Background：Constructing language development milestones and collecting milestone data are not only key steps in language development monitoring, but also the preliminary basis for the development of language screening and diagnostic tools.
Objective：To construct language development milestones for Chinese-speaking children aged 0 to 5.5 years, providing a reference basis for language development screening and diagnostic tool development.
Design：Cross-sectional survey.
Methods：Based on existing developmental assessment tools and literature, a language development milestone item pool was established through expert consultation and cognitive interviews. From October 2022 to November 2022, 1,976 children aged 0 to 6 years were sampled from five provinces including Zhejiang, Sichuan, Liaoning, Jiangxi, and Hainan. Using stratification by urban and rural areas, gender, and age groups, developmental milestone data were collected through parent reports in both primary care settings (age <36 months) and kindergartens (age ≥36 months). The characteristics of language development milestones for children in different age groups were analysed descriptively using an item response theory model. Data comparisons were conducted between the data collected in the current study for Chinese-speaking children and data obtained from other published research on English-speaking children.
Main outcome measures：Response rate, different item function, model fit, and estimated developmental age of each item when passing probabilities is 25%, 50%, and 75%.
Results：A total of 63 language development milestone items were included in the item pool. After data cleaning, 1 659 children were included in the data analysis, including 827 boys and 832 girls, with an average age of (2.5±1.9) years. The response rate for all 63 language milestones was higher than 99%. Three items showed different item function based on maternal education, and 14 items showed poor model fit.
Conclusions：The language development milestones for Chinese-speaking children aged 0 to 5.5 years established using the item response theory model provide a clear description of the language development trajectory of native Chinese-speaking children. This work offers valuable empirical data for the future development of language development evaluation tools for Chinese-speaking children, clinical monitoring of language development, and research into related neural mechanisms.
Background：Neck circumference is a new anthropometric measurement parameter in recent years. However, there is no published study on the reference standard values and the growth charts of neck circumference for children and adolescents in China.
Objective：To establish the reference standard values of neck circumference of children and adolescents aged 3-16 years and then to explore the cut-off values of neck circumference in predicting abdominal obesity in children and adolescents so as to provide a new index and reference for the clinical application of physical assessment in children and adolescents.
Design：A cross-sectional study.
Methods：The subjects were children and adolescents aged 3-16 years who underwent physical examination in the Children's Health Clinic of the Children's Hospital Affiliated to Nanjing Medical University from July 2021 to September 2022. Children with diseases that may affect neck circumference, growth and development, or limb disability, abnormal posture, or deformity were excluded. The neck circumference, height, weight, waist circumference and body composition were measured by 3 surveyors strictly according to the operating manual which was made by ourselves. Ten percent of samples were randomly selected for repeated verification, and the coincidence rate before and after verification should be ≥99%. Double track entry and logical check were carried out for data entry and arrangement. The neck circumference reference standard values of children and adolescents aged 3-16 years were established according to gender and age groups, and the growth charts were constructed by Lambda-median-sigma (LMS) method. Abdominal obesity was defined as waist-to-height ratio (WHtR) >0.48 in boys aged 6-16 years and girls aged 6-9 years, and WHtR >0.46 in girls aged 10-16 years. The association of neck circumference with other physical measures and abdominal obesity was analyzed. The area under the receiver operating characteristic (ROC) curve was used to analyze the accuracy of neck circumference reference in predicting abdominal obesity.
Main outcome measures：The reference standard values of neck circumference for children and adolescents aged 3-16 years and the cut-off values of neck circumference for assessing abdominal obesity for children and adolescents aged 6-16 years.
Results：A total of 18 371 children and adolescents aged 3-16 years were included in the analysis, including 10 701 boys (58.2%) and 7 670 girls. There were 5 407 (29.4%) children with abdominal obesity. In addition to body fat mass, neck circumference, age, height, weight, BMI, waist circumference, WHtR, skeletal muscle and skeletal muscle percentage (PSM) of boys were significantly greater than those of girls, body fat percentage (PBF) of girls was greater than that of boys, and the differences were statistically significant (all P<0.05). The neck circumference of boys and girls aged 3-16 years increased with age, and the neck circumference of boys was always greater than that of girls at each age. The average growth rate was 0.85 cm/year for boys and 0.65 cm/year for girls, which was similar for boys and girls aged 7 to 8 years. The annual growth rate of boys was greater than that of girls before the age of 7 and after the age of 8, and it was more obvious after the age of 12. For boys and girls, neck circumference was positively correlated with abdominal obesity (r male=0.614, r female=0.541), BMI (r male=0.824, r female= 0.800), waist circumference (r male=0.827, r female=0.801), WHtR (r male=0.729, r female=0.683) and PBF (r male=0.669, r female=0.679), and was negatively correlated with PSM (r male=-0.497, r female=-0.470). The optimal cut-off values of neck circumference for assessing abdominal obesity were 27.15-37.05 cm for boys and 26.25-30.50 cm for girls aged 6-16 years, both of which were located in the P75 of all gender and age groups. The area under the curve(AUC) of neck circumference in assessing abdominal obesity were ≥0.83 in boys and ＞0.79 in girls of all ages.
Conclusions：The neck circumference of boys was greater than that of girls in all age groups and it increased with age from 3 to 16 years old. The optimal cut-off values of neck circumference for assessing abdominal obesity were 27.15-37.05 cm for boys and 26.25-30.50 cm for girls aged 6-16 years, and the AUC was≥0.83 in boys and ＞0.79 in girls of all ages, with high accuracy.
Background：Chinese Infectious Disease Surveillance of Pediatrics (ISPED) program collected and summarized the data of antibiotics resistance from 12 member hospitals every year to monitor the bacterial drug resistance and pathogen changes among Chinese children.
Objective：To investigate the antimicrobial resistance profiles of pathogens and bacteria infection in Chinese children and guide the reasonable use of antibiotics.
Design：A cross-sectional survey. MethodsFrom January 1st to December 31rd in 2022, clinical isolates were collected from children hospitals in China enrolled in ISPED program. Antimicrobial susceptibility testing was carried out according to a unified protocol using Kirby-Bauer method or automated systems. Penicillin susceptibility of streptococcus pneumonia was detected by E-test. All of the antimicrobial susceptibility testing results were interpreted according to the criteria set by Clinical and Laboratory Standards Institute (CLSI) in 2022.
Main outcome measures：Distribution of bacteria strains in children, changes of bacteria drug resistance to isolated strains, and detection of multi-drug resistant organisms (MDROs).
Results：A total of 50,399 isolates were collected, of which 38.8% was gram-positive organisms and 61.2% was gram-negative organisms. Top ten pathogens were as follows, Escherichia coli (14.3%), Haemophilus influenza (11.8%), Straphylococcus aureus (11.4%), Streptococcus pneumonia (11.3%), Moraxella catarrhalis (7.3%), Coagulase-negative staphylococci (6.8%), Klebsiella pneunoniae (5.3%), Pseudomonas aeruginosa (4.4%), Acinetobacter baumannii(2.3%) and Enterococcus faecalis (2.1%). E. coli was the most common pathogen in neonates and children over 5 years old. H. influenza was the major pathogen in children from the age of >28 days to 1 year. S. pneumoniae was the main pathogenic bacteria in children at the age of 1 to 5 years old. The proportion of penicillin-insensitive S. pneumoniae (PNSP) from cerebrospinal fluid and non-cerebrospinal fluid were 88.9% and 6.6%, respectively. The ratios of methicillin-resistant S. aureus (MRSA), carbapenem-resistant Enterobacteriaceae (CRE), carbapenem-resistant P. aeruginosa (CR-PA), carbapenem-resistant A. baumannii (CR-AB) were 32.8%, 4.5%, 7.6% and 24.3%, respectively. The detection rates of MRSA, CRE and CR-PA in the neonatal group were 33.2%, 6.4% and 11.3%, much higher than those in the non-neonatal group (32.6%、4.2% and 7.5%). CR-AB in the neonatal group accounted for 10.9%, which was lower than that in the non-neonatal group (26.3%).
Conclusions：The detection rate of MDROs in 2022 shows the continuous decrease compared to the previous years. More attention should be paid to the colonization, infection and spread of MRSA, CRE and CR-PA in the neonatal population.
Background：Clinical cases of children with inflammatory bowel disease complicated with acute pancreatitis are rarely reported in China.
Objective：To summarize and analyze the clinical characteristics, treatment and prognosis of children with inflammatory bowel disease(IBD) with acute pancreatitis(AP) in a single center.
Design：Case series report.
Methods：The basic characteristics, clinical manifestations, physical examination, laboratory examination, imaging examination, treatment and follow-up information were retrospectively collected and analyzed from continuous cases of inflammatory bowel disease with acute pancreatitis hospitalized in the Department of Gastroenterology at Children's Hospital of Fudan University from January 2017 to June 2022. Main outcome measuresAP-related laboratory indicators and IBD endoscopic score.
Results：A total of 406 children with inflammatory bowel disease from January 2017 to June 2022 were retrospectively analyzed, and 11 cases (2.7%) were complicated with acute pancreatitis. Among them, 9 were male and 2 were female. The median age of initial diagnosis of IBD and AP was 9.8(5.5, 13.1) and 10.2(5.7, 14.0) years old, respectively. The median duration of AP disease was 22(7, 56) days. Among the 11 children, IBD was confirmed before AP in 8 cases including 5 cases of Crohn's disease (CD) and 3 cases of ulcerative colitis (UC), and AP was confirmed before CD in 3 cases. Serum amylase was 238 (158,573) U·L-1 and blood lipase was 466 (360,1 376) U·L-1 at the diagnosis of IBD and AP, and both decreased after 3, 6 and 12 months with statistical significance. Imaging examination showed pancreatic lesions in 9/10 cases. The pediatric Crohn's disease activity index (PCDAI) and simplified endoscopic score for Crohn's disease (SES-CD) of 8 CD children were 36.3 (25.6, 49.4) and 17.5 (7.8, 22.2) at the diagnosis of CD and AP, and both decreased after 3 months with statistical significance. The pediatric ulcerative colitis disease activity index (PUCAI) score and Mayo endoscopic score (MES) of the 3 UC children were 40(25, 42.5) and 2(2, 2.5) at the onset of AP, and turned to 15(0, 30) and 2.5(2, 3) after 3 months of discharge. During 3 years of follow-up, there was no recurrence of AP in the 11 children. One UC child treated with 5 aminosalicylic acid and infliximab before onset of AP, who stopped taking the medication themselves after the onset of AP, had persistent hyperamylasemia, hyperlipemia, and pancreatic duct dilatation at 2 years of follow-up, and was progressed to chronic pancreatitis(CP) at 3 years of follow-up.
Conclusions：Children with inflammatory bowel disease can be complicated with acute pancreatitis during the active stage, and acute pancreatitis may also be a rare extraintestinal manifestation of inflammatory bowel disease. During the diagnosis and treatment of inflammatory bowel disease, we should pay attention to the evaluation and follow-up of pancreatic function.
Background：In adult asthma studies, salmeterol/fluticasone propionate combination(FSC) has been shown to achieve better efficacy and comparable safety than fluticasone propionate alone(FP), but reliable clinical evidence is still lacking in children with asthma.
Objective：To conduct a systematic review and meta-analysis on salmeterol/fluticasone propionate combination and fluticasone propionate alone in the step-up treatment of children with asthma, and to explore the efficacy and safety of the two groups.
Design:Systematic review and meta-analysis.
Methods:Randomized controlled trials(RCTs) of salmeterol/fluticasone propionate combination versus fluticasone propionate alone were systematically searched in Cochrane, MEDLINE (via PubMed), Embase, Web of Science, CBM, CNKI and Wanfang databases from the inception to September 2023. Two researchers independently finished literature screening, data extraction, risk of bias assessment, and evidence quality summary. Data analysis was completed through R Studio1.4.1717.
Main outcome measures:Asthma exacerbations and adverse events related to inhaled corticosteroids (ICS) and FSC.
Results:A total of 11 RCTs with 9 438 children with asthma were included. The comparison between fluticasone propionate/salmeterol combination and fluticasone propionate alone showed a statistical difference in the improvement in maximal expiratory flow at 50% vital capacity(MEF50) (MD=0.17, 95%CI: 0.16-0.18,P<0.000 1), mean morning peak expiratory flow(PEF) (MD=4.84, 95%CI: 4.53-5.15,P<0.000 1) before and after treatment, improved percentage of symptom-free days (MD=1.39, 95%CI: 1.36-1.41,P<0.05) and albuterol-free days (MD=1.09, 95%CI: 1.06-1.12, P<0.05) before and after treatment. But there was no statistically significant difference in the reduction in asthma exacerbations(RR=0.87, 95%CI: 0.70-1.09, P=0.22),the incidence of reduced ICS and FSC-related adverse events(RR=0.99, 95%CI: 0.61-1.60, P=0.95) and other adverse events(RR=0.98, 95%CI: 0.91-1.05, P=0.55).
Conclusions:Compared with fluticasone propionate, salmeterol/Fluticasone propionate combined therapy significantly improved lung function (MEF50, mean morning PEF) and asthma symptoms, and reduced the use of salbutamol in treatment, but there was no difference in the reduction in asthma exacerbations. The safety was similar in both groups, with no additional drug-related adverse events or increased incidence of adverse events due to the addition of salmeterol.
Background：Overuse and misuse of empiric antibiotic use for early onset sepsis (EOS) in neonatal intensive care units (NICUs) is widespread, which is associated with adverse outcomes in preterm infants and increased risk of immunerelated diseases in children. The Antimicrobial Stewardship Program (ASP) targeting at EOS can effectively reduce the irrational use of antimicrobial drugs in premature infants.
Objective：To carry out multidisciplinary collaborative ASP to shorten the course of empiric antimicrobial drug treatment for EOS, and to explore the effect of ASP in reducing the use of antimicrobial drugs in the early postnatal period in extremely premature infants.
Design：Quality improvement research.
Methods：Consecutive cases of premature infants who were admitted to the NICU at Children's Hospital of Fudan University within 24 hours after birth from November 1, 2020 to July 31, 2023 and had a gestational age of <32 weeks were included. Those with major congenital anomalies, death or discharge within 7 days, or definite indications for antibiotic prescription within 3 days after birth were excluded. The ASP program was implemented on October 31, 2022. Infants were divided into a control group (before the ASP) and an intervention group (after the ASP). Both two groups have the same subgroups of ruleout sepsis, clinical sepsis and confirmed sepsis. Multidisciplinary ASP team was established to evaluate whether to prescribe empirical antibiotics according to the risk factors of EOS (low, medium, high risk) and the illness severity. ASP team conducted weekly audit of antibiotics for each very premature infant, and provided recommendations and feedback under the supervision of the chief of NICU.
Main outcome measures：Discontinuation rate of early antimicrobial drug (within 72 hours after birth).
Results：From November 1, 2021 to October 31, 2022, 186 cases were retrospectively included in the control group with 102 ruleout sepsis cases and 80 clinical sepsis, and from November 1, 2022 to July 31, 2023, 135 cases were prospectively included in the intervention group with 58 ruleout sepsis cases and 70 clinical sepsis. There was no significant difference between the two groups and ruleout sepsis subgroups in the two groups in terms of infant and maternal characteristics and NICU treatment. Clinical sepsis neonates showed significant differences in gestational age, prenatal hormone use, prenatal intravenous antibiotic treatment, and mechanical ventilation within 7 days after birth. Among the ruleout sepsis infants, the proportion of infants who discontinued initial antibiotics within 72 hours in the preand postASP period showed a statistically significant difference (P=0.008). Ruleout sepsis neonates in the intervention subgroup had a 2.8 times higher early antibiotic discontinuation rate than those in the control subgroup (OR=2.76,95% CI: 1.285.94). The ASP program had no effect on antimicrobial drug use (length of treatment/1,000 patient days), the rate of early antimicrobial use, mortality, the incidence of late sepsis, and necrotizing enterocolitis.
Conclusions：Among very preterm infants with ruleout sepsis, ASP increased the proportion of infants who discontinued empiric antibiotics within 72 hours after birth. Attention should be paid to the diagnosis of clinical sepsis and the time of empirical antibiotic discontinuation, which may increase the rate of early antibiotic discontinuation and reduce the length of treatment during hospitalization.
Background：Periodic discharges (PDs）have attracted more and more attention in electroencephalogram (EEG) monitoring of adult and pediatric critical patients, and the correlation between PDs and seizures is very high. But so far, there are very few reports on PDs in newborns. Neonatal PD is still an EEG phenomenon with unknown clinical significance.
Objective：To investigate the incidence and etiological characteristics of PDs in neonates, and the correlation with seizures and brain injury.
Design：Case series report.
Methods：The data of neonatal cases monitored by video electroencephalogram (vEEG) in Shengjing Hospital Affiliated to China Medical University from January 2018 to December 2022 were collected. Newborns with seizures and PDs were searched in the EEG database, and their EEG data and head magnetic resonance imaging (MRI) results were reinterpreted, and the clinical data were analyzed and summarized.
Main outcome measures：Incidence of PDs in neonates.
Results：Out of 4 685 neonates, 167 (3.6%) developed PDs. The primary causes of PDs for full-term infants were hypoxic-ischemic encephalopathy, white matter injury, and intracranial infection, while for preterm infants the primary causes are cerebral hemorrhage, white matter injury, and hypoxic-ischemic encephalopathy. Electrical or electro-clinical seizures were detected in 93.4% of the neonates, 54.5% had multiple or frequent seizures, and 37.1% had status epilepticus. Sixty-eight cases (40.7%) had recurrent single foci in a certain brain region, 47 cases (28.1%) had multifocal asynchrony, 29 cases (17.4%) had simultaneous appearance in one hemisphere, and 23 cases (13.8%) had simultaneous appearance in both hemispheres. Of the 115 cases with single-focal recurrence and multi-focal asynchrony, 89 cases (77.4%) involved the central and/or midline regions and the temporal region. Among the causes of PDs, statistical significance was found between different PD sites and PD causes of hypoxic ischemic encephalopathy, arterial ischemic stroke, intracranial hemorrhage, intracranial infection, white matter injury, and unexplained convulsion. There were 129 cases (77.2%) with PDs in different parts of brain injury. There was statistical significance between different PD distribution sites and focal or multifocal micro-white matter injury, large area injury in one hemisphere，and extensive whole brain. Among the 132 children who completed at least two monitoring, 43.9% of PDs gradually disappeared 1-7 days after onset, 28.0% disappeared at 8-14 days after onset, and 12.1% disappeared at 15-32 days after onset. Besides, 15.9% of the neonates with persistent PDs had congenital brain structural abnormalities and genetic abnormalities.
Conclusions：The incidence of PDs in neonates is low, and there are many potential causes. It is closely related to seizures. PDs are associated with structural brain injury or dysfunction. PDs can be regarded as one of the characteristic EEG changes in the acute phase of neonatal brain injury.
Background：After the adjustment of COVID-19 prevention and control measures in China, there is insufficient data to prove the relationship between asthma in children and COVID-19 infection.
Objective：To analyze whether COVID-19 infection affects the control and treatment of asthma in children.
Design：A cross-sectional study.
Methods：From March 10th to 31rd in 2023, children were enrolled from the outpatient departments of respiratory, asthma, desensitization and anti-IgE at Guangzhou Women and Children's Medical Center during the first month after the new COVID-19 epidemic prevention policy was launched. The modified COVID-19 Post-infection questionnaire (Modified Questionnaire) for allergic rhinitis and asthma children was used.The children who had COVID-19 infection from November 16th, 2022 to March 16th, 2023 and had previously diagnosis of asthma were taken as the asthma group, including four subgroups of dust mite allergic immunotherapy(AIT)+ omalizumab, dust mite AIT, regular inhaled corticosteroids（ICS）and on-demand medication for different interventions. Children who had no history of asthma were taken as the non-asthma group.
Main outcome measures：Hospitalization proportion by COVID-19 infection for children with asthma.
Results：In total, 317 children who were infected by COVID-19 from November 16th, 2022 to March 16th, 2023 and voluntarily participated in the Modified Questionnaire investigation were enrolled from March 1, 2023 to March 31, 2023. There were 200 cases (63.1%) in the non-asthma group and 117 cases in the asthma group. Of the asthma group, there were 10 cases in dust mite AIT+omalizumab subgroup, 25 cases in dust mite AIT subgroup, 29 cases in ICS subgroup, and 53 cases in on-demand medication subgroup. There was no significant difference in baseline data of gender, age, height, and weight. There were significant differences in diagnosis and comorbidities between the non-asthma group and the asthma group (P<0.05). The proportion of respiratory tract infection in the non-asthma group was higher than that in the asthma group, and the proportion of allergic rhinitis, food allergy, and atopic dermatitis in the asthma group was higher than that in the non-asthma group(P<0.05). The COVID-19 vaccine coverage rate and the second dose of vaccine coverage rate in the asthma group were significantly higher than those in the non-asthma group (P< 0.05).The proportion of asymptomatic infection in the asthma group was higher than that in the non-asthma group, with statistically significant difference (P<0.05). The proportion of fever，peak body temperature，cough and phlegm and vomiting in the non-asthma group was higher than that in the asthma group. The difference was statistically significant (P<0.05). There was no significant difference in hospitalization for COVID-19 infection between the two groups. For remission and acute stages of asthma, there was no statistically significant difference(P> 0.05) between four subgroups in the asthma group before and after COVID-19 infection in terms of the assessment of ACTTM and VAS in the remission period and the assessment of dyspnea, night waking or early waking, and the need to use emergency medication (such as ventorin) in the acute stage.
Conclusions：Compared with non-asthma children, children with asthma had higher rate of asymptomatic COVID-19 infection, and milder clinical symptoms of COVID-19 infection. The use of AIT and/or anti-IgE therapy has no impact on the severity of disease in children with asthma when they are infected with COVID-19.
Background：Timely diagnosis of primary intracranial germ cell tumors (ICGCTs) still posed a big challenge.
Objective：To analyze the risk factors for delayed diagnosis of ICGCTs in children.
Design：Case-control study.
Methods：Children with ICGCTs were enrolled from Department of Pediatrics at Beijing Shijitan Hospital, Capital Medical University between October 2011 to April 2021. ICGCT children with the time from onset to diagnosis ≥ 6 months were taken as the delayed diagnosis group, and those with less than 6 months were put into the non-delayed diagnosis group. According to the reasons that cause delayed diagnosis, the delayed diagnosis group was further divided into disease group, family group, and diagnosis group. The demographic features, clinical manifestations and ancillary examinations were collected. Risk factors were established by univariate analysis and multivariate logistic regression analysis.
Main outcome measures：Risk factors for delayed diagnosis of ICGCTs.
Results：There were 114 males and 44 females in 158 children with ICGCTs．There were 88 cases in the non-delayed diagnosis group and 70 cases in the delayed diagnosis group including 15 cases in the disease group, 23 cases in the family group, and 32 cases in the diagnosis group. The most common primary symptoms were high intracranial pressure symptoms in the non-delayed diagnosis group, endocrine symptoms in the disease group and family group, and neuropsychiatric and endocrine symptoms in the diagnosis group. Multiple tumor lesions were mainly seen in the diagnostic group. In the non-delayed diagnosis group, there were more children with pathological type of NGGCTs, maximum diameter of tumor ≥3 cm, hydrocephalus, and need for ventriculoperitoneal shunt/third ventriculostomy. There are fewer children with β-HCG ≥5 mIU·mL -1 after at least 6 months of onset. Further analysis of the risk factors leading to delayed diagnosis found that endocrine symptoms were risk factors for delayed diagnosis in the family subgroup; the three main signs of high intracranial pressure and the maximum tumor diameter ≥3 cm were protective factors in the diagnosis subgroup; β-HCG ≥ 5 mIU·mL -1 was found after at least 6 months of onset was a risk factor for delayed diagnosis.
Conclusions：The delayed diagnosis of ICGCTs is related to the characteristics of disease, the cognition of the child's family and the level of hospital treatment. An individualized diagnosis and treatment plan needs to be formulated.
Background：Phelan McDermid syndrome (PMS) is a rare neurodevelopmental disorder, and the SHANK3 gene defect has been identified as a key candidate gene for the neurological characteristics of this syndrome. Currently, no clinical diagnostic criteria have been established, and the confirmed diagnosis relies on genetic testing.
Objective：To summarize the clinical phenotype and genetic characteristics of PMS and to explore the clinical diagnostic pathway of PMS.
Design：Case series report.
Methods：Patients diagnosed with PMS who were admitted to the Department of Child Health Care at Children's Hospital of Fudan University from January 2014 to December 2022 were included. The genotype characteristics, developmental characteristics, clinical symptoms, cranial imaging, EEG and other results were retrospectively analyzed. Literature was searched to summarize clinical diagnostic clues for PMS.
Main outcome measures：Genotype and clinical phenotype.
Results：A total of 42 patients were included in the analysis, including 24 males and 18 females with an average age of 3.8 (1.5-12.9)years at the first diagnosis. In this study, the most common clinical features (>50%) were global developmental delay or intellectual disability (100%), absent or severely delayed speech (100%), inattention (100%), ASD (86%), hyperactivity (82%), delayed major motor development milestones (52%). Other were facial deformities including large but poorly formed ears, full or puffy cheeks, anteverted nares, periorbital fullness, flat midface, fleshy hands/feet, bulbous nose, wide forehead or protruding forehead. The new phenotypes included sparse or absent eyebrow tail, excessive body hair, auricular deformities, drooping eye type, and ligament relaxation. Genetic testing revealed that all 42 cases were pathogenic mutations, of which 21 were 22q13.3 deletions (0.1-7.7Mb, average 3.1Mb) including the SHANK3 gene, 4 were only partial exon deletions of the SHANK3 gene, and 17 were heterozygous point mutations in the SHANK3 gene, including 12 frameshift mutations and 5 nonsense mutations.
Conclusions：When there is neonatal hypotonia, significant delays in motor and language development milestones at 18 months, developmental assessments of any age or form suggesting severe developmental lag in at least five functional areas, as well as the presence of large ears disproportionate to head length and fleshy hands/feet disproportionate to body shape, it should be highly suspected that they were likely to be PMS, and further genetic testing was needed to clarify the diagnosis.
Background: Executive functions (EFs) are crucial for the physical and psychological development of children, and exercise is a cost-effective method to enhance EFs in children. Studies have shown that exercise combined with cognitive training (ECT), which involves higher cognitive engagement, may have a more significant effect on children's EFs. However, existing research conclusions are inconsistent.
Objective: To systematically analyzed the intervention effect of ECT on EFs in children.
Design: Systematic review.
Methods: A systematic search was conducted on PubMed, Web of Science, Cochrane, Embase, Google Scholar, and China National Knowledge Infrastructure (CNKI) databases from the inception to October 17, 2023. Inclusion criteria were: randomized controlled trials (RCT) or non-randomized controlled trials（NRCT）; healthy child participants; ECT intervention with both exercise and at least one explicit cognitive task component for the experimental group; any form of exercise other than cognitive engagement or traditional physical education (PE) for the control group; intervention duration longer than 6 weeks; at least one EF-related assessment outcome; articles in Chinese or English. Risk of bias was assessed using the 2010 Physiotherapy Evidence Database (PEDro) scale. The percentage change in each outcome measure before and after the intervention ［(post-test-pre-test) / pre-test × 100%］ was extracted or calculated, with a P-value < 0.05 indicating significant results. The overall effect size of the indicator was evaluated by the proportion of significant results in all included literature, with > 2/3 indicating a significant effect of the intervention strategy.
Main outcome measures: Percentage change in EF indicators before and after the intervention.
Results: Nine English articles were included. Four articles had aerobic exercise (AE) control groups, and 8 had PE control groups. The intervention lasted from 6 to 40 weeks with 1 to 10 times per week and 10 to 150 minutes for single exercise. PEDro scale scores were 5 in 3 articles, 6 in 5 articles and 7 in 1 article.The improvement in working memory in the ECT group was more significant than that in PE group, with an effectiveness of 71.4%. Improvement in cognitive flexibility were more significant in the ECT group compared to both AE and PE groups, with effectiveness of 100% and 75%, respectively.
Conclusions: ECT significantly improves EFs in school-aged healthy children, with a greater enhancement in cognitive flexibility compared to AE and PE, an improvement in working memory superior to PE, and equivalent improvement in inhibitory control when compared to AE and PE.
