简介：AbstractSepsis remains a significant cause of neonatal morbidity and mortality in China. A better understanding of neonatal sepsis in China as compared with other industrialized and non-industrialized countries may help optimize neonatal health care both regionally and globally. Literature cited in this review was retrieved from PubMed using the keywords "neonatal sepsis," "early-onset (EOS)" and "late-onset (LOS)" in English, with the focus set on population-based studies. This review provides an updated summary regarding the epidemiology, pathogen profile, infectious work-up, and empirical treatment of neonatal sepsis within and beyond China. The incidence of neonatal EOS and the proportion of Group B Streptococcus (GBS) within pathogens causing EOS in China seem to differ from those in developed countries, possibly due to different population characteristics and intrapartum/postnatal health care strategies. Whether to adopt GBS screening and intrapartum antibiotic prophylaxis in China remains highly debatable. The pathogen profile of LOS in China was shown to be similar to other countries. However, viruses as potential pathogens of neonatal LOS have been underappreciated. Growing antimicrobial resistance in China reflects limitations in adapting antibiotic regimen to local microbial profile and timely cessation of treatment in non-proven bacterial infections. This review stresses that the local epidemiology of neonatal sepsis should be closely monitored in each institution. A prompt and adequate infectious work-up is critically important in diagnosing neonatal sepsis. Adequate and appropriate antibiotic strategies must be overemphasized to prevent the emergence of multi-resistant bacteria in China.

简介：AbstractImportance:Effective screening strategies for early-onset neonatal sepsis (EONS) have the potential to reduce high volume parenteral antibiotics (PAb) usage in neonates.Objective:To compare management decisions for EONS, between CG149 National Institute for Health and Care Excellence (NICE) guidelines and those projected through the virtual application of the Kaiser Permanente sepsis risk calculator (SRC) in a level 2 neonatal unit at a district general hospital (DGH).Methods:Hospital records were reviewed for maternal and neonatal risk factors for EONS, neonatal clinical examination findings, and microbial culture results for all neonates born at ≥34 weeks’ gestation between February and July 2019, who were (1) managed according to CG149-NICE guidelines or (2) received PAb within 72 h following birth at a DGH in Winchester, UK. SRC projections were obtained using its virtual risk estimator.Results:Sixty infants received PAb within the first 72 h of birth during the study period. Of these, 19 (31.7%) met SRC criteria for antibiotics; 20 (33.3%) met the criteria for enhanced observations and none had culture-proven sepsis. Based on SRC projections, neonates with '≥1 NICE clinical indicator and ≥1 risk factor’ were most likely to have a sepsis risk score (SRS) >3. Birth below 37 weeks’ gestation (risk ratio [RR] = 2.31, 95% confidence interval [CI]: 1.02–5.22) and prolonged rupture of membranes (RR = 3.14, 95% CI: 1.16–8.48) increased the risk of an SRS >3.Interpretation:Screening for EONS on the SRC could potentially reduce PAb usage by 68% in term and near-term neonates in level 2 neonatal units.

简介：AbstractObjective:To investigate the effects of vitrification on the expression of the imprinted gene Snrpn in neonatal placental tissue.Methods:Neonatal placental tissue was collected from women with natural pregnancy (control group) and from women in assisted reproductive technology (ART) pregnancy group, following fresh and vitrified embryo transfer (fresh group and vitrified group, respectively). Snrpn mRNA expression and SNRPN protein levels in placental tissue from these three groups were assessed by real-time reverse transcription polymerase chain reaction and Western blot, respectively. DNA methylation in the Snrpn promoter region was analyzed by bisulfite-pyrosequencing.Results:The expression of Snrpn mRNA and SNRPN protein was found to be higher in placental tissue from the fresh and vitrified ART groups, compared to the control group. There was no significant difference in SNRPN gene or protein expression between the fresh and vitrified groups. DNA methylation at the Snrpn promoter region was not significantly different between these three groups.Conclusions:Human ART may alter the transcriptional expression and protein levels of the imprinted gene Snrpn. However, compared to other ART methods, vitrification may not aggravate or reduce this effect. Moreover, the altered expression of Snrpn is likely not directly related to DNA methylation of the Snrpn promoter region.

简介：ObjectiveTocharacterizemicroRNA(miRNA)expressionprofileinmicrodissectedauditoryepitheliafromtheCorti'sOrganinnewbornandadultrats.MethodsTheTaqManMicroRNAArrayswereusedtoidentifyexpressionofmicroRNAinthenewbornandadultgroups.GOanalysiswasappliedtoanalyzethemainfunctionofthedifferentialexpressiongenesaccordingtotheGeneOntologywhichisthekeyfunctionalclassificationofNCBI.Similarly,PathwayanalysiswasusedtofindoutthesignificantpathwayofthedifferentialgenesaccordingtoKEGG,BiocartaandReatome.ResultsIncreasedexpressionwasseenin16miRNAsinmatureratcomparedtonewbornrats,withincreasedfoldingrangingfrom17to600folds.Expressionlevelsin2miRNAswerereducedinmaturerats,namelyrno-miR-29candrno-miR-29a.Thehigh-enrichmentGOstargetedbyover-expressedmiRNAswerenegativeregulationofepithelialcelldifferentiation,common-partnerSMADproteinphosphorylation,mesenchymal-epithelialcellsignaling,regulationoftransforminggrowthfactorbeta2production,etc.FunctionalanalysisofmiRNAsbyKEGGrevealedthat19signaltransductionpathwayswereupregulatedand14weredownregulated.ConclusionsThedifferenceinmiRNAexpressionpatternsintheorganofCortibetweenneonatalandadultratsmaybecloselyrelatedtomaturationoftheorganofCortiandlossofproliferativecapacityofinnerearhaircells,andTGFβsignalingmayplayanimportantroleinhaircellsregeneration.

简介：MaleWistar7-day-oldratswereinjectedwith40mg/kgketamineintraperitoneally,followedbythreeadditionalinjectionsof20mg/kgketamineeachuponrestorationoftherightingreflex.Neonatalratsinjectedwithequivalentvolumesofsalineservedascontrols.Hippocampalsampleswerecollectedat1,7or14daysfollowingadministration.Electronmicroscopyshowedthatneuronalstructurechangednoticeablyfollowingketaminetreatment.Specifically,microtubularstructurebecameirregularanddisorganized.Quantitativerealtime-PCRrevealedthatphosphorylatedtaumRNAwasupregulatedafterketamine.Westernblotanalysisdemonstratedthatphosphorylatedtaulevelsatserine396initiallydecreasedat1dayafterketamineinjection,andthengraduallyreturnedtocontrolvalues.At14daysafterinjection,levelsofphosphorylatedtauwerehigherintheketaminegroupthaninthecontrolgroup.Tauproteinphosphorylatedatserine404significantlyincreasedafterketamineinjection,andthengraduallydecreasedwithtime.However,thelevelsoftauproteinatserine404weresignificantlygreaterintheketaminegroupthaninthecontrolgroupuntil14days.ThepresentresultsindicatethatketamineinducesanincreaseofphosphorylatedtaumRNAandexcessivephosphorylationoftauproteinatserine404,causingdisruptionofmicrotubulesintheneonatalrathippocampusandpotentiallyresultingindamagetohippocampalneurons.

简介：AbstractObjective:To evaluate the agreement and reliability of intrapartum nonreasurring cardiotocography (CTG) interpretation and prediction of neonatal acidemia by obstetricians working in different centers.Methods:A retrospective cohort study involving two tertiary hospitals (The First Affiliated Hospital of Sun Yat-sen University and Perking University Third Hospital) was conducted between 30th September 2018 and 1st April 2019. Six obstetricians from two hospitals with three levels of experience (junior, medium, and senior) reviewed 100 nonreassuring fetal heart rate (FHR) tracings from 1 hour before the onset of abnormalities until delivery. Each reviewer determined the FHR pattern, the baseline, variability, and presence of acceleration, deceleration, sinusoidal pattern, and predicted whether neonatal acidemia and abnormal umbilical arterial pH < 7.1 would occur. Inter-observer agreement was assessed using the proportions of agreement (Pa) and the proportion of specific agreement (Pa for each category). Reliability was evaluated with the kappa statistic (k-Light’s kappa for n raters) and Gwet’s AC1 statistic.Results:Good inter-observer agreement was found in evaluation of most variables (Pa>0.5), with the exception of early deceleration (Pa= 0.39, 95% confidence interval (CI): 0.36,0.43). Reliability was also good among most variables (AC1 > 0.40), except for acceleration, early deceleration, and prediction of neonatal acidemia (AC1 = 0.17, 0.10, and 0.25, respectively). There were no statistically significant differences among the three groups, except in the identification of accelerations (Pa = 0.89, 95% CI: 0.83,0.95; Pa= 0.50, 95% CI: 0.41,0.60, and Pa= 0.35, 95% CI: 0.25,0.43 in junior, medium and senior groups, respectively) and the prediction of neonatal acidemia (Pa= 0.52, 0.52, and 0.62 in junior, medium and senior groups, respectively), where agreement was highest and lowest in the junior-level group, respectively. The accuracy and sensitivity of the prediction for umbilical artery pH < 7.1 were similar among the three groups, but the specificity was higher in the senior groups (93.68% vs. 92.53% vs. 98.85% in junior, medium and senior groups, P= 0.015).Conclusion:Although we found a good inter-observer agreement in the evaluation of the most basic CTG features and FHR category statistically, it was insufficient to meet the clinical requirements for "no objection" interpretation for FHR tracings. Further specialized training is needed for standardized interpretation of intrapartum FHR tracings.

简介：AbstractFamily integrated care (FICare) is a collaborative model of neonatal care which aims to address the negative impacts of the neonatal intensive care unit (NICU) environment by involving parents as equal partners, minimizing separation, and supporting parent-infant closeness. FICare incorporates psychological, educational, communication, and environmental strategies to support parents to cope with the NICU environment and to prepare them to be able to emotionally, cognitively, and physically care for their infant. FICare has been associated with improved infant feeding, growth, and parent wellbeing and self-efficacy; important mediators for long-term improved infant neurodevelopmental and behavioural outcomes. FICare implementation requires multi-disciplinary commitment, staff motivation, and sufficient time for preparation and readiness for change as professionals relinquish power and control to instead develop collaborative partnerships with parents. Successful FICare implementation and culture change have been applied by neonatal teams internationally, using practical approaches suited to their local environments. Strategies such as parent and staff meetings and relational communication help to break down barriers to change by providing space for the co-creation of knowledge, the negotiation of caregiving roles and the development of trusting relationships. The COVID-19 pandemic highlighted the vulnerability within programs supporting parental presence in neonatal units and the profound impacts of parent-infant separation. New technologies and digital innovations can help to mitigate these challenges, and support renewed efforts to embed FICare philosophy and practice in neonatal care during the COVID-19 recovery and beyond.

简介：AbstractImportance:Parent-infant closeness and active parent participation in neonatal care are important for parent and infant health.Objective:To give an overview of current neonatal settings and gain an in-depth understanding of facilitators and barriers to parent-infant closeness, zero-separation, in 19 countries.Methods:Neonatal intensive care unit (NICU) professionals, representing 45 NICUs from a range of geographic regions in Europe and Canada, were purposefully selected and interviewed June–December 2018. Thematic analysis was conducted to identify, analyze and report patterns (themes) for parent-infant closeness across the entire series of interviews.Results:Parent-infant separation during infant and/or maternity care is very common (42/45 units, 93%), despite the implementation of family integrated care (FICare) practices, including parent participation in medical rounds (17/45, 38%), structured education sessions for parents (16/45, 36%) and structured training for healthcare professionals (22/45, 49%). NICU professionals encountered four main themes with facilitators and barriers for parent-infant closeness on and between the hospital, unit, staff, and family level: Culture (jointly held characteristics, values, thinking and behaviors about parental presence and participation in the unit), Collaboration (the act of working together between and within different levels), Capacities (resources and policies), and Coaching (education to acquire and transfer knowledge and skills).Interpretation:Implementing parent-infant closeness in the NICU is still challenging for healthcare professionals. Further optimization in neonatal care towards zero-separation and parent-infant closeness can be achieved by enforcing the 'four Cs for Closeness’: Culture, Collaboration, Capacities, and Coaching.

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简介：AbstractBackground:Preterm premature rupture of membranes (PPROM) is associated with high neonatal morbidity and mortality. However, the influences of cesarean section (CS) on neonatal outcomes in preterm pregnancies complicated with PPROM are not well elucidated. The aim of this study was to investigate the influence of delivery modes on neonatal outcomes among pregnant women with PPROM.Methods:A retrospective cross-sectional study was conducted in 39 public hospitals in 14 cities in the mainland of China from January 1st, 2011 to December 31st, 2011. A total of 2756 singleton pregnancies complicated with PPROM were included. Adverse neonatal outcomes including early neonatal death, birth asphyxia, respiratory distress syndrome (RDS), pneumonia, infection, birth trauma, and 5-min/10-min Apgar scores were obtained from the hospital records. Binary variables and ordinal variables were respectively calculated by binary logistic regressions and ordinal regression. Numerical variables were compared by multiple linear regressions.Results:In total, 2756 newborns were involved in the analysis. Among them, 1166 newborns (42.31%) were delivered by CS and 1590 newborns belonged to vaginal delivery (VD) group. The CS proportion of PPROM obviously increased with the increase of gestational age (χ2 = 5.014, P = 0.025). Compared with CS group, VD was associated with a higher risk of total newborns mortality(odds ratio [OR], 2.38; 95% confidence interval [CI], 1.102–5.118; P = 0.027), and a lower level of pneumonia (OR, 0.32; 95% CI, 0.126–0.811; P = 0.016). However, after multivariable adjustment and stratification for gestational age, only pneumonia was significantly related with CS in 28 to 34 weeks group (OR, 0.34; 95% CI, 0.120–0.940; P = 0.038). There were no differences regarding to other adverse outcomes in the two groups, including neonatal mortality, birth asphyxia, Apgar scores, RDS, pneumonia, and sepsis.Conclusions:The proportion of CS of pregnant women with PPROM was very high in China. The mode of delivery does not affect neonatal outcomes of pregnancies complicated with PPROM.

简介：AbstractObjective:Despite the fact that adenomyosis is a fairly common gynecological disorder, its pathogenesis remains elusive. Several theories on the pathogenesis of adenomyosis have been proposed, but none of them has been proven experimentally. So far, the most used one is the neonatal feeding of tamoxifen (TAM) in Institute of Cancer Research/cryopreserved (ICR/CD-1) mouse. However, its underlying mechanism of action is unknown. To further delineate the mechanism of TAM-induced adenomyosis in ICR/CD-1 mouse with regard to specific estrogen receptor (ER), we conducted an experiment that neonatal mice were fed with either TAM, or 4,4′,4″-(4-propyl-[1H]-pyrazole-1,3,5-triyl) trisphenol (PPT; an ERα agonist), or 2,3-bis(4-hydroxyphenyl)-propionitrile (DPN; an ERβ agonist), or G-1 (a G-protein coupled receptor 30 agonist), or just vehicle, in an attempt to tease out which specific receptor plays a dominant role in the genesis of adenomyosis induced by neonatal feeding of TAM.Methods:Forty female neonatal mice were randomly divided into 5 equal-sized groups: CTL (control), TAM, PPT, DPN, and G-1. Three months later, all mice were sacrificed and their uterine horns were harvested, weighed, and processed for histological evaluation.Results:All mice in the TAM group developed adenomyosis, so did 4 mice (50%) in the DPN group, a result that should be considered significant given that mice in the CTL group would not develop adenomyosis. No mouse in the PPT or G-1 group developed adenomyosis. Remarkably, all lesions in the DPN group were seen exclusively near the uterine serosa, which are dramatically different from that of TAM mice and reminiscent of extrinsic or external adenomyosis in humans.Conclusions:Neonatal feeding of DPN induces adenomyosis, but the adenomyotic lesions appear to be different from those induced by TAM. Thus, the cause of TAM-induced adenomyosis in ICR/CD-1 mouse cannot be attributable to one specific ER alone. This suggests that the extrinsic/external adenomyosis may have a pathogenesis that is different from other sub-types of adenomyosis.

简介：AbstractBackground:Intensive phototherapy (IPT) and exchange transfusion (ET) are the main treatments for extreme hyperbilirubinemia. However, there is no reliable evidence on determining the thresholds for these treatments. This multicenter study compared the effectiveness and complications of IPT and ET in the treatment of extreme hyperbilirubinemia.Methods:This retrospective cohort study was conducted in seven centers from January 2015 to January 2018. Patients with extreme hyperbilirubinemia that met the criteria of ET were included. Patients were divided into three subgroups (low-, medium-, and high-risk) according to gestational week and risk factors. Propensity score matching (PSM) was performed to balance the data before treatment. Study outcomes included the development of bilirubin encephalopathy, duration of hospitalization, expenses, and complications. Mortality, auditory complications, seizures, enamel dysplasia, ocular motility disorders, athetosis, motor, and language development were evaluated during follow-up at age of 3 years.Results:A total of 1164 patients were included in this study. After PSM, 296 patients in the IPT only group and 296 patients in the IPT plus ET group were further divided into the low-, medium-, and high-risk subgroups with 188, 364, and 40 matched patients, respectively. No significant differences were found between the IPT only and IPT plus ET groups in terms of morbidity, complications, and sequelae. Hospitalization duration and expenses were lower in the low- and medium-risk subgroups in the IPT only group.Conclusions:In this study, our results suggest that IPT is a safe and effective treatment for extreme hyperbilirubinemia. The indication of ET for patients with hyperbilirubinemia could be stricter. However, it is necessary to have a contingency plan for emergency ET as soon as IPT is commenced especially for infants with risk factors. If IPT can be guaranteed and proved to be therapeutic, ET should be avoided as much as possible.

简介：AbstractObjective:Vitrification prevents ice formation within the high concentration of cryoprotectant agents and allows the cells and extracellular milieu to solidify into a glass-like state. This study aimed to provide objective information on the available data regarding singleton births comparing embryo vitrification with fresh embryo transfers.Methods:PubMed and Cochrane databases were searched for studies conducted up to 2017. Low birth weight (LBW), very low birth weight (VLBW), preterm birth (PTB), very PTB, small for gestational age (SGA), large for gestational age, perinatal mortality, cesarean section, and preeclampsia were measured.Results:The search returned 220 articles, and 13 of these met the inclusion criteria. A significantly lower risk of SGA birth was observed in the vitrified embryo transfer group than in the fresh transfer group. Conversely, a higher risk of very PTB, VLBW, large size for gestational age, and perinatal mortality was observed more frequently in the vitrified embryo transfer group.Conclusions:Vitrified embryo transfer was associated with the improved outcome of neonates regarding the SGA rate compared with fresh embryo transfer, but included a higher risk of very PTB, VLBW, large size for gestational age, and perinatal mortality. Caution should be exercised in interpreting these findings given the low level of evidence of the studies.

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简介：AbstractThis paper provides ethical guidance for the professionally responsible clinical investigation of maternal-fetal investigation for fetal or neonatal benefit and its transition into clinical practice. We present an ethical framework based on the ethical principles of beneficence, respect for autonomy, and justice, the professional virtue of integrity, and the ethical concept of the fetus as a patient. We identify the implications of this ethical framework for the qualifications that centers for maternal-fetal intervention should satisfy. These centers have the ethical obligation to provide prospective review and oversight of both innovation (an experiment undertaken to benefit an individual patient) and research (an experiment undertaken to create generalizable knowledge). We describe ethically justified criteria for innovation and early-phase research, for randomized clinical trials, and for the responsible transition into clinical practice. We also identify the elements of the informed consent process, including measures to prevent therapeutic misconception by pregnant patients during the informed consent process. The scientific, clinical, and ethical requirements of maternal-fetal investigation are demanding. However, the commitment to safety and quality requires that they be met. Fulfilling this commitment will result in well-documented professionally responsible investigation of maternal-fetal intervention for fetal and neonatal benefit.

简介：AbstractIntroduction:Congenital nasal pyriform aperture stenosis (CNPAS) is a rare congenital condition of structural nasal obstruction. Respiratory distress, stertor, and poor feeding are often presenting features.Case Presentation:We report a case of a newborn diagnosed with CNPAS at 3 weeks of life. The diagnosis was missed on a nasoendoscopy at day 3 of life but was realised following a facial CT when the infant presented with ongoing symptoms of upper airway obstruction. Nasal dilation was performed successfully.Conclusion:CNPAS should be considered in any neonate with upper airway obstruction. A normal nasoendoscopy does not exclude the diagnosis.

简介：AbstractImportance:During the coronavirus disease 2019 (COVID-19) lockdown, changes in the visiting rules in neonatal units might have affected the initiation and continuation of breastfeeding.Objective:To investigate the effects of the implementation of the COVID-19 lockdown in the UK on mother’s own milk (MOM) feeding in hospital and at the time of discharge in two UK neonatal units.Methods:Retrospective cohort study using routinely recorded data from electronic patient records. Data were retrieved from two neonatal services in the UK East Midlands region. Adjusted logistic regression was used to compare the odds of MOM feeding before, and after the implementation of the UK lockdown.Results:Among 2073 infants, after adjusting for maternal and infant characteristics and underlying trends over time, there were no differences in the odds of infants receiving any MOM during admission; any MOM at discharge or exclusive MOM at discharge before and after the imposition of the lockdown. Infants with birthweight <1000 g were three times less likely to receive any MOM at discharge compared to those with birthweight >2500 g (adjusted odds ratio [OR] 0.33, 95% confidence interval [CI]: 0.22–0.50). Younger mothers were less likely, and Black British mothers more likely, to be feeding MOM to their infants at discharge, while women in the least deprived Index of Multiple Deprivation (IMD) quintiles were 2–4 times more likely to do so, compared to those in the most deprived IMD quintile (adjusted OR 2.78, 95% CI: 1.97–3.90).Interpretation:Despite the difficulties faced during COVID-19 pandemic-induced restrictions, infants in the participating neonatal units continued to receive MOM in similar proportions as before the pandemic.

简介：Inthepresentstudyexpressionofestrogenreceptorsubtype-α(ERα)and-β(ERβ)inthecerebralcortex,cerebellum,andolfactorybulbwasinvestigatedandcomparedbetweenneonatal(1～3-days-old)andadult(250～350g)rats,usingreversetranscription-polymerasechainreaction(RT-PCR).NoERαtranscriptsweredetectableintheadultcerebellumandolfactorybulb,whereasveryweakexpressionofERαwaspresentintheadultcerebralcortex.NosignificantdifferenceinERβtranscriptswasdetectablebetweentheneonatalandadultrats.WhiletranscriptsforbothERsubtypeswereco-expressedinthesebrainareasofneonatalrats,althoughERαexpressionwassignificantlyweakerthanERβ.EveninthecerebralcortexknowntocontainbothERsubtypesinadultrats,ERαtranscriptsinneonatalratsweremuchhigherthaninadult.TheseobservationsprovideevidencefortheexistenceofdifferentexpressionpatternsofERα/ERβtranscriptsinthesethreebrainareasbetweentheneonatalandadultrats,suggestingthateachERsubtypemayplayadistinctroleintheregulationofdifferentiation,development,andfunctionsofthebrainbyestrogen.