【Objective】 To investigate the influencing factors behind the follow-up compliance of patients with low/no phenylketonuria (PKU) for special medical use, in order to provide a basis for regulating the follow-up of PKU patients and ensuring the effectiveness of special diet treatment. 【Methods】 A survey was conducted on PKU patients treated in Urumqi Maternal and Child Health Hospital for over 1 year, from January 2010 to December 2020. Interviews and questionnaires were conducted with their caregivers to collect and analyze the current status of PKU patients undergoing special diet treatment, and to identify the influencing factors behind their compliance with follow-up treatment. 【Results】 Patients who had received neonatal disease screening, neonatal gene diagnosis, and maternal Down′s screening during pregnancy had better compliance, with statistically significant differences (χ²=5.753, 10.993, 9.189, P<0.05). PKU children with parents who had a college education or above showed significantly higher adherence to special diet treatment (χ²=8.321, 7.415, P<0.05). PKU children with parents having a fixed occupation also showed higher compliance, with a statistically significant difference (χ²=20.626, 7.895, P<0.05). Patient age, interval of buying special diet, number of blood samples sent and enrollment of normal age, all had a significant impact on the follow-up compliance of PKU patients with special diet (χ²=19.443, 8.090, 69.482, 12.001, P<0.05). 【Conclusions】 PKU is a treatable genetic metabolic disease. Strengthening health education, formulating standardized follow-up plans and procedures, and improving follow-up treatment compliance are crucial in enhancing the treatment and follow-up effectiveness of PKU patients.

OBJECTIVE: To explore the genetic basis for a child with facial dysmorphism and multiple malformations. METHODS: The child, born at 34⁺⁶ weeks' gestation due to premature rupture of amniotic membrane, dichorionic diamniotic twinning and gestational diabetes, was subjected to chromosomal karyotyping analysis and copy number variations sequencing (CNV-seq). RESULTS: The child was found to have facial dysmorphism, hypospadia, cryptorchidism and hypotonia. He was found to have a 46,XY,del(3)(p26) karyotype in addition with a 9.80 Mb deletion (chr3: 60 000-9 860 000) encompassing 33 protein coding genes. CONCLUSION The 3p26.3p25.3 deletion probably underlay the multiple malformations in this child. Continuous follow-up is required to improve his quality of life.
Humans ; Male ; Chromosome Deletion ; DNA Copy Number Variations ; Quality of Life ; Abnormalities, Multiple/genetics* ; Phenotype

We reported the clinical data of a neonate admitted to the Second Affiliated Hospital (Yuying Children's Hospital) of Wenzhou Medical University in November 2021 with autosomal recessive complete signal transducer and activator of transcription 1 ( STAT1) deficiency identified by whole exome sequencing. The baby boy received bacillus of calmette-guerin (BCG) vaccine 2 d after birth and presented with persistent high fever, increased white blood cell count and increased level of C-reactive protein (CRP) on 21 d after birth. Human cytomegalovirus (HCMV) was detected in both blood and bone marrow specimens. The patient improved after comprehensive treatment with antiviral agents, antibiotics and intravenous gammaglobulin. Oral anti-viral drugs were prescribed on discharge. However, the baby was rehospitalized due to a fever at 55 days. HCMV and Mycobacterium tuberculosis complex were detected in blood samples. The infant was transferred to the Children's Hospital of Fudan University due to persistent high fever even after active management and died after treatment withdrawal at 69 d after birth because of worsening infections and multiple organ failure. A homozygous mutation in the STAT1 gene was detected [c.1011_1012del, NM_007315: exon11: c.1011_1012del (p.V339Pfs*18)] and the child was diagnosed as autosomal recessive complete STAT1 deficiency. We concluded that the clinical manifestations of autosomal recessive complete STAT1 deficiency are bacterial infections caused by lethal low-pathogenic mycobacteria and life-threatening virus infections. Whole exome sequencing is of great value for early diagnosis and timely treatment. The prognosis of this disease is very poor, but the condition of the patients might be improved in a short period with early anti-tuberculosis and anti-viral treatment.

Objective:To study the clinical characteristics of purulent meningitis complicated with hydrocephalus in neonates, and to analyze the risk factors of the disease.Methods:Neonates diagnosed with purulent meningitis complicated with hydrocephalus who hospitalized in the department of neonatology of the Second Affiliated Hospital of Wenzhou Medical University from January 2002 to August 2021 were selected as the case group. Neonates with positive pathogen cultures but no hydrocephalus during the same period were assigned by random number table method as the control group. The ratio of the control group and the case group was 2 ∶1. The clinical data such as bacteria distribution, cranial imaging, therapy and prognosis were compared between the two groups. The risk factors for hydrocephalus were predicted. Statistical analysis was conducted using chi-square test and multiple logistic regression analysis.Results:There were 33 cases in the case group and 66 cases in the control group. A total of 27 cases had confirmed pathogen results, of which 20 cases (74.1%) were Gram-negative bacteria and seven cases (25.9%) were Gram-positive bacteria. The time of diagnosis for hydrocephalus were 13.0(5.5, 28.5) days after the onset. Twenty-six cases received non-surgical treatment, while seven cases received surgery. The cure rate of case group was 42.4%(14/33), which was lower than that of control group (72.7%, 48/66), and the difference was statistically significant ( χ2=8.63, P=0.003). Univariate analysis showed that the incidences of protein>3 g/L in cerebrospinal fluid, glucose<2 mmol/L in cerebrospinal fluid, convulsions, central respiratory failure, intracranial hemorrhage and encephalomalacia in the case group were all higher than those in the control group, with statistical significance ( χ2=19.72, 12.04, 19.04, 5.73, 11.85 and 17.48, respectively, all P<0.050). Multivariate logistic regression analysis showed that convulsions (odds ratio ( OR)=4.476, 95% confidence interval ( CI) 1.091 to 18.363, P=0.037), intracranial hemorrhage ( OR=8.031, 95% CI 1.894 to 34.059, P=0.005) and encephalomalacia ( OR=35.189, 95% CI 2.954 to 419.150, P=0.005) were risk factors for neonatal purulent meningitis complicated with hydrocephalus. Conclusions:Gram-negative bacteria are common pathogen of neonatal purulent meningitis complicated with hydrocephalus. Convulsions, intracranial hemorrhage and encephalomalacia are important predictors for neonatal purulent meningitis complicated with hydrocephalus.

Objective:To explore the relationship between endotracheal tube-bacterial biofilm (ETT-BF) in mechanically ventilated neonates and ventilator-associated pneumonia (VAP).Methods:A total of 30 mechanically ventilated neonates whose mechanical ventilation time were ≥48 h in the Department of Neonatology in The Second Affiliated Hospital of Wenzhou Medical University from January 2019 to January 2020 were included.According to the indwelling time of endotracheal tube, all cases were divided into three groups including group A(two to six days), group B(seven to 14 days) and group C (over 14 days). The morphological results of ETT-BF were scanned by scanning electron microscope (SEM). The incidence of VAP, the positive rates of strains isolated from endotracheal tube surface and lower respiratory tract secretion, the detection of strains and drug resistance were analyzed. Chi-squared test were used for statistical analysis.Results:The results of SEM showed that sheet matrix could be observed on the surface of the inner cavity of endotracheal tube in three days of tracheal catheter retention, and cocci adhered to it in four days. With prolonged indwelling time of endotracheal tube, the structure of bacterial biofilm (BF) had improved.The positive rate of strains isolated from the secretion of lower respiratory tract in 30 neonates was 23.3%(7/30) and all of them were Gram-negative bacteria. There was no patient developed VAP in group A, while there were two patients with VAP in group B, and five patients with VAP in group C. The incidences of VAP in the three groups were statistically significant ( χ2=10.82, P=0.004). There was no significant difference in the positive rate of strains isolated from the surface of endotracheal tube under different indwelling time in 30 cases ( χ2=1.03, P=0.598). Among of 13 neonates in group A, there were seven strains isolated from ETT-BF, mainly Gram-positive bacteria which turned out to be mainly Gram-negative bacteria with the prolongation of endotracheal tube indwelling time. Of the seven VAP cases, strains isolated from the lower respiratory tract secretion were consistent with the strains isolated from the surface of the corresponding endotracheal tube in five cases, which were Serratia liquefaciens, Klebsiella acidogenes, Serratia marcescens, Flavobacterium meningosepticum and Stenotrophomonas maltophilia, and the drug resistance was consistent. Conclusions:The colonization bacteria of early ETT-BF may come from the upper respiratory tract, with less migration which rarely causes VAP. With the prolongation of endotracheal tube indwelling time, the incidence of VAP in neonates increases. The same pathogen can be found in the ETT-BF and lower respiratory tract secretion. The source of pathogen needs further study.

Objective:To summarize the clinical characteristics, diagnosis, treatment, and prognosis of neonatal meningitis caused by Mycoplasma hominis. Methods:We present the clinical data, diagnosis and treatment of a premature infant with Mycoplasma hominis meningitis who was admitted to the Department of Neonatology, the Second Affiliated Hospital of Wenzhou Medical University in June 2020. Relevant literature up to May 2021 was retrieved with the strategy of "( Mycoplasma hominis) AND (meningitis OR central nervous system OR cerebrospinal fluid) AND (newborn)" from CNKI, Wanfang, and PubMed database. The clinical manifestations, examinations, diagnosis, treatments and prognosis of cases with complete clinical data were summarized using two-sample rank sum test. Results:A premature female infant at gestational age of 27 +4 weeks presented with repeated low-grade fever and apnea since the 7 days of life. Cerebrospinal fluid testing in a local hospital showed neutrophil-based leukocytosis, which indicated purulent meningitis. However, empiric antibiotic treatment did not improve the infant's condition. The patient was transferred to our hospital due to dyspnea for 32 days and repeated fever for 25 days. Mycoplasma hominis was detected from the cerebrospinal fluid samples using metagenomic next generation sequencing (NGS). Treatment with erythromycin was ineffective, but the patient improved and discharged after changing to chloramphenicol for 18 d without any side effects. A total of 21 English articles were retrieved, and no Chinese literature was retrieved, involving 22 infants. Of the 23 cases including the present case, 14 were preterm, eight were term and one with no available data; 19 were born by vaginal delivery; the median age of onset was 11.0 d ( P25- P75: 7.0-18.0 d). The initial symptoms included fever, convulsions, irritability, and apnea. Blood routine examination showed elevated white blood cell count in ten cases and elevated C-reactive protein in seven cases. In the cerebrospinal fluid testing, white blood cell count increased in 19 cases, protein increased in 20 cases, and glucose decreased in 13 cases. Eight cases were confirmed by 16S RNA polymerase chain reaction amplification technology, seven by serum antibodies test, two cases by culture and microscopic findings, two cases by culture alone, one case by Mycoplasma kit, and one by NGS. The main treatment was the administration of tetracyclines, quinolones, chloramphenicol, lincosamides, etc. (alone or in combination). Two cases improved without using special anti- Mycoplasma drugs. Of the 23 patients, 15 had hydrocephalus, eight had intracranial hemorrhage, four had cerebral ischemic infarction, and two had cerebral abscess. Four cases had good prognosis,16 cases had adverse prognosis, and other three without available data. The median time to start sensitive antibiotic therapy in children with good prognosis was 4.5 d(3.6-5.0 d) after diagnosis, which was earlier than that in children with adverse prognosis [16.8 d (7.0-25.0 d)]( Z=－2.27, P=0.023). Conclusions:Mycoplasma hominis infection has non-specific clinical manifestations and should be considered for infants with intracranial infection that is not responding to empirical antibiotic treatment. NGS is helpful in detecting Mycoplasma hominis and chloramphenicol can be an option for the treatment.

Objective:To study the changes and influencing factors of splanchnic regional saturation before and after feeding in preterm infants with feeding intolerance (FI).Methods:From December 2018 to August 2019, preterm infants with FI admitted to the neonatal intensive care unit of our hospital within 24 hours after birth were prospectively enrolled in this same-patient before-after study. Splanchnic regional saturation (rSsO 2) and cerebral regional oxygenation (rSc0 2) 5 minutes before feeding and 1 hour after feeding were monitored using near-infrared spectroscopy (NIRS). The average values of rScO 2, rSsO 2 and splanchnic-cerebral oxygenation ratio (SCOR) before and after feeding were calculated. The clinical data including postnatal age, corrected gestational age and feeding methods (breastfeeding or formula feeding) were collected. Single-factor correlation analysis and multiple linear regression were used to analyze the influencing factors of rSsO 2 before and after feeding. Results:A total of 41 preterm infants were included. No significant differences existed in rSsO 2, rScO 2 and SCOR before and after feeding ( P>0.05). The feeding methods showed relative prominent influences on the changes of rSsO 2 and SCOR before and after feeding. The breastfeeding infants had smaller changes of rSsO 2 and SCOR before and after feeding compared with formula feeding infants, the regression equations were Y=5.538-4.065X (model complex correlation coefficient was 0.414 determination coefficient R2=0.171, F=8.050, P<0.01) and Y=0.109-0.075X (model complex correlation coefficient was 0.405 determination coefficient R=0.1642, F=7.655, P<0.01). Conclusions:Proper feeding will not increase rSsO 2 in preterm infants with FI. Comparing with formula feeding infants, breastfeeding infants has more stable post-feeding rSsO 2.Breastfeeding should be the first choice for preterm infants with FI.

Objective:To investigate the clinical characteristics and pathogenic gene mutation of lateral meningocele syndrome(LMS).Methods:We retrospectively collected the clinical manifestations, laboratory examination, imaging examinations, and genetic analysis of a neonate with LMS which was diagnosed at the Department of Neonatology of the Second Affiliated Hospital of Wenzhou Medical University in May 2020. Relevant literature up to February 2021, retrieved from PubMed, OMIM, CNKI, Wanfang, and CQVIP database with the terms of "lateral meningocele syndrome", " NOTCH3", were reviewed to summarize the clinical characteristics, pathogenesis, and genetic etiology of this disease. Results:A full-term male newborn was admitted to our hospital due to feeding difficulty 7 d after birth. The clinical characteristics included hypotonia, dysphagia, hypertension, lateral spinal meningocele, craniofacial anomaly, and cryptorchidism. Abnormal spinal MRI and brainstem evoked potential were also observed. Whole exome sequencing revealed a heterozygous frameshift variation c.6667_6686del(p.Ala2223Profs*12) of NOTCH3 gene located in 19p13.12, which was not detected in the parents. Only 12 English literature were retrieved, with 17 patients from 15 pedigrees. Out of the 18 patients including the index case, 10 were genetically diagnosed as LMS. The age at diagnosis ranged from 15 d to 55 years. Regarding the clinical features, multiple lateral thoracolumbar spinal meningoceles (18/18) was the most common one, followed by retrognathia and low-set ears (16/18), eyelid ptosis and down slanting palpebral fissures (15/18), hypotonia (13/18), hypertension (11/18), developmental delay (9/18), mixed or conductive hearing loss (9/18), cardiovascular dysplasia (7/18), and cryptorchidism (7/10). A total of nine NOTCH3 gene variants were detected, all were heterozygous variants, including six frameshift and three nonsense variants. Conclusions:LMS is caused by NOTCH3 gene mutation with the clinical characteristics including multiple lateral thoracolumbar spinal meningoceles, craniofacial dysmorphisms, hypotonia, hypertension, developmental delay, difficulty in feeding, cryptorchidism, etc.

Objective:To analyze the short-term and medium-term survival status of children with congenital esophageal atresia, and to provide reference for clinical multidisciplinary management of children with congenital esophageal atresia.Methods:The clinical data of neonates with type Ⅲ congenital esophageal atresia who were operated in our hospital between November 2007 to November 2018 and followed up in this hospital were analyzed retrospectively.Results:Among the 62 cases, 16 cases were discharged automatically, 1 case died, and 45 cases were included in the short-term follow-up. 35 cases were classified as gross Ⅲa, 10 as Ⅲb, 5 as long segment type, 44 patients accepted one-stage surgery, 1 infant accepted delayed operation, 9 infants received second operations. Anastomotic leakage occurred in 8 cases (17.8%), anastomotic stenosis in 11 cases (24.4%), recurrence of tracheoesophageal fistula in 2 cases (4.4%), blood flow infection in 14 cases(31.1%), incision infection in 4 cases (8.9%). The medium-term survival status of 38 cases: 2 cases died of aspiration, 29 cases (76.3%) of anastomotic stenosis underwent esophageal dilatation, 5 cases (13.2%) of dysphagia when 1.5 years old, 6 cases (15.8%) of malnutrition. After multidisciplinary collaboration, the survival rate increased (57.1% vs. 85.3%, P=0.013), and the incidence of anastomotic leakage decreased (46.4% vs. 20.6%, P=0.03). Conclusion:The quality of life of children with congenital esophageal atresia can be improved by multidisciplinary cooperation and standardized postoperative follow-up.

Objective To study the clinical value of tumor necrosis factor-α (TNF-α) and resolvin D1 (RvD1) concentrations in cerebrospinal fluid (CSF) of neonatal purulent meningitis(NPM).Method From June 2016 to June 2017,neonates of suspected NPM admitted to the neonatology department of our hospital were studied prospectively.Their CSF was examined before the use of antibiotics.The patients were assigned into NPM group and non-NPM group.After 7 to 10 days of treatment,according to the clinical symptoms and the reexamination results of CSF,patients in the NPM group were further assigned into the improved group and the unimproved group.The levels of TNF-α and RvD1 in CSF were measured using enzyme-linked immunosorbent assay (ELISA) method,and SPSS 22.0 was used for statistical analysis.Result A total of 23 patients were included in the NPM group (18 in the improved group and 5 in the unimproved group) and 30 in the non-NPM group.The levels of TNF-α and RvD1 in the CSF of the NPM group were higher than the non-NPM group [TNF-α:(0.263 ±0.088) pg/ml vs.(0.087 ±0.001) pg/ml,RvD1:(2.017 ± 0.171) pg/ml vs.(0.563 ±0.048) pg/ml] (P ＜0.05).After 7 to 10 days of treatment,TNF-α and RvD1 decreased in the improved NPM group[TNF-α:0.083 (0.078,0.111) pg/ml vs.0.122 (0.098,0.214) pg/ml,RvD1:1.242 (0.740,2.098) pg/ml vs.1.791 (1.371,2.804) pg/ml] (P ＜ 0.05),and increased in the unimproved NPM group [TNF-α:2.239 (1.309,2.806) pg/ml vs.0.102 (0.100,1.312) pg/ml,RvD1:2.614 (1.265,2.940) pg/ml vs.0.139 (0.103,0.276) pg/ml] (P ＜ 0.05).The reexamination results of TNF-oα in the NPM group were lower than the examination results before the use of antibiotics of the non-NPM group,and RvD1 higher than the non-NPM group (P ＜ 0.05).Conclusion TNF-α and RvD1 in CSF have clinical value for the early diagnosis and therapeutic evaluation of NPM.