Prenatal ultrasound diagnosis of fetal microphthalmia / 中华超声影像学杂志

Objective@#To analyze the ultrasonic features, associated malformations and combined genetic abnormalities of microphthalmia .@*Methods@#The characteristics of 15 cases of fetal microphthalmia were retrospectively analyzed. And the proportion of fetal microphthalmia associated malformations were further assessed according to the different organ system.@*Results@#All the orbital diameters of affected eyes of the 15 cases were less than the 5th centile of normal fetal orbital diameter corresponding to gestational age. In which, 26.67%(4/15) fetuses had additional ocular defects, and 66.67%(10/15) were diagnosis with extrocular defects, including 20.00%(3/15) with central nervous system defects, 13.33%(2/15) with orofacial defects, 26.67% (4/15) with cardiac defect, 13.33%(2/15) with limb defect, 33.33% (2/15) with urogenital defect and 40.00%(6/15) with abnormal ultrasonographic soft markers. And the proportion of fetal microphthalmia associated extrocular defects showed no significant difference(P=0.502).@*Conclusions@#Fetal microphthalmia is frequently associated with random and sporadic occurrence of extrocular defects

Prenatal ultrasound diagnosis of fetal microphthalmia / 中华超声影像学杂志

Objective To analyze the ultrasonic features ,associated malformations and combined genetic abnormalities of microphthalmia . Methods The characteristics of 15 cases of fetal microphthalmia were retrospectively analyzed . And the proportion of fetal microphthalmia associated malformations were further assessed according to the different organ system . Results All the orbital diameters of affected eyes of the 15 cases were less than the 5th centile of normal fetal orbital diameter corresponding to gestational age . In which ,26 .67% ( 4/15 ) fetuses had additional ocular defects ,and 66 .67% ( 10/15 ) were diagnosis with extrocular defects ,including 20 .00% ( 3/15) with central nervous system defects ,13 .33% ( 2/15) with orofacial defects ,26 .67% ( 4/15) with cardiac defect ,13 .33% ( 2/15) with limb defect ,33 .33% ( 2/15) with urogenital defect and 40 .00% ( 6/15 ) with abnormal ultrasonographic soft markers . And the proportion of fetal microphthalmia associated extrocular defects showed no significant difference ( P ＝ 0 .502 ) . Conclusions Fetal microphthalmia is frequently associated with random and sporadic occurrence of extrocular defects

Chromosomal anomalies in fetuses with structural malformation detected by ultrasonography at 11-13+6 gestational weeks / 中华围产医学杂志

Objective To investigate the clinical performance of ultrasound screening for fetal structural anomalies at 11-13+6 weeks of gestation and to evaluate the relation of structural anomalies with karyotypes and copy number variations. Methods A retrospective analysis was conducted on fetuses with structural anomalies detected by ultrasound examination at 11-13+6 gestational weeks in First Affiliated Hospital of Sun Yat-Sen University from January 2013 to December 2017. Karyotype and chromosomal microarray analysis(CMA) were offered to these fetuses and ultrasound scans were repeated at 16-18 gestational weeks. All fetuses were followed up to termination or birth. Fisher's exact test was used for statistical analysis. Results A total of 362 fetuses with structural anomalies were studied including 101 (27.9%) fatal malformations, 253 (69.9%) major malformations and eight (0.2%) minor malformations. Cardiac malformation (32.6%, 118/362), central nervous system anomalies (24.9%, 90/362) and anterior abdominal wall defects (20.9%, 76/362) were the three most common abnormalities. Invasive prenatal test was performed in 107 cases including 25 fatal, 79 major and three minor malformations. Thirty (28%) out of the 107 cases had abnormal karyotypes, which were chromosomal aneuploidies (n=28) and chromosomal fragment abnormalities (n=2). Among the 99 cases received CMA, 25 had abnormal karyotypes, and copy number variations were identified in eight [three (4.05%) were pathogenic variations] out of the rest 74 with normal karyotypes. The incidence of chromosomal abnormalities in fetuses with major malformations was higher than that of fetuses with fatal malformation [32.9% (26/79) vs 12.0% (3/25), P=0.045]. Altogether, 117 cases repeated second-trimester ultrasound among which 16 (13.7%) were normal; 19 (16.2%) had cardiac defect which was discordant with the first-trimester evaluation and five (4.2%) were found to have additional malformations. Diagnosis of the other 77 cases were consistent with the first-trimester ultrasound findings. After the second-trimester ultrasound scanning, 49 pregnancies were terminated; 39 twin pregnancies and four triplet pregnancies underwent selective fetal reduction; 25 continued to delivery with good neonatal outcomes. Out of the 23 699 cases without abnormal ultrasound findings at 11-13+6 gestational weeks, 20 182 (85.2%) were successfully followed up, among which structural abnormalities were found in 178 during the second trimester and in 31 after birth. Conclusions A detailed ultrasound examination at 11-13+6 weeks of gestation is important to identify fetal structural defects. However, it could not replace the second-trimester ultrasound. There is a high risk of chromosomal abnormalities in fetuses with early-detected structural defects. CMA is able to identify pathogenic copy number variations with a relatively low detection rate.

Fetal Persistent Left Superior Vena Cava Associated with Abnormal Karyotypes and Copy Number Variations / 中山大学学报(医学科学版)

@#【Objective】To investigate the clinical value of chromosomal microarray analysis（CMA）for fetuses with persistent left superior vena cava（PLSVC）.【Methods】Fetuses that were diagnosed with PLSVC during ultrasound examination and underwent invasive prenatal testing（on which karyotyping and CMA were both performed）from January 2014 to December 2016 at the First Affiliated Hospital of Sun Yat-sen University were reviewed. According to the combination of other ultrasound abnormalities，the cases were divided into isolated group and complicated group.【Results】Karyotype analysis identified chromosomal aberrations in 18.5%（15/81）of the fetuses，while CMA detected pathogenic copy number variations（CNV）in 23.5%（19/81）of the fetuses. There was no significant difference in the detection rate of chromosomal abnormalities between the Karyotype analysis and CMA（P = 0.44）. CMA achieved an incremental yield of 6.1% （4/66）among PLSVC fetuses with normal karyotypes，and only in the complicated cases. There were 12 cases（14.8% ，12/81）in isolated group and 69 cases（85.2% ，69/81）in complicated group. The frequency of genetic anomalies in the complicated group was not significantly higher than that in the isolated group（26.1%，18/69 vs. 8.3%，1/12，P = 0.277）. The incidences of atrioventricular septal defect，facial abnormalities，and multiple soft markers were significantly higher among fetuses with abnormal genetic test results（P= 0.030，P= 0.012，P= 0.014）.【Conclusion】CMA is a valuable tool for identifying additional unbalanced submicroscopic chromosomal abnormalities in fetuses with PLSVC ，especially when PLSVC is accompanied by other ultrasound malformations.

Application of Single Nucleotide Polymorphism Microarray Analysis for the Investigation of Fetuses with Conotruncal Heart Defects / 中山大学学报(医学科学版)

@#【Objective】This study aimed to explore copy number variations（CNV）in fetuses with conotruncal heart defect （CTD）. 【Methods】 Fetuses with ascertained CTD were investigated for chromosomal aberrations including copy number variations with chromosomal microarray analysis（CMA）and QF-PCR. Based on clinical significance of CNV，Fetuses were divided into two subgroups：non- benign CNV group ［（pathogenic CNV and CNV of unknown significance（VOUS）］and benign CNV group. Data on fetal structural malformations，copy number variations，and pregnancy out? comes were collected and compared.【Results】Among 128 cases without chromosomal aneuploidies ，pathogenic CNV ， CNV of VOUS ，and benign CNV were identified in 5.5% ，4.7% ，and 3.9% ，respectively. Compared with cases in benign CNV group（n=115），fetuses in non- benign CNV（n=13）had a significantly higher rate of overall extra- cardiac anomalies（76.9% vs. 43.5%，P=0.037），structural extra-cardiac anomalies（61.5% vs. 24.2%，P=0.022），softer mark? er anomalies（61.5% vs. 20.9% ，P=0.004），and thymus anomalies（30.8% vs. 0.87% ，P=0.000），whereas，no significant difference in that of intra- cardiovascular anomalies was noted（53.9% vs. 53.9%，P=1.000）excepted for that of persistent left superior vena cava（46.2% vs. 13.9% ，P=0.010）. The incidence of natural death in non- benign group was higher than but not statistically different from that of benign group.【Conclusions】Pathogenic CNV contributed to the pathogenesis of CTD. The presence of associated extra-cardiac anomalies including thymus abnormalities correlated with a higher probability of non-benign CNV.

Analysis of copy number variation by CMA in fetus with increased nuchal translucency / 中华妇产科杂志

Objective To investigated the clinical value of chromosomal microarray analysis (CMA)in fetuses with increased nuchal translucency(NT). Methods Totally 101 cases out of 19261 singleton fetuses who underwent the first trimester(11-13+6 weeks)ultrasound examination from January 2015 to June 2017 at First Affiliated Hospital of Sun Yat-sen University were diagnosed with NT ≥2.5 mm and underwent invasive prenatal test for fetal karyotype and CMA. According to the combination of other ultrasound abnormalities,the cases were divided into isolated group(67.3％, 68 / 101)and complicated group(32.7％, 33/101). In addition, the cases were divided into 5 groups according to the thickness of NT,2.5-2.9 mm(borderline thickening;16.8％, 17/101), 3.0-3.4 mm(33.7％, 34/101), 3.5-4.4 mm(16.8％, 17/101),4.5-5.4 mm(15.8％, 16/101),and ≥5.5 mm(16.8％, 17/101). Chi square test was used to detect the different rates of other combined ultrasound abnormalities and abnormal chromosome between 5 groups. Results The median thickness of NT was 3.4 mm(2.5-8.5 mm). And 32 cases(31.7％, 32/101)had abnormal karyotype. There was a significant difference in the frequency of abnormal karyotype between the isolated and the complicated group(20.6％ vs 54.5％, P<0.01). Among 69 cases(68.3％,69/101) of normal karyotype, 3 cases(4.3％, 3/69)were detected with pathogenic copy number variation(CNV) by CMA. Thirty-five cases with chromosomal abnormalities(include abnormal karyotype and pathogenic CNV), there was a significant difference in the frequency of chromosomal abnormalities between the isolated and the complicated group(23.5％ vs 57.6％, P=0.001). The median age of pregnant women in 5 groups was 35 years(24-39 years),33 years(23-46 years),31 years(21-46 years),33 years (21-41 years) and 35 years (21-43 years). The rates of chromosomal abnormalities increased with the increase of NT thickness. There was significant difference in the incidence of associated chromosomal abnormalities among 5 groups(P<0.05). Comparative analysis within the 5 groups, the incidence of associated chromosomal abnormalities between NT 2.5-2.9 mm and ≥5.5 mm was significantly different (P=0.005), while the differences between the other groups were not significant(P>0.05). Conclusions There is a high risk of fetal chromosomal abnormalities in borderline NT thickening (2.5-2.9 mm)at advanced maternal age, but the pathogenic CNV is not detected. Chromosomal microdeletion or microduplication could be further detected in the NT thickening(≥3.0 mm)fetuses with normal karyotype by chromosome microarray analysis, while the positive rate is relatively low, and the variants of unknown significance might be detected.

Prenatal MRI diagnosis of fetal midline dural sinus malformation / 中国医学影像技术

Objective To explore prenatal MRI findings of fetal midline dural sinus malformation(DSM).Methods Eleven fetuses of midline DSM were collected.Abnormalities in the fetal occipital or cerebellar area were found from 21 to 27 weeks of gestation.Then MR scanning in the following week was performed.Of all 11 fetuses,9 were pathologically proved to be midline DSM,and the other 2 were followed up and proved after birth.The imaging findings and pathological features were analyzed.Results MRI of 11 fetuses showed cystic dilation of the occipital cranium of torcular herophili area,with the size of 10 mm× 15 mm to 35 mm× 55 mm,and the adjacent sinuses were also dilated.On axial or coronal images,the lesions were cuneiform,while on sagittal images,the lesions were spindle-or crescent-shaped.The lesions displayed isointensity or slightly hyperintensity on T1WI,while slightly hypointensity,isointensity or slightly hyperintensity on T2WI.In 9 of the 11 fetuses,class round or bar thrombosis on the side wall of the cystic mass were observed,which were hyperintensity on T1WI and isointensity and hypointensity,isointensity or hyperintensity on T2WI.Hemosiderin deposition was observed around the thrombi in 6 fetuses.Lesion diameters in 2 fetuses were more than 30 mm,and the adjacent brain tissue was significantly dislocated.Nine fetuses of postmortem pathology after induced labor showed deformed and dilated venous sinuses,in which eccentric thrombi were seen in 7 fetuses with side branches around them.Normal brain development was observed in 2 live birth newborns.Conclusion Prenatal MRI can accurately diagnose fetal midline dural sinus malformation,and estimate the development of fetal brain,which may be helpful to prognosis prediction.

Effects of two different venous drainage patterns on the prognosis of fetal pulmonary sequestration / 中华超声影像学杂志

Objective To evaluate the effect of two different venous drainage patterns on the prognosis of fetal pulmonary sequestration( PS) . Methods Sixty cases of fetal PS with confirmed venous drainage diagnosed by prenatal ultrasound were retrospectively analyzed . Changes of the volumes of PS lesions and the clinical outcomes were compared between two different venous drainage patterns . Results Among the total 64 cases ,34 cases were pulmonary venous drainage and 30 cases were systemic venous drainage . There was no case combined with any abnormality in pulmonary venous drainage group;whereas , 6 cases combined with other abnormalities in systemic venous drainage group ,between which significant difference was noted( P =0 .02) . In pulmonary venous drainage group ,there was no significant difference in the volumes of PS lesions between at 20-24 weeks′gestational age(WGA) and at 24+1 -30 WGA( P >0 .05) ;but not between at 24+1 -30 WGA or at 20 -24 WGA and at 30+1 -39 WGA ( P 0 .05) . Postnatal respiratory symptoms and postnatal surgery rates were similar between the two groups( P > 0 .05) . Conclusions PS with systemic venous drainage is more likely combined with other abnormalities than PS with pulmonary venous drainage . The lesion volumes of PS with pulmonary venous drainage decreas remarkably during the middle‐late pregnancy . Nevertheless ,the clinical postnatal outcomes are both favorable in the two groups .

Indirect ultrasonic signs of the callosal partial agenesis and hypoplasia in the fetus / 实用医学杂志

Objective To investigate antenatal sonographic findings of the fetal isolated callosal hypoplasia and partial agenesis. Methods A retrospective study was performed on the cases of hypoplasia and partial agenesis of the corpus callosum suspected at antenatal sonographic basic examination from 2006 to 2014, all the cases were confirmed by pathology or magnetic resonance imaging(MRI). For the surviving infants, clinical follow-up had been performed to assess the developmental outcome. Results Thirteen fetuses suspected with callosal underdevelopment were identified at a median gestational age of 31 (range, 18~39) weeks. Ten cases were confirmed by autopsy and MRI, including 9 with partial agenesis and 1 with hypoplasia. Among the 10 fetuses confirmed with isolated partial agenesis or with hypoplasia, incidence of the absent cavum septum pellucidum was 20%, the ‘Tear-drop’ lateral ventricles was 40%, the upward displacement of the third ventricle was 80%. Pregnancy was terminated electively in 8 of the cases with partial agenesis or with hypoplasia. Among the 2 surviving infants, apparent normal development was observed in only one case, but we lost the follow-up of this case at two-year-old. Six fetuses received the chromosome identification, almost all of them were normal. Conclusion The basic ultrasonic examination is feasible for the antenatal diagnosis of isolated callosal underdevelopment the. The indirect classical signs of callosal partial agenesis and hypoplasia are different with those of complete agenesis of the corpus callosum. The incidences of the‘Tear-drop’ lateral ventricles and the upward displacement of the third ventricle are higher than the absence of CSP. The chromosome of isolated callosal partial agenesis or hypoplasia is normal, however, the prognosis is uncertain.

Association between fetal ventricular septal defects and chromosomal abnormalities / 中华妇产科杂志

Objective To evaluate the association between fetal ventricular septal defects (VSD)and chromosomal abnormalities.Methods The 214 fetuses diagnosed VSD in the First Affiliated Hospital of Sun Yat-sen University from January 2008 to September 2011 were included.The VSD were categorized into 3 types:perimembranous,muscular and mixed (the defect could not be classified because the dimensions were larger than 5 mm) type.The perimembranous defect was subdivided into inlet and outlet subtypes.Complicated with other cardiac abnormalities/extracardiac abnornalities or not,the cases were divided into isolated VSD group,VSD complicating cardiac anomalies group (other cardiac and/or great vessels malformation),VSD complicating extracardiac anomalies group (include organ malformation and sonographic soft markers) and VSD with both cardiac and extracardiac anomalies group.G-banding chromosome analysis was advised for all cases.In cases that no karyotype was obtained,the phenotype of the newborns was examined by the pediatricians.And those appeared normal were defined as normal karyotype.Results (1) There were 134 (62.6％,134/214) perimembranous defects,including 91 (42.5％,91/214) inlet lesions and 43 (20.1％,43/214) outlet lesions.There were 35 (16.4％,35/214) muscular defects and 45 (21.0％,45/214) mixed type lesions.(2) Among the 214 VSD fetuses,46 (21.5％) were isolated VSD,34 (15.9％) were cases with other cardiac anomalies,87 (40.6％) were cases with extracardiac anomalies and 47 (22.0％) were cases with both cardiac and extracardiac anomalies.(3) The chromosomal karyotypes were obtained in 105 cases,and 21 cases were considered as normal according to the phenotype.Of all these 126 cases,46 (36.5％,46/126) had chromosomal abnormalities.(4) Inlet defects had the highest risk of chromosomal abnormalities (28/55,50.9％),while the muscular defects had the lowest risk (2/25,8.0％).The incidence of chromosomal abnormalities in outlet and mixed type was 33.3％ (9/27) and 7/19,respectively.The types of VSD were significantly correlated with chromosomal defects (P ＜ 0.01).(5) The incidence of chromosomal abnormalities in the 4 groups were 3.4％ (1/29),2/14,53.6％ (30/56) and 48.1％ (13/27),respectively.The risk of chromosomal abnormalities in the cases complicating extracardiac or both extracardiac and cardiac anomalies was significantly higher than the isolated VSD group (P ＜ 0.01).Conclusion Fetal VSD had a highest risk of chromosomal abnormalities,especially the inlet type and VSD with extracardiac abnormalities,and then the fetal karyotype should be recommended.