Prenatal ultrasonic diagnosis and genetic analysis of fetal congenital heart diseases / 中国医学影像技术

Objective To explore the genetic characteristics of fetuses with congenital heart diseases(CHD)diagnosed by prenatal ultrasound.Methods Data of 613 singletons with prenatal ultrasonic diagnosed CHD were retrospectively analyzed.The cardiac structural abnormalities were classified into 8 types.Whole-exome sequencing(WES)was performed for 40 fetuses since chromosomal karyotyping analysis and/or chromosomal microarray analysis(CMA)showed benign copy number variations(CNV)or variants of uncertain significance(VUS).Results Among 613 fetuses,479 fetuses underwent both chromosomal karyotyping analysis and CMA,genomic abnormalities were detected in 60 fetuses(60/479,12.53％).Among 134 fetuses underwent only CMA,genomic abnormalities were found in 4 fetuses(4/134,2.99％).According to results of chromosomal karyotyping analysis and/or CMA,abnormalities were noticed in 40 fetuses(40/568,7.04％)among 568 fetuses with isolated CHD,while in 15 fetuses(15/45,33.33％)among 45 fetuses with non-isolated CHD,respectively.Abnormality detection rate of chromosomal karyotyping analysis and/or CMA in fetuses with complex CHD(10/41,24.39％)was higher than that in fetuses with non-complex CHD(54/572,9.44％).Among complex CHD fetuses,abnormality detection rate was the highest in fetuses with conotruncal defect(CTD)combined with malformation of venous system(4/13,30.77％),while among fetuses with non-complex CHD,situs inversus viscerum had the highest detection rate(1/4,25.00％).Among 40 fetuses chromosomal karyotyping analysis and/or CMA showed benign CNV or VUS,WES indicated pathogenic CNV/likely pathogenic CNV(P/LP)in 3 fetuses,VUS in 3 fetuses and benign CNV in 34 fetuses.Conclusion Fetuses with CHD,especially extracardiac malformations had possibilities of genomic abnormalities.Fetuses with CTD combined with malformation of venous system had higher possibilities of genomic abnormalities.Compared with CMA alone,chromosomal karyotyping analysis combined with CMA was helpful for detecting genomic abnormalities.

Correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week / 中国医学影像技术

Objective To observe the correlations of pontine biological indicators on fetal brain median sagittal MRI with gestational week.Methods Data of head MRI of 226 normal fetuses without obvious abnormalities of central nervous system(normal group)and 17 fetuses with abnormalities(abnormal group)at gestational age of 23 to 38 weeks were retrospectively analyzed.Pontine biological indicators based on median sagittal MRI were obtained,including pons anteroposterior diameter(PAD),total pons area(TPA),pontine basal anteroposterior length(AP),pontine basal cranio-caudal length(CC),basis pontis area(BPA)and pontine angle of midbrain(MAP).According to the gestational week,the fetuses of normal group were divided into 8 subgroups.The distributing ranges of pontine biological indicators at different gestational weeks were analyzed,and the correlations of pontine biological indicators with gestational week in normal group were explored,and the developmental status of fetal pons in abnormal group were assessed.Results In normal group,PAD,TPA,AP,CC and BPA all showed linear positive correlation(r=0.887,0.914,0.787,0.866,0.865,all P＜0.001),while MAP was not significantly correlated with gestational week(P＞0.05).Among 17 fetuses in abnormal group,abnormal PAD or TPA was found each in 8 fetuses,abnormal AP was observed in 14,abnormal CC was noticed in 3 and abnormal BPA was found in 11 fetuses.Conclusion Fetal pontine biological indicators such as PAD,TPA,AP,CC and BPA on median sagittal MRI were positively correlated with gestational week,hence being able to be used for evaluating fetal pontine development.

Prenatal imaging classification and potential diseases of fetal abnormal sylvian fissure / 中华超声影像学杂志

Objective:To assess the ultrasonographic features and potential diseases of fetal abnormal sylvian fissure(SF), and to explore the value of whole-genome sequencing (WGS) in prenatal detection.Methods:A total of 28 fetuses with a sonographic diagnosis of abnormal SF in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University between October 2018 and October 2020 were prospectively included. The fetal brain was evaluated by neuroultrasound and intrauterine MRI in detail. Amniotic fluid/cord blood obtained by amniocentesis or tissue samples from umbilical cord after birth were collected for WGS. Pregnancy outcomes and postnatal MRI were recorded, and neurodevelopment of live-born infants was followed up for more than 24 months after delivery.Results:During the study period, 28 fetuses with abnormal SF were identified, with a gestational age of 21.3-30.0 (24.8±2.0) weeks. Abnormal SF presented in MCD ( n=15, 53.6%), chromosomal anomalies ( n=3, 10.7%) or single-gene genetic syndromes ( n=3, 10.7%) with the affected fetuses showing developmental delay, hydrocephalus or leukomalacia ( n=4, 14.2%), corpus callosal agenesis with large interhemispheric cysts ( n=1, 3.6%), benign subarachnoid space enlargement with arachnoid cysts ( n=1, 3.6%), and multiple malformations ( n=1, 3.6%). Among the 15 cases with MCD, the most common pathology was lissencephaly/pachygyria, followed by schizencephaly, severe microcephaly, hemimegalencephaly with paraventricular heterotopia, and polymicrogyria. Abnormal SF presented bilaterally in 23 fetuses and unilaterally in 5. All cases were categorized into six types depending on SF morphology in the transthalamic section: no plateau-like or a small insula, linear type, irregular corrugated SF, Z-shaped, and cyst occupying type. In addition to abnormal SF, associated anomalies or mild variations were identified in all fetuses. There were 17 cases underwent intrauterine MRI, and 13 cases underwent postnatal MRI examination.And 25 pregnancies were terminated; 3 were born alive, and 2 had typical syndromic changes with poor neurodevelopmental prognosis. A related pathogenic genetic variant was detected in 57.1% (16/28) fetus, and the incidence of single nucleotide variants(SNVs) was 42.9% (12/28), among which de novo SNVs accounted for 91.7% (11/12). Conclusions:Fetal abnormal SF could be classified based on the ultrasonographic features of transthalamic section. Fetal abnormal SF may indicate MCD, some chromosomal abnormalities or single-gene genetic syndromes that may lead to poor neurodevelopmental outcomes, and may be affected by extra-cortical factors. It is suggested to carry out targeted prenatal genetic diagnosis for fetuses with abnormal SF.

Counting of fetal caudal vertebral body ossification center below terminal conus medullaris in the screening of the closed spine bifida and tethered cord syndrome / 中华超声影像学杂志

Objective:To assess the significance of counting the number of caudal vertebral ossification centers (OCN) below fetal terminal conus medullaris in the screening for closed spina bifida and tethered cord syndrome (TCS).Methods:The OCN was counted in 961 normal fetuses(normal group) between 17 and 41 gestational weeks and in 140 fetuses with closed spina bifida or tethered cord syndrome(abnormal group) from Jan.2013 to Dec.2020 in Affiliated Shenzhen Maternity & Child Healthcare Hospital, Southern Medical University, Women and Children′s Hospital, School of Medicine, Xiamen University and Maternity and Child Health Care of Guangxi Zhuang Autonomous Region. The OCN was counted in the dorsal mid-sagittal section of fetal caudal spine.The reliability and agreement test were evaluated by intraclass correlation coefficients in another 50 normal fetuses. The OCN was compared between two groups. ROC curve and the cut-off value were constructed and calculated.Results:In normal group, the N increased with the growing of gestational age.In the subgroup of 17-20 weeks, the OCN ranged from 5 to 7 in most fetuses. In the others subgroups, the OCN was equal to or greater than 6 in 99.9% cases and more than 6 in 97.1% cases. In abnormal group, OCN was less than 7 in 93.0% fetuses and less than 6 in 82.8% cases. There were statistical differences between the two groups except for the subgroup of 17-20 gestational weeks( P<0.05). With the cut-off value of 6.5, the specificity and sensitivity were 93.0% and 94.3% respectively for predicting the presence of closed spinal dysraphism or TCS. Conclusions:OCN is a simple way to evaluate the position of conus medullaris and to screen for the skin-covered spine dysraphism or TSC. OCN is more than 6 in most normal fetuses. Further evaluation of spine is required in fetuses with N less than or equal to 6.

Feasibility study of prenatal ultrasound in the evaluation of normal fetal sylvian fissure maturation by simplified grading / 中华超声影像学杂志

Objective:To observe the morphological changes of the sylvian fissure on the transthalamic section of fetal brain at 20-32 weeks, and grade the fetal sylvian fissure development by means of a simple scoring system and explore its clinical feasibility.Methods:From September 2018 to June 2020, 487 normal single fetuses of 20-32 weeks were examined in Shenzhen Maternal and Child Health Hospital Affiliated to Southern Medical University. The sylvian fissure maturation was analyzed on the transthalamic section of fetal brain at 20-32 weeks and was graded from 0 to 5: un-visualized (grade 0), shallow arc (grade 1), obtuse-angled platform (grade 2), right-angled platform (grade 3), acute-angled platform (grade 4), and closed operculum (grade 5). The pregnancy outcomes and gestational age were recorded.Statistical analysis was performed by SPSS 20.0 software using box plot, Mann-Whitney U test, Weighted Kappa coefficient. Results:Left sylvian fissuer grades were obtained in 280 fetuses and right sylvian fissure grades were obtained in 247 fetuses. The fetal sylvian fissure maturation at 20-32 weeks was graded from 0 to 5, which increased with advancing gestation. Grade 0 only appeared in 3 fetuses at 20 weeks, and 99.4% fetuses at 20 weeks had grade ≥1. Grade 1 appeared in 20-22 weeks, grade 2 in 20-25 weeks, grade 3 in 22-26 weeks, grade 4 in 25-32 weeks, and grade 5 in 27-32 weeks. Box-plot and Mann-Whitney U test showed that gestational week distribution of sylvian fissure at all grades was symmetric on both sides ( P>0.05). The Weighted Kappa coefficients were 0.857(95% CI=0.750-0.957) and 0.939 (95% CI=0.859-1.000), respectively, with strong consistency regarding inter- and intra-observer agreements. Conclusions:Fetal sylvian fissure maturation at 20-32 weeks can be evaluated by means of a simple scoring system with symmetrical grading of both sides.

Evidence-based Guidelines on Medication Therapy for Purulent Meningitis in Children:A Systematic Review / 中国药房

OBJECTIVE:To systematically review the related evidence-based guidelines of purulent meningitis in children,and to provide evidence-based reference for clinical treatment. METHODS:Retrieved from PubMed,EMBase,CBM,Wanfang Data-base,CJFD and VIP,NGC,GIN,TRIP and websites of domestic and international medical associations and industry bodies,the treatment guidelines about purulent meningitis in children were collected. Evidence-based evaluation was performed after data extrac-tion and quality evaluation. RESULTS:Finally 3 guidelines were enrolled in total,with development time ranging from 2004 to 2012,from USA,Britain and Australia,respectively. All of the recommendations were level B,scope and purpose and clarityshowed the higher scores in AGREEⅡ,more than 70%,and applicability showed generally low scores. Penicillin and cefotaxi-me were recommended in purulent meningitis of neonates,and vancomycin combined with cefotaxime or ceftriaxone were recom-mended for infants and children(it was combined with vancomycin when Streptococcus pneumoniae infection was suspected). The dose and duration of each guideline were certain different,and the period of treatment should be longer in neonates. In addition, the glucocorticoid was recommended in all guidelines. CONCLUSIONS:The recommendations of medicines for the treatment of pu-rulent meningitis are basically unanimous,with no regional difference,but there are some differences about dose and the course of treatment. In addition,the classification criteria of the levels of evidence and recommendation are still suboptimal,which needs fur-ther improvement. And guidelines on purulent meningitis should be improved inrigourandapplicabilityin future.

Prenatal ultrasonic research of fetal optic chiasma / 中华超声影像学杂志

Objective To research fetal optic nerve,optic chiasma and optic tract size using high resolution prenatal ultrasound,establish a scan method and the reference range of optic nerve,optic chiasma and optic tract in normal fetus.Methods Based on the section of circulus arteriosus cerebri,the probe were rotated to get the chiasma section for measuring the diameter of bilateral optic nerve,optic tract and area of optic chiasma in 453 normal fetus respectively.Used gestation age and corresponding biological parameters as independent variables,the regression equation was established analyse the gender differences.Results 26-33 weeks was the preferable gestational age to visualize the chiasma section.It had good repeatability except chiasma area.The bilateral optic nerve and optic tract diameter,optic chiasma diameter and area had an increased along with the gestational age reposefully.There was no significant difference between the two sides of optic nerve and the gender.Conclusions Prenatal ultrasound can assess the size and shape of fetal optic nerve,optic chiasma and optic tract.The normal reference range,established by ultrasound,is helpful to diagnose the abnormality of optic chiasma.

Estimation of Cystatin C as a Marker of Renal Function to Predict Serum Trough Concentrations of Vancomycin / 医药导报

Objective To investigate the clinical efficiency of serum cystatin C as a marker of renal function to predict serum trough concentrations of vancomycin. Methods Data on trough concentrations of vancomycin(Cmea ),serum creatinine (Scr)concentrations,cystatin C( Cys C) concentrations were collected from 81 hospitalized patients who received vancomycin therapy. Predicted vancomycin trough concentrations(Cpre )were calculated based on Scr or Cys C concentrations associating with Bayesian forecasting method through NONMEM software. Finally,the correlations and distinctions between Cpre and Cmea were comparatively analyzed. Results There were both correlation between Cpre and Cmea in relation to Scr or Cys C(r = 0. 678,P<0. 01;r=0. 727,P<0. 01). Besides,the errors of mean predictive error(ME),mean absolute error(MAE)and root-mean-square error(RMSE)for Scr was - 5. 79,6. 86,9. 86 μg · mL-1 , respectively, where as the errors for Cys C was - 0. 82,5. 42, 7. 74 μg·mL-1 ,respectively. Conclusion Cystatin C is a good marker of renal function available for predicting serum vancomycin concentrations.

Study on the methodology and feasibility of an anatomic survey of fetal limbs in the first trimester / 中华医学超声杂志（电子版）

Objective To investigate the methodology and feasibility of an anatomic survey of fetal limbs in the first trimester. Methods In this study, 533 normal fetus and 6 fetal corpse without limb abnormalities form June 2011 to August 2012 underwent an anatomic survey on the limbs in our consultation center. The limbs were scanned using a systematic continuous sequence approach:(1) Displaying upper arm and humerus, forearms and radius/ulna, hands in proximal to distal direction. (2) The thigh and femur, crus and tibia/fibula, feet was attempted from the sagittal section of each structure. (3) If the whole limb couldn′t be visualized in a section then the three segments will be demonstrated respectively. The position and move-ment also should be observed during the scan. Data were collected regarding gestation age, examining time and the structures. Results The limbs except toes of 533 normal fetus were clearly observed, which was completely unaffected by gestational age, with the mean time of scanning is 98.6±37.4 s (rang:36-189 s). The structures (including upper arms and humerus, forearms ,radius and ulna, hands, thigh and femur, crus and tibia, fibula, feet) of fetal limbs were clearly observed on the 6 fetal corpse, but the ossification center of fingers were steadily visualized until 13 weeks and toes after 13 weeks. Conclusions Scanning fetal limbs in the first trimester were feasible by a systematic continuous sequence approach in a short period of time.

Systematic review of clinical guidelines for Guillain-Barré syndrome in children / 临床儿科杂志

Objective To systematic review the methodological quality of guidelines for Guillain-Barré syndrome (GBS) in children, to provide a reference for clinical evidence-based medicine. Methods Guidelines concerning GBS were electronically retrieved from PubMed, EMbase, CBM, Wanfang data, CNKI and Vip. The guide databases includes major medical institutions and industry sites such as NGC, GIN, TRIP , CDC, IDSA, AAP, WHO, Chinese Health and Family Planning Committee website, library of clinical guidelines China and Chinese clinical guidelines for collaboration. All the data were searched from inception of the database or network to Oct. 2013. Two reviews independently screened literature according to the inclusion and exclusion criteria, and assessed the quality of guideline using the AGREEⅡ. Intraclass correlation coefficient (ICC) was used to examine the conformance of the raters' evaluation scores. Results A total of 5 guidelines concerning GBS were included, with a time range from 2003 to 2012, and origins from USA, EU and Canada. The final recommendation levels of the 5 articles were level B. According to the AGREEⅡ, domain 3 and 4 showed the higher scores, and scores were generally low in domain 5. Plasma exchange (PE) and intravenous immuneglobulin (IVIG) showed positive effects on the treatment of GBS. But it was not recommended that combined PE and IVIG. Corticosteroids are also not recommended for GBS treatment. Conclusions The recommendations of medicines for GBS are basically consistent. However, the classification criteria of the levels of evidence and recommendation are still unconsistent and suboptimal. The guidelines on GBS should be improved in“Applicability”in future.