本文關(guān)鍵詞：早產(chǎn)兒相關(guān)臨床問題的多中心流行病學(xué)研究及危重新生兒穩(wěn)定項(xiàng)目的推廣和效果評價(jià)，，由筆耕文化傳播整理發(fā)布。

        新生兒死亡率一直是衡量國民健康、社會(huì)進(jìn)步的重要指標(biāo)之一。2011年我國衛(wèi)生部官方網(wǎng)站公布的新生兒死亡率為7.8‰。所有死亡新生兒中有四分之三發(fā)生在生后第一周,早產(chǎn)和低出生體重、以及和早產(chǎn)相關(guān)的各種并發(fā)癥是新生兒期死亡或致殘的主要原因之一。近二十年來,隨著我國國民經(jīng)濟(jì)的發(fā)展和醫(yī)療改革的推進(jìn),我國各地區(qū)相繼建立新生兒重癥監(jiān)護(hù)病房(Neonatal intensive care unit, NICU),早產(chǎn)兒尤其極低出生體重兒(Very low birth weight infant, VLBWI)的生存率較前顯著提高,但是和發(fā)達(dá)國家相比,仍存在較大差距,且存活早產(chǎn)兒中相當(dāng)部分留有各種后遺癥。因此如何進(jìn)一步降低早產(chǎn)兒的死亡率和并發(fā)癥率,改善其生存質(zhì)量已經(jīng)成為當(dāng)今圍產(chǎn)醫(yī)學(xué)的研究重點(diǎn)。目前發(fā)達(dá)國家的新生兒臨床研究普遍采取建立多中心協(xié)作網(wǎng)絡(luò)的方式,通過大型臨床數(shù)據(jù)庫開展大樣本的流行病學(xué)調(diào)查和隨機(jī)對照試驗(yàn),取得循證醫(yī)學(xué)證據(jù),并進(jìn)一步調(diào)整醫(yī)療實(shí)踐行為,優(yōu)化醫(yī)療資源的利用,改善醫(yī)療質(zhì)量。相比發(fā)達(dá)國家,我國臨床資料的信息化管理程度還較低,缺乏成熟的全國性多中心協(xié)作網(wǎng)絡(luò),新生兒醫(yī)學(xué)很大程度上還停留在經(jīng)驗(yàn)醫(yī)學(xué),缺乏循證依據(jù)。且由于我國的新生兒人群具有自己的種族、社會(huì)經(jīng)濟(jì)狀況、文化的特殊性,無法直接照搬國外的經(jīng)驗(yàn)或結(jié)論。因此建立我國早產(chǎn)兒臨床資料的數(shù)據(jù)庫和協(xié)作網(wǎng)絡(luò),開展多中心流行病學(xué)研究,具有重要的科學(xué)價(jià)值和社會(huì)意義。除了死亡率和患病率的流行病學(xué)監(jiān)測以外,區(qū)域性的適宜技術(shù)推廣也是持續(xù)改善醫(yī)療質(zhì)量的有力舉措。有效的適宜技術(shù)推廣可以在較短時(shí)間內(nèi)提高醫(yī)護(hù)人員的臨床思維能力和疾病處理能力,具有低成本,高效益的特點(diǎn)。本課題的研究重點(diǎn)為在我國Ⅲ級NICU建立多中心協(xié)作網(wǎng)絡(luò),針對不同胎齡和出生體重早產(chǎn)兒的救治現(xiàn)狀開展多中心流行病學(xué)研究,分析其臨床特征、近期臨床結(jié)局及疾病負(fù)擔(dān),探討進(jìn)一步降低死亡率、改善預(yù)后的策略,并就新生兒穩(wěn)定的相關(guān)適宜技術(shù)——Acute Care of at-Risk Newborn (ACoRN)在浙江省的實(shí)施進(jìn)行效果評價(jià)。第一部分VLBWI的全國性多中心流行病學(xué)研究目的：1.分析我國Ⅲ級NICU收治的VLBWI的人口學(xué)特征、各類并發(fā)癥的發(fā)生情況、診治經(jīng)過和近期臨床結(jié)局等。2.將我國資料和發(fā)達(dá)國家的資料進(jìn)行比較,探討進(jìn)一步降低死亡率、改善臨床預(yù)后的策略。方法：回顧性病例資料分析1.收集2010年1月至2010年12月期間入住33家協(xié)作單位NICU的所有VLBWI的臨床資料2.建立多中心協(xié)作組和臨床資料數(shù)據(jù)庫。3.對VLBWI的死亡率和常見疾病患病率、近期結(jié)局和醫(yī)療負(fù)擔(dān)進(jìn)行分析。4.與加拿大新生兒協(xié)作網(wǎng)2010年年報(bào)資料進(jìn)行死亡率和患病率的比較。結(jié)果：1.研究期間33家NICU收治VLBWI共2914例,其中男性1697例(58.2%),平均出生胎齡30.1±2.3周,平均出生體重1239.9±181.1g；宮內(nèi)發(fā)育遲緩766例(26.3%)；超低出生體重兒占8.9%,超不成熟早產(chǎn)兒占25.6%。2.患病率：經(jīng)過頭顱B超篩查的2519例中65.6%未發(fā)現(xiàn)腦室內(nèi)出血(Intraventricular hemorrhage, IVH)。Ⅰ度IVH303例(12.1%),Ⅱ度IVH325例(13.0%),Ⅲ度IVH190例(7.6%),Ⅳ度IVH48例(1.9%)。重度IVH (Ⅲ-Ⅳ度)的發(fā)生率隨出生胎齡和體重的增加而逐漸減少。機(jī)械通氣的應(yīng)用也隨著胎齡和出生體重的增加而減少。接受表面活性物質(zhì)的占39.6%。胎齡<30周和出生體重<1250g的人群中,50%以上需要氨茶堿興奮呼吸中樞。住院時(shí)間>28天的VLBWI中446例(25.8%)符合BPD (Bronchopulmomary dysplasia, BPD)診斷標(biāo)準(zhǔn),其中輕度285例(63.9%),中度128例(28.7%),重度32例(7.2%)。41.5%的BPD患兒接受產(chǎn)后皮質(zhì)激素治療。共493例VLBWI的動(dòng)脈導(dǎo)管未閉(Patent ductus arteriosus, PDA)需要藥物或手術(shù)干預(yù),其發(fā)生率在所有住院時(shí)間>24h的VLBWI中為18.4%,且發(fā)生率隨著出生體重和胎齡的減低而增加�？诜淄春筒悸宸抑委煹谋壤謩e為15.1%和84.9%。20例在藥物治療失敗后手術(shù)結(jié)扎,另有2例未經(jīng)藥物治療直接手術(shù)。共194例VLBWI發(fā)生壞死性小腸結(jié)腸炎(Necrotizing enterocolitis, NEC),占住院時(shí)間>24h的7.2%。NEC患兒中10.3%接受手術(shù)治療。最終治愈出院的136例(70.1%),醫(yī)院內(nèi)死亡15例(7.7%),放棄治療43例(22.2%)。NEC組開始胃腸喂養(yǎng)的日齡中位數(shù)為2d,和未患NEC的VLBWI無差異,但達(dá)到足量喂養(yǎng)的時(shí)間顯著延遲(日齡中位數(shù)32.5dvs.24d)。糾正胎齡達(dá)32周的VLBWI中78%接受了早產(chǎn)兒視網(wǎng)膜病(Retinopathy of prematurity, ROP)篩查,各期ROP的總發(fā)生率為24.5%,未檢出嚴(yán)重ROP致盲病例。23.4%接受了激光手術(shù)。病原學(xué)陽性的醫(yī)院獲得性感染(Hospital acquired infection, HAI)總發(fā)生率為12.8%,其中3.1%住院期間發(fā)生2次以上HAI。呼吸機(jī)相關(guān)性肺炎和血流感染是常見的HAI。病原學(xué)分布以G-菌最常見(276例次,61.1%),G+菌次之(111例次,24.6%),真菌65例次(14.4%)。3.近期結(jié)局：住院期間死亡187例(6.4%),其中30.5%死亡年齡<24h,15.5%死亡年齡24-72h,13.9%死亡日齡3-7d,40.1%死亡日齡>7d。放棄治療出院812例(27.9%),出生當(dāng)天即放棄治療出院或死亡的VLBWI共有218例(7.5%)。隨著出生胎齡和體重的增加,死亡率逐漸下降,但出生胎齡≥35周的亞組死亡率卻顯著高于胎齡31～34周的VLBWI。其余1915例(65.7%)經(jīng)治療達(dá)到出院標(biāo)準(zhǔn)后出院。治愈出院的VLBWI平均住院費(fèi)用為40.9±30.8千元(20.4～53.2千元,中位數(shù)33.1千元),出院時(shí)平均糾正胎齡37.1±2.9周,平均出院體重2076.9±470.5g。出院時(shí)66.8%體重未能達(dá)到糾正胎齡體重的第10百分位。4.和加拿大新生兒協(xié)作網(wǎng)2010年年報(bào)資料比較：我國收治的VLBWI以胎齡28周,體重1000g以上的為主,收治的最低胎齡為24周,僅9例。各胎齡和出生體重亞組VLBWI的存活率都存在顯著差距。由于我國胎齡≤26周和體重<750克的VLBWI存活的人數(shù)很少,因此和加拿大資料不具可比性。在胎齡≥29周和體重≥1000克的VLBWI中,我國BPD、PDA、NEC、ROP的患病率都超過了加拿大資料。結(jié)論：1.我國收治的VLBWI以出生體重大于1000g、胎齡28周以上的為主,ELBWI和EPI僅占很小一部分。2.和發(fā)達(dá)國家相比,我國VLBWI的存活率和救治水平還存在一定差距。3.我國的VLBWI有1/4未能堅(jiān)持完成治療。4.這是我國首次對VLBWI開展的多中心大樣本流行病學(xué)研究。第二部分晚期早產(chǎn)兒的多中心流行病學(xué)研究目的：1.分析晚期早產(chǎn)兒(Late-preterm infant, LPI)的人口學(xué)特征、分娩方式、各種臨床問題患病率、診治經(jīng)過和臨床結(jié)局。2.分析LPI/足月兒呼吸系統(tǒng)疾病的發(fā)病特點(diǎn)、治療經(jīng)過、疾病負(fù)擔(dān),對不同的疾病嚴(yán)重度評估方法進(jìn)行比較。3.研究表面活性物質(zhì)治療LPI/足月兒呼吸窘迫綜合征(Respiratory distress syndrome, RDS)的療效及安全性。方法：1.浙江省11家Ⅲ級NICU的LPI回顧性研究：回顧性收集2007年1月至12月入住浙江省11家Ⅲ級NICU的新生兒臨床資料,分析產(chǎn)科出生新生兒的胎齡分布情況、分娩方式以及NICU收治新生兒的伴發(fā)疾病、診治情況和臨床轉(zhuǎn)歸等,將LPI和足月兒的臨床資料進(jìn)行比較。2.全國7家NICU所收治LPI呼吸系統(tǒng)疾病的前瞻性研究：前瞻性收集2008年11月至2009年10月期間入住全國7家Ⅲ級NICU的出生胎齡≥34周,因呼吸窘迫需要CPAP或機(jī)械通氣支持的患兒的臨床資料。根據(jù)臨床癥狀和血?dú)夥治鼋Y(jié)果進(jìn)行疾病嚴(yán)重度評分。分析LPI和足月兒發(fā)生呼吸窘迫的基礎(chǔ)疾病、臨床特點(diǎn)、近期轉(zhuǎn)歸和疾病負(fù)擔(dān),比較不同疾病嚴(yán)重度評分體系的實(shí)用價(jià)值和相關(guān)性。3.全國8家NICU表面活性物質(zhì)治療LPI和足月兒RDS的前瞻性研究：2010年1月至1010年9月,出生72h內(nèi)入住8家Ⅲ級NICU的LPI/足月RDS患兒納入研究。機(jī)械通氣下FiO2>0.4才能維持PaO2≥50mmHg或SPO2>90%的患兒給予豬肺磷脂注射液,首劑量80-150mg/kg。并按首劑劑量≥100mg/kg和≤100mg/kg分為大劑量組和小劑量組。觀察并記錄患兒的人口學(xué)信息、給藥信息,給藥前及給藥后不同時(shí)間點(diǎn)的生命體征、血?dú)夥治鼋Y(jié)果、呼吸機(jī)參數(shù)、臨床并發(fā)癥,記錄臨床轉(zhuǎn)歸、治療費(fèi)用、藥物不良事件等。通過呼吸機(jī)參數(shù)、血?dú)庵笜?biāo)的動(dòng)態(tài)變化評價(jià)藥物療效。結(jié)果：1.浙江省11家Ⅲ級NICU的LPI回顧性研究2007年1月至12月期間,納入研究的醫(yī)院共有44,362例新生兒出生,早期早產(chǎn)兒占2.7%,LPI占6.2%,總的早產(chǎn)兒出生率為8.9%。58.2%為剖宮產(chǎn)。各醫(yī)院剖宮產(chǎn)率最高75.6%,最低42.3%。LPI的剖宮產(chǎn)率為63.8%,顯著高于早期早產(chǎn)兒組(50.3%)和足月兒組(58.0%)。共10537例新生兒入住NICU,早產(chǎn)兒占33.9%,其中56.9%為LPI。LPI和足月兒占總收治人數(shù)的85.4%。住院新生兒中LPI組剖宮產(chǎn)比例(63.8%)顯著高于早期早產(chǎn)兒組(50.8%)和足月兒組(52.6%)。71.3%的患兒出生72h內(nèi)入住NICU。LPI組最常見的住院原因是呼吸窘迫(n=856,42.1%),其次為高膽紅素血癥(n=357,17.6%)和低血糖(n=176,8.7%)。LPI組中呼吸窘迫(42.1%vs.25.4%)、缺氧缺血性腦病(3.3%vs.2.4%)、顱內(nèi)出血(3.1%vs.1.2%)和低血糖(8.7%vs.2.9%)的發(fā)生率顯著高于足月兒組。LPI組引I起呼吸窘迫的基礎(chǔ)疾病,最常見的是肺炎(39.5%),其次為新生兒暫時(shí)性呼吸困難(22.5%)和RDS(19.0%)。LPI組機(jī)械通氣和CPAP支持的比例分別為15.4%和21.4%,足月兒組分別為11.0%和11.6%,兩組差異顯著。LPI組1777例(87.5%)最終完成治療,199例(9.8%)由于各種原因放棄治療,醫(yī)院內(nèi)死亡16例(0.8%),40例(2.0%)轉(zhuǎn)運(yùn)至其他醫(yī)院接受治療。其醫(yī)院內(nèi)死亡率及轉(zhuǎn)運(yùn)至外院的比例顯著高于足月兒組,完成治療率則低于足月兒組。2.全國7家NICU所收治LPI呼吸系統(tǒng)疾病的前瞻性研究共503例胎齡>34周的呼吸窘迫患兒納入研究,平均胎齡36.8±2.2周,平均體重2734.5±603.5g,男性占69.3%；LPI占49.7%。74.8%剖宮產(chǎn)出生,其中51.1%系選擇性剖宮產(chǎn)。出現(xiàn)呼吸窘迫的年齡為3.2±9.1h,入住NICU的年齡中位數(shù)為4h。LPI組剖宮產(chǎn)率明顯高于足月兒組。LPI組呼吸窘迫的基礎(chǔ)疾病以RDS、新生兒暫時(shí)性呼吸困難和肺炎為主,其中RDS所占比例顯著高于足月兒組(41.6%vs.23.7%)。足月兒組重度呼吸窘迫的比例(10.3%vs.5.2%)和SNAP-Ⅱ評分(17.1±14.2vs.14.5±13.1)顯著高于LPI組。LPI組住院時(shí)間較足月兒長,住院總費(fèi)用高,醫(yī)院內(nèi)死亡率和足月兒組沒有差異。根據(jù)入院時(shí)的呼吸評分,本研究隊(duì)列中輕中度呼吸窘迫占92.2%,重度僅7.8%。重度呼吸窘迫組的平均胎齡、出生體重較輕中度組大,選擇性剖宮產(chǎn)比例最高,入住NICU時(shí)間最晚,5分鐘Apgar評分<7分、需要?dú)夤懿骞苓M(jìn)行復(fù)蘇的比例最高。重度呼吸窘迫組的并發(fā)癥發(fā)生率、死亡率和醫(yī)療費(fèi)用都高于其他兩組。重度呼吸窘迫組的SNAP-Ⅱ評分和最高OI值顯著高于其他兩組。SNAP-Ⅱ評分和呼吸評分呈線性相關(guān)。Logistic回歸分析提示較大胎齡、較高SNAP-Ⅱ評分、較高OI值、5分鐘Apgar評分<7分是LPI/足月兒RDS死亡的獨(dú)立危險(xiǎn)因素。3.全國8家NICU表面活性物質(zhì)治療LPI和足月兒RDS的前瞻性研究共96例患兒納入研究,男性71.9%,平均胎齡36.5±2.1周,平均體重2690.3±562.6g, LPI占59.4%,宮縮發(fā)動(dòng)后的剖宮產(chǎn)占25.0%,選擇性剖宮產(chǎn)占62.5%。診斷RDS的時(shí)齡中位數(shù)為9.9h(0.2～84.2h),胸片RDS分期為Ⅲ-Ⅳ期的65例,占67.7%。首劑豬肺磷脂注射液給藥時(shí)間為出生后13.3h(0-85.5h),首劑給藥劑量為108.5±20.2mg/kg,10.4%的患兒接受第二劑。給藥后0.5h, PaO2、SpO2較給藥前明顯上升,PaCO2、FiO2明顯下降,隨著時(shí)間延長至6h, FiO2進(jìn)一步下降,平均氣道壓也較前下降。給藥后0.5h,PaO2/FiO2、OI、A-aDO2、PaO2/PAO2均較給藥前明顯改善,且給藥后6h持續(xù)改善。機(jī)械通氣的中位小時(shí)數(shù)為110.5h,28.1%出現(xiàn)并發(fā)癥。住院日中位數(shù)為18.0d,住院費(fèi)用中位數(shù)32.9千元。治愈出院73例(76.0%),好轉(zhuǎn)出院17例(17.7%),放棄治療5例(512%),因并發(fā)多臟器功能衰竭而死亡1例(1.0%)。大劑量組和小劑量組首劑的給藥劑量分別為115.8±17.8mg/kg和87.9±9.6mg/kg,大劑量組給藥后6h PaO2/FiO2、OI、A-aDO2、PaO2/PAO2的改善顯著優(yōu)于小劑量組。大劑量組機(jī)械通氣時(shí)間縮短,但不能縮短住院時(shí)間,且住院費(fèi)用、并發(fā)癥發(fā)生率、治愈或好轉(zhuǎn)率和小劑量組相比并無統(tǒng)計(jì)學(xué)差異。結(jié)論：1.我國NICU收治的LPI具有很高的剖宮產(chǎn)率。2.和足月兒相比,LPI中因呼吸窘迫、低血糖、顱內(nèi)出血入院的比例顯著增加,其中呼吸窘迫是最突出的臨床問題。3.豬肺磷脂注射液對于較大胎齡的LPI或足月兒RDS具有顯著的短期療效。4. ACoRN呼吸評分是評估新生兒呼吸窘迫嚴(yán)重程度的有用的工具。第三部分危重新生兒初步穩(wěn)定適宜技術(shù)的推廣和系統(tǒng)評價(jià)目的：1.評估浙江省經(jīng)濟(jì)相對欠發(fā)達(dá)地區(qū)的醫(yī)療資源分布情況及教學(xué)需求。2.對項(xiàng)目醫(yī)院醫(yī)護(hù)人員進(jìn)行ACoRN培訓(xùn),并對培訓(xùn)效果進(jìn)行評估。3.評估ACoRN的教學(xué)內(nèi)容和教學(xué)材料在中國的適用性。4.評估ACoRN教學(xué)模式在中國基層醫(yī)院進(jìn)一步推廣的可行性和必要性。方法：前瞻性隊(duì)列對照研究1.通過問卷調(diào)查對浙江省36個(gè)縣41家Ⅱ級醫(yī)院的醫(yī)療資源和教學(xué)需求進(jìn)行評估,從中選擇15家作為ACoRN培訓(xùn)的項(xiàng)目醫(yī)院。2.對各家項(xiàng)目醫(yī)院進(jìn)行ACoRN培訓(xùn)。3.通過5分制的Likert量表調(diào)查問卷和典型病例對學(xué)員的自信度和專業(yè)知識(shí)技能進(jìn)行評估。4.通過問卷和小組討論對ACoRN教學(xué)材料和教學(xué)模式進(jìn)行評估。結(jié)果：1.15家項(xiàng)目醫(yī)院216名醫(yī)護(hù)人員接受ACoRN培訓(xùn)。2.醫(yī)護(hù)人員處理危重新生兒的自信度由培訓(xùn)前的47.6±10.4分上升至培訓(xùn)后的59.2±7.7分。所有子項(xiàng)的培訓(xùn)后得分均顯著高于培訓(xùn)前(p<0.01)。3.醫(yī)護(hù)人員的臨床知識(shí)和技能總分由培訓(xùn)前的31.5±5.1上升至培訓(xùn)后的34.7±3.5分,改善顯著(p<0.01,效應(yīng)量=0.77)。病例A、B、C,學(xué)員培訓(xùn)后得分提高顯著；病例D的得分培訓(xùn)前后無統(tǒng)計(jì)學(xué)差異。4.學(xué)員對ACoRN教程和培訓(xùn)內(nèi)容、培訓(xùn)模式給予了高度評價(jià),認(rèn)為該教程符合基層醫(yī)院的需求,值得推廣。其中ACoRN的新生兒初步評估法和系統(tǒng)流程圖得到的認(rèn)可度最高。結(jié)論：1. ACoRN項(xiàng)目顯著改善基層醫(yī)院醫(yī)護(hù)人員處理危重新生兒時(shí)的自信心。2. ACoRN項(xiàng)目顯著改善基層醫(yī)院醫(yī)護(hù)人員處理危重新生兒的專業(yè)知識(shí)和技能。3. ACoRN的教學(xué)材料和教學(xué)模式可以很好地被基層醫(yī)院的醫(yī)護(hù)人員接受,具有廣闊的應(yīng)用前景。

    In China, the neonatal mortality reported by the Ministry of Health in2011was7.8%o. The major causes of death were preterm, low birth weight, and preterm related complications. During the past20years, modern perinatal-neonatal care has emerged dramatically in China. Major tertiary centers with neonatal intensive care unit (NICU) are established mainly in provincial and subprovincial cities. Although the mortality of very low birth weight infant (VLBWI) has decresed significantly, there is still a wide gap behind the developed countries. Therefore, how to reduce the mortality and morbidity of preterm infants is still the focus today in perinatal medicine.With the establishment of multi-center collaborative network in developed countries, some randomized controlled trials with large sample size were conducted. Results of these trials could be used as clinical evidence to modify the medical practice and to improve the quality of perinatal care.In China, we still lack of national collaborative network and muti-center clinical database. Due to Chinese newborn population has its own race and socio-economic status, we can not copy foreign experience or conclusions directly. The establishment of national network and database will be the future direction in perinatal medicine.Medical training program for health care giver is an evidence-based, cost-effective intervention for improving perinatal care in low-income countries, particularly in rural settings. It can improve trainee’s self-confidence, knowledge and clinical skills.We conducted this study to explore the mortality, morbidity and short-term outcomes of preterm infants at different gestational age or birth weight subgroup. And we also conducted a prospective, controlled study to evaluate the effect of an educational program on learner satisfaction and knowledge in an economically disadvantaged region of Zhejiang province in China.Part one:A national survey of VLBWI in ChinaObjectives:1. To investigate the clinical characteristics, morbidity and short-term outcomes of VLBWI who admitted to tertiary NICUs.2. To compare the mortality and morbidity of VLBWI between China and developed country.Methods:1. Clinical information of all VLBWI admitted to the33tertiary NICUs was retrospectively collected during the year2010.2. The multi-center collaborative network and clinical database was established.3. The data of mortality, morbidity, short-term outcomes and medical burden was analyzed.4. Compare our data with the data from Canadian Neonatal Network (CNN) annual report of year2010.Results: 1. During the12-month study period, there were2914VLBWI admitted to the33tertiary NICUs, the mean gestational age of this cohort was30.1±2.3weeks, mean birth weight was1239.9Q181.1grams. Of all the infants,58.2%were male. Extremely low birth weight infants (ELBWI) and extremely premature infants (EPI) accounted for8.9%and25.6%respectively.2. Morbidity:Stage Ⅰ/Ⅱ ⅣH was found in25%of the VLBWI cohort, stage Ⅲ/Ⅳ IVH was accounted for9.5%. The rate of stage Ⅲ/Ⅳ ⅣH was decreased with the gestational age or birth weight increasing. Surfactant was received by39.6%VLBWI. Aminophylline was used very common. There were446infants reached the criteria for bronchopulmomary dysplasia (BPD), and7.2%was diagnosed with severe BPD. Almost half of the BPD infants treated with postnatal steroids. Hemodynamically significant patent ductus arteriosus (PDA) was diagnosed in493(18.4%) infants. To close the ductus, ibuprofen was more commonly used than indomethacin (84.9%vs.15.1%). Totally there were22infants closed the ductus by surgical ligation. Necrotizing enterocolitis (NEC) was disgnosed in194infants, which accounted for7.2%in the VLBWI who stay in hospital for more than24hours. Of all the cases,10.3%was treated with surgery. Compare to infants without NEC, it took8more days to reach full feeding in NEC group. Retinopathy of prematurity (ROP) was screened in78%infants of whom discharged after32weeks of corrected gestational age, and about a quarter of them was found any stage of ROP. Laser therapy was done in102(23.4%) cases. Culture positive hospital acquired infection (HAI) was found in346(12.8%) infants. Ventilator associated pneumonia and bloodstream infection was common HAI pattern. Gram negative bacteria accounted for61.1%, which was the most frequently organism. Gram positive bacteria and fungi accounted for24.6%and14.4%respectively.3. Outcomes and medical burden:During the hospitalization, there were187infants died,812infants withdrew medical care for some reason. Totally there were218 infants died or discharged before24hours of age. Mortality decreased with gestational age or birth weight increasing except in the subgroup of gestational age≥35weeks. For the infants who completed the treatment, the median hospital cost was33×103yuan, the mean gestational age at discharge was37.1±2.9weeks, the mean birth weight was2076.9±470.5grams. Extrauterine growth retardation accounted for two-thirds of the infants at discharge.4. Compared with the CNN data, the VLBWI admitted to our tertiary NICUs were more mature and bigger in size. ELBWI and EPI only accounted for small part. The mortality in our VLBWI cohort was higher than that in CNN data. The incidence of BPD, PDA, NEC and ROP in infants with gestational age≥29weeks or birth weight≥1000grams was also higher than that in CNN data.Conclusions:1. Compare to developed country, our VLBWI cohort was more mature and bigger in size.2. The mortality of VLBWI in China still higher than developed country.3. Medical care withdrawal was common in our VLBWI cohort.4. This is the first national survey of VLBWI in China completed with a successfully established NICU collaborative network.Part two:The multi-center epidemiologic study of late-preterm infantsObjectives:1. To explore the birth rate, delivery mode, morbidity and short-term outcomes of late-preterm infants (LPI) who admitted to NICUs in China.2. To investigate the clinical characteristics, therapeutic interventions and short-term outcomes of LPI or term infants who required respiratory support. To compare the value of different illness severity assessment tools.3. To investigate the effect and safety of surfactant when it used to treat LPI or term infants with respiratory distress syndrome (RDS).Methods:1. During the study period, clinical information of all NICU admissions in the11tertiary NICUs in Zhejiang province was retrospectively collected. The clinical characteristics of LPI were described.2. From November2008to October2009, in7tertiary NICUs, the clinical data of infants who born at≥34weeks’ gestational age, admitted at<72hours of age, requiring CPAP or mechanical ventilation for respiratory support was collected prospectively. Three different illness severity assessment tools, the Acute Care of at-Risk Newborn (ACoRN) Respiratory Score, Score for Neonatal Acute Physiology-Version II (SNAP-II) and Oxygenation index (01) were compared.3. Infants who born at≥34weeks’ gestational age and diagnosed with RDS, required mechanical ventilation, admitted to8tertiary NICUs at<72hours of age were enrolled. Surfactant was given if the infant required FiO2≥0.4to maintain PaO2≥50mmHg or SpO2>90%. Before and after surfactant, the results of blood gas, ventilator settings, and the incidence of complications were recorded and analyzed.Results:1. During the12-month study period in2007, there were44362infants born at the11hospitals, the overall preterm birth rate was8.9%, the rate of late preterm birth was6.2%. LPI had higher caesarean section rate than the whole cohort (64.9%vs58.2%). One fifth of the nursery admissions were LPI, of whom,63.8%were delivered by caesarean section. Respiratory distress (42.1%) was the most common medical problem of LPI. Hyperbilirubinemia (17.6%), hypoglycemia (8.7%) and sepsis (5.9%) were also common presentations. The first three primary diagnosis of respiratory distress included pneumonia (39.5%), TTN (22.5%) and RDS (19.0%). Compared with term infants, LPI with respiratory distress needed more respiratory support with CPAP (21.4%vs11.6%) or mechanical ventilator (15.4%vs11.0%), and also had higher in-hospital mortality (0.8%vs0.4%).2. During the study period,503newborn late preterm or term infants required respiratory support. The mean gestational age was36.8±2.2weeks, mean birth weight was2734.5±603.5grams. The majority of the neonates were male (69.4%), late-preterm (63.3%), delivered by cesarean section (74.8%), admitted in the first day of life (89.3%) and outborn (born at other hospitals,76.9%). Of the cesarean section,51.1%were performed electively. The rate of cesarean birth was significantly higher in LPI group. The common causes of respiratory distress in LPI group were RDS, TTN and pneumonia. More term infants developed severe respiratory distress (10.3%vs.5.2%), and had higher SNAP-II score (17.1±14.2vs.14.5±13.1) than LPI. Compared to the term group, the length of hospital stay was longer and the medical cost was higher in LPI group. Infants in the severe group were more mature, had the highest rate of elective cesarean section, Apgar score<7at5minutes and resuscitated with intubation, and also had the highest in-hospital mortality. The incidence of complications was increased significantly in severe group (P<0.05). The medical cost in the severe group was significantly higher than other two groups (P<0.05). ACoRN Respiratory Score was correlated with SNAP-Ⅱ (P<0.01). Higher gestational age, higher SNAP-Ⅱ score or Oxygenation index (OI), and Apgar score at5minutes<5were independent risks for death.3. There were96infants enrolled in this prospective study. The mean gestational age was36.5±2.1weeks, mean birth weight was2690.3±562.6grams. Of whom,71.9% were male,59.4%were LPI,62.5%were delivered by elective cesarean section. RDS was diagnosed at the median age of9.9hours. The first dose of surfactant was given at the median age of13.3hours with the dosage of108.5±20.2mg/kg. The second dose was given to10.4%infants. Half an hour post surfactant, PaO2/FiO2、OI、A-aDO2、 PaO2/PAO2improved significantly, and lasting to6hours. The median length of mechanical ventilation was110.5hours. The incidence of complications was28.1%. The median length of hospital stay was18.0days, median medical cost was32.9×103yuan. There was one case died due to multiple organ failure,5cases withdrew care according to parents’ decision. Compare to small dosage, the improvement of PaO2/FiO2、OI、A-aDO2、PaO2/PAO2was more significant at6hours after relatively large dose (≥100mg/kg) of surfactant, and the length of mechanical ventilation was shorter. But the length of hospital stay, medical cost, and the incidence of complications was not different between these two dosage groups.Conclusions:1. The cesarean section rate of LPI who admitted to Chinese NICUs was very high.2. Compare to term infants, more LPI admitted to NICU due to respiratory distress, hypoglycemia and intracranial hemorrhage. Respiratory distress was the most common reason for NICU admission.3. Surfactant significantly improved the oxygenation in LPI or term infants with RDS.4. The ACoRN Respiratory Score could be used as a tool to evaluate the severity of respiratory distress in newborn infants. Part three:The evaluation of an educational program for newborn stabilization in Zhejiang provinceObjectives:1. To evaluate the distribution of medical resource in the economically disadvantaged region of Zhejiang province.2. To evaluate the effect of ACoRN training program.3. To evaluate the acceptability of ACoRN teaching content and teaching material in Chinese health care giver.4. To assess the applicability of the ACoRN program to Chinese pediatric practitioners.Methods:1. Questionnaires were used to evaluate the medical resource in41level Ⅱ county hospitals in the economically disadvantaged region of Zhejiang province.2. ACoRN courses were delivered at15level Ⅱ county hospitals.3. Participants completed pre-and post-course confidence and knowledge questionnaires.4. Participants provided feedback through post-course focus group discussion.Results:1. A total of216physicians and nurses participated in this training program.2. Participants’ total confidence score increased from47.6±10.4to59.2±7.7after the training (effct size d=1.28).3. The knowledge evaluation indicated that the total knowledge score increased from31.5±5.1to34.7±3.5(effect size d=0.77). Knowledge score for each individual scenario except scenario D increased significantly. 4. The participants rated the utility and function of the program highly with a range from4.2to4.6. The ACoRN primary survey and the systemic framwork sequences were well accepted.Conclusions:1. Confidence relating to neonatal stabilization improved significantly following the ACoRN program.2. ACoRN program appears to be well received by Chinese health care professionals.3. ACoRN program can be applied in other region of China after structured and systematic evaluation.

早產(chǎn)兒相關(guān)臨床問題的多中心流行病學(xué)研究及危重新生兒穩(wěn)定項(xiàng)目的推廣和效果評價(jià)

致謝5-6中文摘要6-14Abstract14-22縮寫詞表23-26目次26-28引言28-30第一部分 VLBWI的全國性多中心流行病學(xué)研究30-72    1.1 前言30-31    1.2 研究內(nèi)容和方法31-34    1.3 結(jié)果34-59    1.4 討論59-71    1.5 結(jié)論71-72第二部分 晚期早產(chǎn)兒的多中心流行病學(xué)研究72-104    2.1 前言72-74    2.2 研究對象和方法74-80    2.3 結(jié)果80-97    2.4 討論97-103    2.5 結(jié)論103-104第三部分 危重新生兒初步穩(wěn)定適宜技術(shù)的推廣和系統(tǒng)評價(jià)104-127    3.1 前言104-107    3.2 研究內(nèi)容和方法107-111    3.3 結(jié)果111-122    3.4 討論122-126    3.5 結(jié)論126-127研究展望127-128全文結(jié)論128-129參考文獻(xiàn)129-140綜述140-160    參考文獻(xiàn)152-160附錄1 ACoRN初步評估法和各系統(tǒng)流程160-169附錄2 各類評估問卷169-176附錄三 ACoRN培訓(xùn)知情同意書176-177附錄四 發(fā)表論文177-195作者簡歷及在學(xué)期間所取得的科研成果195-196

  本文關(guān)鍵詞：早產(chǎn)兒相關(guān)臨床問題的多中心流行病學(xué)研究及危重新生兒穩(wěn)定項(xiàng)目的推廣和效果評價(jià)，由筆耕文化傳播整理發(fā)布。