Objective: To analysis the clinical characteristics of 400 fetuses with heart defects and the impactors of pregnancy decision making, and explore the influence of a multi-disciplinary team (MDT) cooperation approach on it. Methods: Clinical data of 400 fetuses with abnormal cardiac structure diagnosed at Peking University First Hospital from January 2012 to June 2021 were collected, which were divided into 4 groups according to the characteristics of fetal heart defects and the presence of extracardiac abnormalities or not: single cardiac defects without extracardiac abnormalities (122 cases), multiple cardiac defects without extracardiac abnormalities (100 cases), single cardiac defects with extracardiac abnormalities (115 cases), and multiple cardiac defects with extracardiac abnormalities (63 cases). The types of fetal cardiac structural abnormalities and genetic test results, and the detection rate of pathogenic genetic abnormalities, MDT consultation and management situation, and pregnancy decision of fetuses in each group were retrospectively analyzed. A logistics regression was used to analyze the influencing factors of fetal heart defects pregnancy decision. Results: (1) Among the 400 fetal heart defects, the four most common major types were ventricular septal defect 96 (24.0%, 96/400), tetralogy of Fallot 52 (13.0%, 52/400), coarctation of the aorta 34 (8.5%, 34/400), and atrioventricular septal defect 26 (6.5%, 26/400). (2) Among the 204 fetuses undergoing genetic examination, 44 (21.6%, 44/204) pathogenic genetic abnormalities were detected. (3) Detection rate of pathogenic genetic abnormalities (39.3%, 24/61) and pregnancy termination rate (86.1%, 99/115) in the single cardiac defects with extracardiac abnormalities group were significantly higher than those in the single cardiac defects without extracardiac abnormalities group [15.1% (8/53), 44.3% (54/122), respectively] and the multiple cardiac defects without extracardiac abnormalities group [6.1% (3/49), 70.0% (70/100), respectively, both P<0.05], and the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group and the multiple cardiac defects with extracardiac abnormalities group (82.5%,52/63) were significantly higher than that of the single cardiac abnormalities without extracardiac abnormalities group (both P<0.05). (4) After adjusting for age, gravity, parity and performed prenatal diagnosis, maternal age, the diagnosis of gestational age, prognosis grades, co-existence of extracardiac abnormalities, presence of pathogenic genetic abnormalities, and receiving MDT consultation and management were still independent influencing factors of termination of pregnancy of fetuses with cardiac defects (all P<0.05). A total of 29 (7.2%, 29/400) fetal cardiac defects received MDT consultation and management, and compared with those without MDT management, the pregnancy termination rate in the multiple cardiac defects without extracardiac abnormalities group [74.2%(66/89) vs 4/11] and the multiple cardiac defects with extracardiac abnormalities group [87.9%(51/58) vs 1/5] were lower, the differences were statistically significant respectively (all P<0.05). Conclusions: Maternal age, diagnosed gestational age, severity of cardiac defects, extracardiac abnormalities, pathogenic genetic abnormalities and MDT counseling and management are the influencing factors of fetal heart defects pregnancy decision. MDT cooperation approach influences pregnancy decision-making and should be recommended for the management of fetal cardiac defect to reduce unnecessary termination of pregnancy and improve pregnancy outcomes.
Pregnancy ; Female ; Humans ; Retrospective Studies ; Fetal Diseases/diagnosis* ; Heart Defects, Congenital/therapy* ; Fetus ; Decision Making ; Ultrasonography, Prenatal/methods*

OBJECTIVE: To investigate the application value of whole exome sequencing technology in fetuses with congenital structural abnormalities. METHODS: The chromosomal abnormalities of 1147 families were analyzed. According to the follow-up results, the data of fetuses with new phenotypes in late pregnancy or after birth were reanalyzed. Subgroups were divided according to the organs involved and whether single malformation or not. The gene regulatory network map was drawn by using string database and Cytoscape software. Fisher exact probability method was used to compare the difference of the diagnostic rate of pathogenic genes among the groups. RESULTS: A total of 160 fetal cases received positive molecular diagnosed, involving 178 variant sites of 125 pathogenic genes, including 8 cases (4.9%, 8/163) by data reanalysis, and the overall positive diagnosis rate was 13.9%. Diagnostic rate was highest in the group of skeletal malformation (31.5%, 39/124) and lowest in that with thoracic malformation (0, 0/32). The gene clusters of fetal edema and intrauterine growth restriction were independent, and were not associated with the major structural malformations. The probability of each parent carrying the same recessive gene variant was 0.03 (39/1146) and 0.08 (4/53) with positive family history. CONCLUSION For fetuses with congenital structural abnormalities that are negative for conventional genetic tests, 13.9% of phenotypic associated pathogenic/likely pathogenic genetic variants can be detected by whole exome sequencing technology. Its application value for prenatal diagnosis varies in fetus with different organs involved. Reanalysis of sequencing data for cases with new phenotypes in late pregnancy or after birth can further improve the molecular diagnosis rate. Further investigations are needed to explore the related genetic mechanisms.
Female ; Fetal Diseases ; Fetus/diagnostic imaging* ; Humans ; Pregnancy ; Prenatal Diagnosis ; Technology ; Ultrasonography, Prenatal ; Whole Exome Sequencing

BACKGROUNDRight dominant heart (RDH) in fetuses can occur with a number of cardiac as well as noncardiac anomalies. Analysis of the enlargement of the right cardiac chamber in the fetus remains a major challenge for sonographers and echocardiographers. The aim of this study was to report the experience with prenatal diagnosis of RDH in the fetuses over a 7-year period.

METHODSFetuses with prenatal diagnosis of RDH from July 2009 to July 2016 were evaluated in two different categories: according to the gestational age, Group I (n = 154, second trimester) and Group II (n = 298, third trimester); and according to the fetal echocardiography diagnosis, Group A (n = 452, abnormal cardiac structure) and Group B (n = 90, normal cardiac structure). Differences in categorical variables were assessed by Chi-square exact test and continuous variables were evaluated by independent Student's t-test or Mann-Whitney U-test depending on parametric or nonparametric nature of the data.

RESULTSOver a 7-year period, 452 fetuses were referred for the assessment of suspected RDH. Left-sided obstructive lesions were observed most frequently in the fetuses with RDH. When comparing Group I with Group II and Group A with Group B, the latter groups exhibited significant differences in the right/left ventricle (RV/LV) ratio (1.435 vs. 1.236, P = 0.002; 1.309 vs. 1.168, P = 0.047), RV width Z-score (1.626 vs. 1.104, P < 0.001; 1.553 vs. 0.814, P = 0.014), and above +2 cutoff percentages (14.3% vs. 22.5%; P = 0.038; 21.5% vs. 12.2%, P = 0.046). Multivariable logistic regression revealed no variables associated with perinatal survival.

CONCLUSIONSThe study demonstrates that RDH warrants careful attention to the possible presence of a structural cardiac anomaly, especially left-sided obstructive lesions. A diagnosis of RDH is best supported by a combination of the RV Z-score and RV/LV ratio. Most of the fetuses with RDH and structurally normal hearts had favorable outcomes.

Echocardiography ; Female ; Fetal Diseases ; diagnosis ; Fetal Heart ; abnormalities ; Heart Ventricles ; abnormalities ; Humans ; Pregnancy ; Prenatal Diagnosis ; methods ; Ultrasonography, Prenatal

OBJECTIVETo analyze the outcome of chromosomal microarray analysis (CMA) in prenatal diagnosis for fetal abnormalities detected by ultrasonography.

METHODSAmniotic fluid samples from 477 pregnancies with abnormal ultrasound findings but without common aneuploidies were detected by CMA with Affymetrix CytoScan 750K arrays. The results were analyzed with ChAS v3.0 software.

RESULTSAmong the 477 samples, 24 (5.03%) were detected with pathogenic copy number variations (pCNVs) by CMA. Six (9.68%) among 62 cases with structural fetal abnormalities in multiple organ systems were detected with pCNVs, 11 (7.48%) among 147 cases with a single structural anomaly were detected with pCNVs, and 7 (2.61%) among 268 cases with a soft marker were detected with pCNVs.

CONCLUSIONCMA has offered a clear advantage over conventional karyotyping for the detection of fetal chromosomal abnormalities, and can provide an effective diagnostic tool for those with one or more structural abnormalities detected by ultrasound.

Adolescent ; Chromosome Aberrations ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; diagnostic imaging ; genetics ; Fetus ; diagnostic imaging ; Humans ; Karyotyping ; Male ; Microarray Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal ; methods ; Young Adult

OBJECTIVETo report on a sporadic case of Lowe syndrome diagnosed prenatally with ultrasound examination and genetic testing.

METHODSDetailed sonographic fetal screening was performed by an experienced sonographer at 32 weeks of gestation. Fetal cranial magnetic resonance imaging (MRI) was applied to detect potential brain abnormality. Chromosomal microarray analysis (CMA) was conducted on amniotic fluid sample from the fetus and peripheral blood sample from the mother.

RESULTSCongenital cataract and enlarged posterior fossa were detected by fetal ultrasound screening. Fetal cranial MRI found hypoplasia of the gyrus. CMA revealed that the fetus has carried a 633 kb deletion at Xq25-26.1 which encompassed the OCRL gene. The mother was a carrier of the same deletion. Clinical examination after birth confirmed that the neonate was affected with Lowe syndrome in addition with an atrial septal defect.

CONCLUSIONPrenatal diagnosis of Lowe syndrome without a family history largely depends on fetal imaging. Should cataract be found by ultrasound screening, fetal MRI may be considered to rule out central nervous system anomalies. CMA assay should also be considered to facilitate the diagnosis.

Adult ; Child ; Child, Preschool ; Chromosome Deletion ; Chromosomes, Human, X ; genetics ; Female ; Fetal Diseases ; diagnosis ; genetics ; Humans ; Infant ; Male ; Microarray Analysis ; Oculocerebrorenal Syndrome ; diagnosis ; embryology ; genetics ; Phosphoric Monoester Hydrolases ; genetics ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

OBJECTIVETo explore the genetic etiology of fetal abnormalities detected by prenatal ultrasound through single nucleotide polymorphism (SNP array) analysis.

METHODSTwo hundred and eight fetuses were tested with SNP array and conventional karyotyping. Complex copy number variations (CNVs) were verified with fluorescence in situ hybridization (FISH), multiplex ligation-dependent probe amplification (MLPA) and quantitative fluorescence polymerase chain reaction (QF-PCR).

RESULTSFor the 208 cases, the diagnostic yields of conventional karyotping and SNP assay were 8.2%(17/208) and 13.9%(29/208), respectively. For fetuses with malformations of the cardiovascular system, central nervous system or multiple systems, pathogenic CNVs was detected in 4.6% (8/174), 2.3%(4/174), and 1.1% (2/174) of all fetuses, respectively. No pathogenic CNVs was detected among those with abnormalities of the renal system, digestive system, skeletal system, facial dysmorphism or respiratory system.

CONCLUSIONCNVs are significantly related with birth defects. Compared with conventional karyotyping, SNP array is a better platform for CNVs detection and can provide more clues for genetic counseling, recurrence risk assessment and prenatal diagnosis.

Adult ; Chromosome Aberrations ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; diagnostic imaging ; genetics ; Genome-Wide Association Study ; Humans ; Infant, Newborn ; Karyotyping ; Male ; Polymorphism, Single Nucleotide ; Pregnancy ; Pregnancy Complications ; diagnosis ; diagnostic imaging ; genetics ; Prenatal Diagnosis ; Ultrasonography ; Young Adult

OBJECTIVETo assess the value of whole-genome high-resolution chromosome microarray analysis (CMA) for the investigation of fetuses with ultrasound abnormalities.

METHODSWhole genome high-resolution CytoScanHD array from Affymetrix was employed to investigate 651 fetuses with structural abnormalities detected by ultrasound, for whom standard G-banded chromosome analysis has revealed a normal karyotype. The fetuses were divided into a single malformation group (n=264) and a multiple malformations group (n=387). In total there were 130 chorionic villus samples, 192 amniotic fluid samples and 329 cord blood samples. Extraction of fetal DNA and CMA experiment have followed the standard guidelines from the manufacturers. All copy number variations (CNVs) detected by CMA were confirmed by fluorescence in situ hybridization (FISH) or real-time polymerase chain reaction (RT-PCR).

RESULTSCMA analysis has detected genomic CNVs in 475 (73%) cases. Clinically significant CNVs were found in 11.5% (75/651) of fetuses, including two uniparental disomies (UPD) and two cryptic mosaicisms. Variations of unknown significance (VOUS) was found in 2.0% (13/651) of tested fetuses.

CONCLUSIONAbove results have suggested that whole-genome and high-resolution CMA is valuable for the analysis of fetuses with structural abnormalities detected by ultrasound, which can increase the detection rate by approximately 11%. CMA using single nucleotide polymorphism (SNP) array has the ability to detect UPD and low-level mosaicisms. Sufficient communication between technicians and genetic counselors, parental testing and comparison the results with in-house and relevant online databases can significantly reduce the rate of VOUS.

Chromosome Aberrations ; Chromosomes, Human ; genetics ; DNA Copy Number Variations ; Female ; Fetal Diseases ; diagnosis ; diagnostic imaging ; genetics ; Genome, Human ; Humans ; Karyotyping ; Male ; Oligonucleotide Array Sequence Analysis ; methods ; Pregnancy ; Prenatal Diagnosis ; methods ; Ultrasonography

OBJECTIVETo investigate the prenatal ultrasonic manifestations of fetal gray matter heterotopias (FGMH) and evaluate the optimal method its prenatal diagnosis.

METHODSThe prenatal and postnatal ultrasound images and MRI images were analyzed for a fetus with a definitive diagnosis of FGMH. The detection rates of FGMH by prenatal ultrasound and MRI reported in literature were compared.

RESULTSWe identified 11 reports of FGMH from 1998 to 2015, involving 43 cases with prenatal diagnoses. Of the total of 44 cases (including our case), 32 that had been confirmed postpartum had prenatal ultrasound and MRI data, which showed a significantly lower detection rates of FGMH by prenatal ultrasound than by MRI (43.8% vs 93.8%, P<0.001).

CONCLUSIONPrenatal ultrasound can only detect subependymal heterotopia with characteristic manifestations, and the detection of other types of FGMH relies on MRI, which is currently the best option for prenatal diagnosis of FGMH.

Classical Lissencephalies and Subcortical Band Heterotopias ; diagnosis ; Female ; Fetal Diseases ; diagnosis ; Fetus ; Gray Matter ; pathology ; Humans ; Magnetic Resonance Imaging ; Pregnancy ; Prenatal Diagnosis ; Ultrasonography, Prenatal

OBJECTIVETo use combined comparative genome hybridization (array-CGH) and conventional karyotype analysis to study the relationship between ultrasonographic abnormalities of fetuses and chromosomal aberrations.

METHODSOne hundred twenty two fetuses with ultrasonographic abnormalities in middle and late trimesters suspected with chromosomal abnormalities were collected between March 2012 and February 2013.

RESULTSThe pregnant women had an average age of 31 yr (22-38), among whom 35 were above the age of 35. The average gestational age was 27(+5) weeks (18-37 weeks), and the most common abnormal findings have involved heart, central nervous system and bones. Multiple malformations were found in 49 cases. The success rate of the combined methods was 100%. In 24 (19.7%) of the cases, a chromosomal abnormality was detected. Among all cases, 16 (13.1%) were detected by the combined method (12.3%). Seventeen cases (13.9%) of chromosomal abnormalities and 4 cases (3.3%) of polymorphic variation were detected by karyotype analysis, and 23 cases (8.9%) of abnormalities were detected by array-CGH. Meanwhile, 7 cases (5.7%) of abnormalities were detected by array-CGH, but the results of karyotype analysis were normal. One case (0.8%) with low level of chromosome chimerism detected by the karyotype analysis was missed by array-CGH.

CONCLUSIONThe results suggested that multiple congenital deformity of the fetus has a strong correlation with chromosomal abnormalities. For fetuses with ultrasonographic abnormalities, array-CGH can improve the detection sensitivity of the chromosomal disease.

Adult ; Chromosome Aberrations ; Chromosome Banding ; methods ; Chromosome Disorders ; diagnosis ; embryology ; genetics ; Comparative Genomic Hybridization ; methods ; Female ; Fetal Diseases ; diagnosis ; diagnostic imaging ; genetics ; Gestational Age ; Humans ; Karyotyping ; Male ; Pregnancy ; Prenatal Diagnosis ; methods ; Ultrasonography, Prenatal ; methods ; Young Adult

Tetrasomy 18p, one of the most commonly observed isochromosomes, consists of two copies of the p arms on chromosome 18[i(18p)]. It is known as a de novo occurrence of non-disjunction or centromeric mis-division during meiosis II in the vast majority of cases. It has a prevalence of 1/140,000-180,000 live births and affects both genders equally. A 28-year-old woman was referred at 33+2 weeks gestation to rule out fetal congenital heart disease. Her prenatal ultrasonography showed intrauterine growth retardation, cardiomegaly, and imperforate anus. Doppler ultrasonographic finding showed fetal anemia. Tetrasomy 18p was confirmed by conventional karyotyping and fluorescence in situ hybridization. Because of its very low prevalence rate, only several cases of tetrasomy 18p has been reported worldwide and it has not yet been reported in Korea before. Therefore, we report a case of prenatally diagnosed tetrasomy 18p.
Anemia ; Aneuploidy ; Anus, Imperforate ; Arm ; Cardiomegaly ; Chromosomes, Human, Pair 18 ; Coat Protein Complex I ; Female ; Fetal Growth Retardation ; Fluorescence ; Heart Diseases ; Humans ; In Situ Hybridization ; Isochromosomes ; Karyotyping ; Korea ; Live Birth ; Meiosis ; Pregnancy ; Prenatal Diagnosis ; Prevalence ; Tetrasomy ; Ultrasonography, Prenatal