引言
神經發育結局受損是一種與早產相關的重要遠期併發症。胎齡(gestational age, GA)越小，發生神經發育損害及心理和行爲問題的風險越高。
本專題將總結早產存活者嬰兒期之後的遠期神經發育、行爲、心理和功能結局。早產兒的後續神經發育管理參見其他專題。(參見“早產兒遠期神經發育結局的管理”)
此外，早產的發生率及早產兒的生存率、出院後醫學管理及短期併發症的概述參見其他專題。(參見“早產兒的發生率和死亡率”和“早產兒的短期併發症”和“新生兒轉出重症監護病房後的管理”)
定義
早產 — 早產程度通常由出生體重(birth weight, BW)或胎齡來定義，在本專題中使用以下定義(表 1)。
按BW分類如下：
低出生體重兒(low birth weight, LBW)–BW小於2000g
極低出生體重兒(very low birth weight, VLBW)–BW小於1500g
超低出生體重兒(extremely low birth weight, ELBW)–BW小於1000g
按GA分類如下：
晚期早產–GA介於34至36+6周。
中度早產–GA介於32至33+6周。
早期早產(very preterm, VPT)–GA介於28至31+6周。
極早早產(extremely preterm, EPT)–GA不足28周。
現已確定了相應GA的BW百分位數(表 2A-B)。
神經發育結局 — 神經發育結局是一個複合術語，通常指認知、神經系統和/或感覺發育的結局。
傳統上在結局研究中，神經發育損害被定義爲存在一個或多個以下問題：
認知遲緩，判斷依據是標準化認知測試得分低於均值2個標準差(standard deviations, SD)。例如，這相當於貝利嬰兒發育量表(Bayley Scales of Infant Development, BSID)智力發育指數(Mental Developmental Index, MDI)得分小於等於70。
中到重度腦性癱瘓(cerebral palsy, CP)，定義爲大運動功能分級系統(Gross Motor Function Classification System, GMFCS)評分大於等於2。
需要助聽裝置的雙耳聽力缺陷/損失。
嚴重視力障礙，視力較好一側眼睛的最佳常規矯正視力小於等於20/200(即法定盲的定義)。
此外，行爲、心理及功能結局也逐漸被認爲是重要的遠期神經發育結局，也會在本文中討論。
解讀結局資料的困難
由於臨牀實踐(例如，生存力極限)和研究設計(研究人羣、評估工具和結局定義)的差異以及圍生期保健隨時間的變化，新生兒結局文獻的解讀較難。因此，在比較各研究或試圖將文獻結果應用於臨牀時，需要考慮到這些因素。
臨牀實踐的差異：生存力極限 — 在發達國家，對於處於生存力閾值的嬰兒(可確保有較大宮外存活機會的胎兒成熟期)，提供的初始管理水平有全球性和地區性差異[1-3]。臨牀實踐中的這些差異會影響在妊娠22-25周出生的嬰兒的生存率(表 3)，可能還會影響神經發育結局(表 4)。因此，很難比較採用不同復甦方法的研究中EPT嬰兒的生存率及神經發育結局，也很難基於個體患者解讀這些數據。(參見“Periviable birth (Limit of viability)”, section on ‘Impact of initial management’)
處於生存力極限的早產兒的相關數據解讀參見其他專題。(參見“Periviable birth (Limit of viability)”, section on ‘Interpreting the data’)
研究設計因素
研究人羣–界定研究人羣的差異使得比較不同研究的數據存在困難。
•例如，用出生體重而非胎齡來分類可能存在問題，因爲一個出生體重分類中可能包括相對較成熟的宮內發育遲緩(intrauterine growth retardation, IUGR)嬰兒。如果有較多的IUGR患兒，可能會影響結局，因爲IUGR嬰兒發生新生兒併發症和較差結局的風險高於相應的適於胎齡兒(appropriate for gestational age, AGA)，但其結局通常優於同等出生體重的更早產嬰兒[4](參見“胎兒期(宮內)生長受限的嬰兒”)。隨着確定胎齡的技術得到改善，按GA分類已成爲主導。儘管GA分類法可能在同一組中納入大於胎齡兒和小於胎齡兒，但相比於BW分類法，該方法所確定的分組更有可能納入相似胚胎/胎兒發育階段的嬰兒。因此，胎齡分類更常用於報告早產兒的遠期結局。
•轉運嬰兒 vs 非轉運嬰兒–與不需要轉運的嬰兒相比，在沒有三級新生兒重症監護病房(neonatal intensive care unit, NICU)、需要新生兒轉運的中心出生的早產兒，併發症發生率和死亡率似乎更高[5,6]。因此，研究之間非轉運和轉運嬰兒的混合分析可能會影響生存率和遠期結局。
結局測量指標的定義–不同的結局定義，特別是重度神經發育損害(neurodevelopmental impairment, NDI)的定義，會改變結果。例如，對加拿大新生兒隨訪網絡(Canadian Neonatal Follow-up Network)早產兒(胎齡23-28周)數據庫的一項分析顯示，根據不同的定義，重度NDI的發生率爲3.5%-14.9%[7]。NDI通常定義爲至少有以下一種情況：認知或運動測試得分低於均值2個標準差以上；助聽裝置無效的雙耳聽力損失；雙眼法定盲；以及中度、重度或深度腦癱。
評估方法–不同研究中用於評估結局的工具不同，因此結果可能無法直接比較。例如，一些研究顯示，第3版貝利標準(BSID Ⅲ，2006)測定的認知評分高於第2版(BSID Ⅱ，1992)[8-11]。BSID Ⅲ是高估了認知表現還是可以比BSID Ⅱ更準確地評估認知功能，目前還不明確。2019年9月發佈了第4版貝利標準(BSID Ⅳ)，但目前還沒有研究比較BSID Ⅳ與之前版本對早產存活者的評估。
後續混雜因素–可能影響神經發育和入學準備度的後續因素包括社會人口學因素(例如，母親的教育程度)、家庭收入(例如，Medicaid保險是貧困的標誌)、持續存在的健康問題及是否參與早期干預項目。這些因素的存在情況可能各異，因此很難比較不同研究的結果。(參見“School readiness for children in the United States”, section on ‘Factors related to a child's ability to learn’)
生存率隨時間的變化 — 圍生期醫療的進步提高了存活率[12]，因此，更難準確判斷臨牀實踐的變化對改善神經發育結局的影響，因爲生存率提高的速度已經超過了伴隨的遠期神經發育後遺症發生率降低的速度。
隨着圍生期醫療的進步，關於早產兒的神經發育結局是否隨存活情況一併得到改善，相關數據不一致。雖然世界各發達國家的一些大型或人羣研究表明，早產兒的神經發育結局和生存率均有所改善[13-19]，但也有例外[20,21]。結果不一致的原因可能是不同胎齡或出生年份的結局改善有差異。以下研究強調了在比較結局時考慮胎齡的重要性：
法國的一項對早產兒的人羣研究[Etude épidémiologique sur les petits âges gestationnels(EPIPAGE)和EPIPAGE-2]報道，從1997年至2011年，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運動或運動感覺障礙的生存率增加，分別爲45.5% vs 62.3%和82.1% vs 90.3%[22]。然而，在妊娠24周出生的嬰兒或妊娠32-34周出生的嬰兒中，兩個隊列的不伴重大殘疾生存率沒有差異，分別爲29% vs 25.8%和95.7% vs 96.8%。此外，在2011年的隊列中僅有1例在妊娠22-23周出生的嬰兒存活。
在美國國立兒童健康與人類發展研究所(National Institute of Child Health and Human Development, NICHD)網絡的一份報告中，1995-2010年間出生於胎齡25周、26周、27周和28周的嬰兒中，不伴重大新生兒併發症的生存率有所改善，但在胎齡23周和24周出生的嬰兒中沒有變化[12]。
在隨後對EPT嬰兒(胎齡<28周)的一項NICHD研究中，2011-2014年，重度腦癱的發病率下降了43%，輕度腦癱的發病率上升了13%[18]。
臨牀實踐的改變 — 現認爲，觀察到的一些隨時間而發生的臨牀實踐改變是新生兒存活率提高的主要原因，也可能是神經發育結局改善的主要原因[13-16]。因此，對不同時代出生隊列之間的比較應慎重解讀。這在與較近期出生隊列比較早產兒成人期結局時尤爲重要，因爲隨着臨牀實踐改變，2015年出生的EPT嬰兒(胎齡<28周)所接受的治療干預不同於1993年出生的嬰兒，因此，其遠期結局風險可能也不同。例如，美國NICHD的一項研究顯示，隨着臨牀實踐的一些改變(例如，產前皮質類固醇應用增加，以及產後皮質類固醇使用率和產房插管率降低)，新生兒生存率提高，特定併發症發生率降低[例如，重度腦室內出血(intraventricular hemorrhage, IVH)和晚髮型膿毒症][12]。但該研究未評估神經發育結局。另一項meta分析發現，在使用產前類固醇和表面活性物質時代出生的早產兒(胎齡<37周)到5歲或5歲以上時，神經發育結局仍然不如足月出生者，包括學習成績方面的嚴重困難[23]。
預防性干預措施 — 過去數十年，圍生期保健中出現的下列變化/干預可能直接或間接[通過減少相關併發症，如腦室周圍-腦室內出血(periventricular-intraventricular hemorrhage, PIVH)]改善神經發育結局。
產前皮質類固醇治療，可降低死亡率和神經發育損害發生率、減少中度至重度腦癱的發病率、縮短機械通氣時間，以及降低發生重度PIVH的風險[24,25]。(參見下文‘相關病況’和“產前皮質類固醇治療以減少早產導致的新生兒呼吸系統併發症發病率和死亡率”)
避免出生後早期使用皮質類固醇治療，因其與發生腦癱的風險增加有關。關於出生後使用皮質類固醇治療的遠期影響詳見其他專題[26-28]。(參見“支氣管肺發育不良的預防：出生後使用糖皮質激素”)
新生兒通氣的進步，包括採取無創通氣方法[如持續氣道正壓(continuous positive airway pressure, cPAP)]和改進機械通氣策略(例如，容量目標和同步化通氣)，提高了生存率並降低了併發症發生率[如，支氣管肺發育不良(bronchopulmonary dysplasia, BPD)、重度PIVH和肺氣漏]，這可能影響神經發育結局。(參見下文‘相關病況’和“新生兒機械通氣”和“支氣管肺發育不良嬰兒的結局”，關於‘神經發育結局’一節和“新生兒生髮基質-腦室內出血的預防、管理和併發症”，關於‘遠期結局’一節和“新生兒肺氣漏”)
表面活性物質，其與生存率增加相關，特別是對EPT嬰兒。然而，表面活性物質治療與神經發育結局改善沒有直接關係。(參見“早產兒呼吸窘迫綜合徵的預防和治療”)
產前使用硫酸鎂，這與腦癱和重度運動功能障礙風險降低相關。臨牀試驗顯示，母親使用硫酸鎂的早產兒發生腦癱和重度運動功能障礙的風險低於無宮內暴露者。(參見“硫酸鎂對胎兒的神經保護作用”，關於‘隨機試驗和meta分析的療效證據’一節)
無效的預防措施 — 既往觀察數據表明，預防性使用重組紅細胞生成素(recombinant erythropoietin, EPO)具有神經保護作用，然而，一項對941例EPT嬰兒進行的多中心試驗報道，EPO對改善神經發育結局沒有益處[29]。矯正胎齡22-26個月時，EPO組和安慰劑組的主要結局發生率相近(26% vs 26%，RR 1.03，95%CI 0.81-1.32)。主要結局指的是死亡或重度神經發育損害，後者定義爲重度腦癱，或使用BSID Ⅲ得到的運動或認知綜合評分低於70[29]。在該試驗中，受試者在出生後24小時內接受安慰劑或EPO(劑量爲1000U/kg)，每48小時1次，共6次。EPO組和安慰劑組的早產兒視網膜病變(retinopathy of prematurity, ROP)、顱內出血、BPD、壞死性小腸結腸炎(necrotizing enterocolitis, NEC)、死亡或嚴重不良反應發生率相近。因此，不應預防性地使用EPO作爲神經保護劑。
神經發育殘疾和學業成績
結局研究表明，GA和BW越小，神經發育殘疾的風險越高[24,30-36]。下文根據胎齡分類總結了存活者的結局數據。(參見上文‘早產’)
EPT嬰兒
患病率和嚴重程度 — 一些研究顯示，在EPT和/或ELBW嬰兒中，存在神經發育損害的ELBW存活者的比例較高，且通常會隨胎齡增加而降低(表 4)。EPT存活者常發生認知障礙以及運動和感覺神經障礙，且通常較嚴重，會持續到學齡期和成人期。
基於現有文獻，我們與EPT嬰兒的父母及看護人員討論以下臨牀結局指標的風險。如上所述，綜合這些信息存在困難，因爲研究設計不同(例如，結局評估的年齡和重大殘疾的定義)，並且結局數據與較新的出生隊列不同。(參見上文‘解讀結局資料的困難’)
重大殘疾–重大殘疾是指標準化認知和運動測試得分低於均值2個標準差以上和/或存在腦癱、盲和需要助聽裝置的聽力損失。
•1995-2007年出生隊列的6-10歲學齡兒童–人羣研究報道，出生時爲EPT的兒童中，17%-46%有重大殘疾[37-40]。據報道，1995年出生、胎齡<25周的患兒風險最高[38]。
•2008-2011年出生、矯正月齡爲18-24個月的幼兒出生隊列–根據認知測試分數或存在腦癱、盲和需要助聽器的聽力損失，在較近的出生隊列中，約一半EPT出生的兒童有重大殘疾[22,41]。
18-24個月時的重大殘疾可能在整個兒童時期持續存在。
學習障礙及需要專門的教育干預和服務–EPT出生的兒童更有可能在閱讀和數學方面有學習困難，並且教師評分較低[42-45]。這些兒童常需要額外的教育干預和特殊服務[43,46]。
成人結局–僅有1995年的一個出生隊列的成人結局數據，該隊列顯示，約60%的個體在19歲時有至少1種認知功能和視覺運動能力損害，1/3有4類或更多缺陷[47]。45%的EPT出生成人存在認知障礙，而對照組只有3%。
危險因素 — EPT出生者神經發育損害的危險因素還包括[33,48,49]：
母親因素–受教育水平較低、無商業保險、非白人種族、未婚和肥胖。出院後需要兒童保護服務監管的嬰兒在2歲時認知發育延遲的風險增加[50]。
嬰兒因素–宮內生長障礙[4]、男性[37,51]、多胎生產、非白人，以及伴隨重大新生兒併發症(重度IVH、腦室周圍白質軟化和接受大手術)。[39,52]
醫療保健因素–未進行產前保健或產前未使用皮質類固醇，以及陰道分娩。
早期早產兒 — 雖然VPT(胎齡28周至<32周)或VLBW(出生體重<1500g)嬰兒出現神經發育障礙的風險低於EPT或ELBW存活兒，但仍有相當數量存在神經發育缺陷[46,53-60]。對VLBW嬰兒的研究也可能包含ELBW，這可能不成比例地促進不良結局。因此，由於這些研究中ELBW患者的相對百分比不同，結局數據可能存在差異。(參見上文‘研究設計因素’)
研究者在一個包含2901例1997年出生早產兒的前瞻性隊列中說明了VPT嬰兒的風險程度[46]。該研究顯示，在29-32周出生者的早產兒中，在5歲時36%有神經發育障礙，30%使用了特殊的醫療資源(例如，物理治療、言語治療、技能訓練、心理學治療和精神科治療)。即使出院時沒有中度或重度神經障礙的兒童，與足月對照者相比，仍有可能出現全面發育遲緩和學習成績差異[53,54]。出現不良結局的危險因素包括：出生胎齡較小、影像學檢查發現腦病變、宮內生長障礙、未母乳餵養，以及父母社會經濟地位低。在2011年出生的嬰兒隊列中，妊娠27-31周出生的嬰兒2歲時有4.2%出現腦癱，41%出現發育遲緩[22]
其他研究報道，與足月出生的兒童相比，VPT學齡兒童的記憶力評分較差，並且更有可能出現學習困難[59,61]。
在一項文獻系統評價中，5歲以下早期早產兒發生認知發育不良的可能危險因素包括男性、低GA和父母教育水平低[60]。然而，在年長兒中唯一持續存在的危險因素是父母教育水平低下。
其他研究報道，與足月出生的兒童相比，VPT學齡兒童的記憶力評分較差，並且更有可能出現學習困難[59,61]。
中度至晚期早產兒 — 中度(胎齡在32-33+6周)和晚期(胎齡在34周至＜37周)早產兒存在遠期神經發育損害的可能性大於足月兒。對世界各地中度至晚期早產兒的縱向國際性研究基於評估年齡報道了以下神經發育損害[62-70]：
2歲–認知測試結果差，神經心理功能和感覺神經損害。[62,70,71]
學齡前–據家長報告，學齡前發育遲緩。[64]
學齡期–認知測試差，需要特殊教育服務，學業測試或教師評估成績低於預期年級水平[63,66,67,72,73]
晚期早產兒(胎齡爲34-36周)的遠期神經發育結局詳見其他專題。(參見“晚期早產兒”，關於‘神經發育結局’一節)
結構性腦損傷 — 重度新生兒腦損傷(即頭部超聲檢測到異常)的早產存活者有最嚴重的神經發育損害[例如，需要額外的學校服務，以及伴運動、認知或感覺神經損害的重大殘疾(如，腦癱)][74-77]。新生兒腦損傷也可能與青春期精神障礙[例如，重性抑鬱和強迫症(obsessive-compulsive disorder, OCD)]風險增高相關[78]。
MRI證實早產兒在學齡期、青春期和成人期存在大腦結構改變，包括胼胝體變薄、腦室容積增加、腦發育期灰質和白質的相對體積減少，以及總腦容積減少[79-88]。
言語和語言結局 — 早產存活兒中常見言語和語言障礙，其風險和嚴重度與GA成反比。表達性和/或感受性語言的習得及發音清晰度方面可能存在遲緩[9,89-92]。有證據表明，與足月對照組相比，早產兒的言語功能出現部分性追趕，並隨着母親受教育水平等環境因素而增加[92,93]。語言結局與認知功能、聽覺、產前和產後社會經濟地位、環境、族羣以及既往插管相關喉水平結構改變有關[91,94-96]。
行爲和心理影響
早產兒(尤其是EPT或VPT)在兒童期出現特定行爲和心理問題的可能性高於足月出生者。
極早早產和早期早產兒 — EPT或VPT出生的兒童比足月出生的兒童更可能發生行爲和心理問題。對NICHD新生兒研究網絡中2008-2012年出生的EPT嬰兒(胎齡<27周)進行的一項研究報道，在矯正月齡爲18-22個月時，1/3的嬰兒存在行爲問題，1/4存在社會情緒能力缺陷[97]。社會人口學因素(例如，母親受教育程度在高中以下、母親年齡較小)及認知和語言功能缺陷會增加早產兒發生行爲和社會情緒能力問題的風險。然而，與足月兒相比，早產兒在青春期和成年早期傾向於採取風險較低的行爲，且更靦腆[98-102]。
與足月出生的同齡人相比，以下行爲問題和心理問題在EPT或VPT出生的兒童和青少年中更常見。
注意力集中困難[98,102-111]
同伴互動不良[99,105-107,111,112]
多動[102-106,108-110,113]
情緒和品行問題，包括焦慮、抑鬱、退縮和軀體主訴[98,102,103,105-107,109,110,114,115]
孤獨症譜系障礙[109,116,117]
精神障礙[114,118,119]
中度至晚期早產兒 — 雖然數據有限，但根據父母的評估，中度至晚期早產兒在學齡前存在行爲和情緒問題的風險高於足月出生的同齡人[120-122]。另外，一項報告顯示，中度至晚期早產兒在2歲時孤獨症篩查測試陽性的可能性高於足月出生兒[123]。
功能殘疾
與足月出生的同齡人相比，EPT或VPT出生的學齡兒童更可能發生影響其完成日常活動和生活質量的功能障礙，可能爲輕微缺陷，包括運動協調(發育性運動協調障礙，也稱爲非腦癱性運動障礙)[124,125]、社交技能和執行功能(工作記憶、解決問題、規劃和組織)方面的問題[56,72,111,126-130]。胎齡越小，發生功能障礙的風險越高，據報道，在妊娠26周前出生的兒童有40%會出現功能障礙[42,56]。在一些兒童中，這些缺陷可能影響學業、運動和行爲結局。(參見“發育性協調障礙：臨牀特徵和診斷”)
環境對潛在神經功能改善的影響
儘管早產和腦損傷與神經發育障礙之間的關聯已經很清楚，但我們對環境和經驗在調節這些關聯中的作用卻知之甚少。幾項研究報道了環境因素對認知和言語-語言功能的有益影響，包括較高的母親受教育水平、父母干預、高質量的家庭環境和日間看護資源[92,93,131-134]。然而，較高的母親受教育水平對運動結局不存在有益影響[135]。
成人結局
殘疾 — 在既往爲早產的個體中，GA越小，成人期醫學和社會殘疾的風險越高。
一些研究報道，早產存活兒成年後的教育成就、獨立生活的比例、淨收入和終生僱傭率低於足月出生者[136-141]。這些結果很可能由以下兩個原因造成：認知技能差導致學習能力受損，特別是出生體重低於1500g或胎齡低於32周的成人；發生醫學殘疾(腦癱、精神和行爲障礙，以及軀體殘疾)的風險增加[136,142-144]。較高的社會經濟地位似乎可減輕GA對認知功能測試評分的影響[142]。
而其他研究顯示，雖然早產兒出現神經發育障礙的風險較高，但其在成人期可能會克服這些困難，成爲功能正常的年輕成人的比例與足月出生者相當，包括高中畢業、接受高等教育、就業、獨立生活、婚姻和養育子女方面[145,146]。這些研究的結局差異歸因於研究人羣的社會經濟地位較高、教育支持增加或來自國家醫療保健體系的獲益[147]。
生活質量 — 早產年輕成人及其父母報告的功能限制患病率及複雜程度均高於足月出生對照者及其父母所報告的[148]。縱向研究報道，根據健康效用指數標記-3問卷的評估結果，早期早產個體的健康相關生命質量更低[148-150]。對該文獻的一項系統評價顯示，早產兒成年後建立戀愛關係、性關係及養育子女的可能性較小[151]。但在一些研究中，早產成人及其家人所報告的滿意生活質量與足月出生者相似[152-156]。
此外，早產患者及其父母所感受到的生活質量優於醫護人員所判斷的[157]。因此，醫護人員須認識到這種差異，以便不僅重點關注患者的神經發育殘疾，而且拓寬對結局的考慮，將成人存活者憑着對生活質量的積極自我感知從而克服自身限制的能力也考慮在內[145,158,159]。
相關病況
與神經發育結局不良風險增加有關的早產相關新生兒病況包括：
BPD[41,160,161]。(參見“支氣管肺發育不良嬰兒的結局”，關於‘神經發育結局’一節)
此外，出生後應用糖皮質激素治療BPD與腦癱風險增加有關。(參見“支氣管肺發育不良的預防：出生後使用糖皮質激素”)
圍生期感染，包括[41,162,163]：
•壞死性小腸結腸炎(necrotizing enterocolitis, NEC)(參見“新生兒壞死性小腸結腸炎：治療”，關於‘生長髮育’一節)
•膿毒症(參見“早產兒(胎齡小於34周)細菌性膿毒症的治療和預防”，關於‘併發症’一節)
•腦膜炎(參見“新生兒細菌性腦膜炎：治療和結局”，關於‘結局’一節)
ROP。(參見“早產兒視網膜病變的發病機制、流行病學、分類和篩查”)
IVH。(參見“新生兒生髮基質-腦室內出血的預防、管理和併發症”，關於‘結局’一節)
生長不良：
•胎兒生長受限–胎兒生長受限會增加早產兒發生神經發育結局受損的風險。(參見“胎兒期(宮內)生長受限的嬰兒”，關於‘神經發育’一節)
•出生後生長–在VPT嬰兒中，生長障礙，包括頭部生長不良，會造成認知和運動功能受損[164-166]。美國NICHD新生兒研究網的一項報告表明生長改善與神經發育結局改善相關，該研究在矯正年齡爲18-22個月時對ELBW兒進行評估，發現其在新生兒重症監護病房(neonatal intensive care unit, NICU)住院期間的體重增長越多，則CP發病率越低，認知測試評分越好，神經系統檢查異常或神經發育障礙的可能性越低，再住院需求亦越少[167]。
先天性異常–有先天性異常的早產存活者更可能發生認知損害及運動和感覺神經缺陷[168]。
雙胎妊娠的ELBW兒[169]。目前尚無三胎或以上妊娠的類似數據。
出生住院期間接受外科手術[170]。
總結與推薦
由於臨牀實踐、研究設計(研究人羣、評估工具和結局定義)方面的差異，以及圍生期保健的變化，解讀新生兒遠期神經發育結局相關文獻的難度較大(參見上文‘解讀結局資料的困難’)。因此，當回顧文獻數據以便應用於臨牀時，需考慮到這些因素。儘管存在這些侷限性，但結局資料仍充分支持下列有關早產兒神經發育結局的觀察結果：
早產兒出現神經發育結局損害的風險高於足月兒，這些損害包括：認知異常、運動障礙(輕度、精細和/或大運動發育遲緩)、腦性癱瘓(CP)以及視力和聽力損失。出生胎齡(GA)越小，發生損害的風險越高。(參見上文‘神經發育殘疾和學業成績’)
早產出生者比足月出生者更可能出現心理和行爲問題，包括注意缺陷/多動障礙(ADHD)、同伴交往困難、廣泛性焦慮和抑鬱，以及孤獨症譜系障礙。(參見上文‘行爲和心理影響’)
與足月出生的兒童相比，早產兒在學齡期更可能出現影響其完成日常活動的功能障礙(運動協調、社交技能和執行功能方面的問題)。(參見上文‘功能殘疾’)
與足月兒相比，早產兒成年後更可能出現醫學和社會殘疾。然而，相當數量的早產兒在成年後自訴有與足月出生者相似的滿意生活質量。(參見上文‘成人結局’)
有些新生兒併發症與神經發育結局不良的風險增加有關，這些併發症包括：支氣管肺發育不良(BPD)、壞死性小腸結腸炎(NEC)、早產兒視網膜病(ROP)、腦室內出血(IVH)、生長不良和存在先天異常。其他導致神經發育結局不良的因素包括母親因素(例如，母親的教育背景)，以及嬰兒因素(性別和多胎生產)；但圍生期保健的進步(如，產前使用皮質類固醇激素)會改善結局。(參見上文‘相關病況’和‘危險因素’)
致謝
UpToDate的編輯人員感謝對這一專題的早期版本做出貢獻的Yvette Johnson, MD, MPH。
參考文獻
Alleman BW, Bell EF, Li L, et al. Individual and center-level factors affecting mortality among extremely low birth weight infants. Pediatrics 2013; 132:e175.
Rysavy MA, Li L, Bell EF, et al. Between-hospital variation in treatment and outcomes in extremely preterm infants. N Engl J Med 2015; 372:1801.
James J, Munson D, DeMauro SB, et al. Outcomes of Preterm Infants following Discussions about Withdrawal or Withholding of Life Support. J Pediatr 2017; 190:118.
De Jesus LC, Pappas A, Shankaran S, et al. Outcomes of small for gestational age infants born at <27 weeks' gestation. J Pediatr 2013; 163:55.
Amer R, Moddemann D, Seshia M, et al. Neurodevelopmental Outcomes of Infants Born at <29 Weeks of Gestation Admitted to Canadian Neonatal Intensive Care Units Based on Location of Birth. J Pediatr 2018; 196:31.
Mohamed MA, Aly H. Transport of premature infants is associated with increased risk for intraventricular haemorrhage. Arch Dis Child Fetal Neonatal Ed 2010; 95:F403.
Haslam MD, Lisonkova S, Creighton D, et al. Severe Neurodevelopmental Impairment in Neonates Born Preterm: Impact of Varying Definitions in a Canadian Cohort. J Pediatr 2018; 197:75.
Moore T, Johnson S, Haider S, et al. Relationship between test scores using the second and third editions of the Bayley Scales in extremely preterm children. J Pediatr 2012; 160:553.
Vohr BR, Stephens BE, Higgins RD, et al. Are outcomes of extremely preterm infants improving? Impact of Bayley assessment on outcomes. J Pediatr 2012; 161:222.
Silveira RC, Filipouski GR, Goldstein DJ, et al. Agreement between Bayley Scales second and third edition assessments of very low-birth-weight infants. Arch Pediatr Adolesc Med 2012; 166:1075.
Msall ME. Measuring outcomes after extreme prematurity with the Bayley-III Scales of infant and toddler development: a cautionary tale from Australia. Arch Pediatr Adolesc Med 2010; 164:391.
Stoll BJ, Hansen NI, Bell EF, et al. Trends in Care Practices, Morbidity, and Mortality of Extremely Preterm Neonates, 1993-2012. JAMA 2015; 314:1039.
Vohr BR, Wright LL, Poole WK, McDonald SA. Neurodevelopmental outcomes of extremely low birth weight infants <32 weeks' gestation between 1993 and 1998. Pediatrics 2005; 116:635.
Wilson-Costello D, Friedman H, Minich N, et al. Improved neurodevelopmental outcomes for extremely low birth weight infants in 2000-2002. Pediatrics 2007; 119:37.
Doyle LW, Roberts G, Anderson PJ, Victorian Infant Collaborative Study Group. Outcomes at age 2 years of infants < 28 weeks' gestational age born in Victoria in 2005. J Pediatr 2010; 156:49.
D'Amore A, Broster S, Le Fort W, et al. Two-year outcomes from very low birthweight infants in a geographically defined population across 10 years, 1993-2002: comparing 1993-1997 with 1998-2002. Arch Dis Child Fetal Neonatal Ed 2011; 96:F178.
Moore T, Hennessy EM, Myles J, et al. Neurological and developmental outcome in extremely preterm children born in England in 1995 and 2006: the EPICure studies. BMJ 2012; 345:e7961.
Adams-Chapman I, Heyne RJ, DeMauro SB, et al. Neurodevelopmental Impairment Among Extremely Preterm Infants in the Neonatal Research Network. Pediatrics 2018; 141.
Courchia B, Berkovits MD, Bauer CR. Cognitive impairment among extremely low birthweight preterm infants from 1980 to present day. J Perinatol 2019; 39:1098.
Hintz SR, Kendrick DE, Wilson-Costello DE, et al. Early-childhood neurodevelopmental outcomes are not improving for infants born at <25 weeks' gestational age. Pediatrics 2011; 127:62.
Cheong JLY, Anderson PJ, Burnett AC, et al. Changing Neurodevelopment at 8 Years in Children Born Extremely Preterm Since the 1990s. Pediatrics 2017; 139.
Pierrat V, Marchand-Martin L, Arnaud C, et al. Neurodevelopmental outcome at 2 years for preterm children born at 22 to 34 weeks' gestation in France in 2011: EPIPAGE-2 cohort study. BMJ 2017; 358:j3448.
Twilhaar ES, de Kieviet JF, Aarnoudse-Moens CS, et al. Academic performance of children born preterm: a meta-analysis and meta-regression. Arch Dis Child Fetal Neonatal Ed 2018; 103:F322.
Carlo WA, McDonald SA, Fanaroff AA, et al. Association of antenatal corticosteroids with mortality and neurodevelopmental outcomes among infants born at 22 to 25 weeks' gestation. JAMA 2011; 306:2348.
Roberts D, Brown J, Medley N, Dalziel SR. Antenatal corticosteroids for accelerating fetal lung maturation for women at risk of preterm birth. Cochrane Database Syst Rev 2017; 3:CD004454.
Committee on Fetus and Newborn. Postnatal corticosteroids to treat or prevent chronic lung disease in preterm infants. Pediatrics 2002; 109:330.
Watterberg KL, American Academy of Pediatrics. Committee on Fetus and Newborn. Policy statement--postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia. Pediatrics 2010; 126:800.
Doyle LW, Ehrenkranz RA, Halliday HL. Late (> 7 days) postnatal corticosteroids for chronic lung disease in preterm infants. Cochrane Database Syst Rev 2014; :CD001145.
Juul SE, Comstock BA, Wadhawan R, et al. A Randomized Trial of Erythropoietin for Neuroprotection in Preterm Infants. N Engl J Med 2020; 382:233.
Costeloe K, Hennessy E, Gibson AT, et al. The EPICure study: outcomes to discharge from hospital for infants born at the threshold of viability. Pediatrics 2000; 106:659.
Larroque B, Bréart G, Kaminski M, et al. Survival of very preterm infants: Epipage, a population based cohort study. Arch Dis Child Fetal Neonatal Ed 2004; 89:F139.
Tyson JE, Parikh NA, Langer J, et al. Intensive care for extreme prematurity--moving beyond gestational age. N Engl J Med 2008; 358:1672.
Gargus RA, Vohr BR, Tyson JE, et al. Unimpaired outcomes for extremely low birth weight infants at 18 to 22 months. Pediatrics 2009; 124:112.
Leversen KT, Sommerfelt K, Rønnestad A, et al. Prediction of neurodevelopmental and sensory outcome at 5 years in Norwegian children born extremely preterm. Pediatrics 2011; 127:e630.
Serenius F, Källén K, Blennow M, et al. Neurodevelopmental outcome in extremely preterm infants at 2.5 years after active perinatal care in Sweden. JAMA 2013; 309:1810.
Hirvonen M, Ojala R, Korhonen P, et al. Visual and Hearing Impairments After Preterm Birth. Pediatrics 2018; 142.
Kuban KC, Joseph RM, O'Shea TM, et al. Girls and Boys Born before 28 Weeks Gestation: Risks of Cognitive, Behavioral, and Neurologic Outcomes at Age 10 Years. J Pediatr 2016; 173:69.
Marlow N, Wolke D, Bracewell MA, et al. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med 2005; 352:9.
Cheong JLY, Lee KJ, Boland RA, et al. Changes in long-term prognosis with increasing postnatal survival and the occurrence of postnatal morbidities in extremely preterm infants offered intensive care: a prospective observational study. Lancet Child Adolesc Health 2018; 2:872.
Serenius F, Ewald U, Farooqi A, et al. Neurodevelopmental Outcomes Among Extremely Preterm Infants 6.5 Years After Active Perinatal Care in Sweden. JAMA Pediatr 2016; 170:954.
Synnes A, Luu TM, Moddemann D, et al. Determinants of developmental outcomes in a very preterm Canadian cohort. Arch Dis Child Fetal Neonatal Ed 2017; 102:F235.
Johnson S, Fawke J, Hennessy E, et al. Neurodevelopmental disability through 11 years of age in children born before 26 weeks of gestation. Pediatrics 2009; 124:e249.
Johnson S, Hennessy E, Smith R, et al. Academic attainment and special educational needs in extremely preterm children at 11 years of age: the EPICure study. Arch Dis Child Fetal Neonatal Ed 2009; 94:F283.
Taylor HG, Klein N, Anselmo MG, et al. Learning problems in kindergarten students with extremely preterm birth. Arch Pediatr Adolesc Med 2011; 165:819.
Garfield CF, Karbownik K, Murthy K, et al. Educational Performance of Children Born Prematurely. JAMA Pediatr 2017; 171:764.
Larroque B, Ancel PY, Marret S, et al. Neurodevelopmental disabilities and special care of 5-year-old children born before 33 weeks of gestation (the EPIPAGE study): a longitudinal cohort study. Lancet 2008; 371:813.
O'Reilly H, Johnson S, Ni Y, et al. Neuropsychological Outcomes at 19 Years of Age Following Extremely Preterm Birth. Pediatrics 2020; 145.
Kumar P, Shankaran S, Ambalavanan N, et al. Characteristics of extremely low-birth-weight infant survivors with unimpaired outcomes at 30 months of age. J Perinatol 2013; 33:800.
Helderman JB, O'Shea TM, Kuban KC, et al. Antenatal antecedents of cognitive impairment at 24 months in extremely low gestational age newborns. Pediatrics 2012; 129:494.
McGowan EC, Laptook AR, Lowe J, et al. Developmental Outcomes of Extremely Preterm Infants with a Need for Child Protective Services Supervision. J Pediatr 2019; 215:41.
Linsell L, Johnson S, Wolke D, et al. Cognitive trajectories from infancy to early adulthood following birth before 26 weeks of gestation: a prospective, population-based cohort study. Arch Dis Child 2018; 103:363.
Logan JW, Dammann O, Allred EN, et al. Early postnatal illness severity scores predict neurodevelopmental impairments at 10 years of age in children born extremely preterm. J Perinatol 2017; 37:606.
Charkaluk ML, Truffert P, Fily A, et al. Neurodevelopment of children born very preterm and free of severe disabilities: the Nord-Pas de Calais Epipage cohort study. Acta Paediatr 2010; 99:684.
Beaino G, Khoshnood B, Kaminski M, et al. Predictors of the risk of cognitive deficiency in very preterm infants: the EPIPAGE prospective cohort. Acta Paediatr 2011; 100:370.
Kiechl-Kohlendorfer U, Ralser E, Pupp Peglow U, et al. Adverse neurodevelopmental outcome in preterm infants: risk factor profiles for different gestational ages. Acta Paediatr 2009; 98:792.
Aarnoudse-Moens CS, Weisglas-Kuperus N, van Goudoever JB, Oosterlaan J. Meta-analysis of neurobehavioral outcomes in very preterm and/or very low birth weight children. Pediatrics 2009; 124:717.
de Kieviet JF, Piek JP, Aarnoudse-Moens CS, Oosterlaan J. Motor development in very preterm and very low-birth-weight children from birth to adolescence: a meta-analysis. JAMA 2009; 302:2235.
Brydges CR, Landes JK, Reid CL, et al. Cognitive outcomes in children and adolescents born very preterm: a meta-analysis. Dev Med Child Neurol 2018; 60:452.
Fitzpatrick A, Carter J, Quigley MA. Association of Gestational Age With Verbal Ability and Spatial Working Memory at Age 11. Pediatrics 2016; 138.
Linsell L, Malouf R, Morris J, et al. Prognostic Factors for Poor Cognitive Development in Children Born Very Preterm or With Very Low Birth Weight: A Systematic Review. JAMA Pediatr 2015; 169:1162.
Twilhaar ES, de Kieviet JF, van Elburg RM, Oosterlaan J. Academic trajectories of very preterm born children at school age. Arch Dis Child Fetal Neonatal Ed 2019; 104:F419.
Johnson S, Evans TA, Draper ES, et al. Neurodevelopmental outcomes following late and moderate prematurity: a population-based cohort study. Arch Dis Child Fetal Neonatal Ed 2015; 100:F301.
van Baar AL, Vermaas J, Knots E, et al. Functioning at school age of moderately preterm children born at 32 to 36 weeks' gestational age. Pediatrics 2009; 124:251.
Kerstjens JM, de Winter AF, Bocca-Tjeertes IF, et al. Developmental delay in moderately preterm-born children at school entry. J Pediatr 2011; 159:92.
Potijk MR, Kerstjens JM, Bos AF, et al. Developmental delay in moderately preterm-born children with low socioeconomic status: risks multiply. J Pediatr 2013; 163:1289.
Peacock PJ, Henderson J, Odd D, Emond A. Early school attainment in late-preterm infants. Arch Dis Child 2012; 97:118.
Odd DE, Emond A, Whitelaw A. Long-term cognitive outcomes of infants born moderately and late preterm. Dev Med Child Neurol 2012; 54:704.
Harris MN, Voigt RG, Barbaresi WJ, et al. ADHD and learning disabilities in former late preterm infants: a population-based birth cohort. Pediatrics 2013; 132:e630.
Woythaler M, McCormick MC, Mao WY, Smith VC. Late Preterm Infants and Neurodevelopmental Outcomes at Kindergarten. Pediatrics 2015; 136:424.
Cheong JL, Doyle LW, Burnett AC, et al. Association Between Moderate and Late Preterm Birth and Neurodevelopment and Social-Emotional Development at Age 2 Years. JAMA Pediatr 2017; 171:e164805.
Schonhaut L, Armijo I, Pérez M. Gestational age and developmental risk in moderately and late preterm and early term infants. Pediatrics 2015; 135:e835.
Cserjesi R, Van Braeckel KN, Butcher PR, et al. Functioning of 7-year-old children born at 32 to 35 weeks' gestational age. Pediatrics 2012; 130:e838.
Chan E, Quigley MA. School performance at age 7 years in late preterm and early term birth: a cohort study. Arch Dis Child Fetal Neonatal Ed 2014; 99:F451.
Luu TM, Ment LR, Schneider KC, et al. Lasting effects of preterm birth and neonatal brain hemorrhage at 12 years of age. Pediatrics 2009; 123:1037.
Roze E, Van Braeckel KN, van der Veere CN, et al. Functional outcome at school age of preterm infants with periventricular hemorrhagic infarction. Pediatrics 2009; 123:1493.
Marret S, Marchand-Martin L, Picaud JC, et al. Brain injury in very preterm children and neurosensory and cognitive disabilities during childhood: the EPIPAGE cohort study. PLoS One 2013; 8:e62683.
Zayek MM, Benjamin JT, Maertens P, et al. Cerebellar hemorrhage: a major morbidity in extremely preterm infants. J Perinatol 2012; 32:699.
Whitaker AH, Feldman JF, Lorenz JM, et al. Neonatal head ultrasound abnormalities in preterm infants and adolescent psychiatric disorders. Arch Gen Psychiatry 2011; 68:742.
de Kieviet JF, Zoetebier L, van Elburg RM, et al. Brain development of very preterm and very low-birthweight children in childhood and adolescence: a meta-analysis. Dev Med Child Neurol 2012; 54:313.
Soria-Pastor S, Padilla N, Zubiaurre-Elorza L, et al. Decreased regional brain volume and cognitive impairment in preterm children at low risk. Pediatrics 2009; 124:e1161.
Martinussen M, Flanders DW, Fischl B, et al. Segmental brain volumes and cognitive and perceptual correlates in 15-year-old adolescents with low birth weight. J Pediatr 2009; 155:848.
Ment LR, Kesler S, Vohr B, et al. Longitudinal brain volume changes in preterm and term control subjects during late childhood and adolescence. Pediatrics 2009; 123:503.
Nosarti C, Giouroukou E, Healy E, et al. Grey and white matter distribution in very preterm adolescents mediates neurodevelopmental outcome. Brain 2008; 131:205.
Constable RT, Ment LR, Vohr BR, et al. Prematurely born children demonstrate white matter microstructural differences at 12 years of age, relative to term control subjects: an investigation of group and gender effects. Pediatrics 2008; 121:306.
Allin M, Henderson M, Suckling J, et al. Effects of very low birthweight on brain structure in adulthood. Dev Med Child Neurol 2004; 46:46.
Nosarti C, Rushe TM, Woodruff PW, et al. Corpus callosum size and very preterm birth: relationship to neuropsychological outcome. Brain 2004; 127:2080.
Kesler SR, Reiss AL, Vohr B, et al. Brain volume reductions within multiple cognitive systems in male preterm children at age twelve. J Pediatr 2008; 152:513.
Fearon P, O'Connell P, Frangou S, et al. Brain volumes in adult survivors of very low birth weight: a sibling-controlled study. Pediatrics 2004; 114:367.
van Noort-van der Spek IL, Franken MC, Weisglas-Kuperus N. Language functions in preterm-born children: a systematic review and meta-analysis. Pediatrics 2012; 129:745.
Duncan AF, Watterberg KL, Nolen TL, et al. Effect of ethnicity and race on cognitive and language testing at age 18-22 months in extremely preterm infants. J Pediatr 2012; 160:966.
Woods PL, Rieger I, Wocadlo C, Gordon A. Predicting the outcome of specific language impairment at five years of age through early developmental assessment in preterm infants. Early Hum Dev 2014; 90:613.
Nguyen TN, Spencer-Smith M, Haebich KM, et al. Language Trajectories of Children Born Very Preterm and Full Term from Early to Late Childhood. J Pediatr 2018; 202:86.
Luu TM, Vohr BR, Allan W, et al. Evidence for catch-up in cognition and receptive vocabulary among adolescents born very preterm. Pediatrics 2011; 128:313.
Reynolds V, Meldrum S, Simmer K, et al. Dysphonia in very preterm children: a review of the evidence. Neonatology 2014; 106:69.
Reynolds V, Meldrum S, Simmer K, et al. Laryngeal pathology at school age following very preterm birth. Int J Pediatr Otorhinolaryngol 2015; 79:398.
Nguyen TN, Spencer-Smith M, Pascoe L, et al. Language Skills in Children Born Preterm (<30 Wks' Gestation) Throughout Childhood: Associations With Biological and Socioenvironmental Factors. J Dev Behav Pediatr 2019; 40:735.
Peralta-Carcelen M, Carlo WA, Pappas A, et al. Behavioral Problems and Socioemotional Competence at 18 to 22 Months of Extremely Premature Children. Pediatrics 2017; 139.
Hack M, Youngstrom EA, Cartar L, et al. Behavioral outcomes and evidence of psychopathology among very low birth weight infants at age 20 years. Pediatrics 2004; 114:932.
Hille ET, Dorrepaal C, Perenboom R, et al. Social lifestyle, risk-taking behavior, and psychopathology in young adults born very preterm or with a very low birthweight. J Pediatr 2008; 152:793.
Schmidt LA, Miskovic V, Boyle MH, Saigal S. Shyness and timidity in young adults who were born at extremely low birth weight. Pediatrics 2008; 122:e181.
Hack M, Schluchter M, Forrest CB, et al. Self-reported adolescent health status of extremely low birth weight children born 1992-1995. Pediatrics 2012; 130:46.
Van Lieshout RJ, Boyle MH, Saigal S, et al. Mental health of extremely low birth weight survivors in their 30s. Pediatrics 2015; 135:452.
Conrad AL, Richman L, Lindgren S, Nopoulos P. Biological and environmental predictors of behavioral sequelae in children born preterm. Pediatrics 2010; 125:e83.
Lindström K, Lindblad F, Hjern A. Preterm birth and attention-deficit/hyperactivity disorder in schoolchildren. Pediatrics 2011; 127:858.
Samara M, Marlow N, Wolke D, EPICure Study Group. Pervasive behavior problems at 6 years of age in a total-population sample of children born at </= 25 weeks of gestation. Pediatrics 2008; 122:562.
Farooqi A, Hägglöf B, Sedin G, et al. Mental health and social competencies of 10- to 12-year-old children born at 23 to 25 weeks of gestation in the 1990s: a Swedish national prospective follow-up study. Pediatrics 2007; 120:118.
Delobel-Ayoub M, Arnaud C, White-Koning M, et al. Behavioral problems and cognitive performance at 5 years of age after very preterm birth: the EPIPAGE Study. Pediatrics 2009; 123:1485.
Sucksdorff M, Lehtonen L, Chudal R, et al. Preterm Birth and Poor Fetal Growth as Risk Factors of Attention-Deficit/ Hyperactivity Disorder. Pediatrics 2015; 136:e599.
Fevang SK, Hysing M, Markestad T, Sommerfelt K. Mental Health in Children Born Extremely Preterm Without Severe Neurodevelopmental Disabilities. Pediatrics 2016; 137.
Samuelsson M, Holsti A, Adamsson M, et al. Behavioral Patterns in Adolescents Born at 23 to 25 Weeks of Gestation. Pediatrics 2017; 140.
Gire C, Resseguier N, Brévaut-Malaty V, et al. Quality of life of extremely preterm school-age children without major handicap: a cross-sectional observational study. Arch Dis Child 2019; 104:333.
Heuser KM, Jaekel J, Wolke D. Origins and Predictors of Friendships in 6- to 8-Year-Old Children Born at Neonatal Risk. J Pediatr 2018; 193:93.
Franz AP, Bolat GU, Bolat H, et al. Attention-Deficit/Hyperactivity Disorder and Very Preterm/Very Low Birth Weight: A Meta-analysis. Pediatrics 2018; 141.
Mathiasen R, Hansen BM, Forman JL, et al. The risk of psychiatric disorders in individuals born prematurely in Denmark from 1974 to 1996. Acta Paediatr 2011; 100:691.
Pyhälä R, Wolford E, Kautiainen H, et al. Self-Reported Mental Health Problems Among Adults Born Preterm: A Meta-Analysis. Pediatrics 2017.
Johnson S, Hollis C, Kochhar P, et al. Autism spectrum disorders in extremely preterm children. J Pediatr 2010; 156:525.
Kuban KC, O'Shea TM, Allred EN, et al. Positive screening on the Modified Checklist for Autism in Toddlers (M-CHAT) in extremely low gestational age newborns. J Pediatr 2009; 154:535.
Lindström K, Lindblad F, Hjern A. Psychiatric morbidity in adolescents and young adults born preterm: a Swedish national cohort study. Pediatrics 2009; 123:e47.
Dvir Y, Frazier JA, Joseph RM, et al. Psychiatric Symptoms: Prevalence, Co-occurrence, and Functioning Among Extremely Low Gestational Age Newborns at Age 10 Years. J Dev Behav Pediatr 2019; 40:725.
Potijk MR, de Winter AF, Bos AF, et al. Higher rates of behavioural and emotional problems at preschool age in children born moderately preterm. Arch Dis Child 2012; 97:112.
Cserjesi R, VAN Braeckel KN, Timmerman M, et al. Patterns of functioning and predictive factors in children born moderately preterm or at term. Dev Med Child Neurol 2012; 54:710.
Johnson S, Waheed G, Manktelow BN, et al. Differentiating the Preterm Phenotype: Distinct Profiles of Cognitive and Behavioral Development Following Late and Moderately Preterm Birth. J Pediatr 2018; 193:85.
Guy A, Seaton SE, Boyle EM, et al. Infants born late/moderately preterm are at increased risk for a positive autism screen at 2 years of age. J Pediatr 2015; 166:269.
Edwards J, Berube M, Erlandson K, et al. Developmental coordination disorder in school-aged children born very preterm and/or at very low birth weight: a systematic review. J Dev Behav Pediatr 2011; 32:678.
Zhu JL, Olsen J, Olesen AW. Risk for developmental coordination disorder correlates with gestational age at birth. Paediatr Perinat Epidemiol 2012; 26:572.
Mulder H, Pitchford NJ, Hagger MS, Marlow N. Development of executive function and attention in preterm children: a systematic review. Dev Neuropsychol 2009; 34:393.
Burnett AC, Scratch SE, Lee KJ, et al. Executive function in adolescents born <1000 g or <28 weeks: a prospective cohort study. Pediatrics 2015; 135:e826.
Costa DS, Miranda DM, Burnett AC, et al. Executive Function and Academic Outcomes in Children Who Were Extremely Preterm. Pediatrics 2017; 140.
Burnett AC, Anderson PJ, Lee KJ, et al. Trends in Executive Functioning in Extremely Preterm Children Across 3 Birth Eras. Pediatrics 2018; 141.
Miller SE, DeBoer MD, Scharf RJ. Executive functioning in low birth weight children entering kindergarten. J Perinatol 2018; 38:98.
Benavente-Fernández I, Synnes A, Grunau RE, et al. Association of Socioeconomic Status and Brain Injury With Neurodevelopmental Outcomes of Very Preterm Children. JAMA Netw Open 2019; 2:e192914.
Wolke D, Jaekel J, Hall J, Baumann N. Effects of sensitive parenting on the academic resilience of very preterm and very low birth weight adolescents. J Adolesc Health 2013; 53:642.
Johnson DL, Swank P, Howie VM, et al. Does HOME add to the prediction of child intelligence over and above SES? J Genet Psychol 1993; 154:33.
Vandell DL, Belsky J, Burchinal M, et al. Do effects of early child care extend to age 15 years? Results from the NICHD study of early child care and youth development. Child Dev 2010; 81:737.
Laucht M, Esser G, Schmidt MH. Developmental outcome of infants born with biological and psychosocial risks. J Child Psychol Psychiatry 1997; 38:843.
Moster D, Lie RT, Markestad T. Long-term medical and social consequences of preterm birth. N Engl J Med 2008; 359:262.
Hack M, Flannery DJ, Schluchter M, et al. Outcomes in young adulthood for very-low-birth-weight infants. N Engl J Med 2002; 346:149.
Cooke RW. Health, lifestyle, and quality of life for young adults born very preterm. Arch Dis Child 2004; 89:201.
Swamy GK, Ostbye T, Skjaerven R. Association of preterm birth with long-term survival, reproduction, and next-generation preterm birth. JAMA 2008; 299:1429.
Mathiasen R, Hansen BM, Nybo Anderson AM, Greisen G. Socio-economic achievements of individuals born very preterm at the age of 27 to 29 years: a nationwide cohort study. Dev Med Child Neurol 2009; 51:901.
Saigal S, Day KL, Van Lieshout RJ, et al. Health, Wealth, Social Integration, and Sexuality of Extremely Low-Birth-Weight Prematurely Born Adults in the Fourth Decade of Life. JAMA Pediatr 2016; 170:678.
Ekeus C, Lindström K, Lindblad F, et al. Preterm birth, social disadvantage, and cognitive competence in Swedish 18- to 19-year-old men. Pediatrics 2010; 125:e67.
Strang-Karlsson S, Andersson S, Paile-Hyvärinen M, et al. Slower reaction times and impaired learning in young adults with birth weight <1500 g. Pediatrics 2010; 125:e74.
Breeman LD, Jaekel J, Baumann N, et al. Preterm Cognitive Function Into Adulthood. Pediatrics 2015; 136:415.
Saigal S, Stoskopf B, Streiner D, et al. Transition of extremely low-birth-weight infants from adolescence to young adulthood: comparison with normal birth-weight controls. JAMA 2006; 295:667.
Dalziel SR, Lim VK, Lambert A, et al. Psychological functioning and health-related quality of life in adulthood after preterm birth. Dev Med Child Neurol 2007; 49:597.
Hack M, Klein N. Young adult attainments of preterm infants. JAMA 2006; 295:695.
Baumann N, Bartmann P, Wolke D. Health-Related Quality of Life Into Adulthood After Very Preterm Birth. Pediatrics 2016; 137.
Saigal S, Ferro MA, Van Lieshout RJ, et al. Health-Related Quality of Life Trajectories of Extremely Low Birth Weight Survivors into Adulthood. J Pediatr 2016; 179:68.
van Lunenburg A, van der Pal SM, van Dommelen P, et al. Changes in quality of life into adulthood after very preterm birth and/or very low birth weight in the Netherlands. Health Qual Life Outcomes 2013; 11:51.
Mendonça M, Bilgin A, Wolke D. Association of Preterm Birth and Low Birth Weight With Romantic Partnership, Sexual Intercourse, and Parenthood in Adulthood: A Systematic Review and Meta-analysis. JAMA Netw Open 2019; 2:e196961.
Saigal S, Feeny D, Rosenbaum P, et al. Self-perceived health status and health-related quality of life of extremely low-birth-weight infants at adolescence. JAMA 1996; 276:453.
Saigal S, Rosenbaum PL, Feeny D, et al. Parental perspectives of the health status and health-related quality of life of teen-aged children who were extremely low birth weight and term controls. Pediatrics 2000; 105:569.
Saigal S, Stoskopf B, Pinelli J, et al. Self-perceived health-related quality of life of former extremely low birth weight infants at young adulthood. Pediatrics 2006; 118:1140.
Gäddlin PO, Finnström O, Sydsjö G, Leijon I. Most very low birth weight subjects do well as adults. Acta Paediatr 2009; 98:1513.
Hack M, Cartar L, Schluchter M, et al. Self-perceived health, functioning and well-being of very low birth weight infants at age 20 years. J Pediatr 2007; 151:635.
Saigal S, Stoskopf BL, Feeny D, et al. Differences in preferences for neonatal outcomes among health care professionals, parents, and adolescents. JAMA 1999; 281:1991.
Saigal S, Rosenbaum P. What matters in the long term: reflections on the context of adult outcomes versus detailed measures in childhood. Semin Fetal Neonatal Med 2007; 12:415.
Saigal S. Perception of health status and quality of life of extremely low-birth weight survivors. The consumer, the provider, and the child. Clin Perinatol 2000; 27:403.
Laughon M, O'Shea MT, Allred EN, et al. Chronic lung disease and developmental delay at 2 years of age in children born before 28 weeks' gestation. Pediatrics 2009; 124:637.
Twilhaar ES, Wade RM, de Kieviet JF, et al. Cognitive Outcomes of Children Born Extremely or Very Preterm Since the 1990s and Associated Risk Factors: A Meta-analysis and Meta-regression. JAMA Pediatr 2018; 172:361.
van Vliet EO, de Kieviet JF, Oosterlaan J, van Elburg RM. Perinatal infections and neurodevelopmental outcome in very preterm and very low-birth-weight infants: a meta-analysis. JAMA Pediatr 2013; 167:662.
Mitha A, Foix-L'Hélias L, Arnaud C, et al. Neonatal infection and 5-year neurodevelopmental outcome of very preterm infants. Pediatrics 2013; 132:e372.
Cooke RW, Foulder-Hughes L. Growth impairment in the very preterm and cognitive and motor performance at 7 years. Arch Dis Child 2003; 88:482.
Scharf RJ, Stroustrup A, Conaway MR, DeBoer MD. Growth and development in children born very low birthweight. Arch Dis Child Fetal Neonatal Ed 2016; 101:F433.
Raghuram K, Yang J, Church PT, et al. Head growth trajectory and neurodevelopmental outcomes in preterm neonates. Pediatrics 2017; 140.
Ehrenkranz RA, Dusick AM, Vohr BR, et al. Growth in the neonatal intensive care unit influences neurodevelopmental and growth outcomes of extremely low birth weight infants. Pediatrics 2006; 117:1253.
Walden RV, Taylor SC, Hansen NI, et al. Major congenital anomalies place extremely low birth weight infants at higher risk for poor growth and developmental outcomes. Pediatrics 2007; 120:e1512.
Wadhawan R, Oh W, Perritt RL, et al. Twin gestation and neurodevelopmental outcome in extremely low birth weight infants. Pediatrics 2009; 123:e220.
Hunt RW, Hickey LM, Burnett AC, et al. Early surgery and neurodevelopmental outcomes of children born extremely preterm. Arch Dis Child Fetal Neonatal Ed 2018; 103:F227.