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  • Appropriate screening timing and locations for neonatal major congenital heart disease: A systematic review and metaanalysis
  • LU Tianwei, HU Xiaojing, LYU Tianchan, MA Xiaojing, ZENG Ziqian, ZHAO Zhengshan, WANG Dingmei, ZHANG Chongfan, HUANG Guoying
  • 2022 Vol. 17 (4): 281-289. DOI:10.3969/j.issn.1673-5501.2022.04.004
  • Abstract ( 395 ) PDF (4447KB)( 347 )
  • Background There are many reports on the systematic review of the screening protocols for neonatal congenital heart disease, and the appropriate screening timing and locations for screening are also worthy of attention. Objective To evaluate the diagnostic accuracy and false positive rate of neonatal major congenital heart disease (mCHD) screening at different screening timing and locations. Design Meta-analysis of diagnostic accuracy studies. Methods The literature search and selection have been completed in the development of neonatal CHD screening (NCHDS) guideline. The positive infants in screening were diagnosed as mCHD by cardiac ultrasound (gold standard), or infants with symptoms and signs were confirmed as mCHD in the follow-up by cardiac ultrasound, surgery, or cardiac catheterization (gold standard). The risk of bias and clinical applicability of the included literature were evaluated with the QUADAS-2 scale. The data were extracted and the diagnostic accuracy parameters such as sensitivity, specificity and false positive rate were summarized with the random effect model. Main outcome measures Accuracy of neonatal mCHD screening at different timing and locations. Results Among the 16 studies on the screening timing, 9 were in the postnatal period of ≤ 24 h, 7 were in the period of -48 h, 3 were in the period of -72 h and 3 were in the period of 6-72 h. The sensitivity of neonatal mCHD screening at different timing were 0.788(95%CI:0.600-0.921), 0.579(95%CI:0.378-0.757), 0.586(95%CI:0.369-0.775)and 0.897(95%CI: 0.836-0.937), respectively. And the specificity were 0.985（95%CI: 0.946-0.996, 0.998(95%CI:0.994-0.999), 0.996(95%CI:0.987-0.999)and 0.994(95%CI: 0.983-0.998), respectively. The false positive rates were 0.015 (95%CI: 0.004-0.057), 0.002(95%CI: 0.001-0.006), 0.004(95%CI：0.001-0.016)and 0.006(95%CI：0.002-0.019), respectively. The AUC of neonatal mCHD screening at ≤ 24 h, -48 h, -72h and 6-72 h after birth was 0.916, 0.973, 0.939 and 0.973, respectively. Among the 20 literatures on screening locations, there were 15 in maternity hospitals, 2 in NICU, 2 in out of hospital settings, and 1 in maternity hospitals + NICU. The sensitivity of neonatal mCHD screening was 0.701(95%CI: 0.576-0.802), 0.797(95%CI: 0.675-0.881), 0.571(95%CI: 0.230-0.856) and 0.821(95%CI: 0.555-0.944), respectively. The specificity was 0.995 (95%CI: 0.990-0.998), 0.885 (95%CI: 0.778-0.944), 0.993 (95%CI: 0.988-0.996) and 0.916 (95%CI: 0.189-0.998), respectively. The false positive rates of the neonatal mCHD screening in maternity hospital and NICU were 0.006 (95%CI: 0.003-0.011) and 0.030 (95%CI: 0.001-0.636) respectively, and the AUC were 0.960 and 0.757 respectively. The sensitivity and specificity were 0.817 and 0.996 in the subgroup within 24 h after birth, and 0.680 and 0.996 in the subgroup >24 h after birth. Conclusion When pursuing high sensitivity of screening and accepting high false positive rate, screening within 24 hours after birth can be selected. For low false-positive rate, screening after 24 hours after birth can be selected. Neonatal mCHD screening should be implemented in the maternity hospital for its good accuracy and low false-positive rate.
  • Epidemiological study of mycoplasma pneumoniae and chlamydia trachomatis infection in a single center in Shanghai during the COVID-19 pandemic
  • XU Menghua, LIU Pengcheng, LU Lijuan, SU Liyun, CAO Lingfeng, XU Jin
  • 2022 Vol. 17 (4): 290-295. DOI:10.3969/j.issn.1673-5501.2022.04.005
  • Abstract ( 473 ) PDF (1567KB)( 177 )

  • BackgroundSoon after the emergence of community transmission of COVID19, the Chinese government has introduced a series of nonpharmaceutical interventions (NPI) to eliminate COVID19 and these NPIS have already affected the prevalence of other common respiratory pathogens. 
     ObjectiveThis study aimed to analyze the epidemiological characteristics of mycoplasma pneumoniae (Mp) and chlamydia trachomatis (CT) of acute respiratory infections （ARTI） in children during the COVID19 pandemic. 
     DesignObservational study.
     MethodsRespiratory specimens for the detection of Mp, CT and other 9 common respiratory viruses were collected from children with ARTI at Children's Hospital of Fudan University from February 2019 to May 2021. The detection data were divided into the group of single pathogen infection (only Mp and CT were detected) and coinfection (Mp+CT, Mp or CT +any one or more of 9 common respiratory viruses and Mp+CT+ one or more of 9 common respiratory viruses). Respiratory specimens (nasopharyngeal aspirates/bronchoalveolar lavage fluid) were collected and tested in our hospital. a. Three satages were compared including "preCOVID19" period: from February 1, 2019 to January 31, 2020, without actively implemented nationwide NPI; b."COVID19"period, from February 1, 2020 to May 31, 2020, when strict nationwide NPI were implemented and schools were closed; c."postCOVID19"period, from June 1, 2020 to May 31, 2021, when nationwide NPI were relaxed, schools were reopened and social work was resumed. All the enrolled samples were divided into 5 age groups: ≤28 days, ~12 months, ~3 years, ~6 years and ≥7 years according to the age at the time of ARTI diagnosis.
     Main outcome measuresThe epidemiological changes of Mp and CT during the COVID19 pandemic.
     ResultsA total of 10 358 specimens tested for respiratory pathogens were enrolled in this analysis, including 6 080 in the preCOVID19 period, 754 in the COVID19 period and 3 524 in the postCOVID19 period. The total number decreased by 42.04% ［(6 080-3524)/6 080］during postCOVID19 when compared to preCOVID19. Among all the enrolled patients, 6 138 were male and 4 220 were female. The overall detection rate of Mp was 12.39%, the observed prevalence declined sharply and was decreased by 96.29% ( P<0.001) with a significant difference. The overall detection rate of CT was 1.45%. The detection rate showed an increasing trend and was increased by 65.49% (P=0.003). The detection rate of single Mp and CT infection was 10.84%. Compare to the pre-COVID-19 period, the detection rate of Mp was decreased by 96.05% and the detection rate of CT was increased by 119.70% in the post-COVID-19 period, with a significant difference. The overall coinfection rate was 2.89%. The coinfection rate of Mp was decreased by 97.32% (P<0.001), while no significant difference was observed in the coinfection rate of MP+CT and CT. Mp peaked in summer during the pre-COVID-19 period, whereas the annual peak was interrupted after the NPI were adopted. CT was detected throughout the whole study period. The examination rates were sharply decreased with the increase of age in the group of older than 12 months in both three periods, while the detection rate of Mp showed a great increase in the pre-COVID-19 period, an increase in the COVID-19 period and a slight increase in the post-COVID-19 period. The increase in the detection rate of CT was observed in the age of ≤28 days and -12 months in all three periods, while the examination rate and detection rate of CT showed a sharply decrease in children older than 12 months with the increase of age in the whole study period.
     ConclusionThe public health interventions aiming to eliminate COVID-19 have great impact on the prevalence of the atypical pathogens. The detection rate of Mp was significantly reduced, and the seasonality of Mp was disappeared, while the detection rate of CT was significantly increased.





    Key wordsAcute respiratory tract infections;Mycoplasma pneumoniae;Chlamydia trachomatis;Epidemiology

  • 16 cases of acute leukemia in children with peripheral facial paralysis as the initial symptom: Ａ case series report
  • LIU Jing, LU Aidong, ZUO Yingxi, WU Jun, HUANG Zhizhuo, JIA Yueping, DING Mingming, ZHANG Leping, QIN Jiong
  • 2022 Vol. 17 (4): 296-301. DOI:10.3969/j.issn.1673-5501.2022.04.006
  • Abstract ( 531 ) PDF (1100KB)( 241 )
  • Background：At present, there are few reports about acute leukemia in children with peripheral facial paralysis as the initial symptom, and it is easy to be misdiagnosed clinically. Objective：To investigate the clinical characteristics，treatment and prognosis of children diagnosed with acute leukemia presented with peripheral facial paralysis as the initial symptom. Design：Case series report. Methods：The children diagnosed with acute leukemia presented with peripheral facial paralysis as the initial symptom admitted to the Department of Pediatrics of Peking University People's Hospital from January 2010 to September 2021 were included. The clinical characteristics, laboratory examinations, treatment and outcome were analyzed. Main outcome measures：The outcome of facial paralysis，5year eventfree survival（EFS），overall survival（OS）. Results：A total of 1 018 children with acute leukemia were admitted during the study period, including 728 patients with ALL and 290 patients with AML. Sixteen children(1.6%) presented with peripheral facial paralysis as the initial symptom, including 7 males and 9 females, with a median age of 5 years (214 years), and a median time from onset of facial paralysis to diagnosis of facial paralysis was 9.5 days(131 days).There were 2 cases （12.5%) of Bcell leukemia, 1 case(6.2%) of Tcell leukemia and 13 cases(81.3%) of M2 myeloid leukemia. All 16 patients had unilateral leukemia, 5（31.2%）were left and 11（68.8%）were right. 15 cases underwent head MR examination, 2 cases showed dural and leptomeningeal thickening and enhancement (including 1 case with suspicious facial nerve injury), 1 case showed leukemia infiltration of medial rectus muscle and orbital segment of optic nerve, and 3 cases showed mastoiditis.Cerebrospinal fluid(CSF) was examined in 15 cases, of which 1 case had CSF minimal residual positive and transient elevation of CSF protein occurred in 1 case. One patient gave up treatment after leukemia diagnosis, and the other 15 patients received chemotherapy. Eight patients remains continuous remission with regular chemotherapy，6 patients received hematopoietic stem cell transplantation, and 1 patient died after relapse due to multiple organ dysfunction during chemotherapy. The symptoms of facial paralysis disappeared in 13 cases within 1 month, and in 2 case within 3 months. The median followup time was 44.5(0.23111) months，the 5year eventfree survival(EFS) was(48.2±13.0)％，and 5year overall survival(OS) was (87.5±8.3)％．The 5year EFS and 5year OS of 13 AML children were (51.3±14.6) % and (84.6±10.0) %, respectively, with 5year OS 100% in the transplant patients and (87.5±11.7) % in the onlychemotherapy patients, showing no statistical difference (P=0.48). Conclusion：Peripheral facial paralysis as the initial symptom of childhood acute leukemia is likely to be misdiagnosed. For children with peripheral facial paralysis, comprehensive examination should be completed to exclude secondary causes before steroid therapy. Intensive central nervous system therapy should be considered in children with acute leukemia with facial paralysis. The overall survival rate of AML children with facial paralysis was not significantly affected, but they were more likely to relapse.
  • Efficacy of mycophenolate mofetil therapy in myelin oligodendrocyte glycoprotein antibodyassociated disease: A systematic review and meta-analysis
  • WU Pengxia, CHANG Xuting, LI Shangru, ZHANG Jie, WU Ye
  • 2022 Vol. 17 (4): 302-306. DOI:10.3969/j.issn.1673-5501.2022.04.007
  • Abstract ( 308 ) PDF (1645KB)( 184 )
  • Background：There are many widely used immunotherapies for relapse prevention in myelinoligodendrocyte glycoprotein antibodyassociated disease (MOGAD), however, there is no optimal relapse prevention therapy. Objective：To investigate the efficacy of mycophenolate mofetil (MMF) in the treatment of MOGAD. Design：Systematic review and metaanalysis. Methods：English and Chineselanguage articles were searched in PubMed, Embase, Web of Science, Cochrane, Wanfang Data, China National Knowledge Infrastructure (CNKI), and China Science and Technology Journal Database (CQVIP) from the inception to June 1, 2021. All studies related to the efficacy of MMF in treating MOGAD were included regardless of the study design. Inclusion criteria were as the following : the subjects from the original clinical study met the diagnostic criteria of MOGAD, regardless of race, sex, and age; the duration of MMF was ≥ 6 months;the change in annualized relapse rate (ARR) or relapse rate was reported . The literature meeting the following criteria were excluded that studies in which modifying treatment definition was met during treatment; it is unable to obtain the full text; the language is neither English nor Chinese. The metaanalysis was performed using R 4.2.1 and the risk of bias of the included studies was assessed. Main outcome measures：Relapsefree rate and ARR. Results：Twelve studies (161 patients) were included in the metaanalysis, including 1 prospective cohort study and 11 case series reports. Fiftyseven of 161 patients were children, 80 of 161 patients were adults, and age information was unclear in the rest of 24 patients. Age of onset ranged from 1 to 74 years. The followup time ranges from 6 to 67months. Overall, 74% of the patients were relapsefree during followup after MMF therapy (95%CI:58%89%, I2=83%，P＜0.01). ARR was significantly decreased after MMF therapy with a mean reduction of 1.38 times/year (95%CI :0.941.82, I2=0%，P=0.62). Adverse effects was reported in 8%(7/87) of patients, and 5.7%(5/87) of patients discontinued MMF therapy due to serious adverse effects. Conclusion：The metaanalysis showed that the relapsefree rate of MOGAD was 74% after MMF treatment for at least 6 months, and the ARR decreased by 1.38 times/year compared with that pretreatment. More highquality studies were still necessary to confirm the result.
  • 6 cases of neonatal microcephaly caused by ASPM gene defect: A case series report and literature review
  • YU Kexin, MEI Hongfang, CHEN Huiyao, ZHANG Jiantao, HU Liyuan, CHENG Guoqiang, LU Yulan, WANG Huijun, WU Bingbing, ZHOU Wenhao, YANG Lin
  • 2022 Vol. 17 (4): 307-311. DOI:10.3969/j.issn.1673-5501.2022.04.008
  • Abstract ( 702 ) PDF (547KB)( 338 )
  • Background：Primary microcephaly (MCPH) is a rare genetic disorder characterized by occipitofrontal circumference equal to or below -2 SDs at birth, facial deformity and intellectual disability. Objective：To summarize and analyze the clinical and genetic characteristics of patients with primary microcephaly caused by ASPM gene defects (ASPMMCPH) in both the China Neonatal Genome Project (CNGP) and HGMD database. Design：Case series report. Methods：The newborns with biallelic pathogenic/likely pathogenic (P/LP) variants in ASPM gene in the CNGP were included. The clinical and genetic features were summarized. We established the P/LP variant list of ASPM gene from CNGP, HGMD and ClinVar database, and calculated the frequency of carrying ASPM P/LP variants in the whole CNGP cohort. And finally, the genotypephenotype association of ASPMMCPH was summarized by analyzing the records from the HGMD database. Main outcome measures：The assessment of the frequency of carrying ASPM P/LP variants in the whole CNGP cohort. Results：Twelve P/LP variants in ASPM gene were identified in 6 patients, of which 6 variants were novel. Prenatal B-ultrasound showed microcephaly and primary microcephaly was diagnosed after birth for all of the 6 patients. But other typical clinical features were absent. The frequency of carrying P/LP variants in ASPM gene in the whole CNGP cohort was 0.001 206 043. In the previously reported cases, the incidence of microcephaly, facial deformity and mild to moderate developmental delay was more than 50%. Brain MRI showed abnormal gyri and ventricular dilation. Regarding the types of variants, the proportion of lossoffunction variants was 96.43%. There was no statistically significant difference between the effect of lossoffunction and missense variants on the degree of developmental delay. Conclusion：Six novel P/LP variants in ASPM gene were identified in this study. The frequency of carrying P/LP variants in ASPM gene was assessed. Genetic testing was recommended for fetuses with microcephaly.