早产儿支气管肺发育不良临床高危因素及防治策略

目的 探讨早产儿支气管肺发育不良的高危因素,为临床本病防治策略的制定提供理论依据.方法 回顾性分析2013年6月至2015年6月我院收治的172例早产新生儿的临床资料.将发生支气管肺发育不良的40例患儿分为病例组,将未发生支气管肺发育不良的132例患儿分为对照组.对比两组患儿的各项临床资料,并通过Logistic逐步回归分析探讨早产儿支气管肺发育不良发生的高危因素.结果 病例组的胎龄、出生体重、出生第1天血红蛋白均显著低于对照组,而1 min Apgar评分≤7、发生宫内感染、发生新生儿呼吸窘迫综合征、发生动脉导管未闭、发生肺出血、发生巨细胞病毒感染、使用肺表面活性物质、接受有创机械通气治疗、有创机械通气≥7d、接受手术治疗、最高吸入氧体积分数≥400 ml/L以及出生2周内接受红细胞输注的比例均显著高于对照组(P＜0.05);Logistic逐步回归分析结果显示,胎龄、出生体重、巨细胞病毒感染、有创机械通气≥7d、最高吸入氧体积分数≥400 ml/L、接受手术治疗以及出生2周内接受红细胞输注均是早产儿发生支气管肺发育不良的危险因素(P＜0.05).结论 早产儿支气管肺发育不良的发病是由多种因素促成,临床应针对本病发病的高危因素,制定防治措施,降低患儿的发病风险,改善患儿的预后.     

超低出生体质量儿支气管肺发育不良危险因素分析

分析超低出生体质量儿（ELBWI）支气管肺发育不良（BPD）严重程度的危险因素。对2010年1月至2015年12月于四川省人民医院NICU住院的57例患BPD的ELBWI临床资料进行回顾性分析。根据临床分度标准分为轻度BPD 35例,中重度BPD 22例,对不同分度BPD与出生情况、母孕期因素、合并症、临床治疗情况等因素的关系进行分析。 不同分度BPD 与绒毛膜羊膜炎、胎龄、体质量、机械通气（MV）、输血＞3次、新生儿呼吸窘迫综合征（NRDS）、医院感染有关;多元Logistic回归显示MV（OR=0.083,95%CI 0.007～0.978）、母亲患绒毛膜羊膜炎（OR=0.100,95%CI 0.010～0.956）、医院感染（OR=0.044,95%CI 0.005～0.417）是BPD严重程度的独立危险因素。ELBWI发生BPD严重程度与多种因素相关,尽可能减少宫内感染及早产、产后合理进行呼吸支持、预防医院感染可有效预防BPD的进展。     

生后早期血小板参数与早产儿支气管肺发育不良的相关性分析

目的 探讨生后早期血小板参数与早产儿支气管肺发育不良（BPD）的相关性。方法 采用回顾性病例对照研究,收集2013年1月至2020年12月徐州医科大学附属连云港医院新生儿重症监护病房收治的胎龄≤32周的早产儿的临床一般资料和生后2 h、生后24～48 h的血小板参数：血小板计数（PLT）、平均血小板体积（MPV）、血小板压积（PCT）、血小板分布宽度（PDW）,根据早产儿是否患有BPD分为BPD与非BPD组,比较两组的一般资料、围产资料、临床特征及血小板参数。采用二元logistic回归分析BPD发生的危险因素,受试者操作特征曲线（ROC曲线）分析血小板参数对BPD的预测价值。结果 两组间生后2 h内PLT、MPV、PCT、PDW比较差异无统计学意义。BPD组生后24～48 h内MPV水平高于非BPD组[（10.18±0.80）fL比（9.43±0.63）fL],差异有统计学意义;两组间PLT、PCT、PDW差异无统计学意义。多因素logistic回归分析显示出生胎龄小[OR=0.24,95%CI:(0.07,0.87)]、CPAP时间长[OR=1.42,95%CI:(1.08,1.8...     

我国极低出生体质量早产儿并发支气管肺发育不良危险因素的Meta分析

目的 运用循证医学探讨我国极低出生体质量早产儿并发支气管肺发育不良的危险因素。方法 系统检索PubMed、Embase、万方数据库、中国期刊全文数据、中国知网（CNKI）、中文科技期刊全文数据、Cochrane临床对照试验资料库、中国生物医学文献数据库（CBM）,检索时间均从建库至2016年5月。按纳入排除标准进行随机对照试验的筛选、资料提取和文献质量评价,应用Stata 11.0软件进行meta分析。结果 共纳入15篇对照试验研究,mate分析结果显示,胎膜早破（OR=1.90,95% CI：1.16~3.11）,肺透明膜病（OR=6.46,95% CI：4.47~9.35）,吸氧时间（RR=3.01,95% CI：1.34~4.69）,肺部感染（OR=15.76,95% CI：7.51~33.07）,生后窒息（OR=2.23,95% CI：1.09~4.57）,产前感染（OR=3.41,95% CI：2.40~4.84）,动脉导管未闭（OR=3.39,95% CI：2.04~5.64）,胎龄（RR=-2.34,95% CI：-3.42~-1.27）,出生体质量（RR=-2.08,95% CI：-2.91~-1.21）是极低出生体质量早产儿并发支气管肺发育不良的危险因素;产后使用肺表面活性物质（OR=4.09,95% CI：1.65~10.12）是其保护因素。结论 应积极对极低出生体质量早产儿并发支气管肺发育不良危险因素采取预防措施,从而降低支气管肺发育不良的发生率,提高生存率及改善远期生活质量。     

Pharmacokinetics of melatonin in preterm infants

Aims

Preterm infants are deprived of the normal intra-uterine exposure to maternal melatonin and may benefit from replacement therapy. We conducted a pharmacokinetic study to guide potential therapeutic trials.

Methods

Melatonin was administered to 18 preterm infants in doses ranging from 0.04–0.6 μg kg⁻¹ over 0.5–6 h. Pharmacokinetic profiles were analyzed individually and by population methods.

Results

Baseline melatonin was largely undetectable. Infants receiving melatonin at 0.1 μg kg⁻¹ h⁻¹ for 2 h showed a median half-life of 15.82 h and median maximum plasma concentration of 203.3 pg ml⁻¹. On population pharmacokinetics, clearance was 0.045 l h⁻¹, volume of distribution 1.098 l and elimination half-life 16.91 h with gender (P = 0.047) and race (P < 0.0001) as significant covariates.

Conclusions

A 2 h infusion of 0.1 μg kg⁻¹ h⁻¹ increased blood melatonin from undetectable to approximately peak adult concentrations. Slow clearance makes replacement of a typical maternal circadian rhythm problematic. The pharmacokinetic profile of melatonin in preterm infants differs from that of adults so dosage of melatonin for preterm infants cannot be extrapolated from adult studies. Data from this study can be used to guide therapeutic clinical trials of melatonin in preterm infants.     

Pharmacokinetics of oxatomide in preterm infants

The pharmacokinetics and tolerability of oxatomide oral suspension were investigated in preterm infants to evaluate the feasibility of planning a further study to assess its antiinflammatory effects and its effectiveness in preventing chronic lung disease (CLD). Following the administration of oxatomide 1 mg/kg, the peak plasma concentration (Cmax), the elimination half-life (t1/2), the volume of distribution (Vd), and the area under the curve (AUC) 0-36 h were measured and the following results were obtained: 42.2 +/- 15 ng/ml at 2 h after oxatomide administration, 41.4 +/- 2.0 h, 37.4 +/- 4.2 l/kg, and 468 +/- 52 ng/ml/h, respectively. Our study, therefore, demonstrated that a dose of 1 mg/kg/day oxatomide was effective in reaching therapeutic plasma levels in preterm infants without inducing adverse effects.     

Management of bronchopulmonary dysplasia in infants: guidelines for corticosteroid use

Bronchopulmonary dysplasia (BPD) is a common cause of morbidity and mortality in preterm neonates and at present its management is unclear. Over the past three decades there has been a growing use of corticosteroids in the postnatal period; first for the treatment and then, more recently, for the prevention of BPD. The first published use of corticosteroids to treat neonatal lung disease was in 1956; however, it was only in the 1980s and 1990s that their use in neonates became commonplace. Concerns about their long-term neurodevelopmental consequences arose in the late 1990s when follow-up of randomised controlled trials indicated an increased risk of cerebral palsy after postnatal dexamethasone exposure. Dexamethasone has been the most frequently used corticosteroid in neonatal units, although others, including hydrocortisone, prednisolone and methylprednisolone, have been studied, as have inhaled corticosteroids. Systematic reviews indicate that systemic corticosteroids improve respiratory function in the short term and expedite extubation in preterm neonates. However, there is a high risk of hypertension, hyperglycaemia and gastrointestinal complications in corticosteroid-treated neonates and, if administered in the first 4 days of life, an association with long-term neurodevelopmental delay. There should be emphasis on prevention of BPD by reducing the risk factors associated with its development. There is no role for use of corticosteroids in the first 4 days of life as the high risk of long-term adverse effects outweighs any likely short-term benefits. Corticosteroid use should be limited to exceptional clinical circumstances, such as a ventilator-dependent infant after the second week of life who cannot be weaned from ventilation and whose condition is worsening. If used, they should be prescribed at the lowest effective dose for the shortest possible time. Further randomised trials of low-dose corticosteroids given after the first week of life are warranted and should assess both short- and long-term outcomes.     

Pharmacokinetics and metabolism of oral midazolam in preterm infants

AIMS: To characterize the pharmacokinetics and metabolism of oral midazolam in 15 preterm infants. METHODS: After an oral dose (0.1 mg kg(-1)), blood was drawn up to 24 h after administration. Midazolam and 1-OH-midazolam concentrations were determined with GC-MS. In 8 out of these 15 patients the pharmacokinetics of intravenous midazolam was also studied. RESULTS: Apparent oral clearance, apparent volume of distribution, plasma half-life and 1-OH-Midazolam/Midazolam AUC ratio were [median (range)]: 2.7 [0.67-15.5] ml kg(-1) min(-1), 1.4 [0.3-12.1] l kg(-1), 7.6 [1.2-15.1], h and 0.03 [0.01-0.96], respectively. Absolute bioavailability was 0.49 [0.12-1.0]. CONCLUSIONS: Midazolam oral clearance is markedly decreased in preterm infants as compared with older children, probably because of immature CYP3A4 activity.     

常频机械通气和鼻塞式持续气道正压通气致早产儿支气管肺发育不良的临床比较

目的：调查早产儿支气管肺发育不良（BPD）的发病率,探讨常频机械通气（CMV）和鼻塞式持续气道正压通气（NCPAP）对早产儿BPD发病率的影响。方法收集安徽省立医院新生儿病房2013年1月1日至2013年12月31日收治的胎龄＜37周且存活≥28 d早产儿临床资料,根据患儿辅助通气情况,分为CMV组和NCPAP组;生后≥28 d仍然需要吸氧并伴有胸片改变定义为BPD,比较两组BPD的发病率。结果入选早产儿100例,CMV组50例,NCPAP组50例,两组在胎龄、性别、出生体重、住院时间、通气时间、妊娠史及合并疾病等方面差别无统计学意义（P＞0．05）。 BPD总体发病率为49．0％,CMV组BPD发病率明显高于NCPAP组,差别有统计学意义（ P＜0．01）。结论早产儿BPD的发病率仍然较高,CMV较NCPAP更易使早产儿发生BPD,避免CMV可明显降低早产儿BPD的发生,临床应尽量使用NCPAP帮助早产儿度过呼吸困难阶段。     

Bronchopulmonary dysplasia in preterm infants: pathophysiology and management strategies

Bronchopulmonary dysplasia (BPD) has classically been described as including inflammation, architectural disruption, fibrosis, and disordered/delayed development of the infant lung. As infants born at progressively earlier gestations have begun to survive the neonatal period, a 'new' BPD, consisting primarily of disordered/delayed development, has emerged. BPD causes not only significant complications in the newborn period, but is associated with continuing mortality, cardiopulmonary dysfunction, re-hospitalization, growth failure, and poor neurodevelopmental outcome after hospital discharge.Four major risk factors for BPD include premature birth, respiratory failure, oxygen supplementation, and mechanical ventilation, although it is unclear whether any of these factors is absolutely necessary for development of the condition. Genetic susceptibility, infection, and patent ductus arteriosus have also been implicated in the pathogenesis of the disease.The strategies with the strongest evidence for effectiveness in preventing or lessening the severity of BPD include prevention of prematurity and closure of a clinically significant patent ductus arteriosus. Some evidence of effectiveness also exists for single-course therapy with antenatal glucocorticoids in women at risk for delivering premature infants, surfactant replacement therapy in intubated infants with respiratory distress syndrome, retinol (vitamin A) therapy, and modes of respiratory support designed to minimize 'volutrauma' and oxygen toxicity. The most effective treatments for ameliorating symptoms or preventing exacerbation in established BPD include oxygen therapy, inhaled glucocorticoid therapy, and vaccination against respiratory pathogens.Many other strategies for the prevention or treatment of BPD have been proposed, but have weaker or conflicting evidence of effectiveness. In addition, many therapies have significant side effects, including the possibility of worsening the disease despite symptom improvement. For instance, supraphysiologic systemic doses of glucocorticoids lessen the incidence of BPD in infants at risk for the disease, and promote weaning of oxygen and mechanical ventilation in infants with established BPD. However, the side effects of systemic glucocorticoid therapy, most notably the recently recognized adverse effects on neurodevelopment, preclude their routine use for the prevention or treatment of BPD.Future research in BPD will most probably focus on continued incremental improvements in outcome, which are likely to be achieved through the combined effects of many therapeutic modalities.     

Pharmacokinetics of gentamicin in very low birth weight preterm infants

Low birth weight preterm infants with suspected infection were administered gentamicin intramuscularly every 18 h (2.5 mg/kg) or 24 h (3.0 mg/kg). For both dosage regimens plasma gentamicin levels were monitored during a dosage interval on three separate occasions over a 10 day period. Both regimens gave satisfactory plasma concentrations and there was no important statistically significant difference between the two. The body clearance of gentamicin correlated with gestational age (r = 0.76, p less than 0.01). The results indicate either regimen may be useful in the clinical situation but from a practical standpoint administration every 24 h may be easier to comply with then every 18 h.     

布地奈德混悬液氧驱雾化吸入防治早产儿支气管肺发育不良的临床效果

目的 探讨布地奈德混悬液氧驱雾化吸入法防治早产儿支气管肺发育不良(BPD)的临床效果.方法 回顾性分析2012年9月至2015年9月本科新生儿重症监护病房收治的90例符合条件的早产儿的资料.根据治疗方案,分为对照组(n=46,患儿接受常规治疗)和观察组0=44,患儿在常规治疗基础上接受布地奈德混悬液氧驱雾化吸入治疗).患儿治疗2个疗程,每个疗程7d.比较两组患儿血气指标、体重、BPD发生率.结果 两组治疗前血气指标PO2、PCO2及体重无统计学差异(P＞0.05).治疗2周后,两组PCO2有所下降,PO2有所上升,体重也有明显提升,观察组变化幅度更大.两组治疗后血气指标、体重比较有统计学差异(P＜0.05).观察组总吸氧时间显著缩短[(12.5±3.1)d vs.(16.3±4.7)d,t=3.877,P=0.028].观察组BPD发病率显著降低[11.4％ (5/44) vs.30.4％ (14/46),x2=4.911,P=0.038].观察组未见糖皮质激素治疗可能引发的短期副作用.观察组44例患儿中有16例已随访至2岁以上,未见脑瘫等远期并发症.结论 对合并有新生儿呼吸窘迫综合征(NRDS)的早产儿,给予布地奈德混悬液氧驱雾化吸入治疗,可显著改善血气指标,提高体重增长速度,缩短吸氧时间,降低BPD发生率.     

血浆脂氧素 A4和基质金属蛋白酶 9在早产儿支气管肺发育不良中的预测价值

目的探讨血浆中脂氧素 A4(LXA4)和基质金属蛋白酶 9(MMP9)的动态变化及对早产儿支气管肺发育不良( BPD)的预测价值。方法选择 2018年 1—7月入住徐州医科大学附属医院新生儿科 32周以下的早产儿 50例,根据 BPD的诊断标准为 BPD组( 20例)和非 BPD组( 30例)采用酶联免疫吸附法( ELISA)检测病儿第 1、7、14天血浆中 LXA4、MMP9的表达水平。结果生后第 1天 BPD组和非 BPD组血,浆 LXA4表达水平［(330.4±21.6)比( 321.1±35.9)pg/mL］,差异无统计学意义( P＞0.05); BPD组第 7天 LXA4水平为( 281.8±7.0)pg/mL,第 14天 LXA4水平为( 188.4±5.7)pg/mL,随着时间推移逐渐下降,各时间点均低于非 BPD组,不同时间点之间两两比较均差异有统计学意义,非 BPD组 LXA4水平逐渐上升,于第 7天达到峰值( 348.6±4.4)pg/ mL,后又逐渐下降至第 14天的( 270.3±5.4)pg/mL,不同时间点之间两两比较均差异有统计学意义( P＜0.05);第 1天 BPD组和非 BPD组血浆 MMP9表达水平( 23.9±3.9)ng/mL比( 25.3±2.6)ng/mL,差异无统计学意义( P＞0.05),BPD组血浆 MMP9水平逐渐上升,且生后第 7、14天 BPD组血浆 MMP9水平［(32.6±3.9)ng/mL、(39.0±2.1)ng/mL］均高于非 BPD组［(28.8±2.9)ng/mL、(32.2± 3.4)ng/mL］,不同时间点之间两两比较差异有统计学意义( P＜0.05)。依据 BPD组和非 BPD组 LXA4浓度绘制 ROC曲线下面积为 0.670(95%可信区间为 0.580~0.759),依据 BPD组和非 BPD组 MMP9浓度绘制 ROC曲线下面积为 0.749(95%可信区间为 0.667~0.830)。结论生后 7d检测血浆 LXA4和 MMP9的表达水平对早产儿支气管肺发育不良有早期预测价值。     

早产儿Notch3变化在支气管肺发育不良伴肺动脉高压发病中的临床意义

目的通过监测支气管肺发育不良(BPD)患儿BALF及血液中Notch3的表达及肺动脉压力变化,探讨Notch3改变与BPD发病及肺动脉压力的相关性及临床意义。方法选取2013年1月～2015年12月我院NICU收治的胎龄32周、出生体质量1500g并需要机械通气的早产儿,分为BPD组(58例)及非BPD组(40例),其中轻度40例,中重度18例,留取出生后第1、3、7、14、21、28天的BALF及静脉血,ELISA法检测Notch3蛋白表达,无创超声心动图监测肺动脉压力及心功能。结果中重度BPD组、轻度BPD组及非BPD组间左室射血分数、Tei指数、肺动脉压力及肺动脉高压的发病率存在明显差异(P 0.05);BPD组BALF及血浆中Notch3蛋白表达明显高于非BPD组(P 0.05);BPD组BALF与血浆中Notch3蛋白表达量存在正相关关系(P 0.05)。BPD组合并PH患儿测得的肺动脉压力与BALF及血中Notch3蛋白表达量呈正相关(P 0.001)。结论 BALF及血液中Notch3高表达,Notch3可能参与了BPD的发病过程,尤其是肺血管重构等。     

吸入一氧化氮防治早产儿支气管肺发育不良的Meta分析

目的系统评价吸入一氧化氮(i NO)防治早产儿支气管肺发育不良(BPD)的有效性及实际临床意义。方法 (1)搜集Pub Med,中国期刊全文数据库(CNKI),Embase,维普网,Medlin,万方医学网等医学检索数据库内的2000年1月~2014年12月间发表的吸入一氧化氮防治早产儿BPD治疗组与安慰剂或空白对照组的临床随机对照试验(RCT)和半随机对照试验的资料。(2)分别由两个独立的人提取数据,并交叉核对,并对纳入的研究进行偏倚风险评估。(3)运用Revman 5.2软件进行系统分析,对二进制结果使用日志二项式回归模型进行分析,对连续的结果使用线性固定效应模型进行系统分析。结果荟萃分析结果显示:(1)吸入不同浓度结果。吸入量为5ppm时BPD的发生较频繁,风险率为(RR:0.97),95%可信区间为(CI:0.92~1.02);而死亡率比对照组无明显差异,风险率为(RR:0.84),95%可信区间为(CI:0.66~1.07);吸入量为10ppm时与对照组相比BPD的发生率和死亡率无统计学意义;吸入量为20ppm或滴定反应时,BPD发生的风险为(RR=1),说明该量对死亡率及BPD的发生率没有任何影响。(2)不同产重吸入一氧化氮后结果显示,仅对于产重在1000~1250g的早产儿吸入一氧化氮治疗组与对照组相比死亡率及BPD的发生率综合结果有显著意义(38.5%vs 64.1%),风险率为(RR:0.60),95%的可信区间为(CI:0.42~0.86),对单一的BPD的发生率及死亡率无任何影响。结论早产儿没有必要常规吸入一氧化氮治疗防治BPD;对于产重在1000~1250g范围内的早产儿当生后28d仍然对氧有依赖的患儿可以考虑吸入一氧化氮治疗,选择治疗的最佳剂量应为:5ppm吸入剂量20ppm,范围之间。     

阿奇霉素干混悬剂 颗粒剂和胶囊的人体药代动力学研究

目的使用高效液相色谱-质谱(HPLC-MS)联用法测定人血浆中阿奇霉素的浓度,并研究阿奇霉素干混悬剂、颗粒剂和胶囊在健康人体内的药代动力学情况。方法 20名健康男性志愿者单剂量口服500mg阿奇霉素后,采集不同时间点血样测定血药浓度。结果阿奇霉素的线性范围为2.71～1084μg/L,日内和日间相对标准偏差(RSD)均<5.0%。阿奇霉素干混悬剂主要药代动力学参数为:Cmax:(453±130)μg/L;tmax:(2.3±0.9)h;t1/2:(48±6)h;平均驻留时间(MRT):(53±8)h;曲线下面积(AUC)0-t:(4694±903)μg·h-·1L-1;AUC0-∞:(5118±919)μg·h-1·L-1。结论 3种剂型阿奇霉素的药代动力学参数的差异无统计学意义。