Path to impact: A report from the Bill and Melinda Gates Foundation convening on maternal immunization in resource-limited settings; Berlin – January 29–30, 2015

Global initiatives such as the Millennium Development Goals have led to major improvements in the health of women and children, and significant reductions in childhood mortality. Worldwide, maternal mortality has decreased by 45% and under-five mortality has fallen by over 50% over the past two decades [1]. However, improvements have not been achieved evenly across all ages; since 1990, under-five mortality has declined by ∼5% annually, but the average decrease in neonatal mortality is only ∼3% per year.Against this background, the Bill and Melinda Gates Foundation (BMGF) convened a meeting in Berlin on January 29–30, 2015 of global health stakeholders, representing funders, academia, regulatory agencies, non-governmental organizations, vaccine manufacturers, and Ministries of Health from Africa and Asia. The topic of discussion was the potential of maternal immunization (MI) to achieve further improvements in under-five morbidity and mortality rates in children, and particularly neonates and young infants, through targeting infectious diseases that are not preventable by other interventions in these age groups. The meeting focused on effective and appropriately priced MI vaccines against influenza, pertussis, and tetanus, as well as against respiratory syncytial virus, and the group B Streptococcus, for which no licensed vaccines currently exist.The primary goals of the BMGF 2015 convening were to bring together the global stakeholders in vaccine development, policy and delivery together with the Maternal, Newborn and Child Health (MNCH) community, to get recognition that MI is a strategy shared between these groups and so encourage increased collaboration, and obtain alignment on the next steps toward achieving a significant health impact through implementation of a MI program.     

Extrapolation for a pharmacokinetic model for acetaminophen from adults to neonates: A Latin Hypercube Sampling analysis

Physiological and drug-specific parameters need to be adjusted when extrapolating a pharmacokinetic (PK) model from adults to neonates, so as to reproduce the time profiles of the studied drug(s) consistent with clinical, in vivo data or in vitro cell line measurements. In this paper we present a parameter analysis method, i.e. the Latin Hypercube Sampling (LHS) method for an acetaminophen (APAP) PK model. The original model consists of two compartments (the blood and the urine) with Michaelis-Menten kinetic parameters determined for APAP and its metabolites. The physiological parameters are scaled through allometric laws from adults to neonates, and APAP-specific parameters are adjusted for enzymatic maturational changes. The LHS method is used to statistically investigate the interplay between these parameters. The results for the extrapolated APAP model are consistent with published APAP PK data in neonates. We found the sulphation clearance parameter played a crucial role in the neonatal PK model, but its influence was weakened if the volume of distribution parameters were included. We suggest that this kind of in silico experiment could be valuable as the first step in PK model extrapolation between different ages.     

Massage therapy as a non-pharmacological analgesia for procedural pain in neonates: A scoping review

IntroductionNeonates who undergo painful medical procedures should be given analgesics to reduce future adverse risks. The evidence for massage therapy (MT) as an analgesic method still varies, both in its terminology and implementation. Only a few studies on this topic have been conducted using a standardised trial approach. This review can thus become the basis for better future research.ObjectiveThis review aims to identify literature on MT practices as a method to manage or control pain in neonates undergoing painful procedures.MethodsThe methodology for this review followed the JBI scoping review methodology guidelines. Searches were performed in several databases: MEDLINE (PubMed), CINAHL (EBSCO), Scopus (Elsevier) and EMBASE. Data collected were then extracted by two independent reviewers, synthesised and presented in the form of tables and narratives.ResultsFifteen studies involving a total of 1,058 neonates in nine countries were identified in the search as meeting the criteria set for this review. One study was a comparative study, five were quasi-experiment studies and nine were randomised control trials (RCT).ConclusionThe implementation of massage as a non-pharmacological analgesic method for neonates undergoing painful procedures varied among the reviewed studies. Differences were identified in terms of the body part massaged, the duration and intensity of the massage, the level of pressure and the combination of massage with other methods. All studies presented positive results for reducing pain intensity in neonates undergoing procedural pain. Therefore, it is crucial that the method used for giving massage should be practical, accurate and safe.     

新生儿单肺通气的麻醉管理(附20例报告)

目的探讨新生儿食管端端吻合手术中单肺通气(OLV)麻醉的可行性和安全性.方法对20例日龄4h～17d、体重1.5～3.2kg的食管闭锁及气管食管瘘患儿,快速诱导后,在正气管插入单腔气管导管,右侧开胸,使术侧肺脏压迫萎陷造成左侧单肺通气(OLV).术中连续监测心率(HR)、动脉压(ABP)、心电图(ECG)、脉搏血氧饱和度(SpO2)、呼气末CO2分压(PETCO2)、体温(T);记录诱导前后OLV10min、OLV30min,术毕的SpO2、PETCO2、HR值,比较各时段呼吸循环参数变化.结果全部患儿单肺通气后SpO2均有下降,经适当处理,14例患儿SpO2维持在95%以上.3例患儿应用呼气末正压通气(PEEP),可维持SpO2在94%以上.另3例患儿在暂停手术操作、恢复双肺通气后,SpO2恢复正常.与诱导后相比,PETCO2在单肺通气后10min及30min分别为(30.2±3.6)、(29.5±4.8)mmHg,显著低于诱导后的(35.1±0.6)mmHg(P＜0.05).HR在单肺通气后各时段呈显著降低趋势(P＜0.05).结论采用正气管插管技术,应用合理的呼吸管理,适当的麻醉用药,新生儿单肺通气行类似于食管端端吻合手术是安全可行的.     

Molecular epidemiology of invasive and non-invasive group B Streptococcus circulating in Serbia

Streptococcus agalactiae (group B Streptococcus, GBS) remains the leading cause of invasive diseases in neonates and an important cause of infections in the elderly. The aim of this study was to access the prevalence of GBS genito-rectal colonisation of pregnant women and to evaluate the genetic characteristics of invasive and non-invasive GBS isolates recovered throughout Serbia.A total of 432 GBS isolates were tested for antimicrobial susceptibility, capsular polysaccharide (CPS) types and the presence of the hvgA gene. One hundred one randomly selected isolates were further characterized by clustered regularly interspaced short palindromic repeats (CRISPRs) analysis and/or multilocus sequence typing (MLST).The prevalence of GBS colonization in pregnant women was 15%. Overall, six capsular types (Ia, Ib, II to V) were identified, the most common being III (32.2%) and V (25.2%). The hiper-virulent clone type III/ST17 was present in 43.1% and 6.3% (p?<?0.05) of paediatric and adults isolates, respectively. Comparative sequence analysis of the CRISPR1 spacers content indicated that a few clones comprised the vast majority of the tested GBS isolates. Thus, it was estimated that dominant clones recovered from infants were CPS III/ST17 in late-onset infections (19/23; 82.6%), and Ia/ST23 in early-onset disease (44.4%). Conversely, genotype CPS V/ST1 was the most prevalent in adults (4/9; 25.4%). All isolates were susceptible to penicillin. Macrolide resistance (23.1%) was strongly associated with the ermB gene and constitutive resistance to clindamycin (63.9%). The majority of strains was resistant to tetracycline (86.6%), mostly mediated by the tetM gene (87.7%). GBS isolates of CPS V/ST1 and CPS III/ST23 were significantly associated with macrolide and tetracycline resistance, respectively.In conclusion, hyper-virulent CPS III/ST17 and V/ST1 were recognized as dominant GBS clones in this study.     

高频振荡通气下西地那非联合米力农治疗新生儿持续肺动脉高压的疗效观察

目的探讨高频振荡通气下西地那非联合米力农对新生儿持续性肺动脉高压的疗效。方法选取2016年1月至2018年12月于本院确诊的新生儿持续性肺动脉高压患儿120例,随机分为3组,每组40例。A组采用高频振荡通气+西地那非(1 mg/kg,q6h)治疗,B组采用高频振荡通气+米力农[负荷剂量50μg/kg,30 min静脉注射,维持剂量0.75μg/(kg·min)]治疗,C组采用高频振荡通气+西地那非+米力农治疗。检测患儿治疗前、治疗3 d后的动脉血二氧化碳分压(PaCO_2)、吸入氧浓度(FiO_2)、动脉血氧饱和度(SaO_2)、动脉血氧分压(PaO_2)和肺动脉压力(SPAP)的变化,观察患儿不良反应。结果 3组患儿PaCO_2、FiO_2、SaO_2、PaO_2和SPAP治疗前后比较差异具有统计学意义(P<0.05),PaCO_2、FiO_2均较治疗前均明显降低,且C组明显低于A、B组(P<0.05);SaO_2、PaO_2均明显高于治疗前,且C组PaO_2明显高于A、B组(P<0.05);治疗后,SPAP明显低于治疗前,且C组明显低于A、B组(P<0.05)。3组患儿均未发生恶性不良反应,且不良反应发生率较低,差异无统计学意义(P<0.05)。结论高频振荡通气下西地那非联合米力农治疗新生儿肺动脉高压疗效肯定,能够更好的改善患儿的缺氧状态和肺动脉压力,具有良好的临床应用价值。     

新生儿不同时期血清维生素D对缺氧缺血性脑病的诊断价值比较

目的探讨新生儿不同时期血清维生素D对缺血缺氧性脑病的诊断价值。方法回顾性分析2015年5月至2018年5月于本院出生的90名新生儿的血清维生素D水平,根据是否发生缺血缺氧性脑病分为两组,对照组为健康新生儿,观察组为缺血缺氧性脑病患儿,每组45例。通过酶联免疫法分析两组1 d和3 d维生素D水平。采用独立t检验分析两组维生素D水平差异,采用ROC曲线分析维生素D对缺氧缺血性脑病诊断的曲线下面积和诊断临界值。结果观察组在1、3 d维生素D血清水平均显著性低于对照组(P<0.05),观察组3 d维生素D水平显著性低于1 d(P<0.05)。1 d维生素D水平对缺血缺氧性脑病的曲线下面积为(0.754±0.051),而3 d曲线下面积为(0.874±0.035),3 d曲线下面积显著大于1 d(P<0.05)。1 d诊断临界值为22.5 mmol/L,敏感率为66.7%,特异性为69.9%。3 d诊断临界值为21.5 mmol/L,诊断敏感率为80.0%,特异性为73.3%。结论不同时期维生素D均对新生儿缺血缺氧性脑病具有一定的诊断价值。     

H–MRS 半定量技术在新生儿高胆红素血症 脑损伤中的应用

〔摘 要〕 目的：评估氢质子磁共振波谱（1 H–MRS）半定量技术运用于高胆红素血症新生儿脑损伤评估中的诊断作用。 方法：抽选 2018 年 1 月至 2020 年 6 月郴州市第一人民医院诊断的 200 例高胆红素血症新生儿纳入本研究,开展磁共振成 像（MRI）平扫检测、1 H–MRS 半定量技术检测,研究苍白球有改变及无改变新生儿临床各项指标测定结果、1 H–MRS 诊断 指标结果,统计各项检测方式对新生儿是否存在脑损伤的诊断作用。结果：苍白球有改变新生儿总胆红素水平与苍白球无 改变新生儿比较,差异无统计学意义（P ＞ 0.05）;苍白球有改变新生儿总胆红素与白蛋白比值、S100B 蛋白水平高于苍 白球无改变新生儿,且新生儿行为神经测定表（NBNA）评分低于苍白球无改变新生儿,差异具有统计学意义（P ＜ 0.05）。 苍白球有改变新生儿胆碱（Cho）/ 肌酸（Cr）、Cr/N– 乙酰天冬氨酸（NAA）高于苍白球无改变新生儿,NAA/Cr 低于苍白 球无改变新生儿,差异均具有统计学意义（P ＜ 0.05）。以临床诊断结果为金标准,MRI、NBNA 评分、1H–MRS、S100B 蛋白水平诊断新生儿存在脑损伤占比分别与临床诊断比较,差异均无统计学意义（P ＞ 0.05）。结论：为高胆红素血症新 生儿采取 1 H–MRS 半定量技术和 MRI 技术有助于较早评估其脑损伤情况。     

尿N-乙酰-β-D-氨基葡萄糖苷酶水平与新生儿窒息后肾损伤关系

目的探讨新生儿窒息后尿 N-乙酰-β-D-氨基葡萄糖苷酶（N-acetyl-beta-D-glu-cosaminidase,NAG）、血清中α1微球蛋白（α1-microglobulin,α1-MG）、β2-MG 值水平变化以及与窒息程度和急性肾损伤（acute kidney inj ury,AKI）之间的关系,阐述其在窒息新生儿肾损伤中的诊断价值。方法选择围产期窒息新生儿40例（窒息组）,按照新生儿窒息Apgar评分标准分为轻度窒息者22例（轻度窒息组）,重度窒息者18例（重度窒息组）;根据有无发生 AKI 将40例窒息新生儿分为AKI组25例和无 AKI组15例;记录入选新生儿 Apgar评分、胎龄、日龄、体质量。另外选择20例无窒息史新生儿为对照组。所有纳入对象在出生后24 h内采取外周静脉血,同时收集尿液。采用胶乳增强免疫比浊法测定血清中α1-MG、β2-MG的含量;采用 ELISA法测定尿液中 NAG含量;同时用全自动生化仪检测尿素氮及血肌酐水平。结果（1）本研究40例窒息后新生儿 AKI 总发生率为62.5%（25/40）,并且轻度窒息与重度窒息对 AKI 影响不同,重度窒息患儿更易发生严重的肾损伤。（2）窒息组尿 NAG及血清中β2-MG、α1-MG明显高于对照组[（25.48±12.45）U/L 比（8.62±2.49） U/L,（4.82±1.32）mg/L比（2.92±0.89）mg/L,（29.85±5.59）mg/L 比（25.23±5.26）mg/L]。（3）重度窒息组尿 NAG及血清中β2-MG、α1-MG 明显高于轻度窒息组[（32.21±24.32）U/L、（5.89±1.59）mg/L、（34.32±7.64）mg/L]明显高于轻度窒息组[（17.25±7.32）U/L、（2.92±0.89）mg/L、（26.94±5.57）mg/L]。（4）AKI组尿 NAG及血清中β2-MG、α1-MG[（28.24±21.25）U/L、（5.79±1.49）mg/L、（31.32±5.28）mg/L]明显高于无 AKI组[（16.34±6.72））U/L、（2.82±0.79）mg/L、（26.49±5.52）mg/L]。（5）按照对照组尿 NAG及血清中β2-MG、α1-MG值设定在x＋2SD为对照上限值,窒息组中尿 NAG异常率达65%,明显高于血清中β2-MG、α1-MG 异常率（分别为32.5%和7