Comparison of the performance of NIPT and NIPT-plus for fetal chromosomal aneuploidy and high Z-score increases the positive predictive value.

OBJECTIVE: To evaluate non-invasive prenatal testing (NIPT) and expanded non-invasive prenatal testing (NIPT-plus) for detecting aneuploidies at different sequencing depths and assess Z-score accuracy in predicting trisomies 21, 18, 13, 45X, and 47XXX. METHODS: Pregnancies with positive NIPT or NIPT-plus results detected at the prenatal diagnosis center of Nanfang Hospital were included in this retrospective study, between January 2017 and December 2022. Invasive prenatal diagnostic results were collected. Logistic regression analyses were used to study the relationship between Z-score and positive predictive value (PPV). Optimal cut-off values were obtained based on receiver operating characteristic analysis, and PPVs were calculated in different groups. RESULTS: We evaluated 1348 pregnant women with positive results, including 930 reported by NIPT and 418 reported by NIPT-plus. NIPT reported significantly more rare chromosomal aneuploidies (RCAs), and NIPT-plus had a significantly higher PPV for trisomy 21 (T21). Logistic regression analyses showed a significant association (P < 0.001) between Z-score and PPVs for T21 and trisomy 18 (T18). A linear relationship was observed between fetal fraction (FF) and Z-values in the true positive cases of T21 and T18.The high Z-score group had significantly higher PPVs than the low Z-score group for T21, T18, trisomy 13, and 47XXX, but not for 45X. CONCLUSION: The Z-score is helpful in assessing NIPT or NIPT-plus results. Therefore, we suggest including the Z-score and FF in the results. By combining the Z-score, FF, and maternal age, clinicians can interpret NIPT results more accurately and improve personal counsel to reduce patients' anxiety.

Non-invasive prenatal test findings in 41,819 pregnant women: results from a clinical laboratory in southern China.

BACKGROUND: This paper evaluated the clinical utility of massively parallel sequencing-based non-invasive prenatal testing (NIPT) for detecting trisomy 21 (T21), T18, T13, sex chromosome aneuploidies (SCA), and rare chromosome aneuploidies (RCA) among the data collected by a clinical laboratory in southern China. METHODS: In a 3-year period between January 2017 and December 2019, over 40,000 pregnant women underwent NIPT clinical screening test for fetal T21, T18, T13, SCA, and RCA in our laboratory. NIPT samples were processed using the NextSeq CN500 platform. The positive results were confirmed by karyotyping, and chromosomal microarray analysis (CMA) or copy number variants (CNV) sequencing. Details of the pregnancy outcomes were collected via telephone interview. RESULTS: NIPT results were available for 41,819 cases; 691 positive cases were reported. The overall sensitivity for detection of T21, T18, T13, SCA, and RCA was 99.21, 100.00, 100.00, 98.55, and 100.00%, and the specificity was 99.95, 99.94, 99.98, 99.69, and 99.92%, respectively. The positive predictive values (PPVs) for detection of T21, T18, T13, SCA, and RCA were 85.62, 45.24, 40.00, 34.17, and 13.51%, respectively, and those for detection of 45,X, 47,XXY, 47,XXX, 47,XYY, and 46,XY(delX) 20.00, 59.18, 28.95, 61.54, and 25.00%, respectively. Regarding pregnancy outcomes, 92.38% of the pregnancies with confirmed aneuploidies were terminated, and 91.20% of those identified as having a false-positive result were carried to term. Among 252 unconfirmed cases, 24.60% of the pregnancies were terminated and 38.10% carried to term, while 37.30% declined interview. CONCLUSIONS: NIPT is widely used to screen fetal aneuploidies based on its high sensitivity and specificity. However, in this study, the PPVs of NIPT in terms of detecting T18, T13, XO, XXX and RCA were < 50%. In addition, more than one-third of NIPT-positive women did not accept invasive prenatal diagnosis. Confirmatory diagnosis is strongly recommended for women with positive NIPT outcomes before any further decision is made.

Positive predictive value estimates for noninvasive prenatal testing from data of a prenatal diagnosis laboratory and literature review.

OBJECTIVE: Since 2011, noninvasive prenatal testing (NIPT) has undergone rapid expansion, with both utilization and coverage. However, conclusive data regarding the clinical validity and utility of this testing tool are lacking. Thus, there is a continued need to educate clinicians and patients about the current benefits and limitations in order to inform pre- and post-test counseling, pre/perinatal decision making, and medical risk assessment/management. METHODS: This retrospective study included women referred for invasive prenatal diagnosis to confirm positive NIPT results between January 2017 and December 2020. Prenatal diagnosis testing, including karyotyping, chromosomal microarray analysis (CMA) were performed. Positive predictive values (PPVs) were calculated. RESULTS: In total, 468 women were recruited. The PPVs for trisomies 21, 18, and 13 were 86.1%, 57.8%, and 25.0%, respectively. The PPVs for rare chromosomal abnormalities (RCAs) and copy number variants (CNVs) were 17.0% and 40.4%, respectively. The detection of sex chromosomal aneuploidies (SCAs) had a PPV of 20% for monosomy X, 23.5% for 47,XXX, 68.8% for 47,XXY, and 62.5% for 47,XYY. The high-risk groups had a significant increase in the number of true positive cases compared to the low- and moderate-risk groups. CONCLUSIONS: T13, monosomy X, and RCA were associated with lower PPVs. The improvement of cell-free fetal DNA screening technology and continued monitoring of its performance are important.

Association between CYP19A1 rs6493497 and rs936306 polymorphisms and depression susceptibility in the Chinese population.

Aim: The CYP19A1 gene encodes the key aromatase for estrogen biosynthesis, and this study aimed to explore the relationship between CYP19A1 rs6493497 and rs936306 polymorphisms and depression risk. Methods: CYP19A1 rs6493497 and rs936306 genotyping was performed on 502 depression patients and 504 healthy controls. Results: In the general population, no significant association was observed between the CYP19A1 rs6493497 variant and depression, whereas that CYP19A1 rs936306 variant significantly reduced depression risk in the recessive model. In subgroup analysis, a significant association of the CYP19A1 rs6493497 variant with reduced depression risk was found in males aged 46-65 in the genotype, dominant and additive models. Conclusion: The CYP19A1 rs936306 variant may reduce depression risk, and the rs6493497 variant is associated with decreased depression risk in males aged 46-65.

The cause of depression is complex and not fully elucidated; the research evidence suggests that changes in estrogen levels may partly account for the risk of the onset of depression. The CYP19A1 gene encodes the key enzyme for estrogen biosynthesis, and this study aimed to explore whether the two loci (rs6493497 and rs936306) variants of the CYP19A1 gene are associated with the risk of occurrence of depression. Five hundred two patients with depression and 504 healthy controls were enrolled. The results of this study indicate that the CYP19A1 gene rs936306 variant may reduce the risk of occurrence of depression, and the rs6493497 variant is associated with decreased depression risk in men aged 46­65.

Prenatal Diagnosis of a Mosaic Paternal Uniparental Disomy for Chromosome 14: A Case Report of Kagami-Ogata Syndrome.

The Kagami-Ogata syndrome (KOS) is a rare imprinting disorder with a distinct clinical phenotype. In KOS, polyhydramnios is associated with a small bell-shaped thorax and coat-hanger ribs. The genetic etiology of KOS includes paternal uniparental disomy 14 [upd(14)pat], epimutations, and microdeletions affecting the maternally derived imprinted region of chromosome 14q32.2. More than 77 cases of KOS have been reported; however, only one mosaic upd(14)pat case has been reported. Here we report a second mosaic upd(14)pat case. The prognosis of upd(14)pat patients is poor because of severe respiratory insufficiency. We summarized prenatal ultrasound findings of KOS to raise awareness of this condition for possible diagnosis of KOS prenatally when polyhydramnios combination with a small bell-shaped thorax and other related features are first observed. Prenatal diagnosis using methylation-specific multiplex ligation-dependent probe amplification (MLPA) or a single-nucleotide polymorphism-based microarray analysis is recommended.

Trimethylamine N-Oxide increases soluble fms-like tyrosine Kinase-1 in human placenta via NADPH oxidase dependent ROS accumulation.

BACKGROUNDS: Preeclampsia (PE) is characterized as placental vascular disturbance and excessive secretion of soluble fms-like tyrosine kinase 1 (sFlt-1) into the maternal circulation. Trimethylamine N-oxide (TMAO, a gut microbe-derived metabolite) is strongly associated with various cardiovascular and cerebrovascular diseases. Recently, we observe that higher maternal circulating TMAO and sFlt-1 in patients with PE. The aims of the present study are to explore the effects of TMAO on placental sFlt-1 production and the underlying mechanism in human placenta. METHODS: Human placental explants, human placental primary trophoblasts and the extravillous trophoblasts (EVT) cell line (HRT-8/SVneo) were exposured to various concentrations of TMAO (100, 150, 300, and 600 µM). The mRNA expression and protein secretion of sFlt-1 in placental explants, primary trophoblasts and HRT-8/SVneo cells were determined with qPCR and ELISA, respectively. The levels of intracellular reactive oxygen species (ROS) production in primary trophoblasts and HRT-8/SVneo cells were measured by peroxide-sensitive fluorescent probe dichlorofluorescein diacetate. RESULTS: Exposure of placental explants, primary trophoblasts and HRT-8/SVneo cells to TMAO significantly enhanced sFlt-1 at both mRNA and protein levels in a dose dependent manner. Moreover, inhibition of NADPH oxidase with apocynin significantly attenuated TMAO-induced ROS production in primary trophoblasts and HRT-8/SVneo, and suppressed sFlt-1 secretion in placental explants, primary trophoblasts and HRT-8/SVneo. CONCLUSIONS: Our findings indicated the NADPH oxidase dependent ROS pathway played a critical role in mediating TMAO-induced sFlt-1 generation in human placenta. TMAO may become a potential novel target for pharmacological or dietary interventions to reduce the risk of developing PE.

Prenatal detection of chromosomal abnormalities and copy number variants in fetuses with ventriculomegaly.

OBJECTIVES: To systematically investigate chromosomal abnormalities and copy number variants (CNVs) in fetuses with different types of ventriculomegaly (VM) by karyotyping and/or chromosomal microarray analysis (CMA). METHODS: This retrospective study included 312 fetuses diagnosed with VM. Amniotic fluid and umbilical blood samples were collected by amniocentesis and cordocentesis, respectively, and subjected to karyotyping and/or CMA. Subgroup analysis by VM type, including mild VM (MVM) and severe VM (SVM), unilateral and bilateral VM, isolated VM (IVM), and non-isolated VM (NIVM), was performed. RESULTS: The detection rate of chromosomal abnormalities was 12.1% (34/281) by karyotyping and 20.6% when CMA was additionally performed (P < 0.05). Abnormalities were identified by CMA in 17.4% (38/218) of fetuses and pathogenic CNVs in 5.0% (11/218). Notably, CMA detected CNVs in 10.6% (23/218) of fetuses with normal karyotypes. The incidence of chromosomal abnormalities by karyotyping was higher in bilateral than in unilateral VM (20.5% versus 6.5%), whereas the incidence detected by CMA was higher in NIVM than in IVM (21.4% versus 10.3%; both P < 0.05). In NIVM, CMA provided an additional detection rate of 11.4% (16/140) and a detection rate of 10.0% for pathogenic CNVs and aneuploidies. Central nervous system (CNS) abnormalities were the most common other ultrasonic abnormalities. CONCLUSIONS: CMA is highly recommended for prenatal diagnosis of fetal VM together with karyotyping, especially in fetuses with bilateral VM and NIVM with abnormal CNS findings. Further study is necessary to explore the relationships between genotypes and phenotypes to facilitate prenatal diagnosis of fetal VM.

Decidual small extracellular vesicles induce trophoblast invasion by upregulating N-cadherin.

Small extracellular vesicles (sEVs) are important mediators of cell-to-cell communication involved in the successful establishment of a pregnancy. Human decidual stromal cells play a key role in regulating trophoblast invasion. Nevertheless, the regulatory functions of decidual stromal cells-derived sEVs in human trophoblast cells are still unclear. In this study, primary human decidual stromal cells were isolated, and immortalized human endometrial stromal cell line (HESCs) were decidualized into human decidual stromal cells (HDSCs) using hormonal cocktail containing medroxy progesterone 17-acetate (MPA), estrogen and cAMP analog. HDSC-sEVs were isolated from both primary human decidual stromal cells and immortal HDSCs, respectively, and identified by transmission electron microscopy and western blotting. EV uptake assay indicated that HDSC-sEVs could be uptaken by trophoblast cells. HDSC-sEVs could increase the invasiveness and the expression level of N-cadherin of trophoblast cells with elevated phosphorylation of SMAD2 and SMAD3 in the cells. Silencing of N-cadherin could block cell invasion induced by HDSC-sEVs, while knockdown of SMAD2 and SMAD3 could inhibit the upregulation of N-cadherin in trophoblast cells. Taken together, our results suggested a regulatory effect of HDSC-sEVs in the invasion of trophoblast cells, and HDSC-sEVs may be important mediators of trophoblasts during embryo implantation and placentation.

CYP19A1 rs2470152 polymorphism increases susceptibility to depression in Chinese Han population.

Estrogen plays a vital role in the pathogenesis of depression. The cytochrome p450 (CYP) 19A1 gene encodes aromatase, which is responsible for a key step in estrogen production. Previous studies suggested that CYP19A1 polymorphisms increase the risk of depression in the Japanese population. The current study aimed to investigate the correlation between the CYP19A1 rs2470152 polymorphism and the risk of depression in Chinese Han population. In total, 1006 Chinese Han subjects were recruited in this case-control study, including 502 patients diagnosed with depression and 504 healthy gender- and age-matched (from 18-65 years) controls. Genotyping was performed using multiplex PCR and high-throughput sequencing to assess the effects of the CYP19A1 rs2470152 (G > A) polymorphism on the risk of depression in the entire cohort and the subjects were further stratified by gender. No significant differences were observed in allele and genotype frequencies of CYP19A1 rs2470152 between total cases and controls (P > 0.05). However, the CYP19A1 rs2470152 polymorphism in the recessive model (AA vs. GG + GA) was associated with increased risk of depression (χ2 = 4.077, P = 0.043, OR = 1.347, 95% CI = 1.008-1.798). After subjects stratification by gender, neither genotypes nor genetic models showed significant differences between cases and controls (all P > 0.05). The results indicated that the CYP19A1 rs2470152 (G > A) polymorphism in the recessive model (AA vs. GG + GA) was correlated with increased risk of depression in Chinese Han population.

Prognosis of fetuses with ventriculomegaly: An observational retrospective study.

OBJECTIVE: To investigate the prognosis of fetuses with ventriculomegaly (VM). METHODS: Clinical data were collected from 234 cases of fetal VM diagnosed by ultrasound between March 2010 and July 2016. VM progression was monitored, and karyotyping and infection screening performed. Magnetic resonance imaging (MRI) was performed where increasing ventricular diameter was noted. Neonatal behavioral neurological assessment (NBNA) was carried out after birth, and Bayley Scales of Infant Development assessment at 6 months. RESULTS: The in utero outcomes of Group A were better than Group B in 173 pregnancies. Isolated VM (IVM) was associated with better prognosis than nonisolated VM (NIVM); the regression rates were 74.6% (59/79) and 52.1% (49/94), respectively (χ2 = 10.222, .006). The NBNA scores were significantly higher in Group A than Group B (χ2 = 4.231, .004), but not significantly different between IVM and NIVM. The composition ratios of both the psychomotor and mental developmental index (PDI and MDI) scores were not significantly different between Groups A and B (Z = 1.869, .062 and Z = 0.826, .409, respectively). Significant differences in in utero outcomes were observed between IVM and NIVM cases in Groups A and B. CONCLUSIONS: Fetal VM prognosis is affected by the width of ventricle, chromosome abnormalities, coexisted abnormalities, and in utero progression.

Maternal obesity and risk of cerebral palsy in children: a systematic review and meta-analysis.

AIM: Several studies have examined the links between maternal obesity and the risk of cerebral palsy (CP) in children, with inconsistent results. The aim of our study was to investigate whether maternal obesity is associated with increased risk of CP in offspring by using meta-analysis. METHOD: PubMed and Web of Science were searched until August 2017. Observational studies relevant to the maternal obesity and risk of CP in children were extracted and compiled. Meta-analyses were performed for different obesity levels and pooled odds ratios (ORs) and 95% confidence intervals (CIs) were reported. RESULTS: A total of five cohort studies involving 12 324 cases and 7 919 288 participants were included in our meta-analysis. The pooled crude and adjusted ORs (95% CIs) were 1.65 (1.38-1.98) and 1.51 (1.24-1.84) respectively. Additionally, the pooled OR (95% CI) for CP in offspring in relation to maternal obesity class I (body mass index [BMI] 30.0-34.9), class II (BMI 35.0-39.9), and class III (BMI≥40.0) compared with normal weight during prepregnancy or pregnancy was 1.31 (1.15-1.50), 1.65 (1.34-2.02), and 2.37 (1.91-2.94) respectively. INTERPRETATION: This meta-analysis demonstrated that increasing grades of maternal obesity are associated with a higher risk of CP in offspring. WHAT THIS PAPER ADDS: Meta-analysis demonstrates a significant positive association between maternal obesity and the risk of cerebral palsy (CP) in children. Subgroup analysis indicates that higher grades of maternal obesity are associated with increasing risk of CP.

[Clinical value of genome-wide chromosome microarray technique in diagnosis of fetal cerebral ventriculomegaly].

OBJECTIVE: To investigate the clinical value of gnome-wide chromosome microarray (CMA) technique in genetic etiological diagnosis of fetal cerebral ventriculomegaly. METHODS: A retrospective analysis was conducted in 109 women with singleton pregnancy, who were admitted in Nanfang Hospital with the diagnosis of cerebral ventriculomegaly in the fetuses by ultrasound between January, 2014 and December, 2016. Routine karyotype analysis and chromosome microarray analysis were performed to identify the chromosomal abnormalities in the fetuses. RESULTS: Karyotype analysis detected chromosomal abnormalities at a rate of 12.84% in these fetuses, significantly lower than the rate of 26.60% with CMA technique (P=0.004); the combined detection rate of the two techniques was 28.44%. In 17 cases, karyotype analysis yielded normal results while CMA microarray showed abnormalities with an extra abnormal detection rate of 15.60%. Among the 17 fetuses with chromosomal abnormalities, 6 had micro-deletion, 9 had micro-duplication, 1 had both micro-deletion and micro-duplication, and 1 had heterozygous loss of single parent diploid. CONCLUSION: CMA technique can be used to detect abnormal chromosomal copy numbers in fetuses with cerebral ventriculomegaly to increase the detection rate of chromosomal abnormalities and facilitate prenatal consultation and prognostic evaluation.

Association between hypertensive disorders of pregnancy and risk of autism in offspring: a systematic review and meta-analysis of observational studies.

BACKGROUND: Autism spectrum disorder (ASD) is a common severe pervasive neurodevelopmental disorder of undetermined etiology. Environmental exposures, especially pregnancy complications, have been increasingly recognized as a potential risk factor for ASD. Our aim was to (1) systematically evaluate the association between hypertensive disorders of pregnancy (HDP) and the risk of ASD in offspring, (2) specifically draw a subgroup analysis of disease severity in patients with HDP to achieve more sufficient evidence on this issue. RESULTS: A total of 21 studies were identified with more than 6.5 million participants, including 31,027 ASD probands. A comparative meta-analysis established that offspring born premature to HDP were significantly associated with ASD than matched controls (OR = 1.42, 95% CI: 1.34-1.50). Subgroup analysis of clinical classification include: (1) gestational hypertension, (2) pre-eclampsia, (3) chronic hypertension complicating pregnancy (CHP). The offspring of mothers with pre-eclampsia and CHP have slightly higher risk (OR = 1.43; OR = 1.48, respectively) of ASD than those of mothers with gestational hypertension (OR = 1.37). In consistence with most previous researches, higher ASD prevalence was observed in male than female (OR = 1.38), indicating a potential role for gender in the pathophysiology of ASD. MATERIALS AND METHODS: We conducted a systematic literature search on PubMed, EMBASE, Web of Science, PsycINFO database and China National Knowledge Infrastructure up to Jun. 2017. Statistical analysis was performed using Stata 10.0. CONCLUSIONS: This meta-analysis implies a possible link between HDP and the risk of ASD in offspring. However, further investigation should be conducted to confirm this conclusion, and intensive prenatal surveillance and early prediction for ASD is needed.

[Prenatal diagnosis of single umbilical artery: implications for chromosomal abnormalities and neonatal outcome].

OBJECTIVE: To investigate the implications of a prenatal diagnosis of single umbilical artery (SUA) for chromosomal abnormalities and neonatal outcomes. METHODS: From January, 2008 to June, 2012, color Doppler ultrasound identified 44 fetuses with SUA. Prenatal diagnoses with amniocentesis or umbilical blood sampling were subsequently ordered for routine chromosome karyotyping and the newborns were followed up for assessing the neonatal outcomes. RESULTS: Of all the 44 fetuses, 24 had uncomplicated SUA, and 20 had other concurrent abnormalities (including 8 with abnormal ultrasound soft indexes and 12 with chromosomal abnormalities). The two groups of fetuses showed significant differences in gestational weeks at delivery and incidence of chromosomal abnormalities but not in neonatal weight, placenta weight or APGAR score. CONCLUSIONS: Fetuses with a prenatal diagnosis of SUA and other development abnormities need to undergo prenatal chromosomal examination. For fetuses with uncomplicated SUA, careful ultrasound examination is necessary to avoid missed diagnosis of potential congenital abnormalities.

[Prenatal diagnosis of agenesis of corpus callosum and its relationship with fetal chromosomal abnormalities].

OBJECTIVES: To evaluate prenatal imaging diagnosis of agenesis of corpus callosum and to investigate the relationship between ACC and chromosomal abnormalities. METHODS: Forty singleton pregnancies diagnosed ACC prenatally in Southern Medical University,Nanfang Hospital,General Hospital of Guangzhou Military Command of PLA and Shenzhen Maternity and Children Health Care Hospital from 2007 to 2012 were recruited. The correlation between ACC and chromosomal abnormalities, the consistence of sonographic characteristics and MRI diagnosis were analyzed retrospectively. RESULTS: (1) Among the 40 cases, 15 (38%, 15/40) were diagnosed isolated ACC, while 25 (63%, 25/40) were non-isolated ACC.In the non-isolated ACC cases, 18 (72%) had central nervous system abnormalities, including cerebellar vermis hypoplasia,Dandy-Walker syndrome, cerebellar cyst, holoprosencephaly, etc.Extra-CNS abnormalities were identified in 16 cases, including 5 cardiac abnormalities, 3 facial abnormalities, 2 congenital anomalies of urinary system, 1 limb skeletal abnormality and 5 other congenital anomalies.(2) In the 40 cases, 3 were chromosomal polymorphisms, including 2 cases of 46,XX, 1qh+ and 1 case of 46,XY, 13cenh+. Chromosomal abnormalities were identified in 4 cases, including trisomy13, trisomy18, trisomy 21 and 47,XYY.(3) 36 cases(90%, 36/40) diagnosed by ultrasound were consistent with MRI, while 4 cases were different with MRI.37 pregnancies were terminated, in which 28 cases were confirmed by fetal autopsy.3 cases continued pregnancy and ACC was confirmed by postnatal MRI.(4) 25 non-isolated ACC and 12 isolated ACC pregnancies were terminated. Among the 3 isolated ACC cases that continued pregnancy, 2 were term delivery and 1 was premature delivery. All of them were confirmed by postnatal MRI.No mental or growth retardation was found during follow-up. CONCLUSION: MRI was prior to detect cases with non-isolated ACC and could be a supplementary method in the diagnosis and classification of ACC. Compared with isolated ACC, non-isolated ACC had a higher incidence of chromosomal abnormalities.

[Correlation of fetal chromosomal abnormalities to prenatal ultrasound features].

OBJECTIVE: To investigate the correlation between fetal chromosomal abnormalities and the characteristic features of prenatal ultrasound findings. METHODS: A total of 510 cases were underwent chromosome examination by amniotic fluid or cord blood analysis to identify fetal chromosomal abnormalities. The correlation between the abnormalities and the characteristics of the prenatal ultrasound findings was analyzed. RESULTS: Fifty-three cases of abnormal karyotypes were detected with a positivity rate of 10.2%. Of these cases, 32 cases had chromosome number abnormalities, including 15 with 21-trisomy, 11 with 18-trisomy, 2 with 13-trisomy, 2 with 45, XO monomer and 2 with 92, XXXX tetraploid. Chromosome structural abnormalities were found in 21 cases, including 4 with translocation, 3 with insertion, 6 with inversion, 4 with deletion and 4 with derivation. Prenatal ultrasound showed obvious structural abnormalities in 22 cases (41.5%), structural malformation with ultrasonographic soft markers in 18 cases (34.0%), and separate ultrasonographic soft markers in 8 cases (15.1%). CONCLUSION: Prenatal ultrasound fetal abnormalities and chromosome abnormalities are closely related. Prenatal ultrasound of fetal chromosomal abnormalities usually presents with a variety of significant structural abnormalities. A greater number of malformations is associated with a greater risk of chromosomal abnormalities and increased occurrence of ultrasonographic soft markers.