Background：The Chinese Infectious Disease Surveillance of Pediatrics （ISPED） program collects and analyzes the monitoring data of antibiotics resistance from its member units annually to understand changes in pediatric infectious pathogens and resistance patterns in China. Objective：To explore the status of bacterial infections and resistance in children in China for 2023, aiming to guide the rational use of antimicrobial agents in pediatrics. Design：Crosssectional survey. Methods：Clinical isolates were collected from children hospitals in China enrolled in the ISPED program from January 1st to December 31st, 2023. Antimicrobial susceptibility testing was carried out using a unified protocol using the KirbyBauer method or automated systems. Penicillin susceptibility of streptococcus pneumonia was detected by Etest, with results evaluated according to the 2022 standards of the Clinical and Laboratory Standards Institute (CLSI). Main outcome measures：The distribution characteristics of bacteria strains in children, changes in antimicrobial resistance of major isolated strains, and the detection of multidrugresistant organisms (MDROs) in the pediatric population. Results：A total of 58,335 isolates were collected, of which 40% were grampositive organisms and 60% were gramnegative. The top five pathogens were as follows, Escherichia coli (14.5%), Streptococcus pneumonia (12.4%), Staphylococcus aureus (11.8%), Haemophilus influenza (10.2%), and Moraxella catarrhalis (6.4%). The most common pathogens in neonates and nonneonates were S. aureus (17%) and E. coli (14.4%), respectively. The primary specimen was the lower respiratory tract (47.1%), and the most common pathogens were S. pneumonia (24.3%) and H. influenza (19.4%). The rates of βlactamase production in Haemophilus influenzae and Moraxella catarrhalis were high, at 74.7% and 98.6%, respectively. Both S. pneumoniae and S. pyogenes showed highresistance to erythromycin and clindamycin. The proportion of penicillininsensitive S. pneumoniae (PNSP) from cerebrospinal fluid and noncerebrospinal fluid was 93.2% and 9%, respectively. Methicillinresistant S. aureus (MRSA) and Coagulasenegative staphylococci (MRCNS) accounted for 31.2% and 77.2%, respectively. The carbapenemresistant Enterobacteriaceae (CRE), carbapenemresistant P. aeruginosa (CRPA), carbapenemresistant A. baumannii (CRAB) were 3.7%, 8.1% and 30.8%, respectively. The detection rate of CRPA in the neonatal group was higher than that in the nonneonatal group (19.7% vs 7.4%, P<0.01), whereas the detection rate of CRAB was lower than that in the nonneonatal group (23.2% vs 32.1%, P<0.05). CRAB isolated from neonates presented higher resistance to multiple antimicrobials than nonneonates（P<0.05）. The detection rates of MRSA, CRE, CRPA and CRAB in the ICU department were much higher than those in other departments (P<0.001), especially CRAB, which was as high as 62.9%, much higher than that in the hematology department (23.5%, P<0.01) and other departments (28.1%, P<0.001). In addition, the proportion of CRE in hematology patients was 12.8%, higher than the 3.5% in other departments (P<0.001). Conclusion：In 2023, the detection rates of CRE and MRSA in Chinese children showed a decrease compared to previous years, while the overall detection rates of CRAB and CRPA increased compared to the previous two years, with a notably higher detection rate of CRPA in the neonatal group and CRAB in the nonneonatal group. Proactive screening and continuous monitoring of MDROs in the ICU and hematology departments should be strengthened.

Background:Few studies have focused on the adherence to and implementation barriers of clinical practice guideline recommendations. Objective:To assess compliance with the Clinical Practice Guidelines for IntraHospital Transport of Pediatric Patients (2023) among medical staff in the emergency department and PICU and to identify the implementation barriers. Design:Field study Methods:The research was carried out in the emergency department, PICU, and general wards of Children's Hospital of Fudan University. Through participation in the practice of medical staff during intrahospital transport of critically ill children, field notes were used to describe the current situation of oneway transport from the emergency department or PICU to general wards, as well as to analyze the barriers to implementing recommendations in the guideline. Based on recommendations 15 of the guideline, the PICUtotargetdepartment process (Appendix 2G in the guideline), was divided into three phases (pretransport, during transport, and upon arrival at the receiving department) and 10 specific indicators. Descriptive observation, interviews, focus observation, and selective observation were employed to collect data. A template analysis method was used to extract baseline data from the field notes and analyze compliance with specific indicators and barriers. Main outcome measures:Barriers to adhering to recommendations of 15 in the guideline. Results:From January 1st to March 21st, 2024, 49 intrahospital transports of critically ill children involving 25 medical staff (7 emergency nurses, 7 PICU doctors, and 11 PICU nurses) were observed. Ten transports were from the emergency department to the PICU, and 18 and 21 were from the PICU to internal and surgical wards, respectively. The 25 participating medical staff had an average age of 31.3±5.0 years, and the children transported (49 cases) had an average age of 70.0±48.6 months. The average transport time was 16.1±6.0 minutes, with an average bedside handoff time of 6.8±3.5 minutes. Bedside handoffs were interrupted in 11 cases, and two adverse events were recorded during transport: forgetting to carry tube feeding and a child vomiting en route. The 10 indicators across the three phases of transport (pretransport, during transport, and upon arrival at the receiving department) showed partial compliance with the guideline recommendations. The transport decisionmaking, child placement, and inquiry indicators generally aligned with the guideline; the monitoring, telephone communication, and transport planning indicators partially complied, while transport personnel, equipment and medication preparation, evaluation and documentation, and handoff of the child's condition did not meet the guidelines The preparation for receiving the child was in line with the recommendations. Potential barriers to guideline implementation included low enthusiasm among medical staff for adopting new practices, lack of effective communication mechanisms between departments, gaps between recommended practice and clinical situations, poor adherence to specific guideline evidence, and insufficient innovation in the guideline recommendations. Conclusion:Adherence to the guideline recommendations for intrahospital transport of critically ill children is poor. Barriers include insufficient awareness among medical staff regarding the safety of intrahospital transport and a gap between the guideline recommendations and actual clinical transport scenarios.

Objective: To investigate the association between body composition and blood pressure in children. Design: Systematic review/Meta-analysis. Methods: We conducted computer searches in four Chinese databases (CNKI, Wanfang Data, VIP and CBM), as well as four international databases (PubMed, Web of Science, and EBSCO) from inception to August 8, 2023. We included longitudinal cohort studies examining the relationship between body composition and childhood blood pressure. Two reviewers independently screened the literature, extracted data, and assessed the risk of bias in the included studies. We summarized the results quantitatively and qualitatively. Main outcome measures: Association between body composition and childhood hypertension. Results: A total of 9 longitudinal cohort studies were included, investigating the longitudinal relationship between body composition and systolic and diastolic blood pressure in children. Seven of these studies reported the association of fat mass-related indicators with blood pressure in children, showing a positive correlation between childhood fat mass percentage and blood pressure. However, conclusions regarding other fat mass indicators were inconsistent. Two studies reported on the relationship between non-fat mass and childhood blood pressure with inconsistent findings. Three studies reported a positive correlation between fat mass and the occurrence of high systolic and diastolic blood pressure in childhood, although the risk of hypertension may be negatively correlated with neonatal fat mass. Conclusion: The percentage of body fat in children is positively correlated with both diastolic and systolic blood pressure. Body composition has a significant impact on blood pressure in children.

Background：It is still unknown on the etiology, pathogenicity and associated prognostic factors of kawasaki disease(KD). Currently, multiple exposures which are collaborating with genetic background would induce the immunological responses and trigger the onset of KD, even coronary artery injuries. Objective：To explore the significance of genetic susceptibility related to KD, IVIG resistance and coronary artery lesions. Design：Casecontrol study. Methods：Complete KD was diagnosed according to American Heart Association(AHA) guidelines, and coronary artery lesion was defined with echocardiography Zscore>2 according to the JCS/JSCS 2020 guidelines. From April 2020 to January 2022, we continuously recruited complete KD patients at West China Second University Hospital of Sichuan University. The children who were underwent physical examination and blood test from child health department in our hospital were enrolled in the controls. The whole exome sequencing of peripheral blood samples, quality control of raw data, enrichment analysis and site annotation were performed to screen for single nucleotide polymorphisms (SNPs) and associated genes related to KD, IVIG resistance and coronary artery lesions, which helped to compare the response to treatment and clinical outcomes of KD. Main outcome measures：Sites of SNPs and genes which had been associated with KD, IVIG resistance and coronary artery lesions. Results：In total, 171 complete KD patients were enrolled, including 32 cases (27%) of coronary artery lesions and 55 cases (31%) of IVIG resistance, and 139 cases were enrolled in control group. There were no statistical differences in the age between two groups. A total of 609,732 SNPS were screened through upstream analysis. The two groups were separated by the principal component analysis categorized by Han and other ethic minorities, and there was no substructure in the principal component categorized by gender classification. With P<0.000 1 as the threshold, fifteen candidate genes were associated with KD susceptibility, including MYT1L、CYP26B1、NECTIN3、TENM3、GFI1B、KNDC1、LOC100133315、RNF121、SYNE3、MAPKBP1、SLFN14、MYOM1、ABCA7、PIP5K1C、PTGER1(30 SNPs). While six candidate genes had been identified to be associated with coronary artery lesion, including DGKH、CCDC130、KLF7、METTL6、COLQ、PRKN(19 SNPs). Moreover, there were also six candidate genes had been recognized as risk factors with IVIG resistance, including MICALCL、NT5DC3、KRT75、LOC105370980、TXK、BRD2(8 SNPs). Conclusion：In this study,MYT1L（chr2, rs4381806）、NECTIN3（chr3, rs2399373）、MAPKBP1（chr15, rs2303517）have some significance in exploring the pathogenesis of KD. The SNP sites and genes asscociated with IVIG resistance and coronary artery lesions required further investigation.

Background: Skeletal muscle is a vital component of body composition, playing a key role in maintaining normal growth, development, and overall health in children. However, the levels of skeletal muscle development in children and adolescents differ across various social environments and ethnic backgrounds. Objective: To provide genderand agespecific reference standards for skeletal muscle development in children and adolescents, and to compare the patterns of appendicular skeletal muscle development between Chinese and U.S. children and adolescents. Design: Crosssectional study. Methods: A nationwide sample of 12,583 Chinese children and adolescents aged 318 years was drawn from the China Child and Adolescent Cardiovascular Health study (20132019). Data from the National Health and Nutrition Examination Survey (NHANES) for U.S. children and adolescents, aged 818 years from 2011 to 2018 (n=6,467), were also included. Wholebody and appendicular skeletal muscle mass were measured using dualenergy Xray absorptiometry (DXA). Generalized Additive Models for Location Scale and Shape (GAMLSS) method was utilized to estimate the genderand agespecific reference values. Main outcome measures: Appendicular Skeletal Muscle Index (ASMI), Appendicular Skeletal Muscle Ratio (ASMR), Upper Limb Skeletal Muscle Index (ULSMI), and Lower Limb Skeletal Muscle Index (LLSMI). Results: Overall, ASMI, ULSMI, and LLSMI increased with age in children and adolescents. Boys showed a gradual slowing trend of growth after 14 years of age, while girls exhibited a deceleration and even a decrease after 13 years of age. Additionally, for all age groups, U.S. children had higher values for the same Zscores compared to Chinese children, with this difference widening after 14 years of age. ASMR showed a slightly different developmental pattern, with an initial increase followed by a decrease, but the rate of increase was faster in the Chinese population between the ages of 1014 years. All indicators demonstrated significant gender differences, with boys having higher values in all measures. Conclusion: Developmental patterns and disparities of skeletal muscle mass between Chinese and U. S. pediatric population should be assessed based on the sexand agespecific skeletal muscle reference standards of their respective countries.

Background：Polyethylene glycol with electrolyte solution (PEGELS) is safe and effective for bowel preparation in children. The PEG regimen includes oral administration for 14 days. However, longlasting oral administration may cause inconvenience to children's lives, prolong hospitalization, and affect school attendance. It is observed that the intestinal cleanliness is also good in a rapid oral PEGELS protocol of bowel preparation in some children. Objective：To investigate the efficacy, safety and tolerability of rapid or slow bowel preparation protocol using PEGELS in children over 2 years old. Design：Nonrandomized controlled trial. Methods：The newly diagnosed children in Department of Gastroenterology at Children's Hospital of Fudan University receiving the electronic colonoscopy were enrolled from August 1st, 2020 to May 31st, 2021 according to the inclusion and exclusion criteria. The participants were given PEGELS for the bowel preparation. The participants were nonrandomizedly divided into rapidly oral group (PEGELSR) and slowly oral group (PEGELSS). In the PEGELSR group, 2/3 dose of PEGELS was taken orally from the evening on the day before colonoscopy, and the remaining 1/3 dose of PEGELS was orally administered in the morning of the next day. In the PEGELSS group, PEGELS is given orally on the day before colonoscopy, which is divided into 1012 portions and taken one portion every hour. Bowel cleansing was assessed by Boston bowel preparation scale (BBPS). Compliance with PEGELS, adverse events, and tolerability were observed Main outcome measures：Bowel cleanliness. Results：A total of 315 children were enrolled into the study with the average age of (9.8±3.2) years old, 153 cases in PEGELSS group and 162 cases in PEGELSR group, respectively. There were no significant difference in Bristol stool form score between the two groups before electronic colonoscopy. The main reason for colonoscopy was abdominal pain in both groups. The score of BBPS in PEGELSR group was significantly higher than that in PEGELSS group(8.0±1.3 vs 7.1±1.5, P<0.000 1). The rate of excellence in PEGELSR was higher than that in the PEGELSS group［96.3%(156/162) vs 87.6%(134/153), P＜0.000 1］. Both groups of children could complete the dosage of PEGELS well with the completion rate over 90%. The incidence of nausea, vomit, abdominal pain and abdominal distension in PEGELSR group was significantly higher than that in PEGELSS group. There were no adverse events in the two groups. Conclusion：Bowel preparation protocol of PEGELSS and PEGELSR was safe. The bowel cleanliness of PEGELSR regimen is better than that of PEGELSS regimen, but the incidence of adverse reaction of rapid oral PEGELS is higher than that of slow oral administration.

Background: Multisystem inflammatory syndrome in children (MIS-C) is associated with SARS-CoV-2 infection. Most previous studies on MIS-C are case reports or reviews, with refractory MIS-C only documented in individual case reports. Objective: To explore the differences between refractory MIS-C and non-refractory MIS-C and to enhance understanding of the disease. Design: Case-control study. Methods: Consecutive cases of MIS-C from six hospitals in Zhejiang Province were collected. Refractory MIS-C was defined as persistent fever and/or terminal organ involvement after first-line treatment (case group), while the remaining cases were classified as non-refractory MIS-C (control group). The basic information, clinical manifestations, laboratory tests, imaging findings, treatment, and efficacy of the two groups were summarized and analyzed using univariate analysis. Main outcome measures: Clinical characteristics of MIS-C. Results: A total of 23 children with MIS-C were included in this analysis, with an average onset age of 4.8±3.4 years. The interval between SARS-CoV-2 infection or exposure and MIS-C diagnosis was 30±9 days. The case group included 4 children (2 males and 2 females), while the control group included 19 children (10 males and 9 females). There were no statistically significant differences between the two groups in terms of basic information, clinical manifestations, or severe complications. In imaging findings, the case group had higher proportions of involvement in ≥2 serous cavities (75% vs . 16%) and pericardial effusion (75% vs . 11%) compared to the control group. In laboratory tests, the case group showed lower platelet (PLT) counts, higher procalcitonin (PCT), and D-dimer levels, as well as elevated levels of IL-6, IL-10, and IFN-γ, all of which were statistically significant. In the control group, 8 cases (42%) were treated with IVIG alone, 4 cases (21%) with corticosteroids alone, and 6 cases (32%) with a combination of IVIG and corticosteroids. In the case group, all 4 children received additional tocilizumab treatment on top of corticosteroids and IVIG. All 23 children improved and were discharged, with no fatalities. One child in the control group experienced severe intracranial hemorrhage and was left with hemiplegia at discharge and during a 6-month follow-up, but was lost to follow-up thereafter. Another child with coronary artery dilation returned to normal after 1 month of post-discharge follow-up. Conclusion: MIS-C can lead to severe complications such as intracranial hemorrhage, macrophage activation syndrome (MAS), and coronary artery dilation, but generally has a relatively good prognosis. Children with refractory MIS-C exhibit more intense inflammatory responses and more significant multisystem involvement. Tocilizumab is effective in treatment.

Background: Some critically ill children with influenza A virus (IAV) infection may have severe sequelae or even die, but its early clinical manifestations are non-specific. At present, there is a lack of relevant prediction models at home and abroad. Objective: To establish a nomogram prediction model for critical IAV infection in children to help early clinical identification of critical IAV infection. Design: Case-control study. Methods: Consecutive patients with IAV infection who were hospitalized in Children's Hospital Affiliated to Zhengzhou University from January 2018 to November 2023 were enrolled. According to the discharge diagnosis and clinical data, they were divided into critically ill children and non-critically ill children. The demographic data, symptoms on admission, laboratory tests on admission, and co-infection with other pathogens were collected. According to the incidence of IAV in Henan Province, the samle size should be greater than 320 cases. The enrolled children were randomly divided into a modeling group and a validation group at a ratio of 7∶3. The influencing factors of critical IAV infection were screened in the modeling group, and the R 4.3.2 software package was used to construct a nomogram prediction model for critical IAV infection. Main outcome measures: Risk factors for critically ill children with influenza A virus (IAV) infection. Results: Among 391 hospitalized children with IAV infection, 134 cases were critically ill, of whom 20 cases (14.9%) had sequelae, all of them were nervous system damage, and 12 cases (9.0%) died. All the non-critically ill children were cured and discharged. There were 274 cases in the modeling group and 117 cases in the validation group. There was no significant difference in clinical data between the two groups. Multivariate Logistic regression analysis showed that neurological symptoms (OR=6.923, 95%CI: 2.569-18.656), co-infection with other pathogens (OR=3.092, 95%CI: 1.379-6.934), and elevated NLR (OR=1.404, 95%CI: 1.029-1.914) and increased IL-6 (OR=1.009, 95%CI: 1.000-1.018) are risk factors, and propagated rise (OR=0.925, 95%CI: 0.862-0.992) is a protection factor. Taking critical IAV infection as the prediction outcome, a nomogram prediction model was constructed based on neurological symptoms, combined with other pathogen infections, and laboratory indicators such as NLR, IL-6, and ALB. The AUC of the model was 0.949 (95%CI: 0.915-0.982) in the modeling group and 0.912 (95%CI: 0.871-0.952) in the validation group. The nomogram model fitted well (χ2=5.077，P=0.749), the predicted probability was in good agreement with the actual probability, and had a high net clinical benefit rate. Conclusion: The nomogram prediction model based on neurological symptoms, infection with other pathogens and laboratory indexes of NLR, IL-6 and ALB is effective and has good discriminative ability.

Objective：To explore the distribution characteristics of blood uric acid levels and the detection rate of HUA among children attending the hospital. Design： Crosssectional survey. Methods：Children who underwent blood uric acid testing at Children's Hospital Affiliated to Zhengzhou University from July 2022 to July 2023 were included. Eligible subjects were aged >28 days at the time of uric acid testing and had a clear disease diagnosis in their medical records. HUA was defined as peripheral blood uric acid levels of ≥420 μmol·L-1 for males and ≥360 μmol·L-1 for females; levels ≥540 μmol·L-1 were classified as severe HUA. Main outcome measures：Serum uric acid level and the detection rate of HUA. Results：Among 38,317 children with blood uric acid test results, 22,534 were male and 15,783 were female. The overall median blood uric acid level was 259.3 (211.1, 316.1) μmol·L-1, with a statistically significant difference between boys and girls ［262.7 (213.0, 322.3) μmol·L-1 vs. 255.0 (208.3, 308.5) μmol·L-1, Z=10.365, P<0.001］. Blood uric acid levels in boys gradually increased with age, while girls' levels increased until age 14, then gradually declined and increased again after age 17; in all age groups except around ages 8 and 10, boys had higher blood uric acid levels than girls. A total of 3,719 cases of HUA were detected (9.7%), with detection rates of 7.7% (1,730 cases) in boys and 12.6% (1,989 cases) in girls, showing a statistically significant difference (χ2=256.882, P<0.001). The detection rate of HUA in boys increased with age, peaking at 45.8% around age 17; for girls, the detection rate increased until about age 13 (25.7%) and then gradually declined. Before age 13, the HUA detection rate was lower in boys than in girls, but higher after age 14. There were 284 cases of severe HUA (0.7%), with detection rates of 1.0%(222/22,534) in boys and 0.4% (62/15,783) in girls, showing a statistically significant difference (χ2=44.269, P<0.001). The proportion of severe HUA among children with HUA was higher in boys than girls in all age groups except around ages 7 and 17. The highest detection rates of HUA and severe HUA were observed in children with endocrine system diseases (15.3% and 1.8%, respectively), with the highest detection rate in the obesity category (46.3%, 320/691). Conclusion：Pediatric HUA is clinically common, with significant age and gender differences in blood uric acid levels. It is urgent to establish reference values for blood uric acid in children of different ages and genders in China and to develop diagnostic criteria for pediatric HUA to enhance the clinical management of affected children.

Background: Repetitive transcranial magnetic stimulation (rTMS) combined with antidepressants has emerged as a novel therapy for treating depression in children and adolescents. However, predicting early treatment efficacy remains a significant challenge. Objective: To explore potential factors that could predict long-term efficacy during rTMS combined with antidepressant therapy. Design: Retrospective cohort study. Methods: The cohort included children and adolescents under 18 years of age who were newly diagnosed with moderate to severe unipolar or bipolar depression, received rTMS treatment continuously for at least 20 sessions during hospitalization, had daily symptom index (DI-5) scores recorded, and had Hamilton Depression Rating Scale (HAMD) scores recorded before and after the 20th rTMS session. Participants were divided into response and non-response groups based on whether their final HAMD score showed a reduction of ≥50% from baseline. Correlation analysis was conducted between DI-5 and HAMD scores. If a strong correlation was found, the potential of DI-5 assessments during rTMS treatment to predict early response was evaluated. Main outcome measures: Correlation between DI-5 and HAMD scores. Results: A total of 228 children and adolescents with moderate to severe unipolar or bipolar depression met the inclusion and exclusion criteria. The mean age was 14.0 ± 3.0 years, and 111 (48.6%) were male. The Pearson correlation coefficients between DI-5 and HAMD scores before and after rTMS treatment were 0.70 and 0.72, respectively, with both being statistically significant (P< 0.001). After 20 rTMS sessions, there were 101 participants in the response group and 127 in the non-response group. There were no statistically significant differences between the two groups in gender distribution, age, single-parent household proportion, left-behind children proportion, family psychiatric history, age of symptom onset, symptom duration, learning disabilities, language disorders, motor development disorders, weight, height, medication duration, counseling sessions, thyroid dysfunction, time to fall asleep, frequency of dreaming, and picky eating habits (P>0.05). Baseline DI-5 and HAMD scores also showed no statistically significant differences between the response and non-response groups (P>0.05). However, DI-5 scores after the 20th rTMS session were significantly different between the response and non-response groups (P<0.001), as were the final HAMD scores (P<0.001). On the 11th session, the DI-5 scores showed a statistically significant difference between the response and non-response groups (P<0.001). A median reduction of 2 points in DI-5 scores was used as a stratification basis. In the group with a reduction of <2 points on the DI-5 scale, 107 participants (46.9%) had a 98.1% probability of being in the non-response group by the 20th rTMS session. In the group with a reduction of ≥2 points, 64 participants (87.4%) had an 89.2% probability of being in the response group by the 20th rTMS session. Conclusion: A reduction of ≥2 points on the DI-5 scale by the 11th rTMS session may serve as an early predictor of treatment efficacy for rTMS combined with antidepressants in children and adolescents with depression.

Background: Historically, infectious diseases have been the primary focus of pediatric gastrointestinal disorders. However, in recent years, the diagnosis rate of genetic metabolic diseases has gradually increased. Objective: To summarize the clinical phenotypes and genotypes of common genetic metabolic diseases affecting the digestive system. Design: Case series report. Methods: This study included children who presented with gastrointestinal symptoms and had abnormal whole-exome sequencing results at a single center between January 1, 2015, and December 31, 2019. Demographic data, clinical information, and genetic testing results were extracted from the medical records system. Main outcome measures: Clinical phenotypes and genotypes. Results: Among the 320 children who underwent genetic testing in the gastroenterology department, 111 (34.7%) had abnormal results. The mean age at diagnosis was 2.4±2.8 years, and 68 (61.3%) were male. The main disease phenotypes included hereditary liver diseases in 70 cases (63.1%), with Wilson's disease and glycogen storage diseases each accounting for 15 cases, Citrin deficiency for 13 cases, Alagille syndrome, progressive familial intrahepatic cholestasis (PFIC), and bilirubin metabolism disorders for 9 cases each. Other conditions included very early-onset inflammatory bowel disease (VEO-IBD) in 8 cases (7.2%) and progressive muscular dystrophy in 10 cases (9.1%).Wilson's disease commonly presented as asymptomatic persistent transaminase elevation (53.3%), with the ATP7B gene c.2333G>T (p.R778L) being the most common mutation site (53.3%). Glycogen storage disease patients mainly exhibited hypoglycemia, hepatomegaly, abnormal liver function (93.3% for all), and elevated triglycerides (60.0%). Subtypes included type Ⅸa (6 cases), type Ⅲ (5 cases), and one case each of GSD Ⅰa, GSD Ⅱ, GSD Ⅵ, and GSD ⅩⅤ. Alagille syndrome was associated with abnormal liver function in all 9 cases, and 8 (88.9%) visited the hospital due to yellowish discolouration of the skin and sclera. The JAG1 gene mutation (Alagille syndrome type 1) was found in 8 cases (88.9%), and the NOTCH2 gene mutation (Alagille syndrome type 2) was found in 1 case. Citrin deficiency patients were mostly admitted due to yellowish discolouration of the skin and mucous membrane (92.3%) and exhibited abnormal liver enzymes, cholestasis, and hypoglycemia. All 13 cases had mutations in the SLC25A13 gene, with c.851_854del (38.5%) and c.852_855del (30.8%) being the most common mutations. Progressive familial intrahepatic cholestasis (PFIC) was characterized by hepatomegaly, elevated ALT, AST, and total bile acids in all 9 cases. The subtypes included type 2 (6 cases with ABCB11 gene mutations), type 3 (2 cases with ABCB4 gene mutations), and type 1 (1 case with ATP8B1 gene mutation). Bilirubin metabolism disorders were identified in 9 cases presenting with jaundice and/or abnormal liver function, all of which had UGT1A1 gene mutations. The most common mutation sites were c.211G>A (p.G71R) (66.7%) and A(AT)6TAAinsTA (55.6%). VEO-IBD was primarily characterized by chronic diarrhea in all 8 cases, with elevated WBC counts and CRP levels. Endoscopic findings showed cobblestone-like changes and deep ulcers in the colonic mucosa. Seven cases had IL10-RA gene mutations, with c.301C>T (p.R101W) (62.5%) and c.537G>A (p.T179T) (50%) being the most common, and one case had a heterozygous mutation in the IL10-RB gene. Conclusion: Genetic testing plays a crucial role in the diagnosis and treatment of genetic metabolic diseases affecting the digestive system in children.

Background：Children with refractory and relapsed acute lymphoblastic leukemia (ALL) have poor prognosis. It is significant to identify new molecular markers with prognostic value to assist in prognosis assessment. Objective：To explore the expression level of the IDE gene in children with ALL and its correlation with prognosis. Design：Retrospective cohort study. Methods：A total of 77 newly diagnosed ALL patients admitted to Beijing Children's Hospital, Capital Medical University, from January 1st, 2020, to October 31st, 2020, were included in the study as a testing cohort. The expression level of the IDE gene in bone marrow mononuclear cells at diagnosis was analyzed using ROC curve analysis to set the IDE cutoff value, comparing the prognosis of highexpression and lowexpression groups. The validation cohort consisted of ALL patients admitted to Henan Children's Hospital during the same period, and it was used to verify the correlation between the established IDE cutoff grouping criteria and prognosis. Prognostic factors, including clinical biological characteristics and early treatment responses, were also analyzed. Main outcome measures：Eventfree survival (EFS). Results：A total of 77 newly diagnosed ALL patients were included, with 37 in the testing cohort and 40 in the validation cohort. The expression level of the IDE gene at diagnosis was correlated with the prognosis of ALL. Patients with adverse events had significantly higher IDE expression levels at diagnosis than those without adverse events (P<0.001). ROC analysis showed that the IDE gene expression level could predict the prognosis of ALL patients, with an AUC of 0.961 (P<0.001). The cutoff value was set as 0.72 by the ROC curve. In the testing cohort, the highexpression group (IDE≥0.72, n=19) had a significantly worse prognosis than the lowexpression group (IDE<0.72, n=18), with 3year EFS rates of 55.7% and 100%, respectively (P=0.002). In the validation cohort, the highexpression group (n=26) and lowexpression group (n=14) had 3year EFS rates of 64.3% and 96.2% (P=0.009), which was statistically significant. Multivariate analysis indicated that high clinical risk and high IDE expression were independent prognostic factors for EFS in ALL patients, with risk ratios of 4.254 (95% CI: 1.08017.554, P=0.039) and 21.773 (95% CI: 2.632180.125, P=0.004), respectively. The predictive capacity of the recurrence risk index for prognosis, composed of these two independent prognostic factors, was higher than the current clinical risk stratification (AUCs of 0.892 and 0.741, P=0.009). Conclusion：High expression of the IDE gene is closely associated with poor prognosis in children with ALL.

Background: Minimal residual disease (MRD) is used to monitor and assess the treatment response in pediatric acute lymphoblastic leukemia (ALL) and to stratify risk based on MRD levels. Objective: To investigate the prognostic value of regularly monitoring MRD during and after chemotherapy in predicting relapse in children with ALL. Design: Retrospective cohort study Methods: The clinical data of 224 ALL children received CCCG-ALL2015 chemotherapy from January 2015 to February 2020 were retrospectively included in our study. MRD was detected using flow cytometry to analyze the association between regular monitoring of MRD and prediction of recurrence. Main outcome measures: Recurrence free survival (RFS) Results: A total of 224 children were included in this analysis, with 134 males and 90 females, and a median age of 4.8 years. On day 19 (D19) of induction remission, 104 cases (46.4%) were MRD-positive, and on day 46 (D46), 23 cases (10.3%) were MRD-positive. From post-induction remission (week 16) to the end of chemotherapy (week 125), 145 cases remained MRD-negative. During follow-up after the end of chemotherapy (weeks 152-287), 13 cases became MRD-positive, of which 11 (84.6%) relapsed. A total of 28 children relapsed, with a median relapse time of 33 months. Among them, 14 survived, 12 died, and 2 were lost to follow-up. There were 20 cases of bone marrow relapse, including 2 with concurrent testicular relapse and 1 with CNSL and 8 with CNSL alone. The median follow-up time for the 224 children was 52 months (IQR: 36.5-69.5 months), and the 5-year RFS was (84.5±2.8)%. There were statistically significant differences in the 5-year RFS between children with D46 MRD ≥0.01% and <0.01%, as well as between those who remained MRD-negative throughout chemotherapy and those who were MRD-positive at least once (P<0.05). Conclusion: Children with D46 MRD ≥0.01% and those who were MRD-positive at least once during chemotherapy had a poorer prognosis. Regular MRD monitoring during chemotherapy is crucial.

Background: Traditional indicators like BMI are insufficient for comprehensive assessment of children's nutritional status and health risks. Body composition analysis offers a more precise method to evaluate the distribution of fat, muscle, and water content in children's bodies, providing new avenues for health assessment. Objective: To investigate the correlation between body composition and blood pressure levels among schoolage children in two southwestern provinces and one municipality (Sichuan, Guizhou, Chongqing) of China, providing scientific evidence for early prevention of childhood hypertension. Design: Crosssectional survey. MethodsUsing multistage stratified cluster sampling, students from primary and secondary schools in the three areas were recruited. Data on basic information, family circumstances, pubertal development, family medical history, nutritional status, and dietary habits were collected through questionnaires. Standardized physical measurements, blood pressure measurements, and body composition parameters (body fat percentage, muscle ratio, water content, protein, and mineral content) were obtained using bioelectrical impedance analysis. Univariate analysis was conducted for included variables, and restricted cubic splines (RCS) analysis was used to explore the doseresponse relationship between body composition and elevated blood pressure risk. Main outcome measures: Association between body composition and blood pressure. Results: The study analyzed 8,397 students from six schools across the three areas, including 5,722 primary school students and 2,675 secondary school students; 4,593 from urban areas and 3,804 from rural areas. The mean age was (10.9±2.4) years, with 4,445 boys (52.9%) and 3,952 girls. Elevated blood pressure was detected in 784 students (9.3%), with higher prevalence in boys compared to girls, overweight/obese children compared to nonoverweight/obese children, those who had entered puberty compared to those who had not, and those with high salt intake compared to those without (all P<0.05). All five body composition indicators showed significant correlations with blood pressure (all P<0.05). Genderspecific patterns emerged in the relationship between body composition indicators and elevated blood pressure risk. In girls, body fat percentage, water content, muscle ratio, and protein content showed linear correlations with elevated blood pressure risk, while mineral content showed a nonlinear correlation. In boys, body fat percentage and mineral content showed nearly linear correlations with elevated blood pressure, while muscle ratio, water content, and protein content showed nonlinear correlations. Using medium levels of each gender as reference, only low body fat percentage and high water and protein content in boys showed no statistically significant differences in systolic blood pressure, diastolic blood pressure, and mean arterial pressure, while other parameters showed significant increases or decreases. Conclusion: Body composition is closely associated with elevated blood pressure in both male and female primary and secondary school students. Incorporating body composition analysis into cardiovascular health risk assessment may aid in early identification of elevated blood pressure in children.

Background: Current research mostly explored the effect of single behavior on muscle development under traditional regression models, ignoring the temporal relationship between behavior changes. The iso-temporal substitution model can accurately quantify the comprehensive effect of all behavior changes on muscle development. Objective: To explore the association between different physical behaviors and muscle development in children and adolescents in Guangzhou based on the iso-temporal substitution model. Design: ross-sectional survey. Methods: A total of 7,767 children and adolescents aged 6-17 years were enrolled in Guangzhou between November 2020 and June 2021. Questionnaire survey was conducted to collect information on physical activity, sleep, and sedentary behaviors. Body compositions were measured using bioelectrical impedance analysis. Based on linear regression model, iso-temporal substitution model was conducted to evaluate the effect estimates for substitution of sedentary behavior with moderate-vigorous physical activity(MVPA), light physical activity(LPA), or sleep on muscle development, with 30 min·d-1 as the substitution unit. Main outcome measures: Fat-free mass index (FFMI), fat-free mass percentage (FFM%), and appendicular skeletal muscle mass percentage (ASMM%). Results: Replacing 30min of sedentary behavior with MVPA per day significantly increased the Z-scores of FFMI, FFM%, and ASMM% by 0.08, 0.04, and 0.07 units (all P<0.05), respectively. Replacing sedentary behavior with 30 min·d-1 of sleep duration was significantly associated with decrease of FFMI Z score (β=0.04, P<0.05) and increase of FFM% Z score (β=0.03, P>0.05). The stratification analysis by gender and grade level showed similar results, with no significant heterogeneity between subgroups. Conclusion: Replacing sedentary behavior with 30 min of MVPA per day is associated with the increase of FFM and ASMM. The iso-temporal substitution of sedentary behavior with sleep may also be positively associated with muscle development.

Objective: To explore the association between dietary patterns and body composition among children and adolescents in Guangzhou. Design: Crosssectional survey. Methods: Primary and middle school students aged 617 years were enrolled using the stratified cluster sampling method from March to December 2019. Information on dietary intake 13 types of food was collected by questionnaires. Body composition measurements were performed. Factor analysis was used to extract dietary patterns. Multivariate linear regression models were used to analyze the association between dietary patterns and body composition. Main outcome measures: Zscores of body fat percentage (BF%), fatfree mass index (FFMI), and fat mass/fatfree mass ratio (FM/FFM). Results: total of 7,590 children and adolescents were included in the analysis, with an average age of 11.7±2.9 years, and 4064 males (53.5%). Four dietary patterns were constructed, including balanced diet, refined grains and meat, fried and pickled food, and fruit and dairy diet patterns. After adjusting for demographic characteristics, the highest quartile of factor scores in the balanced diet pattern compared to the lowest quartile showed a decrease of 0.07 standard deviations in BF% Zscore (β=-0.07, 95%CI=-0.140.00) and FM/FFM Zscore (β=-0.07, 95%CI=-0.140.00). In the fruit and dairy diet pattern, the highest quartile of factor scores compared to the lowest quartile showed an increase of 0.10 standard deviations in FFMI Zscore (β=0.10, 95%CI=0.030.17). No statistically significant association was found between other dietary patterns and body composition (P>0.05). Conclusion: The balanced diet pattern is associated with a reduction in body fat, and the fruit and dairy diet pattern is associated with an increase in fatfree tissue or muscle.

Background：The diagnosis of true obesity was recommended to be based on body fat quantity and distribution by body composition measurement. However, the riskbased overfat cutoffs were scarce for pediatric population. Objective：To develop cutoffs and the optimal combination for body fat indices for screening persistent hyperglycemia and dyslipidemia among the pediatric population. Design：Prospective cohort study. Methods：Subjects who participated in the 2017 baseline and 2019 followup survey of Schoolbased Cardiovascular and Bone Health (SCVBH) Promotion Program with complete data of body composition and blood test, were selected as the study population. The gold standard was persistent hyperglycemia and dyslipidemia in both baseline and followup surveys, including persistent impaired fasting glucose (IFG), persistent high total cholesterol (TC), persistent high TG, persistent high low density lipoprotein cholesterol (LDLC), persistent low high density lipoprotein cholesterol (HDLC) and persistent high NonHDLC. The predictors included body mass index (BMI) and body fat indices derived from bioelectrical impedance analysis, including fat mass index (FMI), fat mass percentage (FMP), trunk to leg fat ratio (TLR).The area under the receiver operating characteristic curve was used to determine the best combination and optimal cutoffs of body fat indices for detecting persistent hyperglycemia and dyslipidemia. Main outcome measuresThe best combination and optimal cutoffs of body fat indices for detecting persistent hyperglycemia and dyslipidemia. Results：A total of 10 603 (mean age at baseline: 10.9 ± 3.3 years, 49.4% males) children and adolescents aged 618years were included for analysis. Among, 371 (3.5%) were diagnosed as persistent lFG,131 (1.2%) as persistent high TC, 128 (1.2%) as persistent high TG, 118 (1.1%) as persistent high LDLC, 448 (4.2%) as persistent low HDLC, and 212 (2.0%) as persistent high nonHDLC. According to the results for ROC analyses and Delong tests, the capability of FMI+TLR combination for detecting persistent IFG, persistent high TC and persistent high LDLC were statistically higher than BMI in both sexes (All P<0.05). Moreover, the combined use of FMI+TLR presented higher capability for detecting persistent high NonHDLC ［AUCFMI+TLR：0.664 (0.6150.713) vs AUCBMI：0.617 (0.5570.677), P<0.001］ than BMI in girls. According to the ROC analysis, the optimal overfat cutoffs of FMI were determined at the range of 75th percentile to 95th percentile, and TLR were determined at the range of 75th percentile to 90th percentile, varied by indicators for persistent hyperglycemia and dyslipidemia. Conclusion：The FMI + TLR combination presented higher predictability for discriminating persistent hyperglycemia and dyslipidemia among children and adolescents. We suggest the 75th percentile of FMI to be the cutoff for mild general overfat, the 90th percentile of FMI to be the cutoff for severe general overfat, the75th percentile of TLR to be the cutoff for mild central overfat, the 90th percentile of TLR to be the cutoff for severe central overfat.

Background: The prevalence of overweight and obesity among children and adolescents in China is increasing. Existing studies have mostly explored the effects of single lifestyle behaviors on body composition, lacking evidence about the association between integrated lifestyle behaviors and body composition. Objective: To explore the association between healthy lifestyle behavior index and body composition in children and adolescents. Design: Crosssectional survey. Methods: This study enrolled 1,703 students aged 6 to 17 years in April 2019 in a middle school and an elementary school in Guangzhou. Body composition was measured by dualenergy Xray absorptiometry, and a questionnaire survey was performed to collect information about lifestyle behaviors. The healthy lifestyle behavior index was constructed based on seven items, including adequate sleep, moderate sedentary behavioral time, adequate moderate to vigorousintensity activity, daily breakfast, daily vegetables, daily fruits, and no intake of sugarsweetened beverages. For each item meeting, one point was assigned, and the healthy lifestyle behavior index is the total sum of all points achieved, which was further divided into three levels: low (02 points), medium (4 points), and high (7 points). Multiple linear regression models were performed to analyze the association of the healthy lifestyle behavior index and its levels with body composition (Zscores). Main outcome measures: Total body and central adiposity, whole body and appendicular muscle mass. Results: Of the 1,703 students aged 617 years, 924 (54.3%) were boys and 779 (45.7%) were girls. In the statistical analysis, adjustments were made for the age of children and adolescents, the highest educational level of their parents, and annual family income. In boys, the healthy lifestyle behavior index was positively associated with the muscle mass index (MMI) and the appendicular skeletal muscle mass index (ASMI) (all βs=0.07, both 95%CI=0.02 0.12). Compared to the lowlevel behavioral index, the medium and highlevel indices were associated with increased Zscores for MMI (βmedium=0.22; βhigh=0.30) and ASMI (βmedium=0.22; βhigh=0.29). In girls, the healthy lifestyle behavior index was negatively associated with Zscores for BF%, VFA, and FMR (all β=-0.07, all 95%CI=-0.12  -0.01). Compared to the lowlevel index, there was an association between the highlevel index and lower Zscores for BF%, VFA, and FMR, with β coefficients of -0.29, -0.29, and -0.28, respectively. When stratified by age groups, the associations between the healthy lifestyle behavior index and body composition remained statistically significant in pubertal boys (1217 years old) and girls (1017 years old). Conclusion: Healthy lifestyle behavior index is associated with an increase in muscle mass in boys and decreases in total body and central adiposity in girls.

Background：The accuracy of bioelectrical impedance analysis (BIA) in measuring body composition of children and adolescents is controversial, and there is a lack of correction formulas that do not rely on the brand and model of BIA instrument. Objective：To evaluate the consistency of BIA and dualenergy Xray absorptiometry (DXA) in measuring body composition in children and adolescents aged 619 years. Design：Crosssectional survey. Methods：The subjects were selected from the 20132023 China Life Cycle Body Composition Study, and 1,841 schoolage children and adolescents were tested using the same BIA and DXA instruments. Intragroup correlation coefficient (ICC), relative error frequency (RE), and BlandAltman analysis were used to evaluate the consistency of measurements of fat mass (FM), nonfat tissue mass (FFM), and limb skeletal muscle mass (ASM). With DXA as the dependent variable and resistance index (RI) as the independent variable, a prediction model for BIA correction was established. Main outcome measures：ICC, RE, and BlandAltman analysis. Results：In different sexes, compared with DXA, BIA underestimated FM (RMSE=2.60, 2.27 kg, P<0.05), underestimated ASM (RMSE=1.02, 0.91 kg, P<0.05), and overestimated FFM (RMSE=3.07, 2.66 kg, P<0.05) for male and female students. The ICC of FM, FFM and ASM of male and female students were all >0.90 (P<0.05). With the increase of age, the proportion of ICC and RE with absolute value <15% in FM increased gradually, while the proportion of ICC and RE with absolute value <15% in ASM first increased and then decreased. With the increase of BMI, the proportion of ICC and RE with absolute value <15% of FM increased gradually. The BIA corrected prediction model is: FM= 2.336+0.871×RI50-1.739×RI500+0.517×SexM1F2-0.478×Age+0.753×Weight (R2=0.940)；FFM=2.795-1.406×RI50+2.177×RI500-0.329×SexM1F2+0.471×Age+0.243×Weight (R2=0.985); ASM=-1.937-0.697×RI50+1.132×RI500-0.389×SexM1F2+0.119×Age+0.095×Weight (R2=0.976). Conclusion：BIA measured ASM, FFM and DXA in schoolage children and adolescents with good agreement, FM and DXA with poor agreement. The corrected model of FM, FFM and ASM measured by BIA has good fitting effect, and can be used to evaluate the body composition of schoolage children and adolescents with different types of multifrequency BIA instruments.

Background: The traditional treatment for activated phosphoinositide 3-kinase δ (PI3Kδ) syndrome (APDS) has shown limited efficacy in preventing infections. Recently, rapamycin has been used in the clinical treatment of children with APDS type1 (APDS1) caused by PIK3CD gene mutations. Objective: To investigate the efficacy and safety of rapamycin in the treatment of APDS1. Design: Case series report. Methods: This study included consecutive cases diagnosed with APDS1 via genetic testing and treated with oral rapamycin from June 2017 to June 2023 at the Children's Hospital of Zhejiang University School of Medicine. The use of rapamycin for treating non-tumorous lymphoproliferation due to APDS in children is off-label in China. Before treatment, parents were fully informed of the risks and signed informed consent. The oral dosage of rapamycin was 1 mg·m-2·d-1. Main outcome measures: The number of pneumonia episodes within 12 months and ultrasound assessment of liver, spleen, and lymph node enlargement. Results: Among the four children treated with rapamycin for APDS1, three were male and one was female. The average age of onset was 35.5±17.9 months, and the average age at diagnosis was 56.5±35.0 months. Whole-exome sequencing revealed a de novo heterozygous mutation in the PIK3CD gene (c.3061G>A, p.E1021K) in all cases. All presented with recurrent coughing and had hepatosplenomegaly and lymphadenopathy. All had pneumonia. There were 2 cases of recurrent mumps, 2 cases of growth retardation, and one case each of atopic dermatitis, inflammatory bowel disease, and Wegener's granulomatosis. Bronchoscopy showed cobblestone-like bulge in the bronchial mucosa in three cases. All had reduced CD19+ B cells and inverted CD4+/CD8+ ratios; three had elevated IgM levels, and one had decreased IgG. Prior to rapamycin, all received IVIG, anti-infective treatment and corticosteroids, yet continued to suffer from recurrent respiratory infections and hepatosplenomegaly. Additionally, three developed thrombocytopenia and two had anemia. Rapamycin was administered orally to all children from 1 to 44 months after diagnosis for 12 to 58 months. Following 12 months of rapamycin treatment, the average annual number of pneumonia episodes decreased from 5.3 to 1.0. There was significant improvement in hepatosplenomegaly and superficial lymphadenopathy, and Hb and PLT levels returned to normal. However, there were no statistically significant differences in immunological parameters before and after treatment. No rapamycin-related adverse effects, tumors, or deaths were observed during follow-up. Conclusion: Rapamycin is relatively safe and has some efficacy in treating APDS1.

Background: The influencing factors of obesity phenotype were not yet entirely clear. Most existing studies focused on the association between single lifestyle behavior and obesity phenotype but lacking comprehensive investigation of lifestyle behaviors on obesity phenotype. Objective: To explore the association of the healthy lifestyle behavior index and its levels with obesity phenotypes in children and adolescents, and to provide a scientific basis for promoting healthy development of children and adolescents. Design: Crosssectional study. Methods: The questionnaire survey for lifestyle behavior was performed among a total of 8,222 children and adolescents in Guangzhou, and healthy lifestyle behavior index was constructed, and cardiovascular metabolic indexes were tested. The association of the healthy behavior index and its levels with obesity phenotype was analyzed using multivariate logistics regression. Main outcome measures: Obesity phenotypes were classified by combining weight and metabolic status as Metabolically Healthy Normal Weight (MHNW), Metabolically Unhealthy Normal Weight (MUNW), Metabolically Healthy Overweight (MHOW), Metabolically Unhealthy Overweight (MUOW), Metabolically Healthy Obesity (MHO), and Metabolically Unhealthy Obesity (MUO). Results: Each point increase in the lifestyle behavior index was associated with reduced risk of MUNW, MHOW, and MUO (ORs=0.95, 0.91, and 0.88, respectively, all P<0.05). Highlevel behavioral indices reduced the risk of MUNW, MHOW, and MUO by 18%, 29%, and 41%, respectively, compared to a lowlevel index (all P<0.05). Highlevel behavioral indices reduced the risk of MUO by 38% compared to MHO (P<0.05). Increase in healthy lifestyle behavior index was associated with lower risk of MUNW (OR=0.93, P<0.05) in boys and reduced risk of MHOW in girls (OR=0.88, P<0.05). When stratified by age, the highlevel behavioral indices reduced the risk of MUNW by 21% in the age group of 1218 years and MHOW by 41% in the age group of 611 years. Conclusion: The increased healthy lifestyle behavior index is associated with lower risk of MUNW, MHOW, and MUO. Additionally, these associations differ in sex and age.

Background: Maternal separation anxiety is important for children's socialemotional development. However, the influence of postpartum separation anxiety on early childhood and the critical time points of its effect are still unclear. Objective: To explore the impact of maternal separation anxiety at different time points within 2 years at 4 time points after delivery on socialemotional behavior problems of preschool children. Design: Prospective cohort study. Methods: In the Shanghai Sleep Birth Cohort, women during the third trimester, aged 18 to 45, gestational age ≥28 weeks, without any known deformity, longterm resident in Shanghai, delivery in the eastern division of the Renji Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, and single pregnancy were included as the cohort population. The offsprings were included if they were born at term and weighed 2500 to 4000g at birth, and excluded if they were admitted to the NICU after birth, or their Apgar score was ≤7 at 1 or 5 minutes with asphyxia at birth. Maternal education level, family annual income, maternal age at delivery, maternal depression, anxiety, and overall stress level were assessed during late pregnancy, and the offspring were evaluated for temperament type when they were 6 months old. Maternal separation anxiety was assessed by the Maternal Separation Anxiety Scale (MSAS) at 6, 12, 18, and 24 months postpartum, and the offspring's socialemotional development was assessed with the Strengths and Difficulties Questionnaire (SDQ) at age 6. Main outcome measures: Total difficulties score, internalizing problems, and externalizing problems. Results: From May 2012 to July 2013, 262 dyads of pregnant women and their offspring newborns were included according to the criteria for mothers and neonates. There was no statistical significance in the sensitivity analysis of baseline data between the withdrawn samples (n=80) and the final included samples in the current study (n=182). Maternal age at delivery was 29.7±3.3. Most of the mothers attained the highest education level of bachelor or college degree (73.1%). Maternal depression assessed by the Center for Epidemiological Studies Depression Scale, anxiety assessed by State-Trait Anxiety Inventory scale and stress level assessed by Life Events Scale for Pregnant Women represented good overall mental health. Family annual income of 140,000 to 290,000 RMB accounted for 48.6%, <140,000 RMB accounted for 38.1%. Among the temperament types of children aged 6 months, 44.3% were "easy", 39.2% were "intermediate low", and 16.5% were "intermediate high" or "difficult". Maternal separation anxiety gradually decreases at 6, 12, 18, 24 months postpartum. Specifically, maternal separation anxiety at 18 and 24 months postpartum was lower than that at 6 months postpartum, which was statistically significant. Higher family annual income predicted lower separation anxiety at 18 months postpartum, and mothers with higher education had lower levels of separation anxiety at 6 and 18 months postpartum. Maternal age at delivery was significantly negatively correlated with maternal separation anxiety at 18 months postpartum, maternal depression in late pregnancy was significantly positively correlated with maternal separation anxiety at 18 months and 24 months postpartum, and maternal trait anxiety in late pregnancy was significantly positively correlated with maternal separation anxiety at 24 months postpartum. Neither child gender nor temperament was significantly associated with maternal separation anxiety. After controlling for basic demographic information and maternal emotional state during late pregnancy, maternal separation anxiety at 12 and 18 months postpartum was significantly and positively associated with children's internalizing problems at 6 years of age. There was no significant association between maternal separation anxiety at 6 months postpartum and children's internalization problems at 6 years of age, and no significant association between maternal separation anxiety and children's externalization problems and difficulty scores at 6 years of age. Conclusion: Maternal separation anxiety early in life is a unique risk factor for children's socioemotional development and is significantly associated with internalization problems in children at preschool age.