新生儿肠道病毒感染的临床特征分析

目的 分析新生儿肠道病毒感染特别是重症肠道病毒感染的临床特征。方法 回顾性选择244例肠道病毒感染新生儿为研究对象。根据感染严重程度,分为普通感染组（n=231）和重症感染组（n=13）,比较两组患儿的临床特征。结果 244例患儿中,207例（84.8%）在5~10月份发病,其中6~7月份发病人数最多。与普通感染组相比,重症感染组患儿出生胎龄小,早产儿比例高（P < 0.05）。重症感染组患儿发病时间早于普通感染组（P < 0.05）;皮疹、呼吸道症状、少吃少哭少动等败血症表现的发生率,伴发肺炎、心肌炎、坏死性肝炎和弥散性血管内凝血的发生率,以及血小板减少、凝血酶原时间延长、肌酸激酶同工酶升高和丙氨酸氨基转移酶升高的发生率,均高于普通感染组（P < 0.05）。重症感染组患儿病死率高于普通感染组（P < 0.05）。结论 新生儿肠道病毒普通感染和重症感染病例在起病时间、常见临床表现以及伴发疾病等方面均有显著不同。在肠道病毒流行季节,若新生儿出现皮疹和/或少吃少哭少动等败血症表现,特别是实验室检查提示肝功能损害以及凝血功能障碍,需高度警惕重症肠道病毒感染的可能。     

新生儿肠道病毒感染临床诊断治疗

肠道病毒感染是新生儿期常见的病毒感染。与年长儿不同,新生儿肠道病毒感染往往病情较重,临床表现与细菌性败血症难以区分,重症感染者可并发坏死性肝炎、脑膜炎和心肌炎,病情发展迅猛,死亡率高。病初予静脉输注免疫球蛋白治疗可能降低新生儿重症肠道病毒感染死亡率和并发症发生率。尚需进一步研究新型抗肠道病毒药物在新生儿期应用的安全性和...     

新生儿肠道病毒感染诊疗与预防专家共识

肠道病毒是一种主要通过粪-口途径传播的病毒,包括柯萨奇病毒A组和B组、埃可病毒、脊髓灰质炎病毒,以及新分离的肠道病毒68~71型等。肠道病毒感染(enterovirus infection,EI)在温带地区夏季和秋季发生率较高[1],在热带地区全年均会流行。EI最常见于婴幼儿,具有传染性。新生儿EI的危害主要在于其易引发医院感染暴发流行,病情复杂高危,难预见、难控制,可发展为新生儿败血症、急性重型肝炎、心肌炎等,进而威胁患儿生命。如何预防新生儿医院EI及其暴发流行是产科和新生儿科医务人员面临的严峻挑战。为进一步规范和加强新生儿病房EI临床诊治工作,减少重症EI发生,降低病死率,在广泛阅读相关文献并经业内专家讨论的基础上制定本专家建议。     

新生儿肠道病毒性脑膜炎临床分析

目的分析新生儿肠道病毒性脑膜炎的临床特点。方法选取87例中枢神经系统感染新生儿为研究对象,采用回顾性分析的方法,根据脑脊液肠道病毒PCR检测结果,将研究对象分为阳性组(55例)和阴性组(32例),分析入组患儿的临床特点。结果阳性组比阴性组住院时间短[(9.5±5.2)d比(21.8±15.8)d,t=4.295,P<0.001],治愈率高(96.4%(53/55)比81.2%(26/32),χ^2=3.872,P=0.049),夏秋季节发病率高[96.4%(53/55)比62.5%(20/32),χ^2=17.181,P<0.001]。阳性组无死亡病例,阴性组死亡3例(9.4%,3/32)。两组常见的临床表现均为发热,发生率分别为90.9%(50/55)和68.8%(22/32)(χ^2=6.962,P=0.008)。阳性组脑脊液白细胞计数、多核细胞比例、蛋白含量低于阴性组,而单核细胞比例、糖含量高于阴性组(P<0.001)。阳性组血、脑脊液细菌培养均阴性。阴性组血、脑脊液细菌培养均阳性10例,其中无乳链球菌3例,大肠埃希菌6例,脑膜败血性金黄杆菌1例,脑脊液细菌培养阳性患儿预后不良。阳性组颅脑超声、颅脑核磁共振、振幅整合脑电图异常发生率低于阴性组(P均<0.05)。结论肠道病毒是本地区夏秋季非细菌性脑膜炎的常见病原,预后较好,临床上对以发热为首发症状的新生儿,需要早期进行脑脊液的肠道病毒PCR检测。     

新型冠状病毒感染期间足月的晚期新生儿咽拭子肠道病毒核酸检测横断面研究

目的 探讨新型冠状病毒感染疫情期间住院的足月的晚期新生儿咽拭子肠道病毒（enterovirus,EV核酸检测阳性率及其临床特征。方法 该研究为单中心横断面研究,研究对象为2020年10月—2021年9月在新生儿内科病房住院的611例足月的晚期新生儿。于入院时采集咽拭子进行柯萨奇病毒A16型/EV71/EV通用型核酸检测。根据EV核酸检测结果分为EV核酸阳性组（8例）和EV核酸阴性组（603例）,分析比较两组患儿的临床特征差异。结果 611例患儿中,8例EV核酸检测阳性,阳性率为13.1‰,其中7例在5—10月份入院。EV核酸阳性组与EV核酸阴性组患儿起病前与有呼吸道感染症状的家庭成员接触比例分别为75.0%和10.9%(P<0.001)。两组患儿在人口学信息、临床症状、实验室检验方面差异无统计学意义（P>0.05）。结论 新型冠状病毒感染疫情期间住院的足月的晚期新生儿仍有一定比例的咽拭子EV核酸检测呈阳性但比例较低,其临床表现和实验室常规检测结果无特异性;家庭成员之间的传播可能是新生儿感染EV的重要途径。[中国当代儿科杂志,2023,25 (4):339-343]     

新生儿流感嗜血杆菌感染前瞻性多中心流行病学调查与病例对照研究

目的：了解新生儿流感嗜血杆菌( Haemophilus influenza,Hi)感染发生情况、流行菌株生物学分型和菌株耐药背景以及Hi新生儿肺炎临床基本特征。方法采用多中心前瞻性流行病学断面研究方法,对中国川西地区4家医院0~28 d入院初步诊断为新生儿感染性肺炎患儿痰液进行细菌培养,对Hi流行菌株进行生物学分型、PCR鉴定和药敏试验;以出院诊断为新生儿感染性肺炎的Hi分离阳性者为病例组,按1∶1提取同期住院新生儿肺炎Hi分离阴性者为对照组进行病例对照研究。结果2014年11月至2015年10月参加调查的4家医院入院诊断为新生儿感染性肺炎患儿757例,痰培养送检率95.51％(723/757),痰培养病原菌总阳性率15.63％(113/723);Hi阳性率1.94％(14/723),占新生儿呼吸道分离病原菌的12.39％(14/113)。全部14株Hi经PCR鉴定均为不可分型Hi;生物学分型Ⅰ型57.1％(8/14)、Ⅲ型14.3％(2/14)、Ⅳ型28.6％％(4/14);分离的14株流行菌株β-内酰胺酶阳性率35.7％(5/14),β-内酰胺酶阴性氨苄西林耐药7.1％(1/14),β-内酰胺酶阳性氨苄西林耐药35.7％(5/14),头孢呋辛耐药和中介率均为14.2％(2/14),头孢克洛耐药率35.7％(5/14),氧氟沙星耐药率21.4％(3/14),未发现阿莫西林克拉维酸和头孢噻肟耐药菌株。对10例出院诊断为新生儿肺炎的Hi阳性病例进行1∶1配对分析,结果显示病例组与对照组在一般情况、临床主要症状、肺部体征、X线胸片表现以及白细胞分类和C-反应蛋白水平等方面差异均无统计学意义(P>0.05)。结论川西地区新生儿Hi感染流行菌株全部为不可分型,生物学分型为Ⅰ型、Ⅲ型和Ⅳ型;新生儿未分型Hi肺炎临床表现与其感染性肺炎并无明显差异。     

无菌性发热新生儿单个核细胞肠道病毒基因表达的研究

目的　探讨无菌性发热新生儿外周血单个核细胞 (PBMC)中肠道病毒 (EV)基因表达情况和临床表现特点。方法　采用逆转录聚合酶链反应 (RT PCR)、原位杂交和病毒分离技术检测了 2 9例发热待查组和 18例中枢感染组新生儿PBMC、脑脊液及血清中EVRNA ,并对其临床特点进行总结分析。结果　发热待查组EV感染 14例 (48 3% ) ,9例PBMC中EVRNA阳性者 ,血清中全部阳性 ,其中 4例脑脊液中同时阳性 ;中枢感染组EV感染 11例 (6 1 1% ) ,5例外周血PBMC中EVRNA阳性者 ,血清和脑脊液中也全部阳性。两组比较 ,只有RT PCR法检测中枢感染组脑脊液中EVRNA阳性数高于发热组 ,而不同方法检测PBMC和血清中EVRNA两组间差异均无显著性。EV感染的主要症状有喂养困难 (71% )、易激惹 (6 4 % )、腹泻 (6 1% )、嗜睡 (5 4 % )、肝脏肿大 (46 % )及皮疹(36 % )等。结论　EV可感染新生儿的PBMC ;新生儿感染后EV易在全身播散 ;临床表现不典型 ,早期、快速病原诊断可缩短住院天数和减少抗生素的应用 ,有较高的社会和经济效益。     

重症71型肠道病毒感染的临床特征与治疗12例分析

目的 探讨肠道病毒71型(enterovirus 71,EV71)感染所致重症病例的临床特征、病理生理变化,评估治疗效果.方法 对2008年湖北省9家定点医院收治的EV71感染重症手足口病(hand,foot and mouth disease,HFMD)病例的临床资料进行回顾性分析.结果 12例重症病例经RT-PCR检查EV71核酸阳性,其中男10例,女2例,中位数年龄1.96岁.发热持续时间6.5 d,皮疹持续时间7 d,起病至出现重症表现时间为3.7 d.神经系统受累10例,合并呼吸循环衰竭5例.5例X线胸片显示两肺或单侧片状阴影,4例为肺部纹理增多.白细胞计数、血糖、血沉和C-反应蛋白无特征性变化.11例选择大剂量静脉注射丙种球蛋白,7例使用甲泼尼龙治疗;4例肺水肿-呼吸衰竭患儿经呼吸机辅助通气,平均支持72(48～96)h.11例治愈,1例死亡.结论 EV71重症主要发生在年龄小于3岁患儿,以中枢神经系统感染为主,半数可发展为呼吸循环衰竭.早期使用呼吸机辅助呼吸对纠正呼吸循环衰竭,防止多脏器功能不全和降低死亡率尤为重要.     

Neonatal hepatic haemangioendothelioma: Presentation with jaundice and microangiopathic haemolytic anaemia

A neonate with multicentric hepatic haemangioendothelioma complicated by jaundice and microangiopathic haemolytic anaemia is presented. To our knowledge such a constellation has not been previously reported.     

Extended-spectrum beta-lactamase-producing Klebsiella pneumoniae in paediatric wards: a nested case-control study

Aim: A high rate (48.6%) of extended spectrum beta‐lactamase production among Klebsiella pneumoniae (ESBL‐KP) clinical isolates in the paediatric wards of our hospital prompted the introduction of enhanced infection control measures, and after the implementation of these measures, we instituted a prospective surveillance programme, with a nested case‐control study to determine the risk factors for rectal colonisation by ESBL‐KP. Methods: Over a 1‐year period, rectal swabs from patients and samples from the environment and the hands of health‐care workers were cultured. Strain typing of ESBL‐KP isolates was performed using pulsed‐field gel electrophoresis. Characteristics of patients who were colonised with ESBL‐KP during hospital stay were compared with those of patients who remained negative for ESBL‐KP. Multivariate analysis was performed with model‐building using stepwise logistic regression to determine independent risk factors for ESBL‐KP acquisition. Results: Forty (18.5%) of 216 patients became colonised with ESBL‐KP. The strongest independent predictors of ESBL‐KP colonisation were mechanical ventilation (odds ratio (OR): 4.28) and hospitalisation for longer than 14 days (OR: 6.97). Genotyping of the isolates indicated probable patient‐to‐patient transmission; however, we could not determine the route of this spread. During the study period, a 1.6% rate of ESBL‐KP clinical infection per 500 patient admissions was observed, in contrast to a 7% rate in the previous year. Conclusions: Prolonged length of stay and mechanical ventilation were independent predictors of ESBL‐KP colonisation. Enhanced infection control measures, antimicrobial stewardship and screening for rectal carriage were associated with a substantial decrease in paediatric units.     

Severity of parechovirus infections in infants under 3 months of age and comparison with enterovirus infections: A French retrospective study

While enteroviruses (EV) are a well-recognized cause of aseptic meningitis in children, human parechoviruses (HPeV), especially genotype 3, have been increasingly reported as a frequent cause of sepsis-like illness and meningitis among young infants. The aim of this study was to describe the epidemiological, clinical, and laboratory characteristics of HPeV infections in infants and to compare them with those of well-known EV infections. This monocentric retrospective study was carried out at the pediatric unit of Nantes University Hospital from January 2015 to August 2018. All patients under 18 years of age with diagnosis codes referring to fever, for whom viral infection was suspected and cerebrospinal fluid (CSF) specimens were collected, were included. All CSF specimens were screened by duplex real-time polymerase chain reaction (PCR) assay that allows for the simultaneous detection of EV and HPeV in clinical samples. During the study period, 1373 CSF specimens from patients under 18 were included. A total of 312 CSF samples were positive for HPeV (n = 34) or EV (n = 278). Among the 34 HPeV-positive patients, 97% (33/34) were under 3 months of age, whereas the rate was 54% (149/278) for EV-positive patients (P < 0.001); thus, patients under 3 months of age were defined as the study population for the rest of this work. A review of the medical records was carried out for the positive cases. In this population, the HPeV detection rate was 5.6% versus 25.3% (P < 0.001) for EV. All but one of the HPeV samples available for genotyping were HPeV-3. No seasonality was observed for HPeV infections. Length of hospital stay tended to be longer for children infected with HPeV compared with those infected by EV (3 days vs. 2 days, P = 0.05). Clinicians reported more severe illness presentations among HPeV-infected infants, with more frequent administration of fluid bolus (P < 0.02). Regarding laboratory characteristics, a significant lack of cellular reaction in the CSF (P = 0.004) as well as lower C-reactive protein (CRP) levels (P = 0.006) and neutrophil counts (P < 0.001) were noted for HPeV infections compared with EV infections. Our results confirm the early onset of HPeV infections (more than 95% of patients aged under 3 months). The clinical presentation and laboratory characteristics of the two infections was similar. However, some higher clinical severity criteria and a lack of CSF pleocytosis were regularly observed in patients with HPeV infections. Considering the significant proportion (5.6%; 95% CI, 3.7–7.5) of all CSF samples in our series, HPeV detection should be systematically included in the microbiological diagnosis of febrile children under 3 months of age.     

母体高尿酸血症对妊娠结局和新生儿合并症影响的回顾性巢式病例对照研究

背景：高尿酸血症（HUA）患病率逐年增高,不仅与痛风、尿酸盐肾病和肾结石有关,还与内分泌代谢、心脑血管等系统疾病的发生和发展有关。 目的：探讨孕母妊娠晚期血尿酸水平与不良妊娠结局、新生儿尿酸水平及新生儿合并症的关系。 设计：回顾性巢式病例对照研究。 方法：以2020年1~12月在北京大学人民医院产检的孕母为队列人群,根据孕母妊娠晚期血尿酸水平分为HUA组和非HUA组,比较两组妊娠结局和新生儿临床结局。根据孕母妊娠晚期血尿酸水平（μmol·L-1）分为低浓度（<360）、中浓度（~420）和高浓度（>420）,采用线性回归和Logistic 回归模型分析孕母血尿酸水平与早产、低出生体重、小于胎龄儿的关系。孕母妊娠晚期尿酸值及新生儿生后24 h尿酸值相关性分析采用Spearman秩相关分析。 主要结局指标：孕母血尿酸水平与早产、低出生体重和小于胎龄儿的关系。 结果：共纳入孕母2 397例（新生儿2 581例）,HUA组216例（9.0%）,非HUA组2 181例。HUA组孕母所生新生儿出生体重低于非HUA组（2 925 g vs 3 260 g,P<0.001）,差异均有统计学意义;而早产（18.5% vs 8.9%）、低出生体重（23.1% vs 7.1%）、小于胎龄儿（29.2% vs 10.6%）和转儿科比例（19.9% vs 11.1%）均高于非HUA组,差异均有统计学意义（P<0.001）。尿酸水平高浓度组孕母分娩的新生儿出生体重较低浓度组低54.0 g（95%CI：-106.5~-1.6,P=0.043）,发生早产的风险增加74%（OR=1.74,95%CI：1.08~2.8,P=0.023）,发生小于胎龄儿的风险增加85%（OR=1.85,95%CI：1.26~2.73,P=0.002）。新生儿生后24 h内尿酸水平与孕母妊娠晚期尿酸水平呈中等相关（r=0.613,P=0.000）。两组早产儿合并症差异无统计学意义。 结论：母体妊娠晚期HUA与早产、低出生体重、小于胎龄儿的发生相关。     

儿童反复呼吸道感染部分相关影响因素分析

目的：探讨反复呼吸道感染与其部分相关影响因素的关系。方法用病例对照的研究方法，调查分析反复呼吸道感染与其部分影响因素的关系。结果儿童反复呼吸道感染和母乳喂养、微量元素缺乏(锌缺乏)、营养不良、环境因素(室内装修、被动吸烟、饲养宠物)、使用糖皮质激素存在相关性，但与母乳喂养这种相关性只在5岁以下的儿童中发现。还发现了不管出生前或出生后，二手烟与反复呼吸道感染的相关只是在男孩中发现，而在女孩中却不相关。家居装修、微量元素缺乏(锌缺乏)、营养不良、母乳喂养与反复呼吸道感染相关只是在女孩中发现，而在男孩中却不相关，提示各个影响因素对男孩和女孩的影响是不一样。结论反复呼吸道感染是受多因素影响的，而不同的影响因素对性别的影响也不同。     

新生儿呼吸窘迫综合征并发支气管肺发育不良风险基因巢式病例对照研究

背景：既往已有许多针对支气管肺发育不良（BPD）风险基因的研究,但不同研究遗传表型差异大,无法作为呼吸窘迫综合征（RDS）并发BPD的遗传风险基因。 目的：筛选RDS并发BPD的遗传风险因素,明确其对RDS患儿预后的影响。 设计：巢式病例对照研究。 方法：以2016年1月1日至2021年8月1日在复旦大学附属儿科医院住院治疗、临床确诊RDS的患儿为队列人群,以是否并发BPD分为 BPD组和非BPD组。采用倾向性评分策略平衡2组胎龄,采用罕见变异关联性分析和功能富集分析,探索罕见变异基因富集的生物学过程,并筛选在BPD组中存在显著较多有害变异的候选风险基因。从GEO数据库检索RDS并发BPD高度相关基因表达数据,行基因表达模式的时间序列分析,验证本文高变异负荷基因的表达特征。 主要结局指标：RDS并发BPD风险基因。 结果：倾向性评分匹配后BPD组111例,非BPD组157例,2组的胎龄差异无统计学意义。基于2 742个背景基因显著富集的1 558个生物学过程（P<0.01）,蛋白质截断变异最显著富集的基因集与蛋白激酶活性有关（P=0.011）,BPD组中携带蛋白质截断变异的基因总数最多的是阳离子跨膜转运相关基因（P=0.027）。错义/非同义变异最显著富集的基因集与生长发育的调节有关（P=0.001）。BPD组中有26个基因的错义/非同义罕见变异负荷显著高于非BPD组（P<0.05）,其中3个基因（ARSB、B9D2和UVSSA）差异有统计学意义（P<0.01）。通过GEO数据库数据验证,ARSB在重度BPD中显著低表达（P<0.001）,时间序列分析发现ARSB基因在重度BPD新生儿中表达模式与无/轻度BPD新生儿差异有统计学意义（P<0.01）。 结论：ARSB基因为RDS并发BPD的风险基因。     

Acute respiratory infections during pregnancy and congenital abnormalities: a population-based case-control study

Diseases of respiratory system caused by acute infections are among the most common maternal diseases during pregnancy. The objective of the study was to estimate the association between congenital abnormalities and acute respiratory infections during the first trimester of pregnancy. The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities including 22 843 cases with congenital abnormalities, 38 151 population controls without congenital abnormalities and 834 malformed controls with Down syndrome between 1980 and 1996 was evaluated. 2118 cases with congenital abnormalities (9.3%), 3455 population controls (9.1%) and 92 malformed controls with Down syndrome (11.0%) had mothers with acute respiratory infections. Of 25 different congenital abnormality groups, esophageal atresia/stenosis showed a high adjusted prevalence odds ratios (POR) with 95% confidence interval (CI) for acute respiratory infections during the first trimester of pregnancy in case mothers compared with population controls (3.6, 1.4-9.1) and malformed controls (1.9, 1.0-3.5), respectively. In addition there was an association between medically recorded acute respiratory infections during the first trimester of pregnancy and a higher risk for some other congenital abnormalities, such as posterior cleft palate and multiple congenital abnormalities. In conclusion a possible association between some congenital abnormalities, particularly esophageal atresia/stenosis and maternal acute respiratory infections cannot be excluded due to the interactions of the microbial agents, related drug treatments and last but not least the indirect effect of maternal diseases, such as fever-hyperthermia, hypoxia and dietary deficiency. However, periconceptional multivitamin/folic acid supplementation during the early pregnancy was able to reduce the acute respiratory infection related risk for congenital abnormalities.