Background：In recent years, with the rapid development of fetal medicine in China, intrauterine operations have been widely carried out across the country. At present, the evaluation of fetal medical intervention effects is mostly based on single center with a small sample data and the limitation to the perinatal outcome. There is a lack of multicenter, large sample studies on the shortterm and longterm prognosis of fetuses after birth.
Objective：To describe the current status and prognosis of very preterm infants who received intrauterine operations and/or invasive prenatal interventions in 57 NICUs of the Chinese Neonatal Network (CHNN) in 2019.
Design：Cohort study.
Methods：This study took CHNN very preterm infants as the cohort population. Infants who received intrauterine operations and/or invasive prenatal interventions (including fetoscopic laser photocoagulation, selective fetal reduction, fetal transfusion, shunt placement, amnioreduction, and amniotic fluid and/or chorionic villus sampling) were matched to infants without prenatal interventions using propensity scores by the ratio of 1 to 4. Mortality (in NICU, 28 days after birth and 7 days after birth) and major morbidities (severe brain injury, retinopathy ≥ stage Ⅲ, bronchopulmonary dysplasia, necrotizing enterocolitis ≥ stage Ⅱ and sepsis) were compared between the two groups.
Main outcome measures：Mortality.
Results：A total of 9 520 very preterm infants were admitted to 57 NICUs in CHNN in 2019. Among them, 187 (2.1%) infants received intrauterine operations and/or invasive prenatal interventions, including 69 selective fetal reduction, 66 amniotic fluid and/or chorionic villus sampling, 42 amnioreduction, 20 fetoscopic laser photocoagulation, 10 fetal transfusion, and 2 shunt placement. The NICU allcause mortality of very preterm infants undergoing intrauterine operations and/or invasive prenatal interventions was 15.5% (29/187), with 22 deaths occurring within 7 days after birth. The most common morbidities among infants with prenatal interventions were bronchopulmonary dysplasia (41.7%), sepsis (11.8%), and severe brain injury (9.4%). The NICU mortality and rates of major morbidities were not significantly different from infants with prenatal interventions and the matched control group. While the mortality within 7 days (RR=1.69, 95%CI:1.06~2.71) and the incidence of early onset sepsis (RR=3.20, 95%CI:1.28~7.99) were significantly higher in infants who received intrauterine operations and/or invasive prenatal interventions.
Conclusion：Overall, 2.1% of very preterm infants admitted to Chinese NICUs received intrauterine operations and/or invasive prenatal interventions. Intrauterine operations and/or invasive prenatal interventions did not significantly increase mortality and morbidities among very preterm infants.
Background：The prevalence of hyperuricemia (HUA) is increasing, which is not only related to gout, urate nephropathy and kidney stones, but also related to the occurrence and development of endocrine metabolism, cardiovascular and cerebrovascular diseases.
Objective：To assess the association of maternal hyperuricemia with adverse pregnancy outcomes and neonatal disease.
Design：Retrospective nested casecontrol study.
Methods：Data were retrospectively collected from People's Hospital of Peking University between January 1st 2020 and December 31st 2020. According to the maternal uric acid value in the third trimester of pregnancy, the newborns were divided into the group of HUA and normal uric acid. The pregnancy outcomes and clinical outcomes of neonates in two groups were compared. According to the maternal uric acid value in the third trimester of pregnancy(μmol·L-1), pregnant women were divided into the group of low concentration (<360), medium concentration (~420) and high concentration (>420). Linear regression and logistic regression models were used to analyze the relationship between maternal uric acid value and preterm, low birth weight and smallforgestationalage infants. Spearman rank correlation analysis was used to analyze the correlation between maternal uric acid value in the third trimester of pregnancy and neonatal uric acid value at 24 hours after birth.
Main outcome measures：The relationship between maternal uric acid value and preterm and low birth weight and smallforgestationalage infants.
Results：A total of 2 397 pregnant women (2 581 newborns) were enrolled, of which 216 cases (9%) were in the HUA group. The birth weight of newborns in the HUA group was lower than that of the nonHUA group (2 925 g vs 3 260 g, P<0.001). The proportions of preterm birth (18.5% vs 8.9%), low birth weight (23.1% vs 7.1%), small for gestational age (29.2% vs 10.6%), and transfer to pediatrics (19.9% vs 11.1%) were higher in the HUA group (P<0.001). The birth weight of newborns in the high concentration group was lower than those in the low concentration group (-54g，95%CI: -106.48-1.63, P=0.043). The risk of newborns with preterm and smallforgestationalage infants delivery increased by 74% (OR=1.74，95%CI:1.082.8, P=0.023) and 85% (OR=1.85，95%CI：1.262.73，P=0.002), respectively. The uric acid value of the newborn at 24 hours after birth was moderately correlated with the uric acid value of the pregnant mother in the third trimester of pregnancy (r=0.613, P=0.000). There was no significant difference in neonatal complications between the two groups.
Conclusion：Maternal hyperuricemia in the third trimester of pregnancy is associated with the occurrence of perterm, low birth weight and smallforgestationalage infants.
Background：Based on consensusbased standards for the selection of health measurement instruments（COSMIN）, we evaluated the psychometric properties of the evaluation tools for topics in different domains of the clinical practice guideline for children and adolescents with cerebral palsy (CANDLE) and established the inclusion and exclusion criteria of evaluation tools in CANDLE.
Objective：To systematically evaluate Gross Motor Function Measure88 and 66 (GMFM88 and GMFM66) based on COSMIN methods, clarify the evidence level of each psychometric property, provide evidence for its clinical practice, and explore the value of COSMIN methods in assessing field observation evaluation tools.
Design：A systematic review.
Methods：MEDLINE, Embase and SinoMed databases were searched for relevant research literature on GMFM88 and GMFM66 measurement properties. The updated COSMIN Risk of Bias checklist was used to evaluate the methodological quality of all measurement properties, and updated criteria for good measurement properties were used to score each measurement property study. The GRADE method of COSMIN revision was adopted to assess the evidence quality.
Main outcome measures：The content validity of GMFM88 and GMFM66.
Results：GMFM88 had better evidence for content validity than GMFM66, and both of them have highquality reliability research. GMFM88 had more evidence to support its internal consistency and measurement errors than GMFM66, but it lacked structural validity research. GMFM88/66 had highquality evidence in concurrent validity and concurrent responsiveness, and low or very lowquality evidence in discrimination validity and discrimination responsiveness. GMFM66 showed better criterion responsiveness than GMFM88.
Conclusion：GMFM88/66 has highquality evidence in reliability, internal consistency, and construct validity. COSMIN methods could be useful for the assessment of field observation evaluation tools.
Background：There are few clinical studies on newborn screening for Duchenne Muscular Dystrophy（DMD） with creatine kinase（CK） or creatine kinase isoenzymeMM（CKMM）, and the diagnostic accuracy is not clear.
Objective：To systematically evaluate the accuracy of creatine kinase or creatine kinaseMM in newborn screening for DMD.
Design：Systematic review and metaanalysis．
Methods：Literature was searched in databases of Embase, Cochrane Library, Web of Science, Scopus, China National Knowledge Infrastructure (CNKI), China Biomedical Literature Database (CBM), Wanfang database and Chinese Journal Fulltext Database (VIP) from Jan 1, 1975 to Oct 5, 2022, and in database of Medline（PubMed） from Jan 1, 1975 to Nov 5, 2022，in order to collect the studies related to neonatal screening of DMD using CK or CKMM. The QUADAS2 scale was used to evaluate the risk of bias and clinical applicability of the included literature. Data were extracted and then metaanalysis was performed using Stata15 and MetaDisc1.4 software. The sensitivity, specificity, positive likelihood ratio（PLR）, negative likelihood ratio（NLR）and diagnostic odds ratio (DOR) were pooled. Summary receiver operating characteristic curve (SROC) was made and the area under the curve (AUC) and Q index was calculated.
Main outcome measures：Sensitivity and specificity.
Results：Eleven studies were included in newborn screening for DMD using CK with a total of 1 351 953 neonatal samples. Metaanalysis showed that pooled sensitivity, specificity,PLR,NLR and DOR were 97%(95%CI:88%99%),100%(95%CI:100%100%),1 131(95%CI:3703 455),0.01(95%CI:0.000.19),16 476(95%CI:4 11565 963), respectively. The AUC and Q index were 0.995 4 and 0.974 0, respectively. Deeks test（P=0.12）indicating a small possibility of publication bias. Five studies were included in newborn screening for DMD using CKMM with a total of 156 547 neonatal samples.Metaanalysis showed pooled sensitivity, specificity, PLR,NLR and DOR were 100%（95%CI:100%100%）、100%（95%CI:100%100%），3 925（95%CI: 3 9253 925），0.00（95%CI:0.000.00）and 23 094(95%CI:5 77392 384).The AUC and Q index were 0.925 2 and 0.859 4, respectively.
Conclusion：The application of serum CK or CKMM in screening neonatal DMD has high accuracy, which is helpful for early diagnosis of DMD.
Background：There are few cases of children's meningitis caused by Streptococcus gallolytica (SG) at home and abroad, and the overall clinical characteristics are still unclear.
Objective：To systematically review the clinical features of SG meningitis.
DesignSystematic review.
MethodsPubMed, Embase, Web of Science, CNKI, Wanfang, and VIP databases were searched for literature related to SG meningitis from the inception to November 9, 2022. Cases of bacterial meningitis infected by SG in children were included. Publication types of review and conference papers were excluded. The literature unable to get the full text or writing in other languages except Chinese and English was also excluded. Two investigators independently reviewed the literature, extracted literature features, clinical characteristics of cases, laboratory indexes, and antibiotic susceptibility of SG, and assessed the quality of the included literature.
Main outcome measures Survival rate and complications.
ResultsA total of 21 subjects from 17 literature were included in this systematic review, including 16 males, 4 females, and 1 case without reported gender. There were 3 premature infants, 16 fullterm infants, and 2 cases without reported gestational age. The age of onset was (14.5±16.6)d. There were 14 cases with fever, 17 cases with neurologic abnormality, 9 cases with gastrointestinal signs, 9 cases with respiratory symptoms, and 3 cases with tachycardia. CRP level increased in all 11 reported cases. Nine cases showed peripheral WBC counts below 4×109·L-1 and 6 cases had peripheral WBC counts above 10×109·L-1. CSF leukocyte counts increased in all patients. Eighteen cases reported CSF glucose level with 14 cases below 2.2 mmol·L-1, and 17 cases reported CSF protein concentration with 15 cases above 1 700 mg·L-1. Twenty cases were positive in 21 cases of CSF culture, 16 cases were positive in 18 cases of blood culture, 1 case was positive in 5 cases of urine culture, and 1 case was positive fecal culture. SGSP was found in 17 cases, SGSG in 2 cases, and SG in 2 cases. Twelve cases were treated with monotherapy (strains of 11 cases were susceptible to penicillin/ampicillin, 1 case was not reported), 9 cases were treated with 2 antibacterial agents ( strains in 8 cases were susceptible to penicillin/ampicillin, strains in 1 case was resistant), and the course of antibacterial agents was at least 14 days. Complications were reported in 6 cases, including 2 cases with ventricular hemorrhage, 2 cases with ventriculitis, 1 case with hydrocephalus, ventricular dilation, neuromotor delay, poor spontaneous motor mobilization, and hypertonia of the limbs, and 1 case with bilateral reduction in visual evoked potentials, subdural effusion, and seizure.
ConclusionSG meningitis mainly occurred in infants under 2 months. Penicillins or cefotaxime could be selected for treatment and had good clinical outcomes.
FU Pan, WANG Chuanqing, YU Hui, WU Xia, XU Hongmei, JING Chunmei, DENG Jikui, WANG Hongmei, HUA Chunzhen, CHEN Yinghu, CHEN Xuejun, ZHANG Ting, ZHANG Hong, CHEN Yiping, YANG Jinhong, LIN Aiwei, WANG Shifu, CAO Qing, WANG Xing, DENG Huiling, CAO Sancheng, HAO Jianhua, GAO Wei, HUANG Yuanyuan, XIANG Hongxia, ZHUO Zhiqiang, HUANG Meilian
Background：Chinese Infectious Disease Surveillance of Pediatrics(ISPED)was established in 2015. The data of antibiotics resistance were collected from each hospital and summarized every year to monitor the infectious etiology changes and bacterial drug resistance among Chinese children.
Objective：This study is aimed to investigate the bacterial infectious and antimicrobial resistance profiles of pathogens in Chinese children and guide the reasonable use of antibiotics.
Design：A crosssectional survey.
Methods：Clinical isolates were collected from 13 tertiary children hospitals in China from January 1st to December 31st in 2021. Antimicrobial susceptibility testing was carried out according to a unified protocol using KirbyBauer method or automated systems. Penicillin susceptibility of streptococcus pneumonia was detected by Etest. All of the antimicrobial susceptibility testing results were interpreted according to the criteria of Clinical and Laboratory Standards Institute (CLSI) 2021. All members used the standard methods to perform bacterial culture,identification and antimicrobial susceptibility test and reported the isolated effective strains and bacterial resistance data in a structured format every year for data summary and statistical analysis.
Main outcome measures：Detect the distribution of bacteria strains in children and the changes of bacteria drug resistance.
Results：A total of 63 508 isolates were collected, of which 39.9% was grampositive organisms and 60.1% was gramnegative organisms. Top ten pathogens were as follows, Escherichia coli (12.7%), Streptococcus pneumonia (12.3%), Straphylococcus aureus (11.6%), Haemophilus influenza (11.4%), Moraxella catarrhalis (6.5%), Klebsiella pneunoniae (5.2%), Pseudomonas aeruginosa (4.0%), Staphylococcus epidermidis (3.7%), Acinetobacter baumannii (2.4%) and Streptococcus pyogenes (2.1%). The distribution of the primary pathogenic bacteria in different age groups was different. Among them, Saureus had the highest isolation rate in neonates (18.7%), and S.pneumoniae was the main pathogenic bacteria in children aged from >28 d to 5 years old, arranging from 13.6% to 20.8%. E.coli was the most common pathogen in children over 5 years old (22.4%). The proportion of penicillininsensitive S.pneumoniae (PNSP) decreased to 9.6%. Multidrugresistant bacteria (MDROs) showed high levels of resistance to a variety of clinical antibiotics, and the ratios of carbapenemresistant Enterobacteriaceae (CRE), K.pneumoniae (CRKP), P.aeruginosa (CRPA), A.baumannii (CRAB) were 4.6%, 14.8%, 6.7% and 30.7%, respectively. The proportions of CRPA and CRAB showed a decreasing trend in the past 6 years. The former had a higher detection rate in the neonatal group, while the latter had a higher detection rate in the nonneonatal group. Moreover, the resistance rates of CRPA and CRAB to multiple antibiotics were significantly higher in the nonneonatal group than in the neonatal group. Methicillinresistant Saureus(MRSA) was relatively stable, with a detection rate of 33.2% in 2021.
Conclusion：The detection rate of MDROs in 2021 was lower than previous years, and the resistance ratio of MDROs also decreased in pediatric patients. We must pay attention to the infection and colonization of CRPA in the neonatal population.
Background：The indication of vagus nerve stimulation (VNS) is approved for children with drugresistant epilepsy (DRE) older than three years old in China. Nowadays, VNS treatment is also used offlabel to treat infants with DRE in clinical practice, but there is still a lack of relevant research on its efficacy and safety.
Objective：To evaluate the longterm efficacy, safety and efficacyrelated factors of VNS treatment for infants with DRE.
Design：Case series report.
Methods：This study included infants with DRE after VNS treatment in the children epilepsy center of Peking University First Hospital between March 2015 and March 2021. All the patients were regularly programmed and followed up after VNS implantation for at least 1 year with current output over 1mA. Patients who received other newadded antiseizure therapy including epileptic surgery, ketogenic diet, glucocorticoid and adrenocorticotropic hormone, or turned off VNS due to any reason were excluded. The frequency of all seizure types recorded in the epilepsy diary of parents was calculated to evaluate followup responder rate defined as seizure frequency decreasing by ≥ 50% at the last followup compared with 3 months before VNS implantation，and seizure frequency reduction rate so as to investigate the effect of clinical information and programmed parameters on the efficacy and safety.
Main outcome measures：Responder rate and seizure frequency reduction rate after VNS treatment.
Results：Twentyfive infants with DRE after VNS treatment met the inclusion and exclusion criteria, including 16 males (64%) and 9 females. The median age of seizure onset was 4.9 months. The median duration of epilepsy was 1.7 years. The median seizure frequency was 555 times per month, and the median age at VNS implantation was 2.3 years. The number of historical antiseizure medications (ASMs) used and the number of ASMs used 3 months before VNS implantation ranged 310 and 14, respectively. Twelve cases (48%) had specific DRE etiology, and eighteen (72%) were diagnosed with the epileptic syndrome. Four, five, six and ten cases had 4, 3, 2 and 1 seizure types, respectively. All the twentyfive cases of DRE infants implanted with VNS had developmental delay. The median postoperative followup duration was 2.4 years. The change rate of seizure frequency ranged from +1367% to -100% at 1year followup, with a median change rate of -52.8%. The change rate of seizure frequency ranged from +1712% to -100% at 2year followup, with a median change rate of -59.5%. At the last followup, the responder rate was 64%, the seizurefree rate was 20% (5/25) , and the longest seizurefree duration during followup was 2 years and 5 months. The responder rate for 1 year and 2 years after VNS were both 60% (15/25, 9/25). One of fifteen responders at 1 year after VNS became a nonresponder at 2 years after VNS. Two of ten nonresponders at 1 year after VNS became responders at 2 years after VNS. No perioperative and devicerelated adverse reactions were observed, and 4 patients developed stimulationrelated adverse reactions during programming, including 2 cases of transient cough and 2 cases of pharyngeal discomfort, which could be tolerated in a short time. There were no significant differences in clinical information, parameters at the last followup and postoperative ASMs adjustment between responders (16 cases) and nonresponders (9 cases) during VNS efficacyrelated factors analysis.
Conclusion：The responder rate of VNS treatment for infants with DRE could reach 60% at 1 and 2 years of followup, and the safety of VNS treatment was good. The lower age limit of VNS still needs to be further evaluated.
Background：Childhood obesity is one of the leading causes of nonalcoholic fatty liver disease (NAFLD). Waisttoheight ratio (WHtR) is a physical measurement index reflecting the visceral fat and cardiometabolic risk in children and adolescents, but the relationship between WHtR and NAFLD is unclear.
Objective：To investigate the association of WHtR and NAFLD in children and adolescents.
Design：Retrospective analysis of children's physical examination data.
Methods：Resident students who participated in the 20142020 routine annual physical examination in Minhang District, Shanghai were included for the analysis. Suspected NAFLD was defined by the elevation of 97.5 percentile of alanine aminotransferase (ALT) levels according to the ageand sexspecific reference intervals for the healthy children. Based on the results of the WHtR cutoff values proposed for screening cardiometabolic risk in children and adolescents from a national wide data, we defined the WHtR elevation group as WHtR values in boys and girls being equal to or higher than 0.481 and 0.456, respectively. We used unconditional binary logistic regression to assess the association of WHtR and NAFLD after adjustment of age and gender. We used the area under the receiver operating characteristic curve (AUC), sensitivity, specificity, positive predictive value and negative predictive value to assess the ability of WHtR cutoffs in discriminating NAFLD.
Main outcome measures：The association of WHtR and NAFLD.
Results：Compared with the normal WHtR group, the NAFLD prevalence was significantly higher in WHtR elevation group (16.2% vs 2.3%, P<0.001), and increased with age. The NAFLD rate in boys with elevated WHtR was higher than that in girls (21.6% vs 11.0%，P<0.001), but was similar in both genders with normal WHtR (2.3% vs 2.2%，P=0.71). Elevated WHtR was associated with 71% increase in the risk of NAFLD (adjusted OR=1.71, 95% CI:1.262.31，P=0.001), and the association was similar in boys and girls with 77% increase in boys (OR=1.77, 95% CI:1.192.63，P=0.005) and 69% increase in girls (OR=1.69,95% CI: 1.052.71，P=0.005）. The AUC (95% CI), sensitivity, specificity, positive predictive value and negative predictive value of elevated WHtR for identifying NAFLD were 0.73(0.710.76), 63.2%, 83.4%, 16.8%, and 97.7%, respectively.
Conclusion：Elevated WHtR is associated with NAFLD in children and adolescents. For the children and adolescent with elevated WHtR, schools and primary health care institutions should pay attention to the NAFLD occurrence in addition to abnormal blood pressure, glucose, and lipids metabolism.
Background：It is unclear about the effect of the rate of folic acid supplementation and unhealthy life habits in childbearing couples on the level of serum.
Objective：To describe the serum folate levels in childbearing couples in Kunshan City and investigate the associations of tobacco exposure and alcohol drinking with serum folate levels.
Design：Crosssectional study.
Methods：The couples with the age of wife below 45 were enrolled from the premarital or prepregnancy examination clinic in Maternal and Child Health Center in Kunshan City. The questionnaires and blood samples were collected to analyze the relationship of the tobacco exposure defined as smoking or being passively exposed to tobacco smoke in the past 3 months and alcohol drinking defined as drinking alcoholic drink for at least one time in the past 30 days with serum folate levels. As there is no standard reference levels of serum folate for the childbearing couples, we used the P50 of serum folate level in this study to define the low folate group(<P50) and normal group (≥P50) to ensure a maximum statistic power. The covariates included age, sex, BMI, education, and the use of folic acid supplementation.
Main outcome measures：Serum folate levels.
Results：A total of 3 990 couples were enrolled from April 2019 to June 2021. The mean age were 28.5±3.8 and 27.4±3.5 years for the males and females. The prevalence of tobacco exposure, drinking and folic acid supplementation before pregnancy for males and females were 31.3% and 0.9%, 27.9% and 6.0%, 0.7% and 2.7%, respectively. Median serum folate levels in fathers and mothers were 12.7 ng·mL-1 (14.0, 26.1) and 18.8 ng·mL-1 (9.5, 17.0) correspondingly. After adjustment for covariates, the tobacco smoke exposure was associated with higher odds of low serum folate in whole population (OR=1.48, 95% CI:1.281.72), and this association was further observed in males (OR=1.46, 95%CI: 1.261.71), but not in females. Alcohol drinking was significantly associated with low serum folate levels in the whole population (OR=1.24，95%CI：1.091.42),males (OR=1.21，95%CI：1.051.42),and females (OR=1.34，95%CI：1.021.76).
Conclusion：Tobacco exposure and alcohol drinking before pregnancy were associated with low serum folate, which may exist gender difference.
Background: Primary mitochondrial diseases have high clinical and genetic heterogeneity, and peripheral nervous system is one of the most commonly involved organ.
Objective: To investigate the clinical and genetic characteristics of hereditary peripheral neuropathy caused by COX20 gene variants.
Design: Case series report.
Methods: Four patients with hereditary peripheral neuropathy caused by COX20 gene variants treated in the Children's Hospital of Fudan University from May 2018 to May 2020 were enrolled, and their clinical manifestations, molecular tests, data of treatment and followups were retrospectively reviewed. Also, we searched published articles using keyword of "COX20", and "Complex Ⅳ deficiency" in Chinese and English databases from the inception to December 2021. The relationship between COX20 gene variantion and clinical phenotypes was summarized.
Main outcome measures: COX20 gene variantion sites and clinical phenotypes.
Results: Four patients including 2 males and 2 females were enrolled. Three patients had delayed motor mile stones. All 4 patients presented with walking instability onset at early childhood, and nerve conduction study revealed polyperipheral neuropathy especially with sensory axonal damaged. Whole exome sequencing of 4 patients revealed compound heterozygous variants of COX20 gene, including 2 reported missense variants, 1 reported nonsense variant and 1 novel variant—c.262delG(p.E88kfs*35) which has never been reported before. Literature review showed 22 patients from 18 families (including our cases) have been reported till now, with the median age of onset at 5 years old (1.017 years old). All patients presented with walking difficulty or unsteady gait at onset(22/22, 100%). Common clinical manifestations included developmental retardation(11/22, 50.0%), dysarthria(14/22, 63.6%), muscle weakness with or without foot deformity(14/22, 63.6%), ataxia(8/22, 36.4%), dystonia(6/22, 27.3%), and cognitive regression(5/22, 22.7%). Nerve conduction and electromyography tests revealed polyperipheral neuropathy in most patients (19/21, 90.5%). Magnetic resonance imaging revealed spinal cord atrophy in 4 patients (4/10, 40%) and cerebellum atrophy in 4 patients (4/18, 22.2%). Nine patients lost the ability of independent walking at a median age of 10(721) years. A total of 9 pathogenic variants in four types were reported, including five missense variants, two splice site mutations, one nonsense variant and one frameshift variant.
Conclusion: COX20related patients always present with peripheral axonal neuropathy at an early childhood onset. The disease progresses gradually with a high disability rate. Some patients also have dysphagia, ataxia, dystonia, and cognitive regression. Among all the COX20 variants reported now, missense variants are the most common.
Background: Childhood lymphoma with SH2D1A gene mutation is rare in clinical practice and has special clinical features and prognosis.
Objective:To summarize the clinical manifestations, pathological features, treatment and prognosis of childhood lymphoma with SH2D1A gene mutation.
Design:Case series report.
Methods:Consecutive hospitalized patients who were newly diagnosed with lymphoma under the age of 18 and had SH2D1A gene mutation indicated by highthroughput whole exon gene sequence were enrolled from Beijing Children's Hospital affiliated to Capital Medical University between June 2017 and July 2022. The treatment plan was determined according to the pathological diagnosis. Invasive mature Bcell lymphoma was treated based on the modified LMB89 regimen. Mature Tcell lymphoma complicated with hemophagocytic syndrome(HLH) was first controlled by the HLH regimen, and chemotherapy was given after the diagnosis by the SMILE regimen. The efficacy was evaluated in the middle period after 2 to 3 months of chemotherapy. Ultrasound and PET/CT were performed at 3 months after chemotherapy. Tumor ultrasound, liver function, LDH and immune function were tested every 3 months within 1 and 2 years after chemotherapy.
Main outcome measures:Clinical characteristics and prognosis of children lymphoma with SH2D1A gene mutation.
Results:A total of six male patients of childhood lymphoma with SH2D1A gene mutation were summarized. The median age of onset was 5(412) years. The tumor lesions involved the gastrointestinal tract in 3 cases, central nervous system, head and neck, and multiple organs in 1 case each. In terms of clinical stages, there was 1 case of stage Ⅱ, 3 cases of stage Ⅲ, and 2 cases of stage Ⅳ. For pathological types, 3 cases were for diffuse large Bcell lymphoma, 1 case for highgrade mature Bcell lymphoma, 1 case for Burkittlike lymphoma with 11q abnormality, and 1 case for systemic EpsteinBarr virus positive Tcell lymphoma in children. Humoral immunity and/or cellular immunity decreased in 5 cases. Whole blood and plasma EBVDNA were negative in 5 cases at the beginning of the disease, and whole blood EBVDNA increased to ≥105 copy number /mL during the course of the disease in 2 of them. One patient had familial HLH at the beginning of the disease, with multiple whole blood EBVDNA of 106 copies/mL. Six cases showed SH2D1A gene mutation, among which 2 cases showed no abnormal SAP protein detection; 1 case had chromosomal abnormality; 3 cases completed chemotherapy; 2 cases died due to hemophagocytic syndrome, and 1 case received rituximab immunotherapy.
Conclusion:Lymphoma in children with SH2D1A gene mutation is rare in clinical practice. The main pathological manifestation is nonHodgkin lymphoma (mature Bcell lymphoma), and the prognosis is poor. Allogeneic hematopoietic stem cell transplantation may improve the prognosis of the disease when there is a need.
