良[99,105-107,111,112]

多動(dòng)[102-106,108-110,113]

情緒和品行問(wèn)題瓢阴，包括焦慮畅蹂、抑郁、退縮和軀體主訴[98,102,103,105-107,109,110,114,115]

孤獨(dú)癥譜系障礙[109,116,117]

精神障礙[114,118,119]

中度至晚期早產(chǎn)兒 — 雖然數(shù)據(jù)有限荣恐，但根據(jù)父母的評(píng)估液斜，中度至晚期早產(chǎn)兒在學(xué)齡前存在行為和情緒問(wèn)題的風(fēng)險(xiǎn)高于足月出生的同齡人[120-122]。另外叠穆，一項(xiàng)報(bào)告顯示少漆，中度至晚期早產(chǎn)兒在2歲時(shí)孤獨(dú)癥篩查測(cè)試陽(yáng)性的可能性高于足月出生兒[123]。

功能殘疾

與足月出生的同齡人相比硼被，EPT或VPT出生的學(xué)齡兒童更可能發(fā)生影響其完成日呈舅穑活動(dòng)和生活質(zhì)量的功能障礙，可能為輕微缺陷嚷硫，包括運(yùn)動(dòng)協(xié)調(diào)(發(fā)育性運(yùn)動(dòng)協(xié)調(diào)障礙检访，也稱為非腦癱性運(yùn)動(dòng)障礙)[124,125]始鱼、社交技能和執(zhí)行功能(工作記憶、解決問(wèn)題脆贵、規(guī)劃和組織)方面的問(wèn)題[56,72,111,126-130]医清。胎齡越小，發(fā)生功能障礙的風(fēng)險(xiǎn)越高卖氨，據(jù)報(bào)道会烙，在妊娠26周前出生的兒童有40%會(huì)出現(xiàn)功能障礙[42,56]。在一些兒童中筒捺，這些缺陷可能影響學(xué)業(yè)持搜、運(yùn)動(dòng)和行為結(jié)局。(參見(jiàn)“發(fā)育性協(xié)調(diào)障礙：臨床特征和診斷”)

環(huán)境對(duì)潛在神經(jīng)功能改善的影響

盡管早產(chǎn)和腦損傷與神經(jīng)發(fā)育障礙之間的關(guān)聯(lián)已經(jīng)很清楚焙矛，但我們對(duì)環(huán)境和經(jīng)驗(yàn)在調(diào)節(jié)這些關(guān)聯(lián)中的作用卻知之甚少葫盼。幾項(xiàng)研究報(bào)道了環(huán)境因素對(duì)認(rèn)知和言語(yǔ)-語(yǔ)言功能的有益影響，包括較高的母親受教育水平村斟、父母干預(yù)贫导、高質(zhì)量的家庭環(huán)境和日間看護(hù)資源[92,93,131-134]。然而蟆盹，較高的母親受教育水平對(duì)運(yùn)動(dòng)結(jié)局不存在有益影響[135]孩灯。

成人結(jié)局

殘疾 — 在既往為早產(chǎn)的個(gè)體中，GA越小逾滥，成人期醫(yī)學(xué)和社會(huì)殘疾的風(fēng)險(xiǎn)越高峰档。

一些研究報(bào)道，早產(chǎn)存活兒成年后的教育成就寨昙、獨(dú)立生活的比例讥巡、凈收入和終生雇傭率低于足月出生者[136-141]。這些結(jié)果很可能由以下兩個(gè)原因造成：認(rèn)知技能差導(dǎo)致學(xué)習(xí)能力受損舔哪，特別是出生體重低于1500g或胎齡低于32周的成人欢顷；發(fā)生醫(yī)學(xué)殘疾(腦癱、精神和行為障礙捉蚤，以及軀體殘疾)的風(fēng)險(xiǎn)增加[136,142-144]抬驴。較高的社會(huì)經(jīng)濟(jì)地位似乎可減輕GA對(duì)認(rèn)知功能測(cè)試評(píng)分的影響[142]。

而其他研究顯示缆巧，雖然早產(chǎn)兒出現(xiàn)神經(jīng)發(fā)育障礙的風(fēng)險(xiǎn)較高布持，但其在成人期可能會(huì)克服這些困難，成為功能正常的年輕成人的比例與足月出生者相當(dāng)陕悬，包括高中畢業(yè)题暖、接受高等教育、就業(yè)、獨(dú)立生活芙委、婚姻和養(yǎng)育子女方面[145,146]逞敷。這些研究的結(jié)局差異歸因于研究人群的社會(huì)經(jīng)濟(jì)地位較高狂秦、教育支持增加或來(lái)自國(guó)家醫(yī)療保健體系的獲益[147]灌侣。

生活質(zhì)量 — 早產(chǎn)年輕成人及其父母報(bào)告的功能限制患病率及復(fù)雜程度均高于足月出生對(duì)照者及其父母所報(bào)告的[148]×盐剩縱向研究報(bào)道侧啼，根據(jù)健康效用指數(shù)標(biāo)記-3問(wèn)卷的評(píng)估結(jié)果，早期早產(chǎn)個(gè)體的健康相關(guān)生命質(zhì)量更低[148-150]堪簿。對(duì)該文獻(xiàn)的一項(xiàng)系統(tǒng)評(píng)價(jià)顯示痊乾，早產(chǎn)兒成年后建立戀愛(ài)關(guān)系、性關(guān)系及養(yǎng)育子女的可能性較小[151]椭更。但在一些研究中哪审，早產(chǎn)成人及其家人所報(bào)告的滿意生活質(zhì)量與足月出生者相似[152-156]。

此外虑瀑，早產(chǎn)患者及其父母所感受到的生活質(zhì)量?jī)?yōu)于醫(yī)護(hù)人員所判斷的[157]湿滓。因此，醫(yī)護(hù)人員須認(rèn)識(shí)到這種差異舌狗，以便不僅重點(diǎn)關(guān)注患者的神經(jīng)發(fā)育殘疾叽奥，而且拓寬對(duì)結(jié)局的考慮，將成人存活者憑著對(duì)生活質(zhì)量的積極自我感知從而克服自身限制的能力也考慮在內(nèi)[145,158,159]痛侍。

相關(guān)病況

與神經(jīng)發(fā)育結(jié)局不良風(fēng)險(xiǎn)增加有關(guān)的早產(chǎn)相關(guān)新生兒病況包括：

BPD[41,160,161]朝氓。(參見(jiàn)“支氣管肺發(fā)育不良嬰兒的結(jié)局”，關(guān)于‘神經(jīng)發(fā)育結(jié)局’一節(jié))

此外主届，出生后應(yīng)用糖皮質(zhì)激素治療BPD與腦癱風(fēng)險(xiǎn)增加有關(guān)赵哲。(參見(jiàn)“支氣管肺發(fā)育不良的預(yù)防：出生后使用糖皮質(zhì)激素”)

圍生期感染，包括[41,162,163]：

?壞死性小腸結(jié)腸炎(necrotizing enterocolitis, NEC)(參見(jiàn)“新生兒壞死性小腸結(jié)腸炎：治療”君丁，關(guān)于‘生長(zhǎng)發(fā)育’一節(jié))

?膿毒癥(參見(jiàn)“早產(chǎn)兒(胎齡小于34周)細(xì)菌性膿毒癥的治療和預(yù)防”誓竿，關(guān)于‘并發(fā)癥’一節(jié))

?腦膜炎(參見(jiàn)“新生兒細(xì)菌性腦膜炎：治療和結(jié)局”，關(guān)于‘結(jié)局’一節(jié))

ROP谈截。(參見(jiàn)“早產(chǎn)兒視網(wǎng)膜病變的發(fā)病機(jī)制筷屡、流行病學(xué)、分類和篩查”)

IVH簸喂。(參見(jiàn)“新生兒生發(fā)基質(zhì)-腦室內(nèi)出血的預(yù)防毙死、管理和并發(fā)癥”，關(guān)于‘結(jié)局’一節(jié))

生長(zhǎng)不良：

?胎兒生長(zhǎng)受限–胎兒生長(zhǎng)受限會(huì)增加早產(chǎn)兒發(fā)生神經(jīng)發(fā)育結(jié)局受損的風(fēng)險(xiǎn)喻鳄。(參見(jiàn)“胎兒期(宮內(nèi))生長(zhǎng)受限的嬰兒”扼倘，關(guān)于‘神經(jīng)發(fā)育’一節(jié))

?出生后生長(zhǎng)–在VPT嬰兒中，生長(zhǎng)障礙，包括頭部生長(zhǎng)不良再菊，會(huì)造成認(rèn)知和運(yùn)動(dòng)功能受損[164-166]爪喘。美國(guó)NICHD新生兒研究網(wǎng)的一項(xiàng)報(bào)告表明生長(zhǎng)改善與神經(jīng)發(fā)育結(jié)局改善相關(guān)，該研究在矯正年齡為18-22個(gè)月時(shí)對(duì)ELBW兒進(jìn)行評(píng)估纠拔，發(fā)現(xiàn)其在新生兒重癥監(jiān)護(hù)病房(neonatal intensive care unit, NICU)住院期間的體重增長(zhǎng)越多秉剑，則CP發(fā)病率越低，認(rèn)知測(cè)試評(píng)分越好稠诲，神經(jīng)系統(tǒng)檢查異痴炫簦或神經(jīng)發(fā)育障礙的可能性越低，再住院需求亦越少[167]臀叙。

先天性異常–有先天性異常的早產(chǎn)存活者更可能發(fā)生認(rèn)知損害及運(yùn)動(dòng)和感覺(jué)神經(jīng)缺陷[168]略水。

雙胎妊娠的ELBW兒[169]。目前尚無(wú)三胎或以上妊娠的類似數(shù)據(jù)劝萤。

出生住院期間接受外科手術(shù)[170]渊涝。

總結(jié)與推薦

由于臨床實(shí)踐、研究設(shè)計(jì)(研究人群床嫌、評(píng)估工具和結(jié)局定義)方面的差異跨释，以及圍生期保健的變化，解讀新生兒遠(yuǎn)期神經(jīng)發(fā)育結(jié)局相關(guān)文獻(xiàn)的難度較大(參見(jiàn)上文‘解讀結(jié)局資料的困難’)既鞠。因此煤傍，當(dāng)回顧文獻(xiàn)數(shù)據(jù)以便應(yīng)用于臨床時(shí)，需考慮到這些因素嘱蛋。盡管存在這些局限性蚯姆，但結(jié)局資料仍充分支持下列有關(guān)早產(chǎn)兒神經(jīng)發(fā)育結(jié)局的觀察結(jié)果：

早產(chǎn)兒出現(xiàn)神經(jīng)發(fā)育結(jié)局損害的風(fēng)險(xiǎn)高于足月兒，這些損害包括：認(rèn)知異常洒敏、運(yùn)動(dòng)障礙(輕度龄恋、精細(xì)和/或大運(yùn)動(dòng)發(fā)育遲緩)、腦性癱瘓(CP)以及視力和聽(tīng)力損失凶伙。出生胎齡(GA)越小郭毕，發(fā)生損害的風(fēng)險(xiǎn)越高。(參見(jiàn)上文‘神經(jīng)發(fā)育殘疾和學(xué)業(yè)成績(jī)’)

早產(chǎn)出生者比足月出生者更可能出現(xiàn)心理和行為問(wèn)題函荣，包括注意缺陷/多動(dòng)障礙(ADHD)显押、同伴交往困難、廣泛性焦慮和抑郁傻挂，以及孤獨(dú)癥譜系障礙乘碑。(參見(jiàn)上文‘行為和心理影響’)

與足月出生的兒童相比，早產(chǎn)兒在學(xué)齡期更可能出現(xiàn)影響其完成日辰鹁埽活動(dòng)的功能障礙(運(yùn)動(dòng)協(xié)調(diào)兽肤、社交技能和執(zhí)行功能方面的問(wèn)題)。(參見(jiàn)上文‘功能殘疾’)

與足月兒相比，早產(chǎn)兒成年后更可能出現(xiàn)醫(yī)學(xué)和社會(huì)殘疾资铡。然而电禀，相當(dāng)數(shù)量的早產(chǎn)兒在成年后自訴有與足月出生者相似的滿意生活質(zhì)量。(參見(jiàn)上文‘成人結(jié)局’)

有些新生兒并發(fā)癥與神經(jīng)發(fā)育結(jié)局不良的風(fēng)險(xiǎn)增加有關(guān)笤休，這些并發(fā)癥包括：支氣管肺發(fā)育不良(BPD)尖飞、壞死性小腸結(jié)腸炎(NEC)、早產(chǎn)兒視網(wǎng)膜病(ROP)宛官、腦室內(nèi)出血(IVH)葫松、生長(zhǎng)不良和存在先天異常瓦糕。其他導(dǎo)致神經(jīng)發(fā)育結(jié)局不良的因素包括母親因素(例如底洗，母親的教育背景)，以及嬰兒因素(性別和多胎生產(chǎn))咕娄；但圍生期保健的進(jìn)步(如亥揖，產(chǎn)前使用皮質(zhì)類固醇激素)會(huì)改善結(jié)局。(參見(jiàn)上文‘相關(guān)病況’和‘危險(xiǎn)因素’)

致謝

UpToDate的編輯人員感謝對(duì)這一專題的早期版本做出貢獻(xiàn)的Yvette Johnson, MD, MPH圣勒。

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