顧 琴，張金萍

(1.上海市長(zhǎng)寧區(qū)婦幼保健院兒科，上海 200051；2.復(fù)旦大學(xué)附屬兒科醫(yī)院新生兒科，上海 200032)

極低出生體重兒神經(jīng)發(fā)育損害的危險(xiǎn)因素研究

顧 琴1，張金萍2

(1.上海市長(zhǎng)寧區(qū)婦幼保健院兒科，上海 200051；2.復(fù)旦大學(xué)附屬兒科醫(yī)院新生兒科，上海 200032)

目的 探討極低出生體重兒神經(jīng)發(fā)育損害的危險(xiǎn)因素。方法 選擇2011年2月至2015年2月在上海市長(zhǎng)寧區(qū)婦幼保健院出生并存活的64例極低出生體重兒為研究對(duì)象，根據(jù)神經(jīng)發(fā)育評(píng)估結(jié)果分組，其中神經(jīng)發(fā)育正常組34例，神經(jīng)發(fā)育損傷組30例，并對(duì)患兒的臨床資料及其與極低出生體重兒神經(jīng)發(fā)育的相關(guān)性進(jìn)行分析。結(jié)果 神經(jīng)發(fā)育損傷組患兒的低氧血癥、高碳酸血癥的發(fā)生率均高于神經(jīng)發(fā)育正常組，但差異均無統(tǒng)計(jì)學(xué)意義(均P>0.05)。神經(jīng)發(fā)育損傷組患兒的腦損傷(χ2=7.88)、呼吸窘迫綜合征(χ2=6.77)及機(jī)械通氣天數(shù)(t=6.54)均顯著高于神經(jīng)發(fā)育正常組，且差異均有統(tǒng)計(jì)學(xué)意義(均P<0.05)。腦損傷、呼吸窘迫綜合征、機(jī)械通氣天數(shù)均為極低出生體重兒神經(jīng)發(fā)育損傷的危險(xiǎn)因素(χ2值分別為19.879、8.012、15.632，均P<0.05)。結(jié)論 腦損傷、呼吸窘迫綜合征、機(jī)械通氣天數(shù)為極低出生體重兒神經(jīng)發(fā)育損傷的獨(dú)立高危因素，因此需積極采取針對(duì)性的防治干預(yù)措施，改善患兒的神經(jīng)發(fā)育狀況。

極低出生體重兒；神經(jīng)發(fā)育損害；腦損傷；呼吸窘迫綜合征；機(jī)械通氣；危險(xiǎn)因素

隨著圍產(chǎn)醫(yī)學(xué)和新生兒醫(yī)學(xué)水平的提高，極低出生體重兒(very low birth weight infants，VLBWI)的存活率逐年提升。VLBWI多為早產(chǎn)兒，因此身體的各項(xiàng)系統(tǒng)機(jī)能尚未完善，胎齡小對(duì)于新生兒身體的各方面，特別是神經(jīng)系統(tǒng)影響很大[1]。本文對(duì)64例VLBWI的臨床資料進(jìn)行了回顧性分析，旨在探討VLBWI神經(jīng)發(fā)育損害的危險(xiǎn)因素，為指導(dǎo)臨床后期早期干預(yù)與治療，改善患兒神經(jīng)發(fā)育結(jié)局提供理論依據(jù)?，F(xiàn)將研究結(jié)果報(bào)告如下。

1資料與方法

1.1一般資料

選擇2011年2月至2015年2月在上海市長(zhǎng)寧區(qū)婦幼保健院出生并存活的64例VLBWI為研究對(duì)象，所有患兒出生后給予遠(yuǎn)紅外保暖等處理轉(zhuǎn)到復(fù)旦大學(xué)附屬兒科醫(yī)院，其中男性35例，女性29例；胎齡28～33周，平均胎齡(30.5±3.6)周；出生體重1 000～1 500g，平均體重(1 252.8±23.6)g。

入選標(biāo)準(zhǔn)：胎齡小于37周，出生體重小于1 500g，出生12h以內(nèi)入院。剔除標(biāo)準(zhǔn)：嚴(yán)重先天畸形、異常代謝性疾病、妊娠期血小板減少、凝血機(jī)制障礙、狼瘡等疾病患兒。根據(jù)神經(jīng)發(fā)育評(píng)估結(jié)果，將64例分為神經(jīng)發(fā)育正常組34例和神經(jīng)發(fā)育損傷組30例。

1.2方法

所有患兒轉(zhuǎn)到復(fù)旦大學(xué)附屬兒科醫(yī)院后，均先給予急救治療，將其迅速放到暖箱中，體表覆蓋聚乙烯薄膜。監(jiān)測(cè)患兒的生命體征、皮溫、肛溫、血糖水平，減少聲光干擾。在出生早期(24h以內(nèi))采用鼻飼早產(chǎn)兒配方奶0.5mL/次，逐漸加量，并實(shí)施非營(yíng)養(yǎng)性吸允。日齡34天時(shí)可逐漸耐受喂養(yǎng)，經(jīng)精心喂養(yǎng)其體重逐漸增加到2 500g，生活能力增強(qiáng)，吸吮有力，這時(shí)可同于一般新生兒一樣喂養(yǎng)。營(yíng)養(yǎng)參考標(biāo)準(zhǔn)為2010版早產(chǎn)兒腸內(nèi)營(yíng)養(yǎng)支持建議和早產(chǎn)兒營(yíng)養(yǎng)需求建議，同時(shí)給予患兒積極的呼吸治療和防治感染治療[2]。校正月齡18～42個(gè)月，對(duì)患兒進(jìn)行貝利嬰兒發(fā)育量表Ⅱ評(píng)估。如以下情況中有任何一項(xiàng)出現(xiàn)即診斷為神經(jīng)發(fā)育損害[3]。貝利嬰兒發(fā)育量表Ⅱ測(cè)試智力發(fā)育指數(shù)<70分，心理運(yùn)動(dòng)發(fā)育指數(shù)<70分，雙眼失明，聽力受損，中至重度腦性癱瘓。

1.3危險(xiǎn)因素分析

統(tǒng)計(jì)分析患兒的臨床資料，包括性別、胎齡、出生體重、分娩方式、產(chǎn)婦是否有妊娠期高血壓疾病、是否有宮內(nèi)窘迫、胎膜早破、胎盤早剝的情況，新生兒是否出現(xiàn)腦損傷、呼吸窘迫綜合征及機(jī)械通氣天數(shù)。腦損傷的診斷標(biāo)準(zhǔn)：出生時(shí)臍動(dòng)脈血?dú)馑岫刃∮?.0，出生時(shí)何氏評(píng)分1min時(shí)低于3分，在出生12h內(nèi)出現(xiàn)神經(jīng)系統(tǒng)癥狀，伴有其他器官的損傷[4]。

1.4統(tǒng)計(jì)學(xué)方法

應(yīng)用SPSS 17.0軟件分析數(shù)據(jù)，其中計(jì)量資料應(yīng)用組間t檢驗(yàn)，計(jì)數(shù)資料應(yīng)用組間χ2檢驗(yàn)，各因素應(yīng)用Logistic回歸分析，以P<0.05表示差異有統(tǒng)計(jì)學(xué)意義。

2結(jié)果

2.1神經(jīng)發(fā)育損傷的危險(xiǎn)因素分析

經(jīng)單因素分析，兩組的性別、胎齡、出生體重、分娩方式、宮內(nèi)窘迫、胎膜早破、母親妊娠期高血壓疾病、胎盤早剝比較差異均無統(tǒng)計(jì)學(xué)意義(均P>0.05)；神經(jīng)發(fā)育損傷組患兒出現(xiàn)低氧血癥、高碳酸血癥的發(fā)生率均高于神經(jīng)發(fā)育正常組，但差異均無統(tǒng)計(jì)學(xué)意義(均P>0.05)；神經(jīng)發(fā)育損傷組患兒出現(xiàn)腦損傷、呼吸窘迫綜合征的發(fā)生率均高于神經(jīng)發(fā)育正常組(均P<0.05)，神經(jīng)發(fā)育損傷組患兒的機(jī)械通氣天數(shù)也顯著高于神經(jīng)發(fā)育正常組(P<0.05)，見表1。

表1 神經(jīng)發(fā)育損傷危險(xiǎn)單因素分析結(jié)果分析±S]

2.2極低出生體重兒神經(jīng)發(fā)育損傷高危因素Logistic回歸分析

對(duì)單因素分析中與神經(jīng)發(fā)育有明顯關(guān)聯(lián)的各因素進(jìn)行Logistic回歸分析，結(jié)果顯示，腦損傷、呼吸窘迫綜合征、機(jī)械通氣天數(shù)均為VLBWI神經(jīng)發(fā)育損傷的危險(xiǎn)因素，見表2。

表2 VLBWI神經(jīng)發(fā)育損傷高危因素Logistic回歸分析結(jié)果

3討論

3.1極低出生體重兒神經(jīng)發(fā)育損傷高危因素分析

VLBWI的胎齡一般小于33周，過早的離開母體導(dǎo)致胎兒腦細(xì)胞數(shù)量較少，腦重量相對(duì)較低，神經(jīng)系統(tǒng)的成熟受到連續(xù)性阻礙，神經(jīng)發(fā)育較為遲緩[5-7]。本研究發(fā)現(xiàn)，腦損傷是VLBWI神經(jīng)損傷的主要危險(xiǎn)因素。有研究報(bào)道，腦的生長(zhǎng)發(fā)育和神經(jīng)通路的發(fā)育主要在妊娠34～40周形成，50%的皮質(zhì)在此期間生長(zhǎng)發(fā)育，妊娠29周前僅有很少的白質(zhì)髓鞘化[8-9]。腦室周圍的白質(zhì)軟化、腦室內(nèi)出血可導(dǎo)致早產(chǎn)兒出現(xiàn)腦損傷。腦組織損傷，傷及感覺中樞、運(yùn)動(dòng)中樞、神經(jīng)傳導(dǎo)通路，可導(dǎo)致患兒出現(xiàn)神經(jīng)發(fā)育損傷[10]。本研究顯示，VLBWI神經(jīng)發(fā)育損傷組腦損傷率為46.67%，明顯高于神經(jīng)發(fā)育正常組的5.88%(P<0.05)，且Logistic回歸分析顯示，腦損傷為導(dǎo)致VLBWI出現(xiàn)神經(jīng)發(fā)育損傷的高危因素。

本研究顯示，VLBWI神經(jīng)發(fā)育損傷組呼吸窘迫綜合征發(fā)病率為40.00%，明顯高于神經(jīng)發(fā)育正常組的5.88%(P<0.05)，且Logistic回歸分析顯示其為導(dǎo)致VLBWI神經(jīng)發(fā)育損傷的高危因素。早產(chǎn)兒的腦血流是壓力被動(dòng)調(diào)節(jié)，血壓增高及血流異常波動(dòng)時(shí)容易導(dǎo)致腦出血。VLBWI出現(xiàn)呼吸窘迫會(huì)導(dǎo)致血管壁的通透性增強(qiáng)引起出血、滲血，缺氧、缺血會(huì)導(dǎo)致腦室周圍白質(zhì)損傷軟化，進(jìn)而造成腦損傷，致使神經(jīng)發(fā)育受損[11-12]。

本研究顯示，VLBWI神經(jīng)發(fā)育損傷組的機(jī)械通氣天數(shù)平均為9.7±10.4天，明顯高于神經(jīng)發(fā)育正常組的5.1±7.9天(P<0.05)，分析原因可能是由于神經(jīng)機(jī)械通氣的送氣和氣管內(nèi)吸引會(huì)促使患兒腦血流波動(dòng)，增加了患兒顱內(nèi)出血和腦室周圍白質(zhì)損傷的危險(xiǎn)性，且有研究表明，機(jī)械通氣能夠?qū)純旱姆尾吭斐杉甭該p傷，進(jìn)而導(dǎo)致神經(jīng)發(fā)育受損[13]。

3.2防治措施探討

為了提高VLBWI的生活質(zhì)量，有效地防治神經(jīng)發(fā)育損害，建議：①給予患兒合理充足的營(yíng)養(yǎng)護(hù)理，其能夠有效地改善患兒神經(jīng)發(fā)育狀況[14]，對(duì)產(chǎn)婦及其家屬進(jìn)行科學(xué)營(yíng)養(yǎng)喂養(yǎng)指導(dǎo)，保證患兒的營(yíng)養(yǎng)水平；②早期實(shí)施干預(yù)，改善患兒的神經(jīng)行為，出院后加強(qiáng)隨訪，及時(shí)發(fā)現(xiàn)患兒在聽覺、視覺、運(yùn)動(dòng)等方面的異常情況，實(shí)施個(gè)體化的干預(yù)措施及后期治療方案；③正確合理地使用呼吸機(jī)，有效地減少患兒腦內(nèi)出血及白質(zhì)軟化，提高其生存率，降低致殘率；④加強(qiáng)腦血流動(dòng)力學(xué)的檢測(cè)，保持患兒血壓、血氧、血糖、體溫及內(nèi)環(huán)境的穩(wěn)定性，減少腦灌注的波動(dòng)。

總之，腦損傷、呼吸窘迫綜合征、機(jī)械通氣天數(shù)均為VLBWI神經(jīng)發(fā)育損傷的高危因素。VLBWI多見于早產(chǎn)兒，早產(chǎn)兒易發(fā)生呼吸窘迫綜合征，長(zhǎng)時(shí)間的有創(chuàng)通氣與后期腦損傷密切相關(guān)。因此早期干預(yù)，預(yù)防早產(chǎn)，積極救治，盡量縮短機(jī)械通氣上機(jī)時(shí)間，對(duì)改善患兒神經(jīng)發(fā)育結(jié)局有重要意義。

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[專業(yè)責(zé)任編輯： 艾 婷]

Risk factors of neural development damage in very low birth weight infants

GU Qin1, ZHNAG Jin-ping2

(1.Department of Pediatrics, Maternal and Child Health Care Hospital of Shanghai Changning District, Shanghai 200051, China;2.DepartmentofNeonatology,PediatricsHospitalAffiliatedtoFudanUniversity,Shanghai200032,China)

Objective To explore the risk factors of neural development damage in very low birth weight infants (VLBWI). Methods Sixty-four cases of live VLBWI born in Maternal and Child Health Care Hospital of Shanghai Changning District during the period of February in 2011 to February in 2015 were selected as study subjects, and they were divided into normal neural development group (34 cases) and neural development damage group (30 cases). Clinical data and its correlation with the neural development of VLBWI were analyzed. Results The incidence of hypoxia and hyperlipidemia in the neural development damage group was higher than in normal group, but there was no statistical significance (bothP>0.05). The incidence of brain injury (χ2=7.88) and respiratory distress syndrome (χ2=6.77) as well as oscillatory ventilation days (t=6.54) were significantly higher in neural development damage group than in normal group (allP<0.05). Brain injury, respiratory distress syndrome and oscillatory ventilation were the risk factors of neural development damage in VLBWI (χ2value was 19.879, 8.012 and 15.632, respectively, allP<0.05). Conclusion Brain injury, respiratory distress syndrome and oscillatory ventilation are the independent risk factors of neural development damage of VLBWI. Therefore, it is necessary to take positive measures to improve the nerve development of VLBWI.

very low birth weight infant (VLBWI); neural development damage; brain injury; respiratory distress syndrome; oscillatory ventilation; risk factor

2016-04-28

顧 琴(1962-)，女，副主任醫(yī)師，主要從事新生兒相關(guān)疾病的臨床診治工作。

張金萍，副主任醫(yī)師。

10.3969/j.issn.1673-5293.2016.11.005

R729

A

1673-5293(2016)11-1304-02