早产儿相关临床问题的多中心流行病学研究及危重新生儿稳定项目的推广和效果评价
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摘要
新生儿死亡率一直是衡量国民健康、社会进步的重要指标之一。2011年我国卫生部官方网站公布的新生儿死亡率为7.8‰。所有死亡新生儿中有四分之三发生在生后第一周,早产和低出生体重、以及和早产相关的各种并发症是新生儿期死亡或致残的主要原因之一。近二十年来,随着我国国民经济的发展和医疗改革的推进,我国各地区相继建立新生儿重症监护病房(Neonatal intensive care unit, NICU),早产儿尤其极低出生体重儿(Very low birth weight infant, VLBWI)的生存率较前显著提高,但是和发达国家相比,仍存在较大差距,且存活早产儿中相当部分留有各种后遗症。因此如何进一步降低早产儿的死亡率和并发症率,改善其生存质量已经成为当今围产医学的研究重点。
目前发达国家的新生儿临床研究普遍采取建立多中心协作网络的方式,通过大型临床数据库开展大样本的流行病学调查和随机对照试验,取得循证医学证据,并进一步调整医疗实践行为,优化医疗资源的利用,改善医疗质量。
相比发达国家,我国临床资料的信息化管理程度还较低,缺乏成熟的全国性多中心协作网络,新生儿医学很大程度上还停留在经验医学,缺乏循证依据。且由于我国的新生儿人群具有自己的种族、社会经济状况、文化的特殊性,无法直接照搬国外的经验或结论。因此建立我国早产儿临床资料的数据库和协作网络,开展多中心流行病学研究,具有重要的科学价值和社会意义。
除了死亡率和患病率的流行病学监测以外,区域性的适宜技术推广也是持续改善医疗质量的有力举措。有效的适宜技术推广可以在较短时间内提高医护人员的临床思维能力和疾病处理能力,具有低成本,高效益的特点。
本课题的研究重点为在我国Ⅲ级NICU建立多中心协作网络,针对不同胎龄和出生体重早产儿的救治现状开展多中心流行病学研究,分析其临床特征、近期临床结局及疾病负担,探讨进一步降低死亡率、改善预后的策略,并就新生儿稳定的相关适宜技术——Acute Care of at-Risk Newborn (ACoRN)在浙江省的实施进行效果评价。
第一部分VLBWI的全国性多中心流行病学研究
目的：
1.分析我国Ⅲ级NICU收治的VLBWI的人口学特征、各类并发症的发生情况、诊治经过和近期临床结局等。
2.将我国资料和发达国家的资料进行比较,探讨进一步降低死亡率、改善临床预后的策略。
方法：回顾性病例资料分析
1.收集2010年1月至2010年12月期间入住33家协作单位NICU的所有VLBWI的临床资料
2.建立多中心协作组和临床资料数据库。
3.对VLBWI的死亡率和常见疾病患病率、近期结局和医疗负担进行分析。
4.与加拿大新生儿协作网2010年年报资料进行死亡率和患病率的比较。
结果：
1.研究期间33家NICU收治VLBWI共2914例,其中男性1697例(58.2%),平均出生胎龄30.1±2.3周,平均出生体重1239.9±181.1g；宫内发育迟缓766例(26.3%)；超低出生体重儿占8.9%,超不成熟早产儿占25.6%。
2.患病率：经过头颅B超筛查的2519例中65.6%未发现脑室内出血(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)的发生率随出生胎龄和体重的增加而逐渐减少。机械通气的应用也随着胎龄和出生体重的增加而减少。接受表面活性物质的占39.6%。胎龄<30周和出生体重<1250g的人群中,50%以上需要氨茶碱兴奋呼吸中枢。住院时间>28天的VLBWI中446例(25.8%)符合BPD (Bronchopulmomary dysplasia, BPD)诊断标准,其中轻度285例(63.9%),中度128例(28.7%),重度32例(7.2%)。41.5%的BPD患儿接受产后皮质激素治疗。共493例VLBWI的动脉导管未闭(Patent ductus arteriosus, PDA)需要药物或手术干预,其发生率在所有住院时间>24h的VLBWI中为18.4%,且发生率随着出生体重和胎龄的减低而增加。口服消炎痛和布洛芬治疗的比例分别为15.1%和84.9%。20例在药物治疗失败后手术结扎,另有2例未经药物治疗直接手术。共194例VLBWI发生坏死性小肠结肠炎(Necrotizing enterocolitis, NEC),占住院时间>24h的7.2%。NEC患儿中10.3%接受手术治疗。最终治愈出院的136例(70.1%),医院内死亡15例(7.7%),放弃治疗43例(22.2%)。NEC组开始胃肠喂养的日龄中位数为2d,和未患NEC的VLBWI无差异,但达到足量喂养的时间显著延迟(日龄中位数32.5dvs.24d)。纠正胎龄达32周的VLBWI中78%接受了早产儿视网膜病(Retinopathy of prematurity, ROP)筛查,各期ROP的总发生率为24.5%,未检出严重ROP致盲病例。23.4%接受了激光手术。病原学阳性的医院获得性感染(Hospital acquired infection, HAI)总发生率为12.8%,其中3.1%住院期间发生2次以上HAI。呼吸机相关性肺炎和血流感染是常见的HAI。病原学分布以G-菌最常见(276例次,61.1%),G+菌次之(111例次,24.6%),真菌65例次(14.4%)。
3.近期结局：住院期间死亡187例(6.4%),其中30.5%死亡年龄<24h,15.5%死亡年龄24-72h,13.9%死亡日龄3-7d,40.1%死亡日龄>7d。放弃治疗出院812例(27.9%),出生当天即放弃治疗出院或死亡的VLBWI共有218例(7.5%)。随着出生胎龄和体重的增加,死亡率逐渐下降,但出生胎龄≥35周的亚组死亡率却显著高于胎龄31～34周的VLBWI。其余1915例(65.7%)经治疗达到出院标准后出院。治愈出院的VLBWI平均住院费用为40.9±30.8千元(20.4～53.2千元,中位数33.1千元),出院时平均纠正胎龄37.1±2.9周,平均出院体重2076.9±470.5g。出院时66.8%体重未能达到纠正胎龄体重的第10百分位。
4.和加拿大新生儿协作网2010年年报资料比较：我国收治的VLBWI以胎龄28周,体重1000g以上的为主,收治的最低胎龄为24周,仅9例。各胎龄和出生体重亚组VLBWI的存活率都存在显著差距。由于我国胎龄≤26周和体重<750克的VLBWI存活的人数很少,因此和加拿大资料不具可比性。在胎龄≥29周和体重≥1000克的VLBWI中,我国BPD、PDA、NEC、ROP的患病率都超过了加拿大资料。
结论：
1.我国收治的VLBWI以出生体重大于1000g、胎龄28周以上的为主,ELBWI和EPI仅占很小一部分。
2.和发达国家相比,我国VLBWI的存活率和救治水平还存在一定差距。
3.我国的VLBWI有1/4未能坚持完成治疗。
4.这是我国首次对VLBWI开展的多中心大样本流行病学研究。
第二部分晚期早产儿的多中心流行病学研究
目的：
1.分析晚期早产儿(Late-preterm infant, LPI)的人口学特征、分娩方式、各种临床问题患病率、诊治经过和临床结局。
2.分析LPI/足月儿呼吸系统疾病的发病特点、治疗经过、疾病负担,对不同的疾病严重度评估方法进行比较。
3.研究表面活性物质治疗LPI/足月儿呼吸窘迫综合征(Respiratory distress syndrome, RDS)的疗效及安全性。
方法：
1.浙江省11家Ⅲ级NICU的LPI回顾性研究：回顾性收集2007年1月至12月入住浙江省11家Ⅲ级NICU的新生儿临床资料,分析产科出生新生儿的胎龄分布情况、分娩方式以及NICU收治新生儿的伴发疾病、诊治情况和临床转归等,将LPI和足月儿的临床资料进行比较。
2.全国7家NICU所收治LPI呼吸系统疾病的前瞻性研究：前瞻性收集2008年11月至2009年10月期间入住全国7家Ⅲ级NICU的出生胎龄≥34周,因呼吸窘迫需要CPAP或机械通气支持的患儿的临床资料。根据临床症状和血气分析结果进行疾病严重度评分。分析LPI和足月儿发生呼吸窘迫的基础疾病、临床特点、近期转归和疾病负担,比较不同疾病严重度评分体系的实用价值和相关性。
3.全国8家NICU表面活性物质治疗LPI和足月儿RDS的前瞻性研究：2010年1月至1010年9月,出生72h内入住8家Ⅲ级NICU的LPI/足月RDS患儿纳入研究。机械通气下FiO2>0.4才能维持PaO2≥50mmHg或SPO2>90%的患儿给予猪肺磷脂注射液,首剂量80-150mg/kg。并按首剂剂量≥100mg/kg和≤100mg/kg分为大剂量组和小剂量组。观察并记录患儿的人口学信息、给药信息,给药前及给药后不同时间点的生命体征、血气分析结果、呼吸机参数、临床并发症,记录临床转归、治疗费用、药物不良事件等。通过呼吸机参数、血气指标的动态变化评价药物疗效。
结果：
1.浙江省11家Ⅲ级NICU的LPI回顾性研究
2007年1月至12月期间,纳入研究的医院共有44,362例新生儿出生,早期早产儿占2.7%,LPI占6.2%,总的早产儿出生率为8.9%。58.2%为剖宫产。各医院剖宫产率最高75.6%,最低42.3%。LPI的剖宫产率为63.8%,显著高于早期早产儿组(50.3%)和足月儿组(58.0%)。共10537例新生儿入住NICU,早产儿占33.9%,其中56.9%为LPI。LPI和足月儿占总收治人数的85.4%。住院新生儿中LPI组剖宫产比例(63.8%)显著高于早期早产儿组(50.8%)和足月儿组(52.6%)。71.3%的患儿出生72h内入住NICU。LPI组最常见的住院原因是呼吸窘迫(n=856,42.1%),其次为高胆红素血症(n=357,17.6%)和低血糖(n=176,8.7%)。LPI组中呼吸窘迫(42.1%vs.25.4%)、缺氧缺血性脑病(3.3%vs.2.4%)、颅内出血(3.1%vs.1.2%)和低血糖(8.7%vs.2.9%)的发生率显著高于足月儿组。LPI组引I起呼吸窘迫的基础疾病,最常见的是肺炎(39.5%),其次为新生儿暂时性呼吸困难(22.5%)和RDS(19.0%)。LPI组机械通气和CPAP支持的比例分别为15.4%和21.4%,足月儿组分别为11.0%和11.6%,两组差异显著。LPI组1777例(87.5%)最终完成治疗,199例(9.8%)由于各种原因放弃治疗,医院内死亡16例(0.8%),40例(2.0%)转运至其他医院接受治疗。其医院内死亡率及转运至外院的比例显著高于足月儿组,完成治疗率则低于足月儿组。
2.全国7家NICU所收治LPI呼吸系统疾病的前瞻性研究
共503例胎龄>34周的呼吸窘迫患儿纳入研究,平均胎龄36.8±2.2周,平均体重2734.5±603.5g,男性占69.3%；LPI占49.7%。74.8%剖宫产出生,其中51.1%系选择性剖宫产。出现呼吸窘迫的年龄为3.2±9.1h,入住NICU的年龄中位数为4h。LPI组剖宫产率明显高于足月儿组。LPI组呼吸窘迫的基础疾病以RDS、新生儿暂时性呼吸困难和肺炎为主,其中RDS所占比例显著高于足月儿组(41.6%vs.23.7%)。足月儿组重度呼吸窘迫的比例(10.3%vs.5.2%)和SNAP-Ⅱ评分(17.1±14.2vs.14.5±13.1)显著高于LPI组。LPI组住院时间较足月儿长,住院总费用高,医院内死亡率和足月儿组没有差异。根据入院时的呼吸评分,本研究队列中轻中度呼吸窘迫占92.2%,重度仅7.8%。重度呼吸窘迫组的平均胎龄、出生体重较轻中度组大,选择性剖宫产比例最高,入住NICU时间最晚,5分钟Apgar评分<7分、需要气管插管进行复苏的比例最高。重度呼吸窘迫组的并发症发生率、死亡率和医疗费用都高于其他两组。重度呼吸窘迫组的SNAP-Ⅱ评分和最高OI值显著高于其他两组。SNAP-Ⅱ评分和呼吸评分呈线性相关。Logistic回归分析提示较大胎龄、较高SNAP-Ⅱ评分、较高OI值、5分钟Apgar评分<7分是LPI/足月儿RDS死亡的独立危险因素。
3.全国8家NICU表面活性物质治疗LPI和足月儿RDS的前瞻性研究
共96例患儿纳入研究,男性71.9%,平均胎龄36.5±2.1周,平均体重2690.3±562.6g, LPI占59.4%,宫缩发动后的剖宫产占25.0%,选择性剖宫产占62.5%。诊断RDS的时龄中位数为9.9h(0.2～84.2h),胸片RDS分期为Ⅲ-Ⅳ期的65例,占67.7%。首剂猪肺磷脂注射液给药时间为出生后13.3h(0-85.5h),首剂给药剂量为108.5±20.2mg/kg,10.4%的患儿接受第二剂。给药后0.5h, PaO2、SpO2较给药前明显上升,PaCO2、FiO2明显下降,随着时间延长至6h, FiO2进一步下降,平均气道压也较前下降。给药后0.5h,PaO2/FiO2、OI、A-aDO2、PaO2/PAO2均较给药前明显改善,且给药后6h持续改善。机械通气的中位小时数为110.5h,28.1%出现并发症。住院日中位数为18.0d,住院费用中位数32.9千元。治愈出院73例(76.0%),好转出院17例(17.7%),放弃治疗5例(512%),因并发多脏器功能衰竭而死亡1例(1.0%)。大剂量组和小剂量组首剂的给药剂量分别为115.8±17.8mg/kg和87.9±9.6mg/kg,大剂量组给药后6h PaO2/FiO2、OI、A-aDO2、PaO2/PAO2的改善显著优于小剂量组。大剂量组机械通气时间缩短,但不能缩短住院时间,且住院费用、并发症发生率、治愈或好转率和小剂量组相比并无统计学差异。
结论：
1.我国NICU收治的LPI具有很高的剖宫产率。
2.和足月儿相比,LPI中因呼吸窘迫、低血糖、颅内出血入院的比例显著增加,其中呼吸窘迫是最突出的临床问题。
3.猪肺磷脂注射液对于较大胎龄的LPI或足月儿RDS具有显著的短期疗效。
4. ACoRN呼吸评分是评估新生儿呼吸窘迫严重程度的有用的工具。
第三部分危重新生儿初步稳定适宜技术的推广和系统评价目的：
1.评估浙江省经济相对欠发达地区的医疗资源分布情况及教学需求。
2.对项目医院医护人员进行ACoRN培训,并对培训效果进行评估。
3.评估ACoRN的教学内容和教学材料在中国的适用性。
4.评估ACoRN教学模式在中国基层医院进一步推广的可行性和必要性。方法：前瞻性队列对照研究
1.通过问卷调查对浙江省36个县41家Ⅱ级医院的医疗资源和教学需求进行评估,从中选择15家作为ACoRN培训的项目医院。
2.对各家项目医院进行ACoRN培训。
3.通过5分制的Likert量表调查问卷和典型病例对学员的自信度和专业知识技能进行评估。
4.通过问卷和小组讨论对ACoRN教学材料和教学模式进行评估。结果：
1.15家项目医院216名医护人员接受ACoRN培训。
2.医护人员处理危重新生儿的自信度由培训前的47.6±10.4分上升至培训后的59.2±7.7分。所有子项的培训后得分均显著高于培训前(p<0.01)。
3.医护人员的临床知识和技能总分由培训前的31.5±5.1上升至培训后的34.7±3.5分,改善显著(p<0.01,效应量=0.77)。病例A、B、C,学员培训后得分提高显著；病例D的得分培训前后无统计学差异。
4.学员对ACoRN教程和培训内容、培训模式给予了高度评价,认为该教程符合基层医院的需求,值得推广。其中ACoRN的新生儿初步评估法和系统流程图得到的认可度最高。
结论：
1. ACoRN项目显著改善基层医院医护人员处理危重新生儿时的自信心。
2. ACoRN项目显著改善基层医院医护人员处理危重新生儿的专业知识和技能。
3. ACoRN的教学材料和教学模式可以很好地被基层医院的医护人员接受,具有广阔的应用前景。
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 China
Objectives:
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 infants
Objectives:
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 province
Objectives:
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.
目前发达国家的新生儿临床研究普遍采取建立多中心协作网络的方式,通过大型临床数据库开展大样本的流行病学调查和随机对照试验,取得循证医学证据,并进一步调整医疗实践行为,优化医疗资源的利用,改善医疗质量。
相比发达国家,我国临床资料的信息化管理程度还较低,缺乏成熟的全国性多中心协作网络,新生儿医学很大程度上还停留在经验医学,缺乏循证依据。且由于我国的新生儿人群具有自己的种族、社会经济状况、文化的特殊性,无法直接照搬国外的经验或结论。因此建立我国早产儿临床资料的数据库和协作网络,开展多中心流行病学研究,具有重要的科学价值和社会意义。
除了死亡率和患病率的流行病学监测以外,区域性的适宜技术推广也是持续改善医疗质量的有力举措。有效的适宜技术推广可以在较短时间内提高医护人员的临床思维能力和疾病处理能力,具有低成本,高效益的特点。
本课题的研究重点为在我国Ⅲ级NICU建立多中心协作网络,针对不同胎龄和出生体重早产儿的救治现状开展多中心流行病学研究,分析其临床特征、近期临床结局及疾病负担,探讨进一步降低死亡率、改善预后的策略,并就新生儿稳定的相关适宜技术——Acute Care of at-Risk Newborn (ACoRN)在浙江省的实施进行效果评价。
第一部分VLBWI的全国性多中心流行病学研究
目的：
1.分析我国Ⅲ级NICU收治的VLBWI的人口学特征、各类并发症的发生情况、诊治经过和近期临床结局等。
2.将我国资料和发达国家的资料进行比较,探讨进一步降低死亡率、改善临床预后的策略。
方法：回顾性病例资料分析
1.收集2010年1月至2010年12月期间入住33家协作单位NICU的所有VLBWI的临床资料
2.建立多中心协作组和临床资料数据库。
3.对VLBWI的死亡率和常见疾病患病率、近期结局和医疗负担进行分析。
4.与加拿大新生儿协作网2010年年报资料进行死亡率和患病率的比较。
结果：
1.研究期间33家NICU收治VLBWI共2914例,其中男性1697例(58.2%),平均出生胎龄30.1±2.3周,平均出生体重1239.9±181.1g；宫内发育迟缓766例(26.3%)；超低出生体重儿占8.9%,超不成熟早产儿占25.6%。
2.患病率：经过头颅B超筛查的2519例中65.6%未发现脑室内出血(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)的发生率随出生胎龄和体重的增加而逐渐减少。机械通气的应用也随着胎龄和出生体重的增加而减少。接受表面活性物质的占39.6%。胎龄<30周和出生体重<1250g的人群中,50%以上需要氨茶碱兴奋呼吸中枢。住院时间>28天的VLBWI中446例(25.8%)符合BPD (Bronchopulmomary dysplasia, BPD)诊断标准,其中轻度285例(63.9%),中度128例(28.7%),重度32例(7.2%)。41.5%的BPD患儿接受产后皮质激素治疗。共493例VLBWI的动脉导管未闭(Patent ductus arteriosus, PDA)需要药物或手术干预,其发生率在所有住院时间>24h的VLBWI中为18.4%,且发生率随着出生体重和胎龄的减低而增加。口服消炎痛和布洛芬治疗的比例分别为15.1%和84.9%。20例在药物治疗失败后手术结扎,另有2例未经药物治疗直接手术。共194例VLBWI发生坏死性小肠结肠炎(Necrotizing enterocolitis, NEC),占住院时间>24h的7.2%。NEC患儿中10.3%接受手术治疗。最终治愈出院的136例(70.1%),医院内死亡15例(7.7%),放弃治疗43例(22.2%)。NEC组开始胃肠喂养的日龄中位数为2d,和未患NEC的VLBWI无差异,但达到足量喂养的时间显著延迟(日龄中位数32.5dvs.24d)。纠正胎龄达32周的VLBWI中78%接受了早产儿视网膜病(Retinopathy of prematurity, ROP)筛查,各期ROP的总发生率为24.5%,未检出严重ROP致盲病例。23.4%接受了激光手术。病原学阳性的医院获得性感染(Hospital acquired infection, HAI)总发生率为12.8%,其中3.1%住院期间发生2次以上HAI。呼吸机相关性肺炎和血流感染是常见的HAI。病原学分布以G-菌最常见(276例次,61.1%),G+菌次之(111例次,24.6%),真菌65例次(14.4%)。
3.近期结局：住院期间死亡187例(6.4%),其中30.5%死亡年龄<24h,15.5%死亡年龄24-72h,13.9%死亡日龄3-7d,40.1%死亡日龄>7d。放弃治疗出院812例(27.9%),出生当天即放弃治疗出院或死亡的VLBWI共有218例(7.5%)。随着出生胎龄和体重的增加,死亡率逐渐下降,但出生胎龄≥35周的亚组死亡率却显著高于胎龄31～34周的VLBWI。其余1915例(65.7%)经治疗达到出院标准后出院。治愈出院的VLBWI平均住院费用为40.9±30.8千元(20.4～53.2千元,中位数33.1千元),出院时平均纠正胎龄37.1±2.9周,平均出院体重2076.9±470.5g。出院时66.8%体重未能达到纠正胎龄体重的第10百分位。
4.和加拿大新生儿协作网2010年年报资料比较：我国收治的VLBWI以胎龄28周,体重1000g以上的为主,收治的最低胎龄为24周,仅9例。各胎龄和出生体重亚组VLBWI的存活率都存在显著差距。由于我国胎龄≤26周和体重<750克的VLBWI存活的人数很少,因此和加拿大资料不具可比性。在胎龄≥29周和体重≥1000克的VLBWI中,我国BPD、PDA、NEC、ROP的患病率都超过了加拿大资料。
结论：
1.我国收治的VLBWI以出生体重大于1000g、胎龄28周以上的为主,ELBWI和EPI仅占很小一部分。
2.和发达国家相比,我国VLBWI的存活率和救治水平还存在一定差距。
3.我国的VLBWI有1/4未能坚持完成治疗。
4.这是我国首次对VLBWI开展的多中心大样本流行病学研究。
第二部分晚期早产儿的多中心流行病学研究
目的：
1.分析晚期早产儿(Late-preterm infant, LPI)的人口学特征、分娩方式、各种临床问题患病率、诊治经过和临床结局。
2.分析LPI/足月儿呼吸系统疾病的发病特点、治疗经过、疾病负担,对不同的疾病严重度评估方法进行比较。
3.研究表面活性物质治疗LPI/足月儿呼吸窘迫综合征(Respiratory distress syndrome, RDS)的疗效及安全性。
方法：
1.浙江省11家Ⅲ级NICU的LPI回顾性研究：回顾性收集2007年1月至12月入住浙江省11家Ⅲ级NICU的新生儿临床资料,分析产科出生新生儿的胎龄分布情况、分娩方式以及NICU收治新生儿的伴发疾病、诊治情况和临床转归等,将LPI和足月儿的临床资料进行比较。
2.全国7家NICU所收治LPI呼吸系统疾病的前瞻性研究：前瞻性收集2008年11月至2009年10月期间入住全国7家Ⅲ级NICU的出生胎龄≥34周,因呼吸窘迫需要CPAP或机械通气支持的患儿的临床资料。根据临床症状和血气分析结果进行疾病严重度评分。分析LPI和足月儿发生呼吸窘迫的基础疾病、临床特点、近期转归和疾病负担,比较不同疾病严重度评分体系的实用价值和相关性。
3.全国8家NICU表面活性物质治疗LPI和足月儿RDS的前瞻性研究：2010年1月至1010年9月,出生72h内入住8家Ⅲ级NICU的LPI/足月RDS患儿纳入研究。机械通气下FiO2>0.4才能维持PaO2≥50mmHg或SPO2>90%的患儿给予猪肺磷脂注射液,首剂量80-150mg/kg。并按首剂剂量≥100mg/kg和≤100mg/kg分为大剂量组和小剂量组。观察并记录患儿的人口学信息、给药信息,给药前及给药后不同时间点的生命体征、血气分析结果、呼吸机参数、临床并发症,记录临床转归、治疗费用、药物不良事件等。通过呼吸机参数、血气指标的动态变化评价药物疗效。
结果：
1.浙江省11家Ⅲ级NICU的LPI回顾性研究
2007年1月至12月期间,纳入研究的医院共有44,362例新生儿出生,早期早产儿占2.7%,LPI占6.2%,总的早产儿出生率为8.9%。58.2%为剖宫产。各医院剖宫产率最高75.6%,最低42.3%。LPI的剖宫产率为63.8%,显著高于早期早产儿组(50.3%)和足月儿组(58.0%)。共10537例新生儿入住NICU,早产儿占33.9%,其中56.9%为LPI。LPI和足月儿占总收治人数的85.4%。住院新生儿中LPI组剖宫产比例(63.8%)显著高于早期早产儿组(50.8%)和足月儿组(52.6%)。71.3%的患儿出生72h内入住NICU。LPI组最常见的住院原因是呼吸窘迫(n=856,42.1%),其次为高胆红素血症(n=357,17.6%)和低血糖(n=176,8.7%)。LPI组中呼吸窘迫(42.1%vs.25.4%)、缺氧缺血性脑病(3.3%vs.2.4%)、颅内出血(3.1%vs.1.2%)和低血糖(8.7%vs.2.9%)的发生率显著高于足月儿组。LPI组引I起呼吸窘迫的基础疾病,最常见的是肺炎(39.5%),其次为新生儿暂时性呼吸困难(22.5%)和RDS(19.0%)。LPI组机械通气和CPAP支持的比例分别为15.4%和21.4%,足月儿组分别为11.0%和11.6%,两组差异显著。LPI组1777例(87.5%)最终完成治疗,199例(9.8%)由于各种原因放弃治疗,医院内死亡16例(0.8%),40例(2.0%)转运至其他医院接受治疗。其医院内死亡率及转运至外院的比例显著高于足月儿组,完成治疗率则低于足月儿组。
2.全国7家NICU所收治LPI呼吸系统疾病的前瞻性研究
共503例胎龄>34周的呼吸窘迫患儿纳入研究,平均胎龄36.8±2.2周,平均体重2734.5±603.5g,男性占69.3%；LPI占49.7%。74.8%剖宫产出生,其中51.1%系选择性剖宫产。出现呼吸窘迫的年龄为3.2±9.1h,入住NICU的年龄中位数为4h。LPI组剖宫产率明显高于足月儿组。LPI组呼吸窘迫的基础疾病以RDS、新生儿暂时性呼吸困难和肺炎为主,其中RDS所占比例显著高于足月儿组(41.6%vs.23.7%)。足月儿组重度呼吸窘迫的比例(10.3%vs.5.2%)和SNAP-Ⅱ评分(17.1±14.2vs.14.5±13.1)显著高于LPI组。LPI组住院时间较足月儿长,住院总费用高,医院内死亡率和足月儿组没有差异。根据入院时的呼吸评分,本研究队列中轻中度呼吸窘迫占92.2%,重度仅7.8%。重度呼吸窘迫组的平均胎龄、出生体重较轻中度组大,选择性剖宫产比例最高,入住NICU时间最晚,5分钟Apgar评分<7分、需要气管插管进行复苏的比例最高。重度呼吸窘迫组的并发症发生率、死亡率和医疗费用都高于其他两组。重度呼吸窘迫组的SNAP-Ⅱ评分和最高OI值显著高于其他两组。SNAP-Ⅱ评分和呼吸评分呈线性相关。Logistic回归分析提示较大胎龄、较高SNAP-Ⅱ评分、较高OI值、5分钟Apgar评分<7分是LPI/足月儿RDS死亡的独立危险因素。
3.全国8家NICU表面活性物质治疗LPI和足月儿RDS的前瞻性研究
共96例患儿纳入研究,男性71.9%,平均胎龄36.5±2.1周,平均体重2690.3±562.6g, LPI占59.4%,宫缩发动后的剖宫产占25.0%,选择性剖宫产占62.5%。诊断RDS的时龄中位数为9.9h(0.2～84.2h),胸片RDS分期为Ⅲ-Ⅳ期的65例,占67.7%。首剂猪肺磷脂注射液给药时间为出生后13.3h(0-85.5h),首剂给药剂量为108.5±20.2mg/kg,10.4%的患儿接受第二剂。给药后0.5h, PaO2、SpO2较给药前明显上升,PaCO2、FiO2明显下降,随着时间延长至6h, FiO2进一步下降,平均气道压也较前下降。给药后0.5h,PaO2/FiO2、OI、A-aDO2、PaO2/PAO2均较给药前明显改善,且给药后6h持续改善。机械通气的中位小时数为110.5h,28.1%出现并发症。住院日中位数为18.0d,住院费用中位数32.9千元。治愈出院73例(76.0%),好转出院17例(17.7%),放弃治疗5例(512%),因并发多脏器功能衰竭而死亡1例(1.0%)。大剂量组和小剂量组首剂的给药剂量分别为115.8±17.8mg/kg和87.9±9.6mg/kg,大剂量组给药后6h PaO2/FiO2、OI、A-aDO2、PaO2/PAO2的改善显著优于小剂量组。大剂量组机械通气时间缩短,但不能缩短住院时间,且住院费用、并发症发生率、治愈或好转率和小剂量组相比并无统计学差异。
结论：
1.我国NICU收治的LPI具有很高的剖宫产率。
2.和足月儿相比,LPI中因呼吸窘迫、低血糖、颅内出血入院的比例显著增加,其中呼吸窘迫是最突出的临床问题。
3.猪肺磷脂注射液对于较大胎龄的LPI或足月儿RDS具有显著的短期疗效。
4. ACoRN呼吸评分是评估新生儿呼吸窘迫严重程度的有用的工具。
第三部分危重新生儿初步稳定适宜技术的推广和系统评价目的：
1.评估浙江省经济相对欠发达地区的医疗资源分布情况及教学需求。
2.对项目医院医护人员进行ACoRN培训,并对培训效果进行评估。
3.评估ACoRN的教学内容和教学材料在中国的适用性。
4.评估ACoRN教学模式在中国基层医院进一步推广的可行性和必要性。方法：前瞻性队列对照研究
1.通过问卷调查对浙江省36个县41家Ⅱ级医院的医疗资源和教学需求进行评估,从中选择15家作为ACoRN培训的项目医院。
2.对各家项目医院进行ACoRN培训。
3.通过5分制的Likert量表调查问卷和典型病例对学员的自信度和专业知识技能进行评估。
4.通过问卷和小组讨论对ACoRN教学材料和教学模式进行评估。结果：
1.15家项目医院216名医护人员接受ACoRN培训。
2.医护人员处理危重新生儿的自信度由培训前的47.6±10.4分上升至培训后的59.2±7.7分。所有子项的培训后得分均显著高于培训前(p<0.01)。
3.医护人员的临床知识和技能总分由培训前的31.5±5.1上升至培训后的34.7±3.5分,改善显著(p<0.01,效应量=0.77)。病例A、B、C,学员培训后得分提高显著；病例D的得分培训前后无统计学差异。
4.学员对ACoRN教程和培训内容、培训模式给予了高度评价,认为该教程符合基层医院的需求,值得推广。其中ACoRN的新生儿初步评估法和系统流程图得到的认可度最高。
结论：
1. ACoRN项目显著改善基层医院医护人员处理危重新生儿时的自信心。
2. ACoRN项目显著改善基层医院医护人员处理危重新生儿的专业知识和技能。
3. ACoRN的教学材料和教学模式可以很好地被基层医院的医护人员接受,具有广阔的应用前景。
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 China
Objectives:
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 infants
Objectives:
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 province
Objectives:
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.
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