Table of Content

15 September 2024 Volume 42 Issue 9

  

Commentary

Principles and practice of the Born in Guangzhou Cohort Study

QIU Xiu, WEI Dongmei, LIN Shanshan, XIA Huimin, ZHOU Wenhao

Journal of Clinical Pediatrics. 2024, 42(9):  747-752.  doi:10.12372/jcp.2024.24e0823

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Birth cohorts are important research tools and resources for exploring the impacts of early life risk factors on offspring’s health throughout their life courses. However, large-scale birth cohorts with long-term follow-up are lack in China. The Born in Guangzhou Cohort Study (BIGCS), a large general-population parent-child prospective cohort, was officially launched in 2012 to conduct long-term longitudinal observation of participating families from pregnancy to offspring. This cohort collected data and biological samples through face-to-face follow-up at multiple time points, including early pregnancy, mid-pregnancy, late pregnancy, delivery, as well as 6 weeks, 6 months, 1 year, 2 years, 3 years, 6 years, and 8.5 years after birth. Cohort children were planned to be followed up to 18 years of age. Up to June 2024, the BIGCS has recruited over 60000 pregnant women and 53000 children, among whom 27000 children are over 6 years old, with over 2.9 million specimens. The aim of this study is to identify the risk factors associated with adverse maternal and children’s health outcomes and explore their potential mechanisms and provide scientific evidences for developing the strategies to improve women and children’s health. This paper will give a brief introduction to the establishment, research progress, and future development of the BIGCS.

A large birth cohort focusing on the environment and addressing diseases

CHEN Qian, TIAN Ying, SUN Kun, ZHANG Jun

Journal of Clinical Pediatrics. 2024, 42(9):  753-757.  doi:10.12372/jcp.2024.24e0738

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Based on the theory of the developmental origins of health and disease, Shanghai Birth Cohort and the Early Life Plan have been conducted in Xinhua Hospital affiliated to Shanghai Jiao Tong University School of Medicine. Utilizing professional knowledge and perspectives, we focus on the first 1 000 days of life, paying close attention to the various environmental factors such as the social and physiochemistry environment, nutrition and health status of the mother during pregnancy and babies after birth. This research aims to provide a basis for the prevention, and treatment of developmental diseases.

The Shanghai Maternal-Child Pairs Cohort (MCPC) and its application in clinical research

ZHANG Yunhui, SHI Huijing, ZHAI Xiaowen

Journal of Clinical Pediatrics. 2024, 42(9):  758-767.  doi:10.12372/jcp.2024.24e0817

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The rapid development of socio-economics has led to prominent derivative issues such as changes in psychological health, behavioral lifestyles, and environmental quality, which urgently require long-term cohort studies on birth cohorts. These studies should focus on the impact of material and social environmental factors on the health of people in mega-cities and seek the patterns and risk factors of diseases in the new era. The Shanghai Maternal-Child Pairs Cohort (MCPC) adopts a comprehensive and meticulous follow-up approach that integrates "community + obstetric hospitals + schools," conducting 13 follow-ups on 6714 mother-child pairs from early to mid-pregnancy, the delivery period, and the offspring from birth to six years old. MCPC has established a follow-up information database containing millions of data entries, including standardized questionnaires, maternal and child disease diagnosis, child physical growth, body composition, spinal deformities, fingerprint and palmprint, grip strength, physical activity, cognitive ability, and language development level tests, as well as clinical medical records. Additionally, a biobank has been created with 600000 samples from 17 categories, including peripheral blood, umbilical cord blood, finger prick blood, meconium, placenta, urine, feces, buccal mucosa, hair, and nails. Furthermore, 21 standardized SOP documents have been formulated to manage and control the entire process of the sample bank, from collection to cold chain transportation, storage, retrieval, and return. This cohort platform not only provides crucial support for revealing the impact of early-life environmental exposures on population health and multi-omics research but also promotes interdisciplinary innovation.

The origins and development of the healthy life trajectory program: a cohort of community-family-mother-child multidimensional interventions for overweight and obesity in children

FAN Jianxia

Journal of Clinical Pediatrics. 2024, 42(9):  768-773.  doi:10.12372/jcp.2024.24e0818

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The healthy life trajectories initiative (HeLTI) is a prospective birth cohort intervention study led by the World Health Organization (WHO), which involves multiple countries including China, Canada, South Africa, and India. The project aims to explore and establish community-family-maternal-child (CFMC) intervention measures that cover multiple stages such as pre-pregnancy, pregnancy, infancy and early childhood by the advantages of HeLTI in personalized health education and authoritative professional health guidance. It aims to implement continuous and multi-level interventions to build an international collaborative research platform, and to achieve the goal of preventing developmental diseases such as obesity from the earliest stage of life. The life tree project (Sino Canadian health life trajectories initiative, SCHeLTI) is jointly funded by the National Natural Science Foundation of China (NSFC) and the Canadian Institutes of Health Research (CIHR). It is led by the International Peace Maternal and Child Health Hospital, and has formed a research team with well-known universities and institutions such as Xinhua Hospital, Fudan University Obstetrics and Gynecology Hospital, and Sherbrooke University in Canada. The project is mainly implemented in 42 community health service centers in Xuhui District, Changning District, Minhang District, Fengxian District, and Songjiang District of Shanghai. The multi-level comprehensive interventions in this project will be promoted in Shanghai and even throughout the whole China, and provide scientific basis for WHO to develop intervention guidelines for childhood obesity.

Original Article

The application value of metformin in adolescents with T1DM based on continuous scanning glucose monitoring system

LIU Fang, CHEN Qiong, LI Yangshiyu, LI Yuan, CAO Bingyan, WEI Haiyan, ZHANG Miao

Journal of Clinical Pediatrics. 2024, 42(9):  774-781.  doi:10.12372/jcp.2024.23e1198

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Objective To investigate the efficacy of metformin combined with insulin injection in the treatment of adolescents with type 1 diabetes mellitus (T1DM) based on the continuous scanning glucose monitoring system. Methods A total of 99 adolescents with T1DM were followed from January 2018 to May 2023. The observation group, comprising 48 adolescents, received a combination of insulin and metformin, while the control group of 51 patients was treated with insulin alone. The clinical data, monitoring indices and safety profiles of both groups, were compared. Results At the 3-month follow-up, the mean time in the target glucose range (TIR) was significantly higher in the observation group at 76.6%±9.1% compared to 65.9%±15.0% in the control group. The median time above target glucose range (TAR) in the two groups was 7.0% (3.0%-14.3%) and 21.0 % (12.0%-29.0%), respectively. The mean time below target glucose range (TBR) was 14.50%±7.13% in the observation group and 10.2%±6.8% in the control group. At the 6-month follow-up, the mean TIR in the observation group was 76.0 %±8.9 % compared to 65.5 %±14.3 % in the control group. The median TAR in the observation group was 8.0 %(3.3 %-13.8 %), while in the control group it was 24.0 %(15.0 %-29.0 %).The median TBR in the observation group was 14.4 %±5.9 % in contrast to 10.0 %±6.8 % in the control group. The differences in these variables between the two groups were statistically significant (all P<0.05). At the 3-month and 6-month follow-up, the median insulin dosage required by the observation group was lower than that of the control group (all P<0.05). At two follow-up visits, the median insulin dosage, median BMI, average TIR and average TBR of the patients in the observation group were all higher than their baseline level, and the median TAR level was lower than their baseline level, with statistical significance (all P<0.05). Gastrointestinal symptoms were reported in 4 cases (8.33 %) of the observation group, with no severe hypoglycemia observed. Conclusions The combination of metformin with insulin therapy significantly improved TIR in adolescents with T1DM. Although TBR level increases, this treatment regimen does not increase the risk of severe hypoglycemia. Metformin demonstrated a favorable safety profile, suggesting that the insulin-metformin combination is a viable treatment option for adolescents with T1DM.

Genetic variation analysis of neonatal hyperbilirubinemia: a single-center retrospective study

LIU Qingyu, WANG Liwei, LIN Yilin, XIAO Rui, ZHOU Hui, ZHANG Xiaoqian, FU Mengran, MI Hongying

Journal of Clinical Pediatrics. 2024, 42(9):  782-786.  doi:10.12372/jcp.2024.23e1015

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Objective To investigate the variation of genes related to neonatal hyperbilirubinemia jaundice and the diseases caused by hyperbilirubinemia jaundice, and its distribution in different degrees of jaundice. Methods A total of 167 neonates diagnosed with hyperbilirubinemia in NICU from July 2022 to July 2023 were selected and divided into severe and non-severe jaundice groups. Gene detection was performed by high-throughput second-generation gene sequencing technology. The jaundice gene variants were rated as pathogenicity, and the positive, carrying and negative rates of jaundice gene variants in children were analyzed, and the distribution of jaundice gene variation and related diseases in the two groups were also analyzed. Results Among 167 children, 18 cases (10.8%) were positive for jaundice gene variation, 55 cases (32.9%) were carriers, and 94 cases (56.3%) were negative. There were 8 genes involved in UGT1A1, ATP7B, HBB, SLC25A13, ATP8B1, SMPD1, G6PD and SLC10A1, among which the mutation frequency of UGT1A1 gene was up to 45.32%, and c.211G>A was the high frequency mutation site. In the group of 31 children with severe jaundice, 16 (51.6%) had positive results for jaundice gene mutations, and all 15 cases of Gilbert syndrome/Crigler-Najjar syndrome had UGT1A1 gene mutations. Among the 136 non-severe jaundice patients, only 2 cases (1.47%) were positive, and 1 case of Gilbert syndrome / Crigler-Najjar syndrome had a variation in UGT1A1 gene. Comparing the rates of positive, carrying and negative of jaundice gene variation between the two groups, the results showed that the positive rate of severe jaundice group was significantly higher than that of non-severe jaundice group, and the negative rate was significantly lower than that of non-severe jaundice group, with statistical significance (P<0.014). Conclusions Jaundice gene variation is closely related to the occurrence and severity of neonatal hyperbilirubinemia. The common cause is UGT1A1 gene variation, and c.211G>A is the high frequency mutation site. It is of great clinical significance to conduct gene detection for children with hyperbilirubinemia, especially severe hyperbilirubinemia.

Immunobiological properties of peripheral blood MAIT cells in children with chronic hepatitis B

JIANG Tao, LI Shuangjie, TANG Lian, OUYANG Wenxian

Journal of Clinical Pediatrics. 2024, 42(9):  787-790.  doi:10.12372/jcp.2024.23e0751

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Objective This study aimed to investigate the changes and the clinical implications of peripheral blood mucosal associated invariant T (MAIT) cells in children with chronic hepatitis B (CHB). Methods The investigation encompassed 20 patients with CHB and an equal number of age-matched healthy controls (HC). Peripheral blood specimens were obtained and analyzed using flow cytometry to quantify the presence of MAIT cells (defined as CD3⁺CD161⁺TCRVα7.2⁺), their subtypes, and the expression of various markers including PD-1, CD69, perforin, CD107α, CXCR3, CXCR6, and CCR6. Statistical comparisons between the groups were made using the Mann-Whitney U test and Spearman's correlation analysis. Results No significant differences were observed in the proportion of MAIT cells and their subtypes between the CHB and HC groups (P>0.05). However, the CHB group exhibited a significant increase in the proportion of MAIT cells expressing PD-1, CD69, CD107α, CXCR3, CXCR6, CCR6, and perforin (P<0.05). There was no significant correlation between the proportion of MAIT cells expressing CD69, PD-1, CD107α, perforin, CXCR6, CCR6 and CXCR3 and the levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and hepatitis B virus (HBV) DNA fluorescent quantitation (P>0.05). Conclusion The distinct immunological functions of peripheral blood MAIT cells may contribute to the pathogenesis of CHB in pediatric patients.

A novel compound heterozygous mutation in KIF12 causing progressive familial intrahepatic cholestasis: a case report

PEI Haoyue, GONG Yiming, HAN Xinru, BAI Meirong, CHU Xun, ZHOU Ying

Journal of Clinical Pediatrics. 2024, 42(9):  791-797.  doi:10.12372/jcp.2024.24e0378

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Objective To identify KIF12 mutation in an infant with progressive familial intrahepatic cholestasis 8 (PFIC8) and to explore the functional consequences of the mutation. Methods The clinical data of the infant with PFIC8 were analyzed, and whole exome sequencing was conducted on the patient and his parents, and the variation was verified by Sanger sequencing. Immunofluorescence staining, cell phenotyping, qPCR and Western blotting were utilized to investigate the effect of the causative mutations on the gene functions. At the same time, the clinical data and gene variation of 17 reported PFIC8 patients were reviewed. Results The proband, a male infant aged one month and 14 days, exhibited symptoms of fever and jaundice. Whole exome sequencing showed that the KIF12 gene of the patient had a compound heterozygous mutation of c.539G>A+c.928C>T, which had not been reported before. Immunofluorescence staining of liver sections from the patient suggested that the mutation altered the subcellular localization of KIF12 protein within hepatocytes. In 293 T cells, phenotyping of the mutants revealed that c.539A, c.928T and c.539A+c.928T resulted in decreased mRNA levels of KIF12, while c.928T and c.539A+c.928T reduced the protein expression levels of KIF12. A review of the literature revealed seven single site mutations of KIF12 and a compound heterozygous mutation (c.538C>T+c.539G>A) that have been reported. Existing data indicated that the types of KIF12 mutations were not correlated with the extrahepatic clinical phenotypes of PFIC8 patients. Conclusions A novel compound heterozygous mutation was identified in an infant with PFIC8. Among the nine KIF12 mutations identified to date, the mutation types were not associated with the extrahepatic clinical phenotypes of PFIC8.

Megacystis-microcolon-intestinal hypoperistalsis syndrome caused by MYH11 elongating mutation : a case report and literatures review

ZHOU Jie, LIU Keqiang, WANG Jinling, WANG Ying

Journal of Clinical Pediatrics. 2024, 42(9):  798-804.  doi:10.12372/jcp.2024.24e0263

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Objective To report the clinical characteristics and genetic variant of a patient with megacystis-microcolon-intestinal hypoperistalsis syndrome (MMIHS) and to investigate the genotypic-phenotypic correlation through literatures review. Methods The clinical data of a MMIHS child who came to our hospital in October 2023 due to "repeated abdominal distension and vomiting for more than 3 years" were analyzed. Peripheral blood samples were collected from the patient, his parents and his older sister, and the pathogenic mutation was screened by Trio-WES and Sanger sequencing. Relevant literature was summarized and analyzed. Results The patient, a 15-year-old boy, presented with recurrent episodes of abdominal distension, vomiting, and abdominal pain. Abdominal X-ray and upper gastrointestinal contrast study indicated intestinal obstruction. The condition stabilized after treatment with enema, anti-infection and intravenous nutritional support. Genetic testing revealed a heterozygous mutation in the MYH11 gene, identified as c.5819delC (p.Pro1940Hisfs*91), which resulted in the extension of the C-end of the myosin heavy chain and was not detected by either parent or sister. A total of 7 articles related to MYH11 gene mutation were included in the literature review. Mutation types included missense mutations, frameshift mutations, and chromosomal microdeletion. Gender was undetermined in 2 out of 20 patients due to early termination of pregnancy. Among the remaining patients, the male-to-female ratio was 2:1. Genotypic-phenotypic correlation analysis found that 15 patients with dominant heterozygous protein‐elongating MYH11 variants were aged 9 (0-28) years at onset, and no deaths were reported. Five patients with recessive loss-of-function mutations had an onset age of less than 1 year, with 4 deaths (80%). Conclusion This MMIHS patient carries the MYH11 gene c.5819delC (p. Pro1940Hisfs*91) mutation. Compared with patients with MYH11 gene mutation recessive inheritance, those with dominant MYH11 mutations tend to have a later onset, milder clinical manifestations, and a higher survival rate.

Analysis of clinical and genetic detection results of 3 children with FOXG1-related syndrome

SUN Dianrong, WANG Yanyan, LI Jiashan, ZHANG Leihong, HOU Mei

Journal of Clinical Pediatrics. 2024, 42(9):  805-810.  doi:10.12372/jcp.2024.23e1074

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Objective To investigate the clinical phenotypic and genotypic features of FOXG1-related syndrome. Methods The clinical data and genetic test results of 3 children with FOXG1-related syndrome treated in our hospital from January 2018 to January 2022 were analyzed retrospectively. Results Three children with FOXG1-related syndrome were included, all male, with postnatal onset. All the patients had early-onset dyskinesia, global developmental delay and microcephaly. Whole exome sequencing showed that all 3 patients had the pathogenic variation of FOXG1 gene. Brain magnetic resonance imaging (MRI) was characterized by hypoplasia of the frontal cortex and/or corpus callosum or delayed myelination. Case 1 had a frameshift mutation of c.256dupC (p.Gln86Profs*35) at the N-terminal domain site in the FOXG1 gene, and case 2 had a nonsense mutation of c.595G>T (p.Glu199*) in the fork-head binding domain of FOXG1 gene. A nonsense of c.1178C>A (p.S393*) was found in the JARID1B binding domain of FOXG1 gene in case 3. Case 3 had a milder clinical phenotype and brain abnormalities than the other 2 patients. The variations of cases 2 and 3 had not been previously reported in the literature, which expanded the gene spectrum of the disease. Conclusions FOXG1 variation should be considered for individuals with early-onset dyskinesia, developmental delay, microcephaly and characteristic brain imaging lesions.

Literature Review

Research progress of central nervous system injury associated with pediatric acute lymphoblastic leukemia and its treatment

CHU Sijia, TANG Jihong

Journal of Clinical Pediatrics. 2024, 42(9):  811-816.  doi:10.12372/jcp.2024.23e0892

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Acute lymphoblastic leukemia (ALL) is the most common malignancy in children, and its central nervous system complications significantly impact the prognosis of children. In addition to the brain damage caused by ALL itself, recent researches have shown that anti-tumor therapy may also result in adverse effects. Investigating central nervous system injury associated with anti-tumor therapy in children with ALL is crucial for early identification and intervention of complications, ultimately leading to improved prognosis and quality of life for children.

The role of early regular use of emollients in the prevention and treatment of infantile atopic dermatitis

TANG Chuanyi, YAO Zhirong

Journal of Clinical Pediatrics. 2024, 42(9):  817-821.  doi:10.12372/jcp.2024.23e1132

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Impaired epidermal barrier function plays a pivotal role in the pathogenesis of atopic dermatitis (AD). Emollients can fortify the skin barrier, diminish transepidermal water loss, and maintain stratum corneum hydration. AD is closely associated with comorbidities such as food allergies, allergic rhinitis, and allergic asthma. Implementing effective preventive measures in the early stages of AD can alleviate the economic burden on families and society. This review explores the relationship between AD and skin barrier and allergic diseases, as well as the application of emollients in the prevention of AD, and discusses whether regular use of emollients in early neonates can effectively prevent the occurrence of atopic dermatitis and reduce the risk of allergic diseases.

Continuing Medical Education

Supervision status and clinical research of pediatric medical devices in China and the United States

GUO Jiaying, ZHOU Zijing, LI Yaohua

Journal of Clinical Pediatrics. 2024, 42(9):  822-826.  doi:10.12372/jcp.2024.24e0288

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The development of pediatric medical devices faces challenges and cannot meet the clinical needs of pediatric patients, however, conducting clinical research on pediatric medical devices is difficult. This article explores the current development status of pediatric medical devices in China and discusses the relevant regulations and guidelines in both China and the United States. It also delves into the considerations for conducting clinical research in the pediatric population, aiming to provide reference for the implementation of related clinical studies.