Long-term effects of postnatal corticosteroids to prevent or treat bronchopulmonary dysplasia: Balancing the risks and benefits

Postnatal corticosteroids are effective in preventing or treating bronchopulmonary dysplasia (BPD) in preterm newborns, but their benefits need to exceed their risks. Several types of corticosteroids, and different timing and administration modes have been trialed. Systemic corticosteroids, given either early or late, have proven efficacy for reducing BPD and the combined outcome of death or BPD. Inhaled corticosteroids are less effective. However, systemic dexamethasone given early is associated with more neurosensory disability and cerebral palsy in survivors. The risk of adverse neurodevelopment is highest if dexamethasone is given to preterm infants at low risk of BPD. Current trials focus on corticosteroids, mixed with surfactant, delivered intratracheally directly to the lung, which may avoid some systemic adverse effects of corticosteroids. Early trials of intratracheal corticosteroids are encouraging, but more data are needed to determine whether this method of administration is preferable to systemic corticosteroids for preventing or treating BPD.     

Review of use of postnatal corticosteroids in evolving or established bronchopulmonary dysplasia

Bronchopulmonary dysplasia (BPD) is a condition that affects a significant proportion of infants born prematurely. Whilst there have been advances in many aspects of neonatal respiratory care the rates of BPD remain relatively static. Much effort has been put into exploring the role of corticosteroids in potentially reducing inflammation in the developing lung; however, research has been hindered by concerns regarding adverse side–effect profiles and difficulties recruiting adequate numbers to power the results. Currently, two strategies are gaining popularity: low-dose dexamethasone after 7 days of age to facilitate ventilator weaning and prophylactic physiological hydrocortisone use from the first day of life. However, use in practice is limited whilst awaiting full-powered randomised trials. This article briefly discusses the evidence for each approach.     

支气管肺发育不良管理中糖皮质激素选择的循证依据与个体化

尽管超早产儿存活率明显提高,支气管肺发育不良( bronchopulmonary dysplasia,BPD)始终是早产儿主要疾病及影响至成年呼吸和神经健康的最常见并发症,可持续至成年并影响呼吸及神经系统发育。糖皮质激素明显有益于BPD,但用于BPD的防治中还有许多争议,应参考已有的研究结果并结合新生儿临床特点谨慎应用。     

支气管肺发育不良的预防策略

<正>随着近代新生儿学的持续发展和极早早产儿存活率的不断改善,支气管肺发育不良(bronchopulmonary dysplasia,BPD)的定义发生了重大变化。BPD已不再是半个世纪前Nothway等学者提出的因高浓度氧及高压力通气导致的严重呼吸衰竭。新BPD更多发生在极早早产儿中,以损伤发育中的肺及肺血管而产生程度较轻却持续的呼吸问题为表现。由于影响肺及肺血管发育的因素贯穿早产儿产前生后的整个过程,因此对新BPD有效的预防策略应当包含多个角度,共同促进早产儿肺及肺血管的正常发育。近年来,BPD的预防在很多方面都取得了一定的进展,本文在此对部分策略做简单介绍。     

Coagulase-negative staphylococcal sepsis as a predictor of bronchopulmonary dysplasia

AIM: To determine whether sepsis caused by coagulase-negative staphylococci (CoNS) is a risk factor for developing bronchopulmonary dysplasia (BPD) in premature newborns. METHODS: All newborns born at < or = 30 wk of gestation at Orebro University Hospital during 1994-2001 with clinical sepsis caused by CoNS (group A, n = 22) or by other bacteria (group B, n = 17) were included and compared with premature newborns without sepsis (group C, n = 53). Clinical sepsis was defined as a positive blood culture (monoculture) plus clinical symptoms and laboratory findings. BPD was defined as treatment with oxygen > 21% for at least 28 d. RESULTS: The incidence of BPD differed between the three groups, as follows: CoNS sepsis (A) 64%, other sepsis (B) 41% and control (C) 24%. The difference between the control group and the sepsis groups was highly significant (p = 0.006). In a univariate model the crude estimates of relative risk (RR) for occurrence of BPD increased with presence of sepsis and particularly with presence of sepsis with CoNS (A: RR 2.6, 95% CI 1.5-4.6, p = 0.001; B: RR 1.7, CI 0.8-3.5, p = 0.17). When regression was performed with two additional predictive variables in multivariate models including sepsis, gestational age and mechanical ventilation (group A: RR 1.5, CI 1.1-2.0, p = 0.004; group B: RR 0.9, CI 0.6-1.4, p = 0.67), the estimates were lower. CONCLUSION: The relative risk for BPD is significantly increased in premature newborns with sepsis caused by CoNS compared with those with sepsis caused by other bacteria and compared with premature newborns with no sepsis.     

支气管肺发育不良防治的机械通气策略

支气管肺发育不良是早产儿呼吸系统的常见疾病。随着危重新生儿救治技术的不断提升和肺表面活性物质的使用,早产儿的存活率显著提高,而支气管肺发育不良作为早产儿的严重并发症之一,其发病率有增加的趋势,并且严重影响早产儿的生活质量。因此,对于支气管肺发育不良的防治尤为重要。目前,已经有很多不同的、新的治疗方法,其中有些方法减少了其严重性,但仍缺乏有效的方法以降低支气管肺发育不良的发病率。该文对支气管肺发育不良的机械通气治疗进展作一综述。     

Drug treatment for bronchopulmonary dysplasia in Japan: Questionnaire survey

Bronchopulmonary dysplasia (BPD) is one of the most common complications in premature infants. Although several different drugs have been developed for BPD, there is a wide variation in the choice of drug used among facilities. The aim of this study was to carry out a survey of the current drugs used to treat BPD in Japan. Questionnaires regarding the current use of drugs for BPD were sent to tertiary neonatal units. The response rate was 80% (77/96). Most units used antenatal steroids and oral diuretics for the prevention and treatment of BPD, respectively. Only 4% used caffeine for prevention, whereas 88% used systemic corticosteroids for treatment. Few units used inhaled anticholinergics and i.v. vitamins for the prevention and treatment of BPD, respectively. It was found that the drugs used to treat BPD vary greatly among institutions. Further research is required to develop evidence‐based clinical guidelines for BPD in premature infants.     

Low postnatal serum IGF-I levels are associated with bronchopulmonary dysplasia (BPD)

Aim: To characterize postnatal changes in serum insulin-like growth factor-1 (IGF-I) in relation to development of bronchopulmonary dysplasia (BPD) in very preterm infants. Methods: Longitudinal study of 108 infants with mean (SD) gestational age (GA) 27.2 (2.2) weeks. Weekly serum samples of IGF-I were analysed from birth until postmenstrual age (PMA) 36 weeks. Multivariate models were developed to identify independent predictors of BPD. Results: Postnatal mean IGF-I levels at postnatal day (PND) 3–21 were lower in infants with BPD compared with infants with no BPD (16 vs. 26 μg/L, p < 0.001). Longitudinal postnatal change in IGF-I levels (IGF-I regression coefficient (β)), PNDs 3–21, was lower in infants with BPD compared with infants with no BPD (0.28 vs. 0.97, p = 0.002) and mean IGF-I during PMA 30–33 weeks was lower in infants with BPD as compared with infants without BPD (22 vs. 29 μg/L, p < 0.001). In a binomial multiple regression model, lower GA, male gender and lower mean serum IGF-I levels during PND 3–21 were the most predictive risk factors associated with BPD (r² = 0.634, p < 0.001). Conclusion: Lower IGF-I concentrations during the first weeks after very preterm birth are associated with later development of BPD.     

早产儿生后早期应用糖皮质激素预防支气管肺发育不良的Meta分析

目的探讨早期应用糖皮质激素预防早产儿支气管肺发育不良(BPD)的疗效和安全性。方法全面检索Pub Med、Cochrane Library、Embase、中国期刊全文数据库(CNKI)、万方医学网及维普等数据库,收集各数据库从建库至2016年6月有关早产儿早期应用糖皮质激素预防BPD的文献,对符合纳入标准的16项随机对照试验(RCT)应用Review Manager 5.3进行Meta分析。结果 16项RCT共纳入2 962例参与者,其中试验组1 486例,对照组1 476例。Meta分析结果显示,早产儿早期应用糖皮质激素有利于减少纠正胎龄36周时BPD的发生率(OR=0.73,95%CI:0.61~0.87,P=0.0004);但发生高血糖(OR=1.61,95%CI:1.24~2.09,P=0.0003)、高血压(OR=1.63,95%CI:1.11~2.38,P=0.01)、肠穿孔(OR=1.51,95%CI:1.12~2.04,P=0.007)的风险增加。结论目前尚不能推荐早产儿应用糖皮质激素预防BPD,需要进一步研究其优缺点,尤其需注意高血糖、高血压、肠穿孔等不良影响。     

支气管肺发育不良的病因研究进展

支气管肺发育不良是早产儿致病和死亡的主要原因之一,因此支气管肺发育不良的病因及发病机制是目前新生儿医学研究热点之一。目前主要从先天因素包括遗传易患性和肺发育不成熟,后天因素包括氧中毒、气压伤和容量伤、感染或炎症反应。该文就近年来支气管肺发育不良新的病因及发病机制研究进展作一综述。     

Prophylactic postnatal corticosteroids: Early hydrocortisone

Inflammation is a key contributor to the pathogenesis of bronchopulmonary dysplasia (BPD) in preterm infants, and cortisol plays a central role in controlling inflammation. Insufficient cortisol limits the ability of the sick newborn to handle stress and inhibit pulmonary inflammation. Evidence of lower cortisol and lower response to adrenocorticotropic hormone in infants subsequently developing BPD led to studies of early low-dose hydrocortisone to prevent BPD. Based on four randomised clinical trials enrolling almost 1000 extremely preterm infants, prophylaxis of early adrenal insufficiency with low-dose hydrocortisone significantly decreased BPD and mortality, as well as medical treatment for a patent ductus arteriosus. An increase in late-onset sepsis reported in the most immature infants had no adverse effect on mortality or neurodevelopmental outcomes. There was no increase in gastrointestinal perforation in the absence of indomethacin. The demonstrated beneficial effects of early low-dose hydrocortisone make a strong case for its use in extremely preterm infants at high risk for BPD.     

支气管肺发育不良的研究进展

支气管肺发育不良(BPD)是威胁早产儿健康问题的主要原因.随着新生儿治疗新技术的不断应用,"新"BPD已经替代了"老"BPD.BPD的发生涉及多种因素的相互作用,很多预防和治疗策略已用于BPD.

Abstract：

Bronchopulmonary dysplasia(BPD) is one of the main causes which threatend the health of preterm infants. As neonatal intensive care improved, the "new" BPD have replaced the" old" BPD. The development of BPD involved many factors, and several preventative and therapeutic strategies have been used in BPD.     

早产儿支气管肺发育不良的防治

随着围生医学的发展,早产儿存活率上升,支气管肺发育不良(bronchopulmonary dysplasia,BPD)发病率也逐年增高.BPD是一种由多因素引发的慢性肺疾病,其病因及发病机制复杂,早期病死率高,晚期伴有呼吸系统,甚至神经系统的不良结局,严重影响早产儿存活率及生活质量.该文就BPD的防治进展作一综述.     

早产儿支气管肺发育不良预测标志物的研究进展

支气管肺发育不良( bronchopulmonary dysplasia,BPD)是早产儿最常见的严重呼吸系统疾病,严重影响早产儿的生存质量,至今还没有预防和治疗BPD的有效方法。由于BPD的发病机制是多因素的,涉及多种不同的信号分子途径,因此测定体液中的相应标志物有可能早期预测新生儿BPD的发生。     

早产儿支气管肺发育不良发生率及高危因素的多中心回顾调查分析

目的 了解国内早产儿支气管肺发育不良(BPD)的发生率,探讨影响其发病及其严重程度的因素,为早期预防BPD提供指导意见。方法 回顾性收集国内10家NICU2006年1月1日至2008年12月31日收治的胎龄＜37周且存活≥28 d早产儿临床资料,根据患儿出生后28 d是否用氧(＞21％)分为BPD组和非BPD组。生后28 d未用氧为非BPD组;生后持续用氧≥28 d为BPD组。计算各个胎龄BPD发病率;从数字表中随机选取360例非BPD早产儿做为对照组进行对比研究,对两组患儿临床资料进行对比研究;并对两组患儿生后10d内的总液体量、热卡摄入以及体重下降的百分比进行了组间比较。同时根据出生时胎龄在生后不同日龄进行评估疾病严重程度,即如胎龄＜32周,在校正胎龄36周或出院时进行评估;如胎龄≥32周,在生后56 d或出院时评估：①轻度：未用氧;②中度：FiO2＜ 30％;（③重度：FiO2≥30％或需机械通气。比较轻度BPD和中重度BPD两组患儿的临床资料。临床资料结果采用计量或计数资料描述,计量资料采取非参数检验法,计数资料采用卡方检验（fisher精确概率法）比较两组资料的差异;Logistic回归分析逐步向前引入法找出BPD发病及其病情程度的主要影响因素。结果 10家医院胎龄＜37周早产儿共12 351例,其中符合BPD诊断的156例,BPD发生率为1.26％。其中GA≤28、28～、30～、32～、34～、＜37周BPD发生率分别为19.3％、13.11％、5.62％、0.95％和0.09％,BPD发生率随胎龄增加明显降低。多因素逐步Logistic回归分析结果显示,体重低于1.5 kg、动脉导管未闭、早产儿贫血、肺透明膜病、巨细胞病毒感染、机械通气、呼吸机持续时间≥7d及PaO2/FiO2＜ 300这8个因素为支气管肺发育不良患儿的高危因素。BPD组与非BPD组患儿生后5d内液体量摄入组间比较无差异,而BPD组患儿生后10d内热卡摄入以及生后前3d内体重下降的百分比明显减少(P＜0.01)。 156例BPD中,20份因资料丢失过多剔除,剩余136例病例中轻度支气管肺发育不良71例,中重度65例。住院天数、用氧时间及氧浓度大于0.3持续时间、院内感染、巨细胞病毒感染、羊水污染、生后是否使用CPAP、呼吸机持续时间≥7 d、生后第一次血气CO2共9个因素组间差异有统计学意义;多因素逐步Logistic回归分析结果显示,合并院内感染、巨细胞病毒感染、呼吸机持续时间≥7 d这三个因素为中重度支气管肺发育不良患儿的高危因素。结论国内10家医院早产儿BPD发生率为1.26％,发病率随胎龄增加而明显降低。极低生体重、动脉导管未闭、贫血、肺透明膜病、巨细胞病毒感染、机械通气、PaO2/FiO2＜ 300等是其高危因素,BPD组生后10 d内热卡摄入明显低于非BPD组。预防院内感染、巨细胞病毒感染及减少机械通气持续时间可降低BPD严重程度。     

Response to bronchodilators in clinically stable 1-year-old patients with bronchopulmonary dysplasia

Bronchodilators are often used in the treatment of patients with bronchopulmonary dysplasia (BPD). However, few studies evaluate their efficacy in patients with stable disease beyond the newborn period. Therefore, pulmonary function was measured before and after aerosol treatment with salbutamol (0.25 ml Ventolin 0.5%) and subsequently after aerosol with ipratropium bromide (0.25 ml Atrovent 0.025%). Studies were performed at the corrected postnatal age of 52±2 weeks in 52 patients who had been ventilated after birth because of newborn lung disease. Twenty-two of these 52 patients had developed BPD. Pulmonary function was measured after sedation and using the PEDS system. Expiratory resistance (median 52.1 versus 39.1 cmH₂O/l/s; P<.008) and inspiratory resistance (median 42.5 vs 27.8 cmH₂O/l/s; P<.04) were significantly worse in BPD patients at the age of 1 year. Half of the BPD patients had a decrease in pulmonary resistance after salbutamol. However, there was no statistically significant decrease in pulmonary resistance after salbutamol or ipratropium in the BPD patients as a group. After salbutamol pulmonary resistance significantly worsened in the patients who did not develop BPD. Conclusion Although individual patients may benefit, routine administration of bron chodilators seems not warranted in stable BPD patients at the age of 1 year. Received: 14 February 1997 / Accepted in revised form: 14 July 1997     

极低出生体质量儿支气管肺发育不良的临床高危因素分析

目的 探讨极低出生体质量儿发生支气管肺发育不良(bronchopulmonary dysplasia,BPD)的临床高危因素.方法 回顾性分析2006年9月至2009年9月我院NICU收治的49例极低出生体质量儿的临床资料,分为BPD组(n=15)和非BPD组(n=34),分析BPD发生的可能危险因素.结果与非BPD组相比,BPD组患儿在胎龄[(29.30±1.48)周vs(30.54±1.60)周]、院内获得性感染(9例vs 10例)、宫内感染(9例vs 8例)、持续气道正压通气时间[(12.47±5.83)d vs(4.24±4.19)d]、高浓度氧疗时间[(1.47±1.41)dvs(0.18±0.63)d]、动脉导管未闭(5例vs 1例)等方面比较,差异有统计学意义(P均＜0.05).Logistic回归分析结果显示持续气道正压通气时间以及宫内感染是极低出生体质量儿发生BPD的高危因素(P＜0.05).结论 预防宫内感染可降低BPD的发生率和严重程度,长时间的持续气道正压通气可能预示早期BPD的发生.     

早产儿支气管肺发育不良的药物治疗研究进展

支气管肺发育不良（BPD）是存活极早产儿最常见的远期并发症,并且可能导致肺动脉高压,增加新生儿晚期死亡率,以及神经系统发育异常。目前关于早产儿支气管肺发育不良药物治疗的有效性及利弊仍然存在争议。本文综述了BPD的药物治疗研究进展。     

呼吸窘迫综合征并发支气管肺发育不良危险因素分析

目的：探讨呼吸窘迫综合征（RDS）患儿支气管肺发育不良（BPD）的危险因素。方法：对该院2000年1月至2005年8月应用呼吸机治疗并住院28 d以上的呼吸窘迫综合征患儿进行回顾性分析,比较并综合分析20余种高危因素与BPD的关系。结果：72例呼吸机治疗、住院＞28 d呼吸窘迫综合征患儿BPD发生率为23.6%（17/72）,BPD 组 FiO2,PIP,PEEP,MAP,上机日龄、产前应用地塞米松促肺成熟、生后应用肺表面活性物质（PS）等与对照组差异无显著性（P＞0.05）,而胎龄≤30周、出生体重≤1 250 g、上机次数≥2次、合并肺炎、肺出血、上机天数≥5 d、痰培养阳性2次以上等与对照组差异有显著性（P<0.05）;多因素Logistic回归显示：出生体重≤1 250 g、机械通气≥10 d,痰培养阳性3次以上为发生BPD的独立危险因素。结论：避免低体重早产儿、缩短应用机械通气时间、防止及减少肺部感染,尤其是严重感染是预防RDS发生BPD的重要措施。［中国当代儿科杂志,2007,9（1）：15-18］