Postnatally confirmed COL4A1 mutation in a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia / 中华围产医学杂志

We report a fetus with recurrent intraparenchymal hemorrhage and cystic leukomalacia during pregnancy who was postnatally detected with a de novo mutation in the COL4A1 gene by genetic testing of umbilical cord blood. Multiple fresh hemorrhagic foci were detected in the fetal brain parenchyma and cerebellar hemisphere by ultrasound at 25 gestational weeks. Regular re-examination of the nervous system's ultrasound and magnetic resonance imaging (MRI) indicated recurrent multiple intraparenchymal hemorrhages followed by cystic leukomalacia. However, karyotyping and chromosomal microarray analysis of amniotic fluid showed no abnormality. The newborn was born by cesarean section at 37 +3 gestational weeks with an Apgar score of 10 at 1 and 5 min. Repeated apnea occurred after birth. MRI detected new intraparenchymal hemorrhage and cystic leukomalacia on the six-day of life. The infant's limb muscle tone remained low on the 90-day follow-up. The patient was lost to follow up. Whole-exome sequencing of the cord blood identified a de novo heterozygous mutation- c.4738G>A in the COL4A1 gene (NM_001845.4; p.G1580S) neither parent carried. It suggests that the genetic test of the COL4A1 mutation should be considered for fetuses with intracranial hemorrhage in the prenatal diagnosis, especially those with recurrent fetal intraparenchymal hemorrhage followed by cystic leukomalacia. Genetic tests could help analyze the fetal prognosis, and guide the delivery mode.

Prenatal diagnosis and management of fetal/neonatal thyroid dysfunction / 中华围产医学杂志

Thyroid diseases in fetuses and newborns are rare but can be severe in some cases. Early diagnosis and treatment are the keys to improve the prognosis. This review focuses on the diagnosis and treatment strategies of this disease during the fetal and neonatal periods. For fetuses with goiter, the main clinical issue is to differentiate hyperthyroidism or hypothyroidism and offer appropriate management on this basis. Management of maternal, fetal, and neonatal thyroid diseases requires an experienced multidisciplinary team including adult and pediatric endocrinologists, obstetricians, and sonographers.

Outcomes and prognosis of fetal intraventricular hemorrhage / 中华围产医学杂志

Objective:To investigate the neonatal outcomes and prognosis of fetuses who were prenatally diagnosed with intraventricular hemorrhage(IVH) to provide evidence for clinical consultation and management.Methods:Clinical data of fetal IVH cases ( n=89) diagnosed by fetal neurosonogram (NSG) in Peking University First Hospital from January 2012 to April 2020 were retrospectively collected, and neonatal outcomes were analyzed, involving fetuses with different grades of IVH and coexisting abnormalities. These patients were followed up for more than three months after birth. Two child development screening systems, Ages & Stages Questionnaires (Third Edition) (ASQ-3) and Ages & Stages Questionnaires: Social-Emotional (ASQ-SE), were used to assess the development of the patients from several aspects including physical growth, oral communication, motor ability and social emotions. Descriptive statistical analysis was used in this study. Results:(1) A total of 89 fetuses were enrolled and 66.3% (59/89) of them underwent fetal cranial MRI examination after ultrasound diagnosis. Among these 59 cases, 32(54.2%) had the same results with fetal NSG; 20(33.9%) with the diagnosis of remote ventricular cystic hemorrhage by fetal NSG, but misdiagnosed by MRI, were all confirmed by neonatal craniocerebral ultrasound; 7(11.9%) were lost to follow-up or terminated. In addition to IVH that was consistent with the ultrasound diagnosis, MRI also found three cases of cortical malformation, three cases of subdural hemorrhage and two cases of cerebral parenchymal hemorrhage. (2) Among the 89 cases, 37 (41.6%) underwent neonatal craniocerebral ultrasound examination after birth showing small amount of remote IVH, which was consistent with previous fetal NSG diagnosis. (3) There were 38 cases complicated by lateral ventricular widening (three lost to follow-up, 18 were terminated , one died in uterus, 15 with good and one with poor outcome), 10 cases by severe IVH sequelae (one lost to follow-up and nine were terminated) and 10 by craniocerebral malformation (one lost to follow-up, eight were terminated and one with poor neonatal prognosis). Two cases with extracranial malformation (ureteropelvic junction obstruction) were healthy after birth. (4) There were 29, 30, 16 and 14 cases of gradeⅠ,Ⅱ,Ⅲ andⅣ of fetal IVH, respectively. Among all cases, 12 were lost to follow-up; three died in uterus (all with gradeⅣ IVH); 31 were terminated and 43 were born and followed up. During the follow-up of the 43 cases, two (one grade Ⅰ case with corpus callosum dysplasia and one grade Ⅲ case with fetal cytomegalovirus infection) had poor prognosis, while the other 41 (one gradeⅢ, 17 gradeⅡ and 23 gradeⅠcases) showed no severe abnormalities.Conclusions:Fetal NSG is the first choice in screening fetal IVH and MRI can be a valuable aid. The neonatal prognosis may be associated with the grade of hemorrhage and coexisting abnormalities. Fetuses with isolated grade Ⅰ or Ⅱ IVH usually have a relatively good prognosis.

Hemodynamic changes and the significance of near-infrared spectroscopy monitoring in neonatal hypoxic-ischemic encephalopathy during mild hypothermia treatment / 中华围产医学杂志

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.

Clinical characteristics and treatment of infantile lactose intolerance and evaluation of the diagnostic value of fecal pH / 中华实用儿科临床杂志

Objective@#To investigate the clinical characteristics, diagnostic approach, and treatment of infantile lactose intolerance, and to evaluate the diagnostic value of fecal pH.@*Methods@#The feces and clinical data of all infants(less than 1 year old) diagnosed with simple diarrhea but without signs of infection were collected, who were treated at 4 Grade Ⅲ-Class-A hospitals within the period of June 2012 to June 2015 in Beijing were collected.Lactose intolerance was diagnosed based on urine galactose level, lactose tolerance test, and fecal pH.The clinical characteristics, therapeutic effects and detection methods of lactose tolerance group and intolerance group were analyzed.Then the diagnostic value of fecal pH was evaluated.@*Results@#A total of 217 infants were enrolled in the study, consisting of 113 boys and 104 girls.Their age ranged from 3 to 330 days, 174 infants (80.2%) were less than 6 months old.Among them, 156 infants were diagnosed with lactose intolerance (71.9%), their median age 90.0 days (3-330 days), while the median age of the lactose tolerant group was 51.5 days (3-300 days). The incidence of lactose intolerance in infants less than 6 months old was 70.6%, and 76.7% in those older than 6 months.Clinical characteristics showed that more infants in the lactose intolerant group were breastfed compared with the lactose tolerant group [73/156 cases(46.8%) vs.16/61 cases(26.2%), χ2=7.666, P<0.05], the occurrence of loose foamy feces was higher in the lactose intolerant group [67/156 cases(42.9%) vs.15/61 cases (24.6%), χ2=6.287, P<0.05], the median duration of diarrhea in the lactose intolerant group was 30 days (1-210 days), and that in the lactose tolerant group was 30 days (1-300 days). The incidence of diarrhea more frequent than 10 times per day in the lactose intolerant group was 9.0% (14/156 cases), while that in the lactose tolerant group was 6.6% (4/61 cases). The rate of infection in the lactose intolerant group was similar to that in the lactose tolerant group [32/165 cases((20.5%) vs.17/61 cases(27.9%)]. The median time of recovery by feeding lactose-free formula milk was 2 days (1-60 days), recovery by feeding lactase lasted a median of 4 days (2-25 days), while recovery by using pro-biotics and dioctahedral smectite lasted a median of 2 days (1-5 days). The characteristics of fecal pH showed that mean pH value of fecal and the incidence of fecal pH<5.5 had no statistical significance between the lactose intolerant and tolerant group, between infants ≤6 months and infants>6 months, between the breastfeeding group and formula-feeding group, or between those with infection and those without infection (all P>0.05).@*Conclusions@#Infants with lactose intolerance often manifest foamy feces and tend to be breastfed.Lactose-free treatment efficacy was better than that with lactase.Clinical symptoms when combined with urine galactose level and lactose tolerance test can help diagnosis.However, the decrease of fecal pH proves to be unhelpful in aiding diagnosis.

Study progress of screening and prognosis of celiac disease in children / 中华实用儿科临床杂志

Celiac disease is immune-mediated systemic disorder that occurs in genetically predisposed individuals after ingestion of gluten and related prolamines.Patients may suffer from intestinal symptoms such as chronic diarrhea, accompanied by multiple extraintestinal manifestations.Celiac disease is a screenable and treatable disease.If celiac disease in children are delayed, some complications may significantly affect children′s growth and development.The prognosis of the children can be improved if the diagnosis is made in time and the gluten-free diet is given strictly.Now, the relevant literature on screening and prognosis of children′s celiac disease in recent years was summarized.

Study progress of screening and prognosis of celiac disease in children / 中华实用儿科临床杂志

Celiac disease is immune-mediated systemic disorder that occurs in genetically predisposed individuals after ingestion of gluten and related prolamines.Patients may suffer from intestinal symptoms such as chronic diarrhea,accompanied by multiple extraintestinal manifestations.Celiac disease is a screenable and treatable disease.If celiac disease in children are delayed,some complications may significantly affect children's growth and development.The prognosis of the children can be improved if the diagnosis is made in time and the gluten-free diet is given strictly.Now,the relevant literature on screening and prognosis of children's celiac disease in recent years was summarized.

Clinical characteristics and follow-up study of 47 neonates with gastroesophageal reflux / 中华实用儿科临床杂志

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.

Gastroesophageal reflux: twenty-four-hour esophageal multichannel intraluminal impedance-pH monitoring in full term newborns / 中国新生儿科杂志

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.

A study on the interleukin-10 receptor gene mutations and neonatal very early onset inflammatory bowel disease in 5 infants / 中国新生儿科杂志

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.

A preliminary study on the postnatal neurodevelopment of fetus with ventriculomegaly / 中国新生儿科杂志

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.

Neonatal hyperammonemia and citrullinemia caused by argininosuccinate lyase gene mutations / 中华围产医学杂志

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.

Caspase-12 expression in hyperoxia-induced corpus callosum damage in newborn mice / 中国新生儿科杂志

Objective To study the relationship between Caspase-12 expression and the hyperoxia-induced corpus callosum damage. Methods A total of 12 groups of C57 / BL6 mice were randomly assigned into hyperoxia group (80% O2 ) and control group (21% O2 ) at day 6 after birth (P6). The pups were sacrificed after 24 h and 48 h of hyperoxia exposure and at P10, P12, P15 and P30. Immunohistochemical ( IHC) method was used to detect the expression of myelin basic protein (MBP) in corpus callosum. Real-time PCR, Western Blot and IHC were used to detect the expression of mRNA and protein of Caspase-12 in corpus callosum. The corpus callosum apoptosis was measured using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling ( TUNEL ) method. Results The expression of MBP in hyperoxia group were significantly lower than the control group at P10 and P12 (P = 0. 004 and 0. 016); however, no significant differences existed between the two groups at P15 and P30 (P > 0. 05). The expression of Caspase-12 mRNA after 24 h and 48 h hyperoxia exposure were significantly higher than the control group [24 h: (1. 549 ± 0. 098) vs. (1. 080 ± 0. 101); 48 h:(1. 333 ± 0. 076) vs. (1. 022 ± 0. 089); P < 0. 05]. The expression of cleaved Caspase-12 protein after 24 h and 48 h hyperoxia exposure were also significantly higher than the control group [24 h: (1. 582 ± 0. 010) vs. (0. 994 ± 0. 078); 48 h: (1. 370 ± 0. 095) vs. (0. 978 ± 0. 069); P < 0. 05] . The Caspase-12 positive cell were significantly increased after 24 h and 48 h hyperoxia exposure comparing with the control group. The apoptosis index in hyperoxia group was significantly higher than the control group at P10 and P12 [P10: (18. 742 ± 2. 503) vs. (4. 587 ± 2. 353); P12 (36. 184 ± 3. 655) vs. (5. 351 ± 2. 678); P < 0. 05]. Conclusions Hyperoxia exposure induces corpus callosum damage in newborn mice. Over-expressed Caspase-12 may induce corpus callosum cell apoptosis excessively.

Inflammatory bowel disease in neonates: report of three cases and review of the literature / 中华围产医学杂志

Objective To analyze and summarize clinical manifestations of inflammatory bowel disease (IBD) in neonates.Methods From 2007 to 2013,three neonates were diagnosed with IBD in Peking University First Hospital.Data on these three cases with neonatal IBD were analyzed.The coding region of the interleukin 10 receptor A (IL10RA) gene was detected using direct Sanger sequencing in one of the patients.The literature was reviewed.Results The three newborns were 4-12 days old,all had symptoms of diarrhca,mucosanguineous feces and oral ulcers,accompanied by hypoalbuminemia and a family history.Two of these infants had perianal lesions,and one had liver damage and scizures.All three patients had elevated white blood cells and were anti-proteinase 3 positive.Two had elevated C-reactive protein and erythrocyte sedimentation rate,and one had positive antinuclcar antibodies and double stranded DNA antibodies.Colonoscopy showed multiple ulcers affecting the ileocecum and colon.The infants received treatment including antibiotics,switching formula feeding and 5-aminosalicylic acid.After treatment,one infant was cured,one died although glucocorticoids and azathioprine were used,and the other with a IL10RA gene mutation recovered,this infant had a compound heterozygous mutation with c.301C ＞ T (p.Arg101Trp),c.421G ＞ A (p.Gly141Arg) and whose parents were carriers.The literature review showed that fever and abnorrnal defecation were the main clinical features,and examination of serum antibodies showed a lower positive rate.The patients had a poor response to medications and most required surgery.IL10RA gene mutations were detected in some patients.Conclusions Neonates with diarrhea and a family history may have IBD and should undergo colonoscopy as early as possible.

Characteristics and its risk fastors of amplitude-integrated electroencephalography in the early brain development of preterm infant / 中华围产医学杂志

Objective To study the characteristics and its risk fastors of brain development of the preterm infant early after birth in amplitude-integrated electroencephalography(aEEG). Methods The 153 preterm infants who had seen a doctor in Peking University First Hospital from April 2009 to August 2013 accepted the aEEG check at term of corrected gestational age ( ≥ 38 weeks but < 42 weeks of corrected gestational age). The risk factors of brain development, such as gestational age ( < 30, 30 ≤ - ≤ 33+6 and 34≤-≤36+6 weeks), clinical informations [relatively stable group including 104 cases without any serious complications or brain injury, the group only suffering from a serious brain injury (19 cases), and the group only suffering from severe systemic disease (30 cases)] and nutrition (good or malnutrition), were analyzed. Also the relationship between the aEEG and the cranial ultrasound detected at the same time and the Gesell Developmental Scale at six months of corrected gestational age. Theχ2 test, two independent samples t-test and Logistic regression analysis were used for statistical analysis. Results The aEEG of 52%(79/153) cases reached the level of normal full-term newborn at term of corrected gestational age, only 48% (74/153) were abnormal. The abnormal rate of aEEG results in relatively stable preterm infants decreased from 3/6 (<30 weeks) to 35%(13/37) at 34 ≤ - ≤ 36+6 weeks, but the difference was not statistically significant (χ2=1.998, P=0.353). The abnormal rate of aEEG results in the group suffering from a serious brain injury was higher than the relatively stable preterm infants [14/19 vs 44%(46/104) ,χ2=5.578, P=0.024]. In relatively stable preterm infants, there was no difference of the abnormal rate of the aEEG results between intrauterine malnutrition group and good nutrition group [46%(19/41) vs 43%(27/63),χ2=0.122, P=0.727]. Neither was between extrauterine malnutrition group and good nutrition group [52%(13/25) vs 42%(33/79),χ2=0.805, P=0.369]. Serious brain injury was independent risk factor of abnormal aEEG (OR=3.453, 95%CI: 1.177-10.132, P=0.024). The coincidence rate of aEEG and the cranial ultrasound examination or the scores of Gesell Developmental Scale was 57%(56/98) and 50%(10/20), respectively. Conclusions The brain catch-up development may appears early after birth in preterm infants, which are impaired by lower gestational age and the severe brain injury. It is more effective of aEEG for evaluating the brain development of preterm infants when combines with other methods.

Analysis of clinical features of 6 patients with infantile type glycogen storage disease type II / 中华儿科杂志

<p><b>OBJECTIVE</b>To summarize clinical features and diagnosis of Chinese infantile patients with glycogen storage disease type II (GSD II).</p><p><b>METHOD</b>Six infant patients with GSD II diagnosed from January 2012 to June 2014 in the Department of Pediatrics, Peking University First Hospital were enrolled into this study. Clinical information of the 6 patients, including clinical manifestation, blood biochemistry, chest X-ray, echocardiogram, electrocardiogram, acid alpha-glucosidase (GAA) activity and GAA gene mutation analysis by direct sequencing of polymerase chain reaction (PCR) product were reviewed.</p><p><b>RESULT</b>Of the 6 patients, five were female and one was male, five of whom were classic infantile type while the other one was atypical. The age of onset ranged from birth to 3-month-old. All patients had varying degrees of generalized muscle weakness, hypotonia and development retardation or retrogression. Other common findings were feeding difficulties in two patients, tongue weakness in two patients, respiratory distress in four patients, macroglossia in one patient, and hepatomegaly in two patients. Left ventricular hypertrophy and cardiomegaly were obvious in all the six patients. All six patients were found to have a enlarged heart in physical examination, and three patients who underwent a chest X-ray examination had an enlarged heart shadow. Four patients who had an echocardiography were found to have myocardial hypertrophy. The electrocardiogram in three patients showed short PR intervals and high voltage. The creatine kinase (CK) levels were three to seven times elevated. The mildest elevated CK was 441 IU/L, and the highest CK level was 1 238 U/L. Assay of GAA enzyme activity in whole blood showed significantly reduced activity (1.3 nmol/ (spot·d) to 2 nmol/(spot·d)) in the patients tested. Gene sequencing in 4 patients showed 8 pathogenic mutations, including 6 missense mutations, one nonsense mutation and one frameshift mutation. The missense mutations were c.998C > A (p.Thr333Lys), c.1280T > C (p.Met427Thr), c.1760T > C (p.Leu587Pro), c.1924G > T (p.Val642Phe), c.2012T > A (p.Met671Lys) and c.2105G > A (p.Arg702His). The nonsense mutation was c2662G > T (p.Glu888X), and the frameshift mutation was c2812_2813delTG (p.Cys938fs). The 5 classic infantile patients died at the age of 7 to 22 months. The atypical infantile patient was 2 years and five months old according to our latest follow up.</p><p><b>CONCLUSION</b>Infantile GSD II had similar motor manifestations and cardiac involvements, blood biochemical test, imaging findings, enzyme assays, though there were slight differences. The probability of GSD II should be taken into consideration if an infant has both muscular disease and cardiac involvement.</p>

Prognosis and risk factors of neonatal cerebral infarction / 中华围产医学杂志

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.

Systematic evaluation of risk factors of cerebral infarction in newborns / 中华围产医学杂志

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.

Clinical characteristics and prognostic indicators of neonatal refractory seizures / 中华围产医学杂志

Objective To investigate the etiology,clinical characteristics and prognostic indicators of neonatal refractory seizures.Methods Forty-six newborns admitted to the neonatology ward of Peking University First Hospital from January 1,2000 till July 31,2011 with refractory seizures were chosen as the subject,and another 42 newborns with nonrefractory seizures who were admitted at the same period were chosen as the nonrefractory seizures group.The etiologies,clinical characteristics and prognosis of newborns in the two groups were compared.The newborns with refractory seizures were further divided into two subgroups:one was composed of 11 newborns with normal prognosis,and the other was composed of 35 newborns with unfavorable prognosis.The etiologies and clinical characteristics of seizure in thses two subgroups were also compared.Chi-square or Fisher's exact test was applied to compare the difference between groups; Logistic regression analysis was applied to determine the risk factors of refractory seizures and its prognosis.Results (1) The first three common causes of neonatal refractory seizures were severe perinatal brain damage (8/46,17.4％),encephalodysplasia (7/46,15.2％) and congenital metabolic diseases (3/46,6.5％).Seizure attack every day,severe abnormal electroencephalogram,statural convulsivus and unfavorable prognosis were significantly higher in the refractory seizure group than that in the nonrefractory seizures group [91.3％ (42/46) vs 57.1％ (24/42) ; 55.6％ (25/45) vs 5.4％ (2/37) ;17.4％(8/46) vs 0.0％(0/42) ; 76.1％(35/46) vs 21.4％(9/42),x2 =13.665,23.123,Fisher's exact test and 26.236,respectively,all P＜0.01].Seizure attack everyday (OR=3.811,95％CI:1.019-14.258,P =0.047) and severe abnormal electroencephalogram (OR =16.384,95％ CI:3.421-78.472,P=0.000) were independent risk factors of refractory seizures.(2) Among those newborns with refractory seizures and unfavorable prognosis,the failure rate of phenobarbital administration was 80.0％(28/35),higher than those with normal prognosis (4/11) (Fisher's exact test,P=0.010).Therefore,poor phenobarbital therapeutic efficacy indicated an unfavorable prognosis (OR=12.444,95％CI:2.530-61.217,P=0.002).Conclusions The common causes of neonatal refractory seizures are perinatal brain damage,encephalodysplasia and congenital metabolic diseases.The clinical characteristics of refractory seizure are frequent seizure attacks (more than once a day),severe abnormal electroencephalogram and statural convulsivus,and unfavorable prognosis is common.Poor therapeutic effect of phenobarbital prompts adverse outcome.

Correlation between neonatal infectious diseases and brain injury / 中华围产医学杂志

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.