Objective:To investigate the differences in electrophysiological brain development of neonates in Tibet and Beijing.Methods:This prospective cohort study included neonates with gestational ages of 28 to 40 weeks and 6 days, without asphyxia, hypoxia, or brain injury, who were born between January 2022 and June 2024 at the Tibet Autonomous Region People's Hospital and Peking University First Hospital. The first electroencephalographic (EEG) monitoring was completed within 48 hours to 7 days after birth, which included a 4-channel amplitude-integrated EEG (aEEG) and a 12-channel continuous EEG (cEEG). Two electrophysiology experts scored the EEG results according to a rating scale, and the intraclass correlation coefficient (ICC) was used to explore the consistency between different evaluators. Preterm infants with gestational ages of 32 to 36 weeks and 6 days and post-menstrual age (PMA) less than full-term at the first EEG monitoring were re-examined with aEEG and cEEG at PMA of 37 to 40 weeks and 6 days. Infants were grouped based on PMA at the first EEG monitoring. Spearman rank correlation was used to analyze the correlations between total aEEG+cEEG scores, individual aEEG and cEEG scores, and PMA, gestational age, birth weight, and head circumference at the first EEG monitoring. Mann-Whitney U test, Kruskal-Wallis H test, and Bonferroni correction were used to compare the differences in total aEEG+cEEG scores, individual aEEG and cEEG scores between Tibet and Beijing, among adjacent PMA groups, and for premature infants at full-term PMA. Results:(1) A total of 341 neonates were included in this study, including 154 cases from Tibet (nine cases in the PMA of 28-29 weeks and 6 days group, 13 cases in the PMA of 30-31 weeks and 6 days group, 28 cases in the PMA of 32-33 weeks and 6 days group, 38 cases in the PMA of 34-36 weeks and 6 days group, and 66 cases in the PMA of 37-40 weeks and 6 days group) and 187 cases from Beijing (10 cases in the PMA of 28-29 weeks and 6 days group, 10 cases in the PMA of 30-31 weeks and 6 days group, 16 cases in the PMA of 32-33 weeks and 6 days group, 91 cases in the PMA of 34-36 weeks and 6 days group, and 60 cases in the PMA of 37-40 weeks and 6 days group). (2) Inter-rater consistency:the consistency of PMA inferred based on the total aEEC+CEEC score and actual PMA was high in two raters ( ICCrater one=0.96, ICCrater two=0.94, both P<0.01). (3) The correlation between total aEEG+cEEG score and PMA ( r=0.80) was stronger than that between the aEEG alone or cEEG scores and PMA ( r were 0.79 and 0.66, respectively). The total aEEG+cEEG score also correlated with gestational age at birth ( r=0.74), birth weight ( r=0.69), and head circumference at first EEG monitoring ( r=0.69) (all P<0.01). (4) Regardless of whether in Tibet or Beijing, the total aEEG+cEEG score increased sequentially in the PMA of 30- 31 weeks and 6 days, 32-33 weeks and 6 days, 34-36 weeks and 6 days, and 37-40 weeks and 6 days groups; the cEEG score increased sequentially in the PMA of 32-33 weeks and 6 days group, 34-36 weeks and 6 days group, and 37-40 weeks and 6 days groups; the aEEG score in the PMA 32- 33 weeks and 6 days group was higher than that in the 30-31 weeks and 6 days group, and the score in the PMA 37-40 weeks and 6 days group was higher than that in the 34-36 weeks and 6 days group (Bonferroni correction, all P<0.05). (5) At PMA of 34-36 weeks and 6 days, the total aEEG+cEEG score [25 points (22-26 points) vs. 26 points (24-28 points), Z=－2.62, P=0.009] and cEEG score [12 points (12-14 points) vs. 15 points (13-16 points), Z=－4.77, P<0.001] of newborns in Tibet were lower than those in Beijing, while the aEEG score was higher than those in Beijing [12 points (10-13 points) vs. 11 points (10-12 points), Z=2.17, P=0.030]; at PMA of 37-40 weeks and 6 days, the cEEG score of newborns in Tibet was lower than those in Beijing [16 points (15-17 points) vs. 17 points (15-18 points), Z=－2.27, P=0.023]. (6) The total aEEG+cEEG score of preterm infants born at 32 to 33 weeks and 6 days in Tibet was lower at PMA full-term compared to those in Beijing [27 points (26-28 points) vs. 29 points (28 -30 points), Z=－2.94], and also lower compared to the total aEEG+cEEG score of full-term gestational age newborns in Tibet during their first EEG monitoring [29 points (27-30 points)] (both P<0.05). Conclusions:In the high-altitude hypobaric hypoxic environment, the electroencephalographic development of newborns, especially premature infants, maybe lag behind of plain areas. The combined use of aEEG+cEEG may provide a better evaluation of neonatal brain development than using cEEG or aEEG alone.

Objective:To investigate the differences in electrophysiological brain development of neonates in Tibet and Beijing.Methods:This prospective cohort study included neonates with gestational ages of 28 to 40 weeks and 6 days, without asphyxia, hypoxia, or brain injury, who were born between January 2022 and June 2024 at the Tibet Autonomous Region People's Hospital and Peking University First Hospital. The first electroencephalographic (EEG) monitoring was completed within 48 hours to 7 days after birth, which included a 4-channel amplitude-integrated EEG (aEEG) and a 12-channel continuous EEG (cEEG). Two electrophysiology experts scored the EEG results according to a rating scale, and the intraclass correlation coefficient (ICC) was used to explore the consistency between different evaluators. Preterm infants with gestational ages of 32 to 36 weeks and 6 days and post-menstrual age (PMA) less than full-term at the first EEG monitoring were re-examined with aEEG and cEEG at PMA of 37 to 40 weeks and 6 days. Infants were grouped based on PMA at the first EEG monitoring. Spearman rank correlation was used to analyze the correlations between total aEEG+cEEG scores, individual aEEG and cEEG scores, and PMA, gestational age, birth weight, and head circumference at the first EEG monitoring. Mann-Whitney U test, Kruskal-Wallis H test, and Bonferroni correction were used to compare the differences in total aEEG+cEEG scores, individual aEEG and cEEG scores between Tibet and Beijing, among adjacent PMA groups, and for premature infants at full-term PMA. Results:(1) A total of 341 neonates were included in this study, including 154 cases from Tibet (nine cases in the PMA of 28-29 weeks and 6 days group, 13 cases in the PMA of 30-31 weeks and 6 days group, 28 cases in the PMA of 32-33 weeks and 6 days group, 38 cases in the PMA of 34-36 weeks and 6 days group, and 66 cases in the PMA of 37-40 weeks and 6 days group) and 187 cases from Beijing (10 cases in the PMA of 28-29 weeks and 6 days group, 10 cases in the PMA of 30-31 weeks and 6 days group, 16 cases in the PMA of 32-33 weeks and 6 days group, 91 cases in the PMA of 34-36 weeks and 6 days group, and 60 cases in the PMA of 37-40 weeks and 6 days group). (2) Inter-rater consistency:the consistency of PMA inferred based on the total aEEC+CEEC score and actual PMA was high in two raters ( ICCrater one=0.96, ICCrater two=0.94, both P<0.01). (3) The correlation between total aEEG+cEEG score and PMA ( r=0.80) was stronger than that between the aEEG alone or cEEG scores and PMA ( r were 0.79 and 0.66, respectively). The total aEEG+cEEG score also correlated with gestational age at birth ( r=0.74), birth weight ( r=0.69), and head circumference at first EEG monitoring ( r=0.69) (all P<0.01). (4) Regardless of whether in Tibet or Beijing, the total aEEG+cEEG score increased sequentially in the PMA of 30- 31 weeks and 6 days, 32-33 weeks and 6 days, 34-36 weeks and 6 days, and 37-40 weeks and 6 days groups; the cEEG score increased sequentially in the PMA of 32-33 weeks and 6 days group, 34-36 weeks and 6 days group, and 37-40 weeks and 6 days groups; the aEEG score in the PMA 32- 33 weeks and 6 days group was higher than that in the 30-31 weeks and 6 days group, and the score in the PMA 37-40 weeks and 6 days group was higher than that in the 34-36 weeks and 6 days group (Bonferroni correction, all P<0.05). (5) At PMA of 34-36 weeks and 6 days, the total aEEG+cEEG score [25 points (22-26 points) vs. 26 points (24-28 points), Z=－2.62, P=0.009] and cEEG score [12 points (12-14 points) vs. 15 points (13-16 points), Z=－4.77, P<0.001] of newborns in Tibet were lower than those in Beijing, while the aEEG score was higher than those in Beijing [12 points (10-13 points) vs. 11 points (10-12 points), Z=2.17, P=0.030]; at PMA of 37-40 weeks and 6 days, the cEEG score of newborns in Tibet was lower than those in Beijing [16 points (15-17 points) vs. 17 points (15-18 points), Z=－2.27, P=0.023]. (6) The total aEEG+cEEG score of preterm infants born at 32 to 33 weeks and 6 days in Tibet was lower at PMA full-term compared to those in Beijing [27 points (26-28 points) vs. 29 points (28 -30 points), Z=－2.94], and also lower compared to the total aEEG+cEEG score of full-term gestational age newborns in Tibet during their first EEG monitoring [29 points (27-30 points)] (both P<0.05). Conclusions:In the high-altitude hypobaric hypoxic environment, the electroencephalographic development of newborns, especially premature infants, maybe lag behind of plain areas. The combined use of aEEG+cEEG may provide a better evaluation of neonatal brain development than using cEEG or aEEG alone.

Cerebellar hemorrhage（CBH）in preterm infants is a significant risk factor affecting the neurodevelopmental prognosis of preterm infants，with an increasing incidence over time.Early intervention and treatment by analyzing the risk factors of CBH can improve the survival rate and quality of life for preterm infants.However，there is currently limited research on the risk factors associated with CBH in preterm infants.Cranial ultrasound is the preferred neuroimaging method for diagnosing CBH.With advancements in ultrasound technology，the diagnostic rate of CBH has improved.This article provides a comprehensive review of the risk factors of CBH in preterm infants and the progress on cranial ultrasound diagnosis research，aiming to strengthen the diagnosis，treatment，and follow-up care of cerebellar hemorrhage in preterm infants.

To improve the therapeutic effect of mild hypothermia, avoid the adverse impact of mild hypothermia on cerebral blood flow, and improve the prognosis of hypoxic-ischemic encephalopathy, it is necessary to further explore the mechanism of cerebral hemodynamic disorder in hypoxic-ischemic encephalopathy under mild hypothermia treatment, the influence of systemic hemodynamic changes on cerebral blood flow, and the use of near-infrared spectroscopy to monitor cerebral blood flow and adjust the dosage of vasoactive drugs for avoiding large fluctuation of cerebral blood flow during mild hypothermia treatment and rewarming.

Objective To explore the clinical features, treatment and follow-up of Cockayne syndrome with renal involvement. Method The clinical data of one child with Cockayne syndrome confirmed by gene detection with renal injury were reviewed, and the clinical features of renal involvement in Cockayne syndrome were summarized. Results A male child aged 3 years and 8 months had clinical manifestations of mental retardation, growth retardation, special face and photosensitive dermatitis, and renal involvement was manifested by nephrotic syndrome. Cranial CT showed symmetrically calcification in bilateral basal ganglia. The targeted next generation sequencing results showed homozygous mutations of c.394_398del and p.Leu132Asnfs in ERCC8 gene (NM_000082) of the child, and the same heterozygous mutation was found in both his parents (non-consanguineous marriage). After the diagnosis of nephrotic syndrome, full dose prednisone was given for experimental treatment. The urine protein decreased but did not disappear, which was considered hormone resistance. After 4 months of combined treatment with cyclosporin, the urine protein turned negative. During 20 months of follow-up, urine protein remained negative and renal function remained stable. The renal involvement in Cockayne syndrome was seldomly reported, and its clinical manifestations are heterogeneous. Condusion Renal involvement in Cockayne syndrome may be manifested with nephrotic syndrome which should be noticed.

Objective To study the clinical characteristics of the newborns with gastroesophageal reflux (GER),and to compare the complications and outcomes of different degrees of reflux retrospectively. Methods Neo-nates diagnosed with GER by using upper gastrointestinal series admitted to neonatal ward of Peking University First Hospital from August 2008 to September 2017 were enrolled for the study. Data of demographic characteristics,radio-graphic imaging findings,treatment methods and efficacy of therapy of patients were collected. Infants enrolled in this study were followed up for 1 year after being discharged from hospital. The lasting time of reflux symptoms with different degrees of reflux were compared. Results A total of 47 cases of GER were enrolled,of whom 23 cases were male,and 24 cases were female. There were 42 term infants and 5 preterm infants. Their gestational age ranged from 34 to 41 weeks[(38. 9 ± 1. 6)weeks],and birth weight was from 1990 g to 4430 g[(3157. 3 ± 574. 0)g]. The median onset age was 2 days,ranged from 1 to 21 days. The clinical manifestations were recurrent vomiting (40 / 47 cases,85. 1％) and paroxysmal cyanosis (7 / 47 cases,14. 9％). Complications presented as poor weight gain (42 / 47 cases,89. 4％), aspiration pneumonia (24 / 47 cases,51. 1％)and apnea (1 / 47 cases,2. 1％). The findings of upper gastrointestinal imaging assigned the patients into 2 groups,13 cases of mild reflux group and 34 cases of severe reflux group. After po-sitional therapy together with domperidone,44 patients showed improvement of symptoms. After their discharge,the lasting time of reflux symptoms in the mild reflux group was significantly shorter than in the severe group [4 weeks(2 -8 weeks)vs. 8 weeks (2 - 40 weeks)],and the difference was significant(Z = - 2. 336,P < 0. 05). Conclusions Neonates with GER mainly manifest recurrent vomiting,and most of them have a favorable prognosis. The reflux symp-toms last for less time in the mild reflux infants than in the severe patients.

Objective To study the characteristics of gastroesophageal reflux (GER) in term neonates and the association between the reflux behaviors and gastroesophageal reflux events by multichannel intraluminal impedance-pH monitoring retrospectively.Method Full term neonates suspected to have gastroesophageal reflux,admitted to neonatal ward of our Hospital from November 2016 to December 2017 were enrolled for the study.All underwent 24-hour esophageal multichannel intraluminal impedance-pH (24 h MII-pH) monitoring.They were assigned into physiologic GER group and pathologic GER group.Data of demographic characteristics,clinical symptoms,24 h MII-pH results and indecies for evaluating the association between symptoms and reflux events were collected and analyzed.Result A total of 31 cases were enrolled.The median age of starting 24 MII-pH monitoring was 7 days (range from 2 to 28 days).15 cases were diagnosed with pathologic GER (48.4％),and 16 cases were diagnosed with physiologic GER.The symptoms and signs were persistent vomiting,incessant crying,desaturation (oxygen desaturation) and unexplained transient events (including cyanosis or suspected seizure),case number was 12,9,6,2,and 1 respectively.In the pathologic group,the median of total acid reflux 52 (7 to 80),total weakly acidic reflux 58 (19 to 114);In the physiologic group was 36 (3 to 55),35 (6 to 55) respectively.The neonates in pathologic group had more acidic reflux (both before and after feeding),total weak acid reflux and liquid reflux than physiological GER group,which showed statistical significance (P ＜ 0.05).While there was no significant difference in acid reflux time of total,before feeding and after feeding (P ＞0.05).It was proved that the percentage of positive symptom indices of vomiting,postprandial transient events,incessant crying after feeding,and desaturation associated with GER were 100％,100％,66.7％and 33.3％ retrospectively,which indicate that postprandial transient events were associate with GER,and incessant crying,desaturation were partially related to GER.And no association was found between bradycardia and reflux events.Conclusion Pathological GER of term neonates mainly manifest as reflux of weakly acidic and liquid.24 h MII-pH monitoring could detect weakly acidic reflux and weakly alkaline reflux,so it would be the recommended diagnostic tool for neonatal gastroesophageal reflux.Despite vomiting,special attention should be paid to symptoms associated with GER,such as incessant crying,and unexplained transient events et al.

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 study the neurological prognosis of neonates with ventriculomegaly and its influencing factors.Method A retrospective study was conducted among neonates with ventriculomegaly in Peking University First Hospital from January 2013 to December 2015.A series of cranial ultrasonography were performed after birth and the Gesell development scale was conpleted after six months.x2 test and two-independent-sample t test were used for statistical analysis.Result Among 103 cases of ventriculomegaly,95 cases (92.2％) had mildly enlarged lateral ventricles and 8 cases (7.8％) significantly enlarged.83 cases received serial cranial ultrasound examinations after birth.The lateral ventricles of 9 patients (10.8％) bacame wider and 74 (89.2％) not.The Gesell development scales were completed in 65 cases 6 months after birth.Among them,8 patients with widening lateral ventricles got poor prognosis (100％).Among 57 patients without progressively widening lateral ventricles,6 (10.5％) had poor prognosis.The difference was statistically significant (P ＜ 0.001).No correlation was found between the severity of the lateral ventricle widening and the neurological outcome (P =1.000).There were 2 cases with other abnormalities,and 1 case got poor prognosis on follow-up.Conclusion Most neonatal ventriculomegaly patients have mild and isolated lateral ventricle enlargement.Most of them remain stable or gradually return to normal.The patients with progressively widening lateral ventricles are likely to have adverse neurological prognosis.

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.