Objective:To explore the clinical manifestations and genetic characteristics of Wolf-Hirschhorn syndrome (WHS) to improve the ability of diagnosis and differential diagnosis of the disease.Methods:The clinical features and auxiliary examinations and treatment of a proband with WHS caused by microdeletion of 4p16.3 segment who admitted to the Third Affiliated Hospital of Zhengzhou University in December 2021 were recorded, and whole exome sequencing (WES) of the family was performed. The prognosis was followed up.Results:The female proband, 11 months old, presented with convulsions at the age of 8 months, with the characteristics of heat sensitivity and cluster seizures, and her identical twin sister had a similar medical history. Physical examination found malnutrition, retarded development, special face, prominent forehead, wide nasal bridge, small jaw, precordial murmur and grade 3/6 murmur in the whole period, hyperactivity of P2, and low limb muscle tone. The whole exon and copy number variation (CNV) test of the family revealed that the proband had a 1.99 Mb heterozygous deletion in the chromosome 4p16.3 segment, including WHSC1 (NSD2), WHSC2 (NEFLA) and other genes. Copy number variation sequencing (CNV-Seq) of the proband and her sister showed 1.97 and 1.92 Mb heterozygous deletion of chromosome 4p16.3, respectively. Genealogical analysis by quantitative polymerase chain reaction revealed that the CNV was de novo, and it was determined to be a pathogenic variant according to the American College of Medical Genetics and Genomics guidelines. The proband took sodium valproate orally, and her sister took oral sodium valproate, zonisamide, and levetiracetam successively, and at the same time they received family rehabilitation training. The age at the last follow-up was 1 year and 8 months. Neither of them had convulsions again in the past 3 months, but the developmental delay was obvious. Conclusion:WHS patients may present with growth retardation, epilepsy, Greek warrior helmet-like special face, and congenital heart disease, and may have microdeletions in the chromosome 4p16.3 segment.

Objective:To study the incidences of complications in twins with birth weight discordance (BWD) during hospitalization.Methods:From January 2011 to December 2020, twins born in the Department of Obstetrics and hospitalized in NICU of our hospital were retrospectively studied. Twins with BWD>15% were assigned into BWDT group and BWD≤15% into twins with birth weight concordant (BWCT) group. Complications during hospitalization were compared between the two groups.Results:A total of 1 546 pairs of twins were enrolled, including 486 (31.4%) in BWDT group and 1 060 (68.6%) in BWCT group. Compared with BWCT group, BWDT group had significantly higher incidences of pulmonary surfactant (PS) utilization (47.7% vs. 42.2%), continuous positive airway pressure ≥ 24 h (40.5% vs. 35.0%), high-flow nasal cannula ≥ 24 h (22.8% vs. 16.3%), neonatal respiratory distress syndrome (52.9% vs. 47.1%), bronchopulmonary dysplasia (BPD) (15.6% vs. 11.1%), persistent pulmonary hypertension of the newborn (3.1% vs. 1.4%) and anemia (79.6% vs. 70.1%) (all P<0.05). After adjusting for confounding factors, the risks of pulmonary hemorrhage ( OR=2.036, 95% CI 1.119-3.703, P=0.020) and BPD ( OR=2.960, 95% CI 1.656-5.219, P=0.010) in BWDT group were higher than BWCT group. Conclusions:BWD twins has higher incidences of complications during hospitalization than BWC twins.

Objective:To investigate the clinical utility of intracavitary electrocardiogram (IC-ECG) localization technique in locating the tip of umbilical venous catheterization (UVC).Methods:From April 2020 to March 2021, premature infants admitted to the Department of Neonatology of the Third Affiliated Hospital of Guangzhou Medical University and received UVC were collected for a prospective study. According to whether IC-ECG was used to determine the position of umbilical vein catheter tip during catheterization, they were divided into IC-ECG group and control group. The differences of catheterization success rate, total incidence of catheter-related complications were compared between the two groups. The relationship between characteristic P waves and the position of the catheter tip in the IC-ECG group was also analyzed.Results:A total of 104 premature infants were enrolled, including 52 cases in IC-ECG group and 52 cases in control group. The catheter placement accuracy rate of the IC-ECG group was higher than that of the control group (53.8% vs. 28.8%, P<0.05). There was no statistically significant difference of the total incidence of catheter-related complications between the two groups ( P>0.05). Among the 40 cases with characteristic P wave changes in the IC-ECG group, 21 cases had normal P wave, of which 13 cases (61.9%) were with the correct position. And 19 cases had low-amplitude bimodal P waves, of which 15 cases (78.9%) were with the correct position. There was no statistically significant difference of the exact position rate of the catheter tips between the two types of P waves ( P>0.05). Conclusions:The use of IC-ECG localization technique in the process of catheterization of umbilical vein can increase the exact position rate of catheterization. Furthermore, when IC-ECG monitoring shows characteristic P wave changes to normal P wave or low-amplitude bimodal P wave, the tip of the UVC catheter may be located accurately.

Objective:To analyze the risk factors of bronchopulmonary dysplasia(BPD)in very preterm infants(VPI), and to provide scientific basis for the prevention and treatment of BPD in VPI.Methods:A prospective multicenter study was designed to collect the clinical data of VPI in department of neonatology of 28 hospitals in 7 regions from September 2019 to December 2020.According to the continuous oxygen dependence at 28 days after birth, VPI were divided into non BPD group and BPD group, and the risk factors of BPD in VPI were analyzed.Results:A total of 2 514 cases of VPI including 1 364 cases without BPD and 1 150 cases with BPD were enrolled.The incidence of BPD was 45.7%.The smaller the gestational age and weight, the higher the incidence of BPD( P<0.001). Compared with non BPD group, the average birth age, weight and cesarean section rate in BPD group were lower, and the incidence of male infants, small for gestational age and 5-minute apgar score≤7 were higher( P<0.01). In BPD group, the incidences of neonatal respiratory distress syndrome(NRDS), hemodynamically significant patent ductus arteriosus, retinopathy of prematurity, feeding intolerance, extrauterine growth restriction, grade Ⅲ~Ⅳ intracranial hemorrhage, anemia, early-onset and late-onset sepsis, nosocomial infection, parenteral nutrition-associated cholestasis were higher( P<0.05), the use of pulmonary surfactant(PS), postnatal hormone exposure, anemia and blood transfusion were also higher, and the time of invasive and non-invasive mechanical ventilation, oxygen use and total hospital stay were longer( P<0.001). The time of starting enteral nutrition, cumulative fasting days, days of reaching total enteral nutrition, days of continuous parenteral nutrition, days of reaching 110 kcal/(kg·d) total calorie, days of reaching 110 kcal/(kg·d) oral calorie were longer and the breastfeeding rate was lower in BPD group than those in non BPD group( P<0.001). The cumulative doses of amino acid and fat emulsion during the first week of hospitalization were higher in BPD group( P<0.001). Multivariate Logistic regression analysis showed that NRDS, invasive mechanical ventilation, age of reaching total enteral nutrition, anemia and blood transfusion were the independent risk factors for BPD in VPI, and older gestational age was the protective factor for BPD. Conclusion:Strengthening perinatal management, avoiding premature delivery and severe NRDS, shortening the time of invasive mechanical ventilation, paying attention to enteral nutrition management, reaching whole intestinal feeding as soon as possible, and strictly mastering the indications of blood transfusion are very important to reduce the incidence of BPD in VPI.

Objective:To study the effects of gender on clinical outcomes of extremely low birth weight infants (ELBWI) and to analyze the risk factors of mortality.Methods:From January 2011 to December 2020, ELBWI (birth weight <1 000 g) admitted to the Neonatology Department of our hospital were retrospectively studied. The infants were assigned into the male group and the female group. Incidences of major complications, survival rate and mortality rate were compared between the two groups. The infants were also assigned into survival group and death group according to their clinical outcomes. Binary multivariate unconditional Logistic regression was used to analyze the risk factors of mortality in ELBWI.Results:A total of 637 ELBWI cases were included. 311 cases were in the male group with a survival rate of 57.9% (180/311) and 326 cases were in the female group with a survival rate of 57.4% (187/326). The incidences of neonatal respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), pulmonary hemorrhage and severe intraventricular hemorrhage (IVH) in the male group were significantly higher than the female group ( P<0.05). Significant increases of survival rate existed for both groups year by year ( P<0.01).No significant differences existed in survival rate, mortality rate of infants receiving proactive treatment and mortality rate of infants withdrawing treatment between the two groups ( P>0.05). Multivariate unconditional Logistic regression analysis showed that withdrawing treatment ( P<0.01) and pulmonary hemorrhage ( P<0.05) were associated with increased risks of mortality. Conclusions:Male ELBWI have higher risks of RDS, BPD and severe IVH than female ELBWI. Withdrawing treatment and pulmonary hemorrhage are common risk factors of mortality for both male and female ELBWI.

Objective:To study the clinical characteristics of hepatic injury following umbilical vein catheterization, so as to improve the safety and use of umbilical vein catheterization in the newborn.Methods:Data of infants undergoing umbilical vein catheterization during hospitalization in the neonatology department of the Third Affiliated Hospital of Guangzhou Medical University from Jan 1st, 2015 to Dec 31st, 2019 were collected retrospectively.The clinical characteristics, diagnoses and treatments of the infants with hepatic injury following umbilical vein catheterization were summarized and analyzed.And the relative literature was reviewed.Results:A total of 1 721 infants underwent umbilical vein catheterization, and seven cases(0.4%)had hepatic injury, including six cases of exudative necrosis in the liver and one case of hepatic hematoma.There was no significant difference in gestational age[(31.12±2.64)weeks vs.(30.62±2.75)weeks]or birth weight[(1 493±525)g vs.(1 374±473)g]between hepatic injury group and non-hepatic injury group( P>0.05). Clinically, it was found that the tip position of umbilical vein catheter was below the diaphragm(between the 9th and 11th thoracic vertebrae)in all seven cases.Except one case with no obvious clinical symptoms, the other six cases had clinical symptoms, mainly manifested as abdominal distension, repeated gastric retention, decreased bowel sounds, and additional with shock and anemia in hepatic hematoma.Blood sample tests showed elevated C-reactive protein, white blood cell count and transaminase.X-ray examination revealed cystic translucent shadow in the liver, and ultrasound and/or computed tomography examination showed the lesion in more detail.After removal of the catheter and administration of antibiotic, the hepatic injury recovered gradually. Conclusion:The hepatic injury following umbilical vein catheterization in neonates is not common.The catheter tip under the diaphragm is the main risk factor.And the diagnosis is dependent on imaging examination.

Objective:To study the effects of hypertensive disorders of pregnancy (HDP) on the birth weight (BW) differences in twins.Method:From January 2011 to January 2020, twins delivered in our hospital were retrospectively analyzed. The twins born to HDP mothers were the HDP group and those born to healthy mothers were the control group. The maternal and neonatal data of the two groups were collected and the effects of HDP on the BW differences were analyzed.Result:The age of the mothers, the proportion of mothers of older ages and more-than-once delivery in HDP group (418 cases) were significantly higher than the control group (499 cases) [(31.4±5.3) years vs. (30.4±3.8) years, 26.6% (111/418) vs. 12.6% (63/499), 20.6% (86/418) vs. (15.0% (75/499)] ( P<0.05). The gestational age (GA) of newborns in the HDP group (836 cases) was significantly lower than the control group (998 cases) [(35.1±2.2) weeks vs. (36.7±1.2)]( P<0.05). The proportion of twins with GA <34 weeks in the HDP groups was significantly higher than the control group [24.2% (101/418) vs. 3.8% (19/499)] ( P<0.05). Cesarean section was the main delivery mode in both groups. The BW differences of the twins in the HDP group were larger than the control group [22.4% (9.1%, 31.9%) vs. 13.1% (5.8%, 19.6%)]. Significantly more twins in the HDP group showed ≥30% BW difference than the control group [28.7% (120/418) vs. 3.8% (19/499)] ( P<0.05). The incidences of BW discordant in twins (BWDT) in the HDP group was significantly higher than the control group [BWDT≥15%:61.5% (257/418) vs. 38.3% (191/499), BWDT≥20%: 51.4% (215/418) vs. 25.3% (126/499)] ( P<0.05).Among twins with GA of 34~37 weeks, the BW of the bigger infants and the smaller infants in the HDP group were all lower than the control group and the percentage of BW difference was significantly higher than the control group ( P<0.05). Conclusion:HDP may influence the intrauterine growth of the twins, aggravate the BW differences and increase the incidences of BWDT. It is necessary to make better prenatal management of HDP and closely monitor the intrauterine growth of the fetuses.

Objective:To investigate the effect of Budesonide (BUD) on pulmonary vascular development and the expression of vascular endothelial growth factor (VEGF) and nucleotide binding oligomerization domain-like receptor protein 3 (NLRP3) in newborn rats with bronchopulmonary dysplasia (BPD) caused by intrauterine infection.Methods:The 15-day-pregnant SD rats were divided into control group and infection group [intraperitoneal injection of 0.35 mg/(kg·d) lipopolysaccharide], and the newborn rats born by the above groups were divided into 3 groups: BUD group (0.5 mg of BUD suspension), normal control group (NC group, equal amount of 9 g/L saline), BPD group (equal amount of 9 g/L saline), with 40 rats in each group, all of them were inhaled twice a day for 14 days.Ten newborn rats were selected at birth, on the 3 rd, 7 th and 14 th day after administration.Pulmonary histopathological changes and radial alveolar counts (RAC) were observed after HE staining, and the thickness of alveolar respiratory membrane was measured; the platelet-endothelial cell adhesion molecule (PECAM-1/CD 31) in lung tissue was detected by immunohistochemistry, and the density of pulmonary microvessels was calculated; the expressions of VEGF, NLRP3 and Caspase-1 were detected by Western blot; and the levels of serum interleukin( IL)-1β and IL-18 were measured by enzyme-linked immunosorbent assay. Results:With the increase of day-old, the lung tissue of newborn rats in NC group was gradually developed and matured, the structure of alveoli was clear, the size was uniform, the count was significantly increased, and no obvious pathological changes were observed.In BPD group, the lung tissue structure was disordered, the alveoli were different in size and few in count, and inflammatory cells were exuded from the alveoli or the alveoli space.Compared with BPD group, the pathological changes of lung tissue in BUD group were significantly reduced.On the 3 rd, 7 th and 14 th day after administration, compared with NC group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were lower, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly higher, and the differences were statistically significant(all P<0.05). Compared with BPD group, the RAC, average integral optical density of CD 31 positive cells, density of pulmonary microvessel and level of VEGF protein in lung tissue of BPD group and BUD group were significantly higher, and the differences were statistically significant (all P<0.05); while the thickness of respiratory membrane, level of NLRP3, Caspase-1 proteins in lung tissue and serum levels of IL-1β, IL-18 were significantly lower, and the differences were statistically significant (all P<0.05). Conclusions:The occurrence and development of pathological changes of BPD newborn rats caused by intrauterine infection can affect the development of pulmonary vessels through the inflammatory response of lung tissue.BUD can alleviate pathological changes in lung tissues of BPD newborn rats by reducing inflammatory reaction and up-regulating VEGF expression, promoting pulmonary vascular remodeling, and increasing pulmonary microvascular density.

Objective:To investigate the status of enteral feeding and the incidence of feeding intolerance in premature infants less than 32 weeks of gestation age, as well as the difficulties during enteral feeding.Methods:A retrospective analysis was conducted on preterm infants less than 32 weeks of gestation age admitted to the Neonatal Intensive Care Unit of the Third Affiliated Hospital of Guangzhou Medical University from January to December 2018.The infants were divided into 2 groups: 76 cases in the feeding tolerance group, 45 males (59.2%, 45/76 cases), mean gestational age (29.43±1.42) weeks; 79 cases in the feeding intolerance group, 48 males (60.8%, 48/79 cases), mean gestational age (29.16±1.60) weeks.The incidence of feeding intolerance was explored, and the enteral feeding, growth and main diagnosis as well as treatment during hospitalization between the 2 groups were compared.Results:(1) For preterm infants less than 32 weeks of gestation age, 92.9%(144/155 cases) of infants were given formula milk within 48 hours after birth, and 76.1% (118/155 cases) of infants were given formula milk within 24 hours after birth, the initial milk feeding volume of the 2 groups were [(12.24±4.37) mL/ (kg·d) vs.(11.23±4.88) mL/(kg·d), t= 0.812, P>0.05]. (2) The rate of milk volume increase in the feeding tolerance group and feeding intolerance group were [(8.69±4.30)mL / (kg·d) vs.(4.29±4.02) mL / (kg·d) in week 1; (8.43±0.45) mL / (kg·d) vs.(4.26±2.75) mL / (kg·d) in week 2, t=6.583, t′=13.294, all P<0.05)]. (3) The duration of achieving sufficient enteral feeding in the feeding tolerance and feeding intolerance group premature infant were[(20.55±9.66) d vs.(34.88±15.02) d, t=7.489, P<0.05]. (4) The feeding tolerance group had shorter hospital stay, more weight gain and lower incidence of extrauterine growth retardation than the feeding intolerance group.(5) The incidence of feeding intolerance was 50.9% (79/155 cases) in preterm infants less than 32 weeks of gestation age, delayed meconium excretion, blood transfusion, non-invasive mechanical ventilation, use of hormones, use of antibiotics for more than 2 weeks, bronchopulmonary dysplasia may be associated with feeding intolerance. Conclusion:Enteral feeding is not ideal for preterm infants less than 32 weeks of gestation age, and the incidence of feeding intolerance is high.The feeding plan of medical staff needs to be improved.

Objective: To explore the relationship between different mutation characteristics and clinical phenotype of children with Dravet syndrome (DS) with SCN1A gene mutation, and to summarize the drug efficacy. Methods: The clinical data of children diagnosed as DS from the Department of Pediatrics Neurology, the Third Affi-liated Hospital of Zhengzhou University from January 2014 to May 2018 were collected.The peripheral blood DNA of the children was detected by adopting next generation sequencing for epilepsy-related gene-panel, while the parents′ were screened by using Sanger sequencing for family verification.Multiple ligation-dependent probe amplification technology was used to detect large fragment variation of SCN1A gene if the mutations of the children were negative.The Gesell scale and cavity Wechsler intelligence scale for children(C-WISC) were used to evaluate the intelligence of children. Results: A total of 50 cases of DS were collected, 38 cases of them were positive for SCN1A mutation, and the mutation rate was 76.0%(38/50 cases), of which, the missense mutation[50.0%(19/38 cases)] and frameshift mutation[28.9%(11/38 cases)] were dominant.The average onset age of 50 patients was 6 months, of which onset of seizures was triggered by fever(temperature>37.5 ℃) in 68.0%(34/50 cases)of children, the history of seizures in hot baths was found in 60.0%(30/50 cases) of children, status epilepticus was found in 74.0%(37/50 cases), cluster-like episodes was found in 80.0%(40/50 cases), ≥2 seizure types was found in 92.0%(46/50 cases). Mental retarda-tion was found in most of the children, of which 30.0% (15/50 cases) were mild mental retardation, 38.0% (19/50 cases) were moderate mental retardation, 14.0% (7/50 cases)were severe intelligence retardation.Interictal abnormalities of electroencephalogram(EEG) before 1 year old was found in 24.0%(12/50 cases), and the average age of EEG abnormalities was 30.12 months old; the top three drug efficacy rates were 70.0% (28/40 cases) of Topiramate, 48.0% (24/50 cases) of Sodium Valproate, 45.7% (16/35 cases) Clonazepam or Clobazam.The time of onset of myoclonus and atypical absence of the truncation mutation group was earlier than that of the missense mutation group(14.75 months vs.21.20 months; 16.82 months vs.26.00 months), and the difference was statistically significant(P<0.05). The proportion of clustered episodes in the truncation mutation group was higher than that in the missense mutation group [94.7%(18/19 cases)vs.63.2%(12/19 cases)], and the difference was statistically significant (P<0.05). There was no significant correlation between the SCN1A gene mutation (type and position) and age of onset, type of seizure, proportion of convulsion persistence, the mental development or abnormal proportion of EEG and seizure frequency before 1 year old(all P>0.05). Conclusions The SCN1A gene mutation rate is high in children with DS, and the SCN1A gene mutation characteristics has a certain correlation with DS clinical phenotype.Topiramate is the most effective drug among children with DS.