Genetic background of idiopathic neurodevelopmental delay patients with significant brain deviation volume / 中华医学杂志(英文版)

BACKGROUND@#Significant brain volume deviation is an essential phenotype in children with neurodevelopmental delay (NDD), but its genetic basis has not been fully characterized. This study attempted to analyze the genetic factors associated with significant whole-brain deviation volume (WBDV).@*METHODS@#We established a reference curve based on 4222 subjects ranging in age from the first postnatal day to 18 years. We recruited only NDD patients without acquired etiologies or positive genetic results. Cranial magnetic resonance imaging (MRI) and clinical exome sequencing (2742 genes) data were acquired. A genetic burden test was performed, and the results were compared between patients with and without significant WBDV. Literature review analyses and BrainSpan analysis based on the human brain developmental transcriptome were performed to detect the potential role of genetic risk factors in human brain development.@*RESULTS@#We recruited a total of 253 NDD patients. Among them, 26 had significantly decreased WBDV (<-2 standard deviations [SDs]), and 14 had significantly increased WBDV (>+2 SDs). NDD patients with significant WBDV had higher rates of motor development delay (49.8% [106/213] vs . 75.0% [30/40], P  = 0.003) than patients without significant WBDV. Genetic burden analyses found 30 genes with an increased allele frequency of rare variants in patients with significant WBDV. Analyses of the literature further demonstrated that these genes were not randomly identified: burden genes were more related to the brain development than background genes ( P  = 1.656e -9 ). In seven human brain regions related to motor development, we observed burden genes had higher expression before 37-week gestational age than postnatal stages. Functional analyses found that burden genes were enriched in embryonic brain development, with positive regulation of synaptic growth at the neuromuscular junction, positive regulation of deoxyribonucleic acid templated transcription, and response to hormone, and these genes were shown to be expressed in neural progenitors. Based on single cell sequencing analyses, we found TUBB2B gene had elevated expression levels in neural progenitor cells, interneuron, and excitatory neuron and SOX15 had high expression in interneuron and excitatory neuron.@*CONCLUSION@#Idiopathic NDD patients with significant brain volume changes detected by MRI had an increased prevalence of motor development delay, which could be explained by the genetic differences characterized herein.

Interpretation for the International League Against Epilepsy task force on neonatal seizure expert (2021) / 中华实用儿科临床杂志

Seizure is the most common neurological critical disease in the neonatal period, most of which is symptomatic.Seizure is usually caused by acute brain injury, and only electrical seizure is more commonly seen.Neonatal seizures are not easy to be included in the epilepsy classification established by the International League Against Epilepsy (ILAE). As a result, a Neonatal Seizures Task Force was established by the ILAE to develop a modification of the 2017 ILAE classification of seizures and epilepsies.The neonatal classification framework emphasizes the role of electroencephalography (EEG) in the diagnosis of neonatal seizure, which includes a classification of seizure types especially in newborns.The type of seizure in adults and older children mainly depends on clinical characteristics, while many newborns only have electric seizures.Therefore, electric seizures are included in the classification scheme.Clinical events without corresponding EEG changes are not included.Neonatal seizures are all focal seizures, and focal and generalized seizures are unnecessarily to be categorized.Seizures can be classified by abnormal motor episodes (automata, clonic, myoclonic, tonic) and non-motor episodes (autonomic, behavioral changes) or sequential presentation.The new classification can be used to more specifically classify neonatal seizures.

Progress in clinical application of neonatal renal oxygen saturation monitoring / 中华实用儿科临床杂志

The incidence of acute kidney injury (AKI) in Neonatal Intensive Care Unit (NICU) is about 30%.The morbidity and mortality of AKI are higher in very premature infants, very low birth weight infants and infants with long mechanical ventilation.Serum creatinine (Scr) and urine output are diagnostic indicators for AKI, which usually change within 12-48 hours after the onset of irreversible injury, and cannot be used for early diagnosis and clinical intervention.Therefore, it is necessary to search for indicators of early renal insufficiency, aiming to intervene and prevent early-stage AKI or reduce the occurrence of AKI.Near-infrared spectroscopy (NIRS) is a non-invasive, continuous, real-time monitoring method, which serves as a supplement to conventional biochemical markers.It provides evidence of early-stage renal ischemia and hypoxia, which contributes to prevent or reduce AKI.This study reviews the clinical application of neonatal renal oxygen saturation monitoring, thus providing clinical reference for renal function protection in critically ill neonates to reduce the occurrence of AKI and improve their prognosis.

Neonatal encephalopathy: identification of multiple causes / 中国小儿急救医学

Neonatal encephalopathy (NE) is one of the major causes of neonatal death and severe disability in childhood.The etiology of NE is complex, which can occur in prenatal or delivery, and some neonates may even have high risk factors in both prenatal and delivery.Prenatal maternal diseases, hereditary diseases and genetic predisposition, hypoxic-ischemic encephalopathy, infections, placental abnormalities, thrombosis, abnormal blood coagulation, and metabolic diseases can all directly cause NE.Some patients of NE have comorbidities such as neuromuscular diseases, congenital heart disease, severe anemia, and severe pulmonary diseases, which lead to the disturbance of extrauterine adjustment during delivery, and the occurrence of hypoxic-ischemia leading to NE.NE is a heterogeneous disease, and the selection of appropriate assessment based on the medical history and examination, identification of the etiology of NE and treatment for the etiology can improve the prognosis.

Characteristics of video electroencephalogram and cranial magnetic resonance imaging in newborns with inherited metabolic disorders and predictive value for prognosis / 中国新生儿科杂志

Objective:To study the characteristics of video electroencephalogram (VEEG) and cranial magnetic resonance imaging (MRI) in neonates with inborn errors of metabolism (IEM) and to determine the predictive value for prognostic.Method:From June 2016 to December 2018, a retrospective study was performed on newborns diagnosed with IEM receiving VEEG examinations at the Neonatology Department of our hospital. VEEG and cranial MRI were used as prognostic indicators and the follow-up results were used as criteria predicting the accuracy of prognosis. The accuracy of the prediction was calculated using a 4 × 4 table.Result:A total of 21 eligible cases with 14 types of IEM were included. The most common type of IEM was organic acidemia (47.6%, 10/21). 16 cases (76.2%) had abnormal VEEG background patterns, including 8 cases of organic acidemia, 3 cases of urea cycle disorders, 1 case of energy metabolism disorder and 4 cases of other IEMs. No significant differences existed in the abnormality rate of VEEG background patterns among these groups ( P=0.882). VEEG showed 3 cases of seizures including 2 cases of electrographic-only seizures. Interburst interval durations were shortened on VEEG background with the decrease of blood ammonia level. The positive predictive values of the moderate-to-severe abnormal VEEG background and the presence of major cerebral lesions on MRI in predicting poor prognosis were 90.0% (95% CI 55.5%~99.7%) and 100% (95% CI 66.4%~100%), respectively, and the negative predictive values were 50.0% (95% CI 18.7%~81.3%) and 85.7% (95% CI 42.1%~99.6%), respectively. Conclusion:Neonates with IEM have higher incidences of abnormal VEEG. Continuous VEEG may accurately diagnose neonatal seizures and effectively monitor brain function. VEEG is a useful tool monitoring infants with IEM and predicting adverse outcomes, especially when used in combination with brain MRI.

MEGDHEL syndrome caused by SERAC1 gene variation: a case report and literature review / 中华围产医学杂志

Objective:To investigate the clinical and genetic features of 3-methylglutaconic aciduria, dystonia-deafness, hepatopathy, encephalopathy, Leigh-like syndrome(MEGDHEL syndrome) caused by SERAC1 gene variation. Methods:This study retrospectively described the clinical and molecular features and prognosis of a baby boy who was transferred to Children's Hospital of Fudan University and later diagnosed with MEGDHEL syndrome in August 2016. A summary of the clinical and genetic manifestations of MEGDHEL syndrome cases reported in China and foreign areas was conducted through a literature review.Results:(1) Case report: The 2-day-old patient was transferred to Children's Hospital of Fudan University due to hyperlactic acidemia after birth. Physical examination revealed scattered petechiae and ecchymoses of the skin. Laboratory examination showed coagulation disorders and cranial MRI revealed abnormal signals in both basal ganglia. A homozygous variation of c.442C>T(p.Arg148*) in the SERAC1 gene was detected in the patient, which is a pathogenic variant included in the Human Gene Mutation Database. Both of his parents were heterozygous carriers, thereby the diagnosis of MEGDHEL syndrome was confirmed. Followed up to the age of three years and 11 months, he was found to have psychomotor retardation, spasticity, dystonia, deafness, and loss of language ability. (2)Literature review: Together with the case reported in this study, a total of 88 cases were retrieved, involving 57 different variants. The clinical features were homogenous, with onset mostly in the neonatal period (72%, 62/86), and severe reversible liver dysfunction (49%, 38/77) and neonatal hypoglycemia (44%, 35/80) were the main features. Nervous system was affected since infancy and common symptoms, included hypotonia (86%, 68/79), progressive spasticity (82%, 67/82), dystonia (80%, 66/82), intellectual disability (88%, 58/66) and sensorineural hearing impairment (74%, 59/80). Furthermore, bilateral basal ganglia involvement on cranial MRI (93%,70/75) and 3-methylglutaconic aciduria (98%,80/82) were also seen. Supportive care is currently the main management, however, the prognosis is extremely poor. Conclusions:MEGDHEL syndrome should be highly suspected when reversible neonatal liver dysfunction or hypoglycemia of unknown reasons in neonatal period, followed by progressive deafness-dystonia syndrome in infancy. As the prognosis of these patients is usually poor, genetic testing may provide an early diagnosis in neonatal period.

New thoughts on neonatal hypoxic-ischemic encephalopathy in post-cooling era / 中华围产医学杂志

Management of the neonatal hypoxic-ischemic encephalopathy (HIE) has been evolving from a pre-cooling era with supportive therapy to standardized cooling era and currently to a post-cooling era over the last two decades. To further decrease the mortality and morbidity of HIE in post-cooling era, we need to focus on the selection of HIE patients who may benefit from cooling and optimization of the available cooling approaches, and to identify research gaps with regard to therapeutic strategies such as combining cooling with promising neuroprotective agents.

KCNQ2 gene and its related diseases / 国际儿科学杂志

KCNQ2 encodes a voltage-gated potassium channel that is expressed in the brain.KCNQ2 mutation causes different disease severity ranging from benign familial neonatal seizures 1 with mild clinical symptoms and good psychomotor development at the mild end to early infantile epileptic encephalopathy 7 with severe clinical symptoms and moderate to severe psychomotor developmental abnormalities.At present, according to mutation sites, the pathogenesis of KCNQ2-related disorders includes loss-of-function effects and gain-of-function effects.This article reviews the pathogenesis and clinical manifestations of KCNQ2 gene and KCNQ2-related disorders.

Neurological monitoring and evaluation of neonates during extracorporeal membrane oxygenation / 中华实用儿科临床杂志

Extracorporeal membrane oxygenation (ECMO) is the last resort for the severe and reversible respiratory or cardiac diseases in neonates and has been increasingly used in China.With the advancement of medical management and surgical techniques and the accumulation of ECMO treatment experience, the overall survival rate has increased.However, neurological complications and long-term poor outcomes is still common.Therefore, the monitoring and evaluation of neurological functions in the progress of ECMO treatment make sense.The combination of multiple monitoring methods can minimize neurological damage and improve long-term prognosis.In this review, the indications, advantages and disadvantages, timing and frequency, duration and neurodevelopmental outcome evaluation of monitoring techniques commonly used in neonatal ECMO therapy were reviewed.

Effect of red blood cell transfusion on cerebral tissue oxygenation in premature infants / 中华实用儿科临床杂志

Objective To analyze the changes in cerebral oxygen saturation( CrSO2 )and cerebral fractional oxygen extraction ratio(CFOE)before,during and after red blood cell(RBC)transfusion in premature infants,and to explore the effect of RBC transfusion on the cerebral tissue oxygenation in premature infants. Methods The preterm infants With gestational age﹤37 Weeks Who Were treated With RBC transfusion Were selected from September 2017 to March 2018 in Neonatal Department of Children＇s Hospital of Fudan University. Near－infrared spectroscopy( NIRS) Was applied to continuously monitor CrSO2 from 2 h before RBC transfusion to 24 h after RBC transfusion. Transcuta﹣neous arterial oxygen saturation(TcSaO2 ),heart rate(HR)and blood pressure(BP)Were synchronously measured by using multi－function monitor. CFOE could be calculated based on the monitored TcSaO2 . Results A total of 71 cases Were included in the study,39 males and 32 females,With a medium gestational age of 29(24－37)Weeks,a mean birth Weight of 2 195(710－3 950)g,17 cases in moderate anemia group and 54 cases in severe anemia group. Compared With the data 2 h before transfusion,CrSO2 increased( t ﹦9. 536,P﹤0. 001),While CFOE decreased( t ﹦ －8. 688,P ﹤0. 001)during transfusion in the Whole study population. The CrSO2 at 2 h before blood transfusion,during blood transfu﹣sion,2,6,12 and 24 h after transfusion Were 0. 579 ± 0. 037,0. 591 ± 0. 032,0. 599 ± 0. 035,0. 596 ± 0. 035,0. 595 ± 0. 027,0. 585 ± 0. 022,respectively in moderate anemia group and Were 0. 571 ± 0. 038,0. 592 ± 0. 039,0. 605 ± 0. 038, 0. 603 ± 0. 035,0. 596 ± 0. 032,0. 596 ± 0. 032,respectively in severe anemia group. The CFOE at 2 h before blood trans﹣fusion,during blood transfusion,2,6,12 and 24 h after transfusion Were 0. 40 ± 0. 04,0. 38 ± 0. 03,0. 37 ± 0. 04,0. 38 ± 0. 04,0. 38 ± 0. 03,0. 38 ± 0. 03,respectively in moderate anemia group and Were 0. 42 ± 0. 04,0. 39 ± 0. 04,0. 38 ± 0. 04, 0. 38 ± 0. 04,0. 39 ± 0. 03,0. 39 ± 0. 03,respectively in severe anemia group. CrSO2 increased(t﹦3. 874,P﹤0. 05), While CFOE decreased(t﹦ －4. 091,P﹤0. 05)at 2 h after transfusion in moderate anemia group. In severe anemia group,CrSO2 significantly increased( t ﹦9. 221,P ﹤0. 001),While CFOE significantly decreased( t ﹦ －8. 583,P ﹤0. 001)during transfusion,and this effect lasted until 2 h after transfusion(t﹦5. 926,－5. 556,P﹤0. 001). Compared With the data 2 h before transfusion,CrSO2 Was significantly increased(t﹦6. 894,P﹤0. 001),While CFOE Was signifi﹣cantly decreased(t﹦ －8. 536,P﹤0. 001)at 24 h after transfusion in severe anemia group. HoWever,there Was no signi﹣ ficant difference in CrSO2 and CFOE betWeen the 24 h after transfusion and 2 h before in the moderate anemia group. Conclusions RBC transfusion improves cerebral tissue oxygenation,and severe anemia group benefit more from blood transfusion. Cerebral oxygenation monitoring With NIRS monitor may provide neW insights for the clinical management of RBC transfusion in preterm infants.

Application of cerebral regional oxygen saturation monitoring in neonatal blood exchange transfusion / 中华实用儿科临床杂志

Objective@#To observe the changes in cerebral regional oxygen saturation (CrSO2) during neonatal blood exchange transfusion(BET) and its effect on the level of bilirubin in neonates with severe hyperbilirubinemia.@*Methods@#From January 2017 to March 2018, 52 newborns with severe hyperbilirubinemia were hospitalized in the Department of Neonatology, Children′s Hospital of Fudan University.Every newborn was treated with BET.Near infrared spectroscopy was used to monitor CrSO2 in the process of BET.The monitoring lasted from 2 hours before the beginning of BET to 2 hours after the completion of BET.The CrSO2 were recorded every 2 minutes and total surem bilirubin (TSB) and transcutaneous bilirubin(TCB) was measured.During this period, it is accompanied by the monitoring of neonatal body temperature, heart rate, respiration and bolld oxygen saturation(SpO2). The differences in CrSO2 changes at different time points during BET were compared.At the same time, the correlations between CrSO2 and blood oxygen saturation, TSB and TCB levels were analyzed.The results of repeated measurement analysis of variance compared between the two groups were corrected by Bonfferoni.@*Results@#Among the 52 children, there were 33 males (63.46%) and 19 females (36.54%). The gestational age, average birth weight and average head circumference of newborns were (38.6±2.1) weeks, (3 338±444) g and (33.6±3.2) cm, respectively.The Apgar score of newborn was (8.1±1.6) scores at 1 minute after birth.The level of TSB detected for the first time after admission was (457.9±97.8) μmol/L.The CrSO2 after BET (74.6%-76.0%) was significantly higher than that before BET (69.4%-69.0%), and the difference was statistically significant (P<0.05). Correlation analysis showed that during BET, CrSO2 showed a gradual upward trend, SpO2 also showed a synchronous increase, while the level of bilirubin showed a downward trend, and the downward trend of TSB level was more obvious than that of TCB.@*Conclusions@#CrSO2 can reflect the improvement of cerebral oxygenation during neonatal blood exchange transfusion and avoid cerebral hypoxia in the course of treatment.

The influence of gestational age and postnatal age on neonatal cerebrospinal fluid parameters / 中国新生儿科杂志

Objective To study the influence of gestational age (GA) and postnatal age on neonatal cerebrospinal fluid parameters.Method From January 2013 to December 2015,the results of WBC counts,glucose and protein concentrations of cerebro-spinal fluid(CSF) were collected from neonates admitted to neonatal department of our hospitals.The neonates were assigned into different groups according to their GA and postnatal age.The CSF parameters were compared between different groups,and the changes of CSF parameters were analyzed.STATA 12.0 software was used for statistical analysis.Result A total of 1 410 infants were included.516 (36.6％) cases were preterm infants.1 208 cases (85.7％) received antibiotics before lumbar puncture.WBC counts in CSF between preterm and term infants showed no significant differences (upper reference limit,12.5 × 106/L).CSF glucose in term infants (lower reference limit,1.8 mmol/L) was higher than preterm infants (lower reference limit,1.6 mmol/L).CSF protein in preterm infants (upper reference limit,226.6 mg/ dl) was significantly higher than term infants (upper reference limit,140.3 mg/dl).CSF WBC counts decreased with the growth of postnatal age in preterm infants (regression coefficients-0.030,P=0.035).CSF protein also declined significantly with the increase of postnatal age in term infants (regression coefficients-1.254,P＜0.001).CSF glucose showed no significant decrease with the increase of postnatal age (regression coefficients-0.009,P=0.012).Conclusion GA and postnatal age did not produce an effect on WBC counts of CSF.The preterm infants had lower glucose level and higher protein level in CSF.CSF protein declined significantly with the increase of GA and postnatal age.

The exploration of Guardian real-time continuous monitoring system in high-risk infants with hypoglycemia / 中华实用儿科临床杂志

Objective To explore the feasibility of Guardian real-time continuous monitoring system (GRT) in high-risk infants with hypoglycemia.Methods The glucose of 72 infants admitted to Neonatal Intensive Care Unit (NICU) of Children's Hospital of Fudan University between May 2015 and December 2016 were detected by GRT (provided by Medtronic),there were 43 males and 29 females with gestational age [(35.25 ± 4.45) weeks],and birth weight [(2 385.69 ± 1 062.63) g].At the same time,the capillary glucose was monitored intermittently detected by using ACCU-CHEK(R).Results A total of 1 134 paired glucose levels were collected.A good correlation between the paired capillary[(5.23 ± 1.96) mmol/L] and GRT continuous monitor measurements [(5.19 ± 1.99) mmol/L] was found(r =0.88,P ＜ O.05),and the value of mean absolute difference (MAD) was 11.88％.Through the Clarke error grid analysis,there were 98.24 ％ points located in region A and region B,only 20 paired(1.76％) glucose located in region D.Hypoglycemia was defined as glucose concentration ＜ 2.6 mmol/L,while hyperglycemia was defined as glucose concentration ＞ 7.0 mmol/L.A high/low blood glucose detected by peripheral blood glucose monitoring is a high/low blood glucose event,and a high/low blood glucose detected by GRT in a continuous period is a high/low blood glucose event.Twelve cases of hypoglycemia,26 episodes of hypoglycemia,29 cases of hyperglycemia,and 151 episodes of hyperglycemia were detected by using fast blood glucose meter.Twenty-six cases of hypoglycemia,88 episodes of hypoglycemia,38 cases of hyperglycemia,and 229 episodes of hyperglycemia were detected by using GRT.Sixty-two episodes of hypoglycemia were not detected by the fast blood glucose meter,with 14 episodes lasting longer than 30 min,4longer than 60 min,and 5 longer than 90 min.There were 78 hyperglycemic episodes that were not detected by the fast blood glucose meter,with 44 episodes lasting longer than 30 min,15 longer than 60 min,and 70 longer than 90 min.There were significant differences in the testing of hypoglycemia and pathoglycemia(x2 =7.00,18.60;all P ＜ 0.05),but,there was no significant difference in the testing of hyperglycemia between the 2 kinds of detection(x2 =2.26,P ＞0.05).GRT was acceptable to parents,medical staffs and children as only 3 infants bled when the continuous glucose sensor was imbedded,but there was no progressive increase in blood loss.There was no redness,edema,infections,or effusions at the insertion sites.Conclusions The use of GRT continuous monitoring system in high-risk infants of hypoglycemia was feasible.Compared with the conventional intermittent peripheral blood glucose monitoring,more abnormal blood glucose events and their duration could be detected.

Neonates with enterovirus infection: retrospective study on clinical characteristics of 81 case and prognostic scoring system / 中国新生儿科杂志

Objective To study the clinical features of neonates with enteroviral infection.Method We collected all neonates with enteroviral infection confirmed pathologically in the Department of Neonatology in the Children's Hospital of Fudan University from March 2009 to July 2016 retrospectively.The clinical data of the patients (clinical manifestation,first laboratory examinations,imaging findings,treatment procedures and outcomes) were retrieved to summarize the clinical features of neonatal enterovirus infection and to analyze the factors affecting the prognosis of neonatal enterovirus infection.Result A total of 81 neonates with enterovirus infection were included in the study.Among them,55 were full-term infants and 26 were premature infants,and the birth weight was (3 029±728)g.The median age of hospital admission was 5 (1,16) d,and multiple systemic manifestations were common in the course of the disease.Among them,19.8％(16/81)died.The factors for death are preterm birth,decreased hemoglobin,platelet count or serum albumin levels,abnormal coagulation,elevated blood lactate levels and acidosis.A scoring system was established based on high-risk factors.A score of ≥ 4 could reliably predict adverse outcomes,with a specificity of 92.3％ and a sensitivity of 93.8％.Conclusion Enteroviral infection in neonates can be highlt critical multiple system involvement.Neonates enterovirus infections with high risk factors(premature delivery,hemoglobin/ platelet/ albumin hypoplasia,coagulation dysfunction,lactic acid increase and acidosis) had higher mortality rate.There is a need to identify these neonates for intensive care and better treatment is warranted to improve the prognosis of these patients early.

PEX1 gene related Zellweger syndrome: a report of 2 cases and literature review / 中国新生儿科杂志

Objective To study the phenotypic and genotypic characteristics of Zellweger syndrome caused by PEX1 gene mutation.Method The clinical data of 2 neonates with Zellweger syndrome admitted to the Hospital were retrospectively analyzed.The databases of CNKI,Wipp and Wanfang were retrieved with “peroxisomal disease”,“Zellweger syndrome”,“Zellweger pedigree disorder”,and “PEX1 gene” as key words and the human gene mutation database (HGMD) was retrieved with “PEX1” as the gene name.The biomedical literature database (PubMed),Web of Science database and Embase database were retrieved with “Zellweger syndrome”,“Zellweger spectrum disorder PEX1 gene” as key words.All the databases were retrieved up to Nov 8,2018 to summarize the clinical phenotype and genotype characteristics of children with Zellweger syndrome.Result A total of 2 neonates with Zellweger syndrome were admitted to our Hospital,including 1 male and 1 female.Both the newborns presented with hypotonia,feeding difficulties clinically and showed dilated cerebral ventricles in neuroimaging.They were detected compound heterozygous for PEX1 mutations.Case 1 with the variants [NM_000466:exon 12:c.2050C＞T (p.Q684X);NM_000466:exon20:c.3043G＞T(p.E1015X)] have suffered from seizure at 2 months old.Case 2 with the variants [NM_000466.2:exon5:c.892_895dupTATA (p.Asn299IlefsTer2);NM_000466:exon19:c.2927-2delA] died in the neonatal period.No cases of newborn Zellweger syndrome caused by PEX1 gene mutation have been reported in China.There was a total of 6 articles and 13 cases were reported from foreign literature databases.All the cases presented as hypotonia,abnormal liver function,wide sutures (large fontanelle),hypertelorism and broad nasal bridge clinically.2 newborns carrying 2 missense variants were diagnosed as mild Zellweger spectrum disorder and atypical Zellweger syndrome the 10 newborns with 2 variants typed frameshift,nonsense or splice site were diagnosed as Zellweger syndrome.Conclusion Zellweger syndrome caused by defective gene PEX1 manifested as hypotonia,abnormal liver function,wide sutures (large fontanelle),hypertelorism and broad nasal bridge in neonatal period.Newborns with frameshift,nonsense or splice site variants in PEX1 have more severe clinical phenotypical features.

Effect of red blood cell transfusion on the oxygenation of mesenteric tissue in premature infants / 中华儿科杂志

Objective@#To investigate the effect of red blood cell transfusion on the oxygenation of mesenteric tissue in premature infants.@*Methods@#In this prospective cohort study, preterm infants with gestational age <37 weeks who were treated with red blood cell transfusions were enrolled from June 2017 to March 2018 in Department of Neonatology, Children's Hospital of Fudan University. The infants were categorized into feeding intolerance group and feeding tolerance group according to the feeding intolerance standard. Near-infrared spectroscopy was applied to continuously monitor intestinal oxygen saturation from 2 h before red blood cell transfusion to 48 h after red blood cell transfusion. Intergroup differences of basic conditions were analyzed with t test, Mann-Whitney U test and χ2 test. Mixed linear model was used to compare intragroup and intergroup differences in intestinal oxygen saturation over time.@*Results@#A total of 73 cases with gestational age <37 weeks were enrolled, of whom 41 were males and 32 were females, with mean gestational age of (30±4)weeks and mean birth weight of (1 543±688)g; there were 33 cases in feeding intolerance group and 42 cases in feeding tolerance group. The average intestinal oxygen saturations at 2 h before blood transfusion, during blood transfusion, 2, 6, 12, 24, and 48 h after transfusion were 0.50±0.07, 0.52±0.07, 0.52±0.08, 0.51±0.08, 0.51±0.07, 0.51±0.08, and 0.51±0.07 respectively in feeding intolerance group and were 0.51±0.04, 0.55±0.04, 0.57±0.05, 0.57±0.04, 0.56±0.04, 0.56±0.04, and 0.56±0.05 respectively in feeding tolerance group. Compared with 2 h before transfusion, intestinal oxygen saturation were increased during transfusion in both group (feeding intolerance group t=4.992, P=0.000; feeding tolerance group t=9.615, P=0.000), however this effect lasted until 48 h after transfusion in feeding tolerance group (t=5.519, 12.409, 10.033, 9.133, 7.983, all P=0.000). Additionally, the increasement of intestinal oxygen saturation over time were lower in feeding intolerance group(F=8.876, P=0.000). Besides, the level of intestinal oxygen saturation was positively correlated with postmenstrual age (PMA)(F=4.863, P=0.031). In infants with PMA<30 weeks, particularly in feeding intolerance group, the level of intestinal oxygen saturation significantly decreased at 2 h after transfusion (t=23.063, P=0.002).@*Conclusions@#Feeding status and PMA may play a role in development of transfusion-associated necrotizing enterocolitis. Red blood cell transfusion may increase the risk for mesenteric ischemia and is more likely to cause necrotizing enterocolitis in preterm infants with PMA <30 weeks as well as feeding intolerance.@*Clinical Trail@#Children's Hospital of Fudan University, NCT02544100.

Clinical value of arterial blood gas within 72 h after birth in evaluating neonatal asphyxia induced brain injury / 中国新生儿科杂志

Objective To study the clinical value of neonatal arterial blood pH,base excess and lactate levels within 72 h after birth in assessing early brain injury in asphyxia neonates.Method From June 2015 to November 2016,a retrospective study was performed on the asphyxia newborn admitted to newborn department of Children's Hospital of Fudan University.The data of brain magnetic resonance imaging (MRI),video electroencephalogram (VEEG),and artery blood gas analysis (within 12 h and 72 h) were all collected.The neonates were assigned into brain injury group (severe or moderate injury) and control group (normal or mild injury) according to MRI and VEEG results.The differences of arterial blood pH,base excess and the level of lactate between the two groups were analyzed and indicators of brain injury were evaluated using ROC curves.Result A total of 63 cases were included in the study.Thirty patients were in the control group and 33 patients the brain injury group.The pH within 12 h was lower [(7.32 ±0.09) vs.(7.38 ±0.08)],and the lactic acid level in 12 h and at 24-72 h were significantly higher in the brain injury group than the control group [(7.9 ±4.2) mmol/L vs.(4.9 ±2.4) mmol/L and (3.7 ±3.2) mmol/L vs.(2.2 ± 1.1) mmol/L].The differences were statistically significant (P ＜0.05).The areas under the ROC curve of pH,lactate within 12 h and at 24-72 h were 0.323,0.715,0.643 (P =0.016,0.003,0.051).The cut-off value of lactic acid within 12 h in assessing of brain injury was 7.5 mmol/L,with the sensitivity of 0.46 and the specificity of 0.97.Conclusion The artery lactate level within 72 h after birth can be used to evaluate the severity of brain injury in neonatal asphyxia infants.

Clinical features of neonatal purulent meningitis caused by different pathogens / 中国新生儿科杂志

Objective To analyze the clinical features of neonatal purulent meningitis (NPM caused by Gram-positive and Gram-negative bacteria.Method From January 2008 to December,2015,the clinical data of NPM with positive cerebrospinal-fluid (CSF) culture admitted to Children's Hospital of Fudan University were reviewed retrospectively.Patients were assigned into Gram-positive group and Gramnegative group according to CSF culture,and general information,clinical presentation,laboratory examination and outcome were compared between the two groups.Wilcoxon Rank-Sum test was used to compare means.Proportions were compared using x2 test.Result A total of 82 NPM patients with positive CSF culture were enrolled in the study,and 44 (53.7％) were male.The average gestational age was 38.5 (35.6,39.6) weeks and the mean birth weight was 3100 (2600,3380) grams.16 (19.5％) cases were early-onset meningitis and 66 (80.5％) were late-onset.In 82 cases,43 (52.4％) showed Gram-positive bacteria and 39 (47.6％) Gram-negative in CSF culture.The five most common pathogens were escherichia coli (22 cases,26.8％),group B streptococcus (GBS) (10 cases,12.2％),enterococcus faecium (8 cases,9.8％),coagulase-negative staphylococcus(8 cases,9.8％) and klebsiella pneumoniae (5 cases,6.1％).In early-onset patients,the main causative pathogens isolated from CSF were GBS (3 cases,18.8％) and enterococcus (3 cases,18.8％).Escherichia coli (20 cases,30.3％) and coagulase-negative staphylococcus (8 cases,12.1％) were the most common pathogens in late-onset patients.Gram-positive group and Gram-negative group had similar clinical presentation (P ＞ 0.05).The ratio of patients with blood C-reactive protein ＞ 8 mg/L in Gram-negative group was higher than that in Grampositive group (P ＜ 0.05).Those with Gram-negative bacterial meningitis had a higher incidence of hydrocephalus than Gram-positive (P ＜ 0.05).Conclusion The main pathogens of NPM are escherichia coli and GBS.Neonates with Gram-positive bacteria meningitis have similar clinical presentation with those with Gram-negative meningitis,but have different laboratory examination and complication characteristics.

Clinical managements of therapeutic hypothermia in newborns with hypoxic-ischemic encephalopathy / 中华实用儿科临床杂志

Therapeutic hypothermia is believed to improve neurodevelopment outcome of infants with moderate-to-severe hypoxic-ischemic encephalopathy(HIE),however,the severe brain injury and neurologic sequelae still can be observed in some infants received therapeutic hypothermia.Optimal monitor and management of systematic complications presented by infants during cooling treatment are necessary for improvement of overall outcome.Therefore,it is essential to understand the functional change of each system of the whole body,to adapt adequate diagnostic methods and to train multidisciplinary staffs to monitor and manage moderate-to-severe HIE infants during therapeutic cooling.With the development of therapeutic hypothermia,it is currently considered as a standard of care for infants with moderate-to-severe HIE.It is recommended that any neonatal intensive care unit(NICU) using routinely therapeutic hypothermia to reference the national or international benchmarking protocols in order to improve the medical quality and prognosis of infants.

Significance of cerebrospinal fluid lactate level in diagnosing neonatal bacterial meningitis / 中华实用儿科临床杂志

Objective To study the significance of the cerebrospinal fluid(CSF)lactate level in diagnosing neonatal bacterial meningitis(BM). Methods The CSF samples were collected from neonates admitted to Neonatal Ward of Children's Hospital of Fudan University between January 2014 and March 2015. CSF lactate and glucose con-centrations were measured with blood - gas analyzer. CSF and serum glucose levels were measured with glucometer. The enrolled neonates were divided into 2 groups based on CSF culture,CSF white blood cells(WBCs)and clinical presenta-tion:observation group(neonates with BM)and control group(neonates without BM). Statistical analysis of data was performed with Stata 12. 0. Results A total of 93 infants(16 assigned to observation group and 77 assigned to control group)met the inclusion criteria. Neonates in observation group had higher median CSF lactate level(4. 2 mmol/ L)and CSF lactate/ glucose ratio(L/ Gcsf)(2. 32 mmol/ L),than those in control group(1. 3 mmol/ L,0. 52),and there were significant differences(Z = - 6. 19,- 5. 92,all P ﹤ 0. 05). CSF glucose levels were lower in observation group(me-dian,1. 25 mmol/ L)than those in control group(median,2. 5 mmol/ L),and the difference was significant(Z = 4. 97, P ﹤ 0. 05);CSF/ serum glucose ratio(CSF/ Sglu)were lower in observation group(median,0. 44 vs 0. 81 in control group),and the difference was significant(Z = 4. 43,P ﹤ 0. 05). The optimal CSF lactate cutoff point of 2. 2 mmol/ L had a positive predictive value(PPV)of 72. 7% and negative predictive value(NPV)of 100. 0% for bacterial meningi-tis. The optimal L/ Gcsf cutoff point of 1. 24 had a PPV of 94. 1% and NPV of 100. 0% . The optimal CSF glucose cutoff point of 2. 0 mmol/ L had a PPV of 65. 0% and NPV of 95. 9% . The optimal CSF/ Sglu cutoff point of 0. 6 had a PPV of 60. 0% and a NPV of 96. 9% . Conclusion CSF lactate may be an excellent biomarker for early diagnosis of neo-natal BM.