早产儿动脉导管开放的处理

动脉导管开放(PDA)是早产儿常见病症,导致早产儿血流动力学不稳定,严重者可危及生命,应积极处理.药物关闭PDA仍是最有效、方便和经济的治疗方法,吲哚美辛一直是内科保守治疗的主要用药,PDA关闭率为46%～89%,但吲哚美辛有效血药浓度安全范围较窄,且可导致肾功能障碍、颅内出血、坏死性小肠结肠炎和肠穿孔等不良反应.近年国外采用布洛芬治疗早产儿PDA,取得较好疗效,关闭率为73.0%～95.5%,且对肾脏、脑及消化道血流动力学影响显著减少.药物治疗无效且严重影响心肺功能者可选择手术治疗.     

动脉导管未闭的药物治疗进展

正常足月儿生后24～48 h动脉导管已呈功能性关闭,而早产儿的动脉导管常不能关闭,或功能性关闭后又重新开放.有呼吸窘迫综合征的极低出生体重儿,生后第3天动脉导管未闭(PDA)的发生率约为40%[1].PDA的临床结果取决于左向右分流的程度,可加重呼吸窘迫、促发充血性心力衰竭、支气管肺发育不良、肾脏低灌注及脑缺血、继发肠缺血.70%胎龄小于28周的早产儿需要药物或手术关闭动脉导管[2].手术结扎动脉导管有血压波动、感染、乳糜胸、喉神经麻痹,甚至死亡的危险.故在大多数新生儿重症监护病房中,药物治疗PDA是首选.     

早产儿动脉导管未闭管理及其争议

动脉导管未闭(PDA)是早产儿的特殊生理状态,其自发关闭率较高,但持续PDA开放,不仅导致一系列的并发症,还可增加患儿的死亡率。环氧化酶抑制剂吲哚美辛和布洛芬,其关闭PDA的疗效已被公认,但也引起心、脑、肾、肠的血流减少,布洛芬对器官血流的影响更小,特别是能降低坏死性小肠结肠炎(NEC)和一过性肾功能不全的发生率。手术结扎是目前关闭PDA的最确实方法,但仍存在发生单侧声带麻痹、气胸、乳糜胸及脊柱侧弯等并发症的潜在风险。     

早产儿动脉导管未闭的临床研究

目的　观察早产儿动脉导管未闭 (PDA)发生率、影响因素及血流动力学的变化 ,提供监测及干预治疗的建议。方法　 86例胎龄 2 8～ 3 6周、无呼吸机治疗 (未用或已停用 )的早产儿 ,出生 2～ 5d行首次超声心动图检查。对诊断为PDA的早产儿动态超声心动图监测。结果　生后 3～ 4d超声心动图诊断PDA 2 2例 ,胎龄 (3 3 .1± 2 .0 )周。生后 8.5d 2 0例复查 ,16例动脉导管自行关闭 ;4例PDA早产儿经治疗 ,动脉导管关闭 2例 (1例吲哚美辛 ;1例动脉导管再开放 )。最终遗留PDA 3例。单因素及多因素Logistic回归分析发现 ,出生体质量越低 ,PDA发生机率越高 (χ2 =2 .890 7　P =0 .0 891) ;生后窒息及严重疾病增加PDA发生的危险性 (χ2 =4.3 72 9　P =0 .0 3 65 ;χ2 =11.65 90　P =0 .0 0 0 6)。PDA存在使早产儿左心房 /主动脉根内径比值增高 (1.0 8± 0 .18vs 1.0 0± 0 .0 7　P =0 .0 48) ,心功能良好。结论　平均胎龄 3 3周、平均日龄 3d、一般状况较好的早产儿超声心动图诊断PDA机率 2 5 .6% ,85 %早产儿PDA可自行关闭。低出生体质量、出生窒息、严重疾病及症状性PDA发生或持续均是高危因素。     

前列腺素在动脉导管未闭中的作用研究进展

动脉导管是胎儿血液循环的重要生命通道。前列腺素(prostaglandins, PG)参与了胎儿时期动脉导管的扩张以及出生后动脉导管的解剖学重塑。动脉导管未闭(patent ductus arteriosus, PDA)是早产儿较为常见的先天性心脏病之一。目前通过抑制局部PG合成是临床上治疗PDA的主要手段, 其中吲哚美辛和布洛芬是最常使用的药物, 但不良反应较多, 因此, PG合成途径的其他靶点成为研究者的重点关注。该文通过复习相关文献, 结合PG在不同时期对动脉导管的生理作用, 对当前治疗PDA的药物及其相关研究进展进行综述, 以期对该病的治疗和未来研究提供新的思路。     

不同治疗方式对早产儿动脉导管未闭的疗效及安全性评价

目的 探讨早产儿动脉导管未闭(PDA)的临床治疗方式及效果,总结手术治疗PDA 的经验。方法 2013 年1 月至2014 年12 月诊断为PDA 并行手术治疗的早产儿19 例为手术组,同期未行手术治疗的19 例PDA 早产儿为非手术组。分析两组在病史因素、临床因素、病死率及主要并发症等方面的差异,同时从术前准备及手术结果方面分析手术治疗的特点及临床效果。结果 非手术组早产儿胎龄及出生体重均大于手术组(PP1.3 及导管直径的平方/出生体重(d2/BW)比值>9 mm2/kg 的发生率均高于非手术组(PPP>0.05)。结论 对有临床症状且内科保守治疗或药物治疗无好转的早产儿PDA,外科结扎术是相对安全有效的方法。     

动脉导管未闭的药物治疗进展

正常足月儿生后24～48h动脉导管已呈功能性关闭，而早产儿的动脉导管常不能关闭，或功能性关闭后又重新开放。有呼吸窘迫综合征的极低出生体重儿，生后第3天动脉导管未闭(PDA)的发生率约为40％。PDA的临床结果取决于左向右分流的程度，可加重呼吸窘迫、促发充血性心力衰竭、支气管肺发育不良、肾脏低灌注及脑缺血、继发肠缺血。70％胎龄小于28周的早产儿需要药物或手术关闭动脉导管。     

早产儿动脉导管持续开放相关并发症及预后分析

目的探讨动脉导管持续开放对早产儿的影响和危害。方法采用回顾性调查研究,选择2007—2010年我院新生儿科住院治疗的动脉导管未闭(PDA)早产儿,根据出院时或死亡前动脉导管关闭情况分为动脉导管关闭组和动脉导管持续开放组。比较两组早产儿相关并发症的发生情况、氧疗情况、预后及住院费用等多方面的差异。结果动脉导管持续开放组(59例)发生充血性心力衰竭、喂养不耐受和Ⅲ～Ⅳ级脑室内出血的比例、需要呼吸支持的比例及用氧时间均高于动脉导管关闭组(112例),差异有统计学意义[50.8%比32.1%,33.9%比17.9%,8.5%比0.9%,66.4%比32.1%,7.0天(3.0,13.0)比6.0天(0,9.8),P均<0.05];两组发生NEC、Ⅰ～Ⅱ级脑室内出血、支气管肺发育不良和早产儿视网膜病的比例差异无统计学意义(P>0.05)。导管持续开放组住院时间和住院费用均多于动脉导管关闭组[(26.3±14.9)天比(20.0±12.9)天,(21079±13166)元比(17761±10849)元,P均<0.05]。结论动脉导管持续开放可使早产儿相关并发症增加,对呼吸支持的要求增多,也增加了住院时间和费用。     

布洛芬治疗极低出生体质量儿动脉导管未闭效果的相关因素北大核心CSCD

目的探讨布洛芬治疗早产儿动脉导管未闭（PDA）的相关影响因素。方法对2013年1月至2015年12月在河南省人民医院新生儿科住院且出生体质量〈1 500 g的1 236例早产儿进行分析。于出生7 d行床边超声心动图检查,对发生PDA的早产儿排除口服布洛芬的禁忌证者入组。实际进入调查376例。予口服/鼻饲布洛芬治疗后72 h再次床边超声心动图检查了解PDA的关闭率,分析引起布洛芬治疗PDA失败的高危因素。结果单因素分析显示,小胎龄、低出生体质量、宫内窘迫、出生窒息病史、呼吸窘迫综合征、感染、呼吸支持、导管直径、导管两端压差、导管水平峰值流速等是引起PDA药物治疗失败的高危因素（均P〈0.05）;Logistic回归分析显示,呼吸窘迫综合征、感染、呼吸支持、导管直径、导管两端压差、导管水平峰值流速等是PDA发生的独立高危因素,胎龄和出生体质量为保护性因素。结论关注引起早产儿PDA药物治疗失败的高危因素,早期防治PDA可提高早产儿的存活率和生存质量。     

早产儿动脉导管未闭临床治疗研究的循证医学证据

动脉导管未闭（PDA）是早产儿常见的先天性心脏病。与动脉导管已经闭合的早产儿相比,有PDA的早产儿更易发生严重的呼吸窘迫综合征、支气管肺发育不良、颅内出血等并发症,而且死亡的机率更高。1972年Kitterman首次应用外科治疗方法闭合动脉导管;1976年Heymann首次应用消炎痛治疗早产儿PDA。他们试图通过这些治疗手段来改善PDA患儿的预后。其后,有许多学者进行了早产儿PDA治疗方面的研究,他们都记录了用环氧合酶抑制剂（消炎痛、布洛芬、甲芬那酸等）或外科治疗方法进行早产儿PDA治疗的效果与安全性;与此同时,也有许多学者对这些治疗手段的效果和安全性进行比较和系统评价。现拟就关于早产儿有显著左向右分流的PDA使用不同治疗方法的比较研究介绍如下。     

The use of non-steroidal anti-inflammatory drugs for patent ductus arteriosus closure in preterm infants

Over the last four decades, non-steroidal anti-inflammatory drugs have been widely used to induce closure of the patent ductus arteriosus (PDA) in preterm infants. Evidence to support this practice is lacking, despite performance of >50 randomized trials. The credibility of those trials may have been compromised by high rates of open treatment in controls, era of study prior to advent of modern practices, or inclusion of insufficient numbers of very immature infants. Meta-analyses show little impact of those factors on main conclusions. Essentially all trials reporting important long-term outcomes (other than mortality) initiated treatment within five days after birth, so no evidence regarding later treatment is available. Accruing clinical experience suggests that long-term outcomes are not compromised, and may be improved, with non-interventional management strategies. Future studies to identify preterm infants at greatest risk of potential harm from a persistent PDA, particularly after the second postnatal week, are urgently needed.     

早产儿喂养不耐受临床诊疗指南（2020）

早产儿喂养不耐受是目前新生儿最常见的临床问题之一，常导致达全肠内营养时间延迟，住院时间延长。防治早产儿喂养不耐受对提高早产儿存活率有重要意义。该指南基于目前国内外研究，采用证据推荐分级的评估、制定与评价方法（GRADE）进行证据分级制定早产儿喂养不耐受的临床诊疗指南，旨在帮助新生儿科医生、护理人员、营养治疗师等对早产儿喂养不耐受进行早期识别与规范管理。     

吸入一氧化氮治疗早产儿低氧性呼吸衰竭的应用

动物实验表明,吸入一氧化氮（inhaled NO,iNO）可减少早产动物肺部炎症发生率,提高表面活性物质功能,促进肺生长。自20世纪90年代初iNO首次被用于治疗持续性肺动脉高压以来,已逐渐在新生儿重症监护病房得到应用。虽然多项研究结果均证实iNO治疗早产儿低氧性呼吸衰竭（hypoxic respiratory failure,HRF）的有效性,但至今尚无确切证据表明对早产儿可常规使用iNO治疗。本文结合国内外近年文献,就目前iNO治疗早产儿的作用机制、治疗的临床方案、iNO的有效性及安全性做一综述,以期为临床提供参考。     

Patent ductus arteriosus management and the drift towards therapeutic nihilism – What is the evidence?

The published literature on patent ductus arteriosus (PDA) management is challenging to interpret due to poorly designed trials with high rates of open label treatments, homogenisation of patients with varying physiological subtypes, poor treatment efficacy, and spontaneous closure in more mature infants. The perceived lack of clinical benefit has led to a drift away from medical and surgical treatment of all infants with a PDA. This therapeutic nihilism as a default response to PDA management fails to recognise the physiological relevance of a left-to-right shunt with early haemodynamic instability after birth and subsequent pulmonary volume overload with prolonged exposure. Clinicians need to know if therapeutic nihilism is safe. This review will provide an overview of the available data on the efficacy of known PDA treatments, conservative management and supportive care measures that are currently applied.     

Role of neonatologist-performed echocardiography in the assessment and management of patent ductus arteriosus physiology in the newborn

Neonatologist-performed echocardiography (NPE) is an indispensable tool in the haemodynamic management of critically ill newborn infants. NPE is used to facilitate timely diagnosis of a patent ductus arteriosus (PDA) in preterm infants and to assess its haemodynamic significance. Before treatment is considered, it is obligatory to confirm structural cardiac normality. Importantly, NPE offers the ability to guide therapeutic interventions, allowing an individualised haemodynamic management approach to the PDA. After discussing PDA pathophysiology, an overview is provided on the role of NPE in the assessment and management of PDA in preterm infants.     

Short versus prolonged indomethacin therapy for patent ductus arteriosus in preterm infants

OBJECTIVE: To evaluate whether a prolonged low-dose course of indomethacin would produce an improved closure rate and have fewer side effects compared with a short standard dosage schedule in the management of patent ductus arteriosus (PDA) in preterm infants. STUDY DESIGN: Sixty-one infants of gestational ages 24 to 32 weeks with a PDA confirmed with echocardiography were randomized to receive 0.2 to 0.1 to 0.1 mg/kg indomethacin in 24 hours (short course, n = 31) or 0.1 mg/kg every 24 hours 7 times (long course, n = 30). Echocardiography was done 3, 9, and 14 days after the treatment was started, and side effects were monitored. RESULTS: Primary PDA closure occurred more often in the short course group (94% vs 67%, P =.011), but the sustained closure rates were not different (74% vs 60%). Surgical PDA ligations were less frequent in the short course group than in the long course group. The short course group had a shorter duration of oxygen supplementation, less frequent symptoms of necrotizing enterocolitis, and a lower rate of urea retention. Mortality and other neonatal morbidity rates were similar. CONCLUSION: A prolonged low-dosage indomethacin regimen offers no advantage compared with a standard-dosage short course in the management of a hemodynamically significant PDA in preterm infants.     

Patent ductus arteriosus in preterm infants

Patent ductus arteriosus (PDA) is a major morbidity in preterm infants, especially in extremely premature infants less than 28 weeks. The clinical signs and symptoms of PDA in preterm infants are non specific and insensitive for making an early diagnosis of significant ductal shunting. Functional echocardiography is emerging as a new valuable bedside tool for early diagnosis of hemodynamically significant ductus, even though there are no universally accepted criteria for grading the hemodynamic significance. Echocardiography has also been used for early targeted treatment of ductus arteriosus, though the long term benefits of such strategy are debatable. The biomarkers like BNP and N-terminal pro-BNP are currently under research as diagnostic marker of PDA. The primary mode of treatment for PDA is pharmacological closure using cyclo-oxygenase inhibitors with closure rate of 70–80%. Oral ibuprofen is emerging as a better alternative especially in Indian scenario where parenteral preparations of indomethacin are unavailable and side effects are comparatively lesser. Though pharmacological closure of PDA is an established treatment modality, there is still lack of evidence for long term benefits of such therapy as well as there is some evidence for the possible adverse effects like increased ROP and BPD rates, especially if treated prophylactically. Hence, it is prudent to reserve treatment of PDA to infants with clinically significant ductus on the basis of gestation, birth weight, serial echocardiography and clinical status to individualize the decision to treat.     

The treatment of patent ductus arteriosus in preterm infants. A review and overview of randomized trials

Patent ductus arteriosus (PDA) is a common problem in very preterm infants. It results in a significant left-to-right shunt and an increase in left ventricular output. Pulmonary compliance can be reduced. Systemic effects result from the diastolic steal and retrograde diastolic blood flow. Randomized controlled trials of PDA closure fall into three groups: (i) prophylactic treatment in the first 24 h, (ii) pre-symptomatic treatment on ultrasound evidence of a PDA or the first clinical signs and (iii) treatment when it becomes haemodynamically significant. Prophylactic treatment with indomethacin reduces the incidence of intraventricular haemorrhage. All the trials have a decreased need to treat a subsequent PDA in the treatment group. There are no other improvements in outcome, without any change in mortality, bronchopulmonary dysplasia, necrotizing enterocolitis or retinopathy of prematurity. Clinical decisions on the treatment of the ductus should be individualized and based on the gestation of the baby, the respiratory condition and the size of the ductal shunt.     

Genetics of the patent ductus arteriosus (PDA) and pharmacogenetics of PDA treatment

Patent ductus arteriosus (PDA) is a frequent, complex, and difficult to treat clinical syndrome among preterm infants in the neonatal intensive care unit. In addition to known clinical risk factors, there are emerging data about genetic predisposition to PDA in both animal and human models. Clinical response and toxicity from drugs used to treat PDA are highly variable. Developmental and genetic aspects of pharmacokinetics and pharmacodynamics influence exposure and response to pharmacologic therapies. Given the variable efficacy and toxicity of known drug therapies, novel therapeutic targets for PDA treatment offer the promise of precision medicine. This review addresses the known genetic contributions to prolonged ductal patency, variability in response to drug therapy for PDA, and potential novel drug targets for future PDA treatment discovery.     

早产儿脑损伤生物标志物的研究进展

随着围产及新生儿监护技术的不断发展,早产儿的生存率不断提高,与此同时早产儿脑损伤的发生率也在逐渐上升,常遗留不同程度的认知障碍与运动障碍。脑损伤生物标志物检测是诊断脑损伤的重要手段,根据损伤细胞的性质不同可分为神经胶质细胞损伤标志物、神经元损伤标志物及其他生物标志物等几大类,而其中较为成熟并广泛应用于临床的有S100B蛋白、髓鞘碱性蛋白、神经元特异性烯醇化酶等生物标志物。最新研究发现胶质纤维酸性蛋白、神经丝轻链蛋白、α-Ⅱ血影蛋白裂解产物、趋化因子、褪黑素及尿液代谢组学等指标可提示早产儿潜在脑损伤,检测这些生物标志物有助于早产儿脑损伤的早期诊断及早期治疗,对改善其神经发育预后至关重要。该文就早产儿脑损伤生物标志物的最新研究进展作一综述,以期为早产儿脑损伤的早期诊断及早期治疗提供有效依据。