ObjectiveTo recognize risk factors, types and prognosis of cerebral white matter injury i n preterm infants. MethodsThrough image examination, we obse rved the development of periventricular white matter injury in 64 preterm infant s. Follow-up was done to evaluate the mental development of them. We also anal yzed the perinaltal risk factors (maternal complications during pregnancy, and n eonatal diseases at early age) that related to periventricular leukomalacia (PVL ). Results Sixty-four preterm infants showed different d egrees of periventricular white matter injury: (1) Eighteen infants had PVL, of whom 6 had multi-site PVL, and 12 presented local PVL; (2) Eight infants had pe rsistent periventricular hyperecho; (3) Thirty-eight infants had transient abno rmality. Forty-six infants were followed up. The incidence of DQ≤75 was 100% a nd 33 33% in 6 infants with multi-site PVL and in 6 infants with local PVL res pectively. Logistic analysis showed that intraventricular hemorrhage (IVH) combi ned with expanded ventricle coorrelated with cerebral white matter injury. Babie s of mother who had pregnant complications had high incidence of PVL. ConclusionPeriventricular white matter injury, especially PVL is har mful in the prognosis of preterm infant. IVH combined with ventricular expansion is an important high risk factor of periventricular white matter injury.

Objective To investigate the correlation between hypoglycemia and brain injury of newborns.Methods Medical records and follow-up data of 110 newborns with hypoglycemia (blood glucose level≤2.2 mmol/L) who admitted into neonatal department of Peking University First Hospital from December 2006 to December 2009 were studied.All patients were divided into 3 groups:no brain injury group,mild and severe brain injury group according to their clinical manifestation,cerebral radiological characteristics and cerebral functional tests.By using receiver operating characteristic (ROC) curve and x2 test,the potential optimal blood glucose level and duration of hypoglycemia for predicting brain injury were confirmed.Multivariate Logistic regression was taken to determine independent predictors for brain injury.The analyzed factors included gender,preterm/small for gestational age,hyperbillirubinemia,fetal distress,asphyxia,infection,seizures and maternal hypertensive disorder complicating pregnancy and hyperglycemia.Results Among the 110 hypoglycemia newborns,33 (30.0％) infants suffered from brain injury,of which 23 were mild and 10 were severe.Blood glucose ≤1.7 mmol/L had high specificity (73％) and sensitivity (60％)for predicting brain injury.When blood glucose≤ 1.7 mmol/L,the incidence of brain injury and severe brain injury was 43.6％ (24/55) and 18.2％ (10/55),which was higher than those [16.4％(9/55) and 0.0％ (0/55)] of patients whose glucose level ＞1.7 mmol/L(x2 =9.74 and 11.00,P＜0.01 respectively).Blood glucose ≤ 1.2 mmol/L had high specificity (100％) and sensitivity (81％) for predicting severe brain injury.When blood glucose ≤1.2 mmol/L,the incidence of severe brain injury was higher than that of the patients whose glucose level was higher than 1.2 mmol/L [34.5％ (10/29) vs 0.0％ (0/81),x2 =30.72,P＜0.01].Duration of hypoglycemia ≥12 h had specificity (100％) and sensitivity (36 ％) for predicting brain injury.When duration of hypoglycemia ＜12 h,the incidence of brain injury was lower than that of the patients whose duration of hypoglycemia≥12 h [21.4％ (21/98) vs 6/6,x2 =27.69,P＜0.01].Multivariate Logistic regression showed that fetal distress (OR=4.69,95％CI:1.47-14.97,P=0.009),glucose level≤1.2 mmol/L (OR =5.16,95％CI:1.56-17.03,P=0.007),duration of hypoglycemia≥12 h (OR=8 885 220 297.12,95％CI:0.00-∞,P =0.000) and maternal hyperglycemia (OR =3.34,95％CI:1.01-11.02,P=0.048) were independent risk factors for neonatal brain injury.Conclusions Low blood glucose level and prolonged hypoglycemia might induce injury of neurol system.Fetal distress and maternal hyperglycemia might increase the incidence of brain injury in newborns with hypoglycemia.

Objective To study the changes of neuron-specific-enolase (NSE), S100B protein and neuropeptide Y (NPY) levels in serum and cerebrospinal fluid of children with viral encephalitis and their clinical significance. Methods The NSE, S100B protein and NPY levels in the serum and cerebrospinal fluid of 50 children with viral encephalitiswere were measured, and another 20 children without central nervous system infection were selected as controls. Results The NSE, S100B protein and NPY levels in the serum and cerebrospinal fluid of children with viral encephalitis[serum: (18.90 ± 5. 50)μg/L, (0. 57 ±0. 26) μg/L, (267. 3 ± 54. 7 ) μg/L; GSF: ( 10. 45 ± 4. 40) μg/L, (0. 93 ± 0. 53 ) μg/L, (347.2 ± 60. 6) μg/L] were higher than those in control group [serum: ( 10. 35 ± 2. 49 ) μg/L, ( 10 ± 0. 06 ) μg/L, ( 67. 8 ±22.5)μg/L;GSF:(3.96 ± 1.57)μg/L,(0. 29 ±0. 18)μg/L,(102.6 ±38.9) μg/L] ( P <0.01). The levels of serum and CSF NSE S100B protein and NPY in critical patient[serum: (21.93 ±5.39)μg/L,(0.71 ±0. 31)μg/L, (32. 5 ± 62. 8) μg/L;GSF: (13.05 ±4.41)μg/L, (1.23 ± 0. 66) μg/L, (407.3 ±68. 1 ) μg/L] were higher than ordinary patients [serum: ( 15.93 ± 4. 02 ) μg/L, ( 0. 42 ± 0. 14 ) μg/L,(234.7 ±51.2)μ.g/L;GSF:(8.05 ± 1.77) μg/L,(0. 63 ±0.26)μg/L, (320.2 ±59.5) μg/L] ( P <0. 01 ). Conclusion NSE, S100B protein and NPY can be used to evaluate encephalitis condition, brain damage degree and prognosis of viral encephalitis.

Objective To investigate the effect of neonatal hypoxic myocardial injury and bradycardia on cerebral hemodynamics and brain tissue regional oxygen saturation (rSO2),and to provide patho-physiological evidence for treatment of neonatal hypoxic-ischemic encephalopathy (HIE) in acute phase.Methods Ninety nine full-term newborns admitted into Department of Neonatology,Peking University First Hospital from December,2005 to December,2008 were enrolled in this study.There were 18 newborns with both myocardial injury and HIE (group 1),31 newborns with HIE but without myocardial injury (group 2) and 50 cases of neonatal jaundice (control group).From 3 to 7 days after birth,Doppler ultrasound was used to measure systolic velocity (Vs),diastolic velocity (Vd) and resistance index (RI) of the anterior cerebral artery; and brain tissue rSO2 was detected by near infrared spectroscopy.The differences among groups were compared by variance analysis and LSD test.Brain tissue rSO2 before and after treatment of 20 newborns with bradycardia for various causes were detected and the difference was compared by paired t test.Results (1) Vs of group 1,group 2 and the control group was (19.35±5.13),(29.35±4.28) and (32.62±7.47) cm/s respectively; Vd was (6.43±2.98),(11.21±3.16) and (11.50±3.03) cm/s; RI was 0.68±0.10,0.62±0.03 and 0.64±0.06; brain tissue rSO2 was (52.4± 2.8)％,(54.6±3.1)％ and (62.1±1.9)％.There were significant differences among the three group(F=29.999,19.393,5.283 and 137.952,P＜0.01).Vs,Vd and rSO2 of group 1 were lower than that of group 2 and the control group (P＜0.05).RI of group 1 was higher than that of group 2 and the control group (P＜0.05).Vs and rSO2 of group 2 were lower than that of control group,but there were no differences between the two groups in Vd and RI.(2) The brain tissue rSO2 of newborns with bradycardia after treatment was higher than that before treatment [(58.7±4.6)％ vs (50.9±3.2)％,t=6.239,P＜0.01].Conclusions The disturbance of cerebral hemodynamics and cerebral oxygenation in HIE newborns are aggravated by hypoxic myocardial injury.Stable heart rate might be very important to early treatment for HIE.

Objective To determine the prognosis and risk factors of neonatal cerebral infarction.Methods From January 2002 to December 2010,44 newborn infants were diagnosed with cerebral infarction by imaging examinations at Peking University First Hospital.The neurodevelopmental outcomes of these newborn infants were followed up and evaluated by clinical manifestations,Gesell development scale,cranial imaging,electroencephalogram and auditory evoked potential.Factors related to prognosis were analyzed with single and multi-factor Logistic regression analysis.Results Thirty-eight (86％) cases were followed up,and of these cases,five children died and the results of three were inconclusive due to small age (less than 6 months old).Among the remaining 30 children,neurodevelopmental outcome was normal in 15 cases and abnormal in the remaining 15 cases,thus,the incidence of sequelae was 50％ (15/30) and the mortality rate was 13％ (5/38).Of the 15 abnormal cases,all had cerebral palsy and movement retardation,eight cases had cognitive impairment,eight cases had epilepsy and five had visual impairment.The incidence of large cerebral infarction (more than one lobe) was 14/15,worse cranial imaging outcome (one month after treatment,cerebral infarction lesion still present or had expanded)was 13/15,and severe complications was 8/15 in the newborns with sequelae,which were higher than in those without sequelae (4/15,5/15 and 1/15,respectively) (x2=13.889,8.889 and 7.778,all P＜0.05).Logistic regression analysis showed that large cerebral infarction was a risk factor for sequelae (OR=38.500,95％C1:3.749-395.407,P=0.002),however,worse cranial imaging outcome (OR=8.563,95％CI:0.909-80.683,P=0.061) and severe complications (OR=18.024,95％CI:0.516-630.163,P=0.111) were not risk factors for sequelae.Cerebral infarction with middle cerebral artery injury had a high risk of movement retardation (OR=6.000,95％CI:1.172-3.725,P=0.025),and those with a large cerebral infarction were more likely to have epilepsy (x2=7.273,P=0.010).The incidence of large cerebral infarction in the newborn infants with cognitive impairment was 8/8,which was much higher than in those without cognitive impairment (46％,10/22),thus,infarct area may be related to cognitive ability (x2=7.273,P=0.010).Conclusions Neonatal cerebral infarction might result in many types of sequelae,with motor impairment being the most common form.A large cerebral infarction is more likely to result in abnormal neurodevelopmental outcome.

ObjectiveTo analyze the characteristics of neonatal hyperammonemia and citrullinemia caused by argininosuccinate lyase (ASL) gene mutations, and to have a better understanding of this disease. MethodsA neonatal patient with the onset of hyperammonemia and citrullinemia admitted to the Department of Pediatrics of Peking University First Hospital on April 2, 2014, was retrospectively studied. Peripheral blood leukocyte DNA of the patient and his parents was collected to detectASS1,ASL andSLC25A13 gene mutations. The literature related to neonatal hyperammonemia, citrullinemia and argininosuccinic aciduria was reviewed. ResultsThe baby in this case appeared lethargic, had weaker crying and food refusal since three days after birth, and analysis of blood amino acid found a marked increase in blood ammonia (1 332μmol/L) and a significant rise in citrulline (759.12μmol/L). Sanger sequencing detection revealed compound heterozygous mutations in theASL gene (c.434 A>G, c.857A>C) and this c.857A>C mutation was the first reported case in China. This case of hyperammonemia and citrullinemia was confirmed as argininosuccinic aciduria caused by ASL gene mutations. A protein-limited diet and the treatment of arginine and L-carnitine were given. His blood ammonia decreased to normal level and there was a significant improvement in physical and intellectual progress at five months old. Unfortunately, he had an intestinal infection when he was over five months old and the blood ammonia level tested in the local hospital was 480μmol/L. Gradually there was a disturbance of consciousness, then coma, and he finally died after active rescue in the local hospital.ConclusionsHyperammonemia and citrullinemia in neonates are likely to be argininosuccinic aciduria and a gene mutation test may be helpful for diagnosis.

Objective To study the clinical features,diagnosis and treatment of neonatal very early onset inflammatory bowel disease(VEO-IBD) to improve the diagnosis and treatment of the disease.Method From Jan 2013 to Dec 2015,five infants with VEO-IBD admitted to Peking University First Hospital were reviewed and analyzed.Their clinical data included general condition,clinical symptoms,laboratory tests,autoimmune antibodies (ANCA,dsDNA,ANA and ENA),colonoscopy,pathological results and therapeutic response.Interleukin-10 receptor A (IL-10RA) gene was examined in all patients.All the patients were followed up for more than 1 year.Result Three of the five patients had a family history.Persistent diarrhea was the most common presenting symptom.One of them received surgery because of intestinal necrosis and developed typical symptoms of IBD half a year later.Bloody stool or positive fecal occult blood test were found in all infants.Fever,anemia,oral ulcer,perianal lesions and malnutrition were common concomitant symptoms.Most of the patients had elevated WBC,CRP and ESR,and 4 of them had positive autoimmune antibodies.Colonoscopy showed multiple ulcers affecting the colon.Intestinal biopsies revealed acute and chronic inflammation.4 of patients were found to have cryptitis and crypt abscesses.Gene sequencing revealed IL-10RAgene mutation in all five patients,including 1 case with homozygous mutation and 4 heterozygous mutations.4 patients received steroid and mesalazine therapy and only 1 patient's symptoms were controlled.However,the colonoscopy result was still abnormal in this patient.4 patients had poor response to further infliximab and (or) thalidomide therapy.1 of them received surgery because of intestinal obstruction at 2-year-old.Conclusion Neonatal VEO-IBD was associated with IL-10RA gene mutation.The patients had severe symptoms and poor response to conventional medications.The effects of biological agents and thalidomide were still not sure.

Objective To investigate the correlation between neonatal infectious disease and brain injury.MethodsClinical data of 1266 newborns with infectious diseases were collected from Peking University First Hospital from November 2005 to August 2010.The occurrence of brain injury was summarized.Related factors of brain injury caused by infection and the risk factors for severe brain injury were analyzed by Logistic regression model. Results Among the newborns with neonatal infectious diseases, the incidence of brain injury was 8.6％(108/1266), including 101 (8.0％)mild cases and seven (0.6％) severe cases. The incidence of brain injury for the newborns with severe infectious diseases was higher than those with mild infectious diseases [38.7％(29/75) vs 6.7％(79/1191),x2=92.787,P=0.000].The incidence of brain injury for the newborns withobviousinflammatoryreactionwassignificantlyhigherthanthosewithout [(13.0％(26/200) vs 7.5％ (77/1025),x2=6.544,P=0.011].Severe infection was independent risk factor for severe brain injury by Logistic regression model analysis (OR =15.750,95％ CI:1.756-141.281,P=0.014).ConclusionsIniectious diseases could cause injury on central nervous system,especially when there are severe infections or inflammatory reactions. The severer the infection,the severer the brain injury,especially when complicated by some factors such as asphyxia and hypoglycemia.

Objective To investigate the risk factors of cerebral infarction in newborns and to provide a theoretic basis for prevention.Methods From January 2002 to December 2010,8840 newborns were admitted into the Neonatology Department of Peking University First Hospital,among which 44 patients were diagnosed as cerebral infarction by review of brain imaging and medical records.These patients were taken as study group,and 175 patients were randomly selected as the control group matched by birthday and gestational age.Risk factors of neonatal cerebral infarction were analyzed by univariate analysis and binary Logistic regression.Results Of 27 352 infants born in Peking University First Hospital,21 infants were diagnosed as neonatal cerebral tnfarction,giving the prevalence of neonatal cerebral infarction of 7 per 10 000 live births (21/27 352).Of the 8840patients in Department of Neonatology,neonatal cerebral infarction accounts for 5.0‰ (44/8840).81.8％ (36/44) of the affected babies were delivered at term.The incidence of hypoxia and polycythemia in study group were 50.0％ (22/44) and 11.4％ (5/44),higher than those in control group [27.4％(48/175) and 2.9％(5/175)],differences were statistical significant (x2 =8.237,OR=2.646,95％CI:1.343-5.211,P=0.004; x2 =5.838,OR=4.359,95％CI:1.203-15.796,P=0.030).Logistic regression showed that hypertensive disorder complicating pregnancy (OR=3.388,95％CI:1.174-9.778,P=0.024),polycythemia (OR=4.319,95％CI:1.136-16.427,P=0.032)and hypoxia (OR =2.860,95％ CI:1.415-5.782,P =0.003) were risk factors for neonatal infarction.Further analysis suggested that the severity of hypoxia (x2 =- 3.470,P =0.001 ) and hypertensive disorder complicating pregnancy (x2=-2.074,P=0.038) had positive correlation with neonatal cerebral infarction.Conclusions Hypertensive disorder complicating pregnancy,polycythemia and hypoxia were risk factors of cerebral infarction,especially when preeclampsia and severe hypoxia occurred.

Objective To explore risk factors of cerebral infarction in newborns by systematic reviews.Methods Case-control studies and case reports on risk factors of cerebral infarction in newborns from January 1997 to December 2011 were collected from database of CNKI,CQVIP,Wanfang Database,PubMed,OVID,Springer,Medline,Science Direct On Site,Besco and MD Consult.Meta analysis was performed on case-control studies with fixed or random effect model by Review Manager 5.0.Constitution ratio of risk factors of cerebral infarction in newborns in case reports was investigated.Results Two hundred and sixty-nine articles were found and among which,36 articles in English were selected for this study.Three case-control studies were found and adopted for meta analysis.Cumulative number of patients and control cases were 80 and 228,respectively.The pooled OR and 95 ％CI of selected factors were as follows:decreased fetal movement [7.10 (2.92-17.24)],abnormal fetal heart rate [4.45 (2.54-7.80)],vacuum delivery [2.99 (1.23-7.25)],resuscitation at birth [(3.14 (1.17-8.46)],premature rupture of membranes [2.40 (0.62-9.29)],cesarean section [2.64 (1.44-4.82)],preeclampsia [3.05 (1.44-6.43)],history of infertility [1.25 (0.18-8.67)],primiparous [1.79 (0.51-6.36)],oxytocin used [2.05 (0.99-4.25)],fetal growth restriction [0.99 (0.47-2.11)],meconium stained amniotic fluid [2.08 (0.94-4.58)],adverse pregnancy history [0.85 (0.43-1.68)] and breech presentation [0.38 (0.10-1.46)].Meta analysis showed that decreased fetal movement,abnormal fetal heart rate,vacuum extraction,resuscitation at birth,cesarean section and preeclampsia were risk factors of neonatal cerebral infarction.Decreased fetal movement,abnormal fetal heart rate and resuscitation at birth suggested that newborns suffered from perinatal hypoxia,vacuum extraction,cesarean section suggested abnormal delivery.It suggested that perinatal hypoxia and abnormal delivery were high risk factors of neonatal cerebral infarction.Among those factors,proportion of abnormal labor,fetal distress and hypercoagulabe state was 31.70％,21.13％ and 20.19％ respectively.Conclusions Abnormal birth,hypoxia,preeclampsia and hypercoagulation state might relate to neonatal cerebral infarction.