Prenatal diagnosis of non-mosaic sex chromosome abnormalities: a 10-year experience from a tertiary referral center.

OBJECTIVES: The aim of this study was to explore the frequency and profile of non-mosaic sex chromosome abnormalities detected in prenatal diagnosis over the past 10 years. METHODS: We retrospectively reviewed pregnancies diagnosed with non-mosaic sex chromosome abnormalities between January 2012 and December 2021, using karyotyping and/or single nucleotide polymorphism (SNP) array. Maternal age, indications for testing, and outcomes were recorded. RESULTS: Traditional karyotyping identified 269 (0.90 %) cases of non-mosaic sex chromosome abnormalities among 29,832 fetuses, including 249 cases of numerical abnormalities, 15 unbalanced structural abnormalities, and 5 balanced structural abnormalities. The overall detection rate of common sex chromosome aneuploidies (SCAs) was 0.81 %, with 47,XXY, 47,XXX, 47,XYY, and 45,X accounting for 0.32 , 0.19, 0.17, and 0.13 % respectively. All showed a fluctuating upward trend over the study period, except for 45,X. During the first five years (2012-2016), the major indication for testing was advanced maternal age (AMA), followed by abnormal ultrasound, abnormal noninvasive prenatal testing (NIPT), and abnormal maternal serum screening (MSS). In the second five years (2017-2021), the most frequent indication was abnormal NIPT, followed by AMA, abnormal ultrasound, and abnormal MSS. Among the 7,780 cases that underwent SNP array in parallel, an additional 29 clinically significant aberrations were detected. The most frequent aberration was a microdeletion in the Xp22.31 region, which was associated with X-linked ichthyosis. CONCLUSIONS: Fetal sex chromosome abnormalities are important findings in prenatal diagnosis. The application of NIPT and SNP array technology has greatly improved the detection of SCAs and submicroscopic aberrations associated with sex chromosomes.

Fetal mosaicism, should conventional karyotype always be performed?

BACKGROUND AND PURPOSE: The application of classical cytogenetic and DNA-based molecular techniques to detect cell lineages of mosaicism derived from cultured or noncultured fetal cells may result in discordant results. This retrospective study aimed to assess the inconsistent diagnostic outcomes, technical availability, and limitations of chromosomal microarray analysis (CMA) and karyotyping for mosaicism. METHODOLOGY: A total of 75 fetuses diagnosed with mosaicism by karyotype analysis or CMA were selected, and the results from both the methods were compared and further analyzed. RESULTS: A total of 42 (56%, 42/75) CMA results were consistent with karyotypes, consisting of 22 cases of mosaic sex chromosomal abnormalities, 8 routine autosomal aneuploidy cases, 8 other autosome aneuploidy cases, 3 large cryptic genomic rearrangements, and 1 small supernumerary marker chromosome. Discrepancy between karyotype analysis and CMA was observed in 33 (44%, 33/75) mosaicisms involving 15 sex chromosomal abnormalities, 1 routine autosomal aneuploidies, 5 other autosome aneuploidy cases, 8 large cryptic genomic rearrangements, and 4 small supernumerary marker chromosomes. CONCLUSION: Considering the disparities between methods as well as the cell populations analyzed, both CMA and karyotype analysis have their own advantages and disadvantages. Therefore, CMA should ideally be used in combination with karyotyping to detect more cases of mosaicism than using either test alone.

Single nucleotide polymorphism array (SNP-array) analysis for fetuses with abnormal nasal bone.

PURPOSE: This study aims to evaluate the prevalence of submicroscopic chromosomal abnormalities found on single nucleotide polymorphism array (SNP array) in pregnancies with either an absent or hypoplastic nasal bone. METHODS: This retrospective study included 333 fetuses with either nasal bone hypoplasia or absence identified on prenatal ultrasound. SNP array analysis and conventional karyotyping were performed in all the subjects. The prevalence of chromosomal abnormalities was adjusted for maternal age and other ultrasound findings. Fetuses with either an isolated nasal bone absence or hypoplasia, those that had additional soft ultrasound markers, and those where structural defects were found on ultrasound were divided into three groups: A, B, and C, respectively. RESULTS: Among the total cohort of 333 fetuses, 76 (22.8%) had chromosomal abnormalities, including 47 cases of trisomy 21, 4 cases of trisomy 18, 5 cases of sex chromosome aneuploidy, and 20 cases of copy number variations of which 12 were pathogenic or likely pathogenic. The prevalence of chromosomal abnormalities in group A (n = 164), B (n = 79), and C (n = 90) was 8.5%, 29.1% and 43.3%, respectively. The incremental yields by SNP-array compared with karyotyping in group A, B, and C were 3.0%, 2.5% and 10.7%, respectively (p > 0.05). Compared to karyotype analysis, SNP array detected an additional 2 (1.2%), 1 (1.3%), and 5 (5.6%) pathogenic or likely pathogenic CNVs in groups A, B, and C, respectively. In the 333 fetuses, the prevalence of chromosomal abnormalities in women with advanced maternal age (AMA) was significantly higher than that in non-AMA women, (47.8% vs. 16.5%, p < 0.05). CONCLUSION: In addition to Down's syndrome, many other chromosomal abnormalities are present in fetuses with abnormal nasal bone. SNP array can improve the prevalence of chromosomal abnormalities associated with nasal bone abnormalities, especially in pregnancies with non-isolated nasal bone abnormalities and advanced maternal age.

Fetal growth restriction: associated genetic etiology and pregnancy outcomes in a tertiary referral center.

BACKGROUND: The etiology of fetal growth restriction (FGR) is complex and currently, there is a paucity of research about the genetic etiology of fetal growth restriction. We investigated the genetic associations and pregnancy outcomes in cases of fetal growth restriction. METHODS: A retrospective analysis of 210 pregnant women with fetal growth restriction was performed using karyotype analysis and single nucleotide polymorphism arrays (SNP-array). The differences in pathogenic copy number variation (CNV) detected by the two methods were compared. At the same time, the fetuses were divided into three groups: isolated FGR (n = 117), FGR with ultrasonographic soft markers (n = 48), and FGR with ultrasonographic structural anomalies (n = 45). Further, the differences in pathogenic copy number variations were compared among the groups. RESULTS: The total detection rate of pathogenic CNVs was 12.4% (26/210). Pathogenic copy number variation was detected in 14 cases (6.7%, 14/210) by karyotype analysis. Furthermore, 25 cases (11.9%, 25/210) with pathogenic CNVs were detected using the SNP-array evaluation method. The difference in the pathogenic CNV detection rate between the two methods was statistically significant. The result of the karyotype analysis and SNP-array evaluation was inconsistent for 13 cases with pathogenic CNV. The rate of detecting pathogenic CNVs in fetuses with isolated FGR, FGR combined with ultrasonographic soft markers, and FGR combined with ultrasonographic structural malformations was 6.0, 10.4, and 31.1%, respectively, with significant differences among the groups. During the follow-up, 35 pregnancies were terminated, two abortions occurred, and 13 cases were lost to follow-up. Of the 160 deliveries, nine fetuses had adverse pregnancy outcomes, and the remaining 151 had normal postnatal growth and developmental assessments. CONCLUSIONS: Early diagnosis and timely genomic testing for fetal growth restriction can aid in its perinatal prognosis and subsequent intervention.

[Ultrasonographic phenotype and genetic analysis of fetuses with 17q12 microdeletion].

OBJECTIVE: To analyze the ultrasonographic phenotype and result of genetic testing in six fetuses carrying a 17q12 microdeletion. METHODS: Chromosomal microarray analysis (CMA) was carried out for 6200 pregnant women undergoing prenatal diagnosis from December 2016 to May 2021. RESULTS: CMA has identified 6 fetuses with a microdeletion in the 17q12 region, which spanned approximately 1.4 Mb and encompassed at least 13 OMIM genes. All fetuses have shown bilateral renal parenchymal echo enhancement. Four fetuses also had other ultrasonographic phenotypes. The parents of 4 fetuses had refused parental verification, whilst the remaining two fetuses were confirmed to be de novo in origin. CONCLUSION: The prenatal ultrasonographic phenotype of 17q12 microdeletion is mainly enhanced bilateral renal parenchymal echos. CMA can facilitate detection of the 17q12 microdeletion.

[Prenatal ultrasonographic manifestations and genetic analysis of eight fetuses with 16p11.2 microdeletions].

OBJECTIVE: To analyze the intrauterine phenotype and genotype of eight fetuses carrying a 16p11.2 microdeletion. METHODS: 5100 fetuses undergoing routine prenatal diagnosis were subjected to single nucleotide polymorphism-based microarray (SNP-array) analysis. Fetuses harboring a 16p11.2 microdeletion were analyzed for their ultrasonographic characteristics. RESULTS: Eight fetuses were found to harbor a microdeletion in the 16p11.2 region. Among these, six had a typical 500-600 kb deletion, while the remaining two had an atypical 220 kb deletion at the distal part of 16p11.2. Four fetuses showed vertebral malformations, two had mild left ventriculomegaly, one had hydrocephalus, and one had pulmonary valve stenosis with regurgitation. The parents of five fetuses have accepted pedigree verification, and the results confirmed that the 16p11.2 microdeletions carried by fetuses all had a de novo origin. CONCLUSION: The intrauterine phenotypes of fetuses carrying a 16p11.2 microdeletion may be variable, and the deletion can be effectively detected with the SNP-array assay.

Prenatal diagnosis of Pallister-Killian syndrome and literature review.

Pallister-Killian syndrome (PKS) is a rare sporadic genetic disorder usually caused by mosaicism of an extra isochromosome of 12p (i(12p)). This retrospective study analysed the prenatal ultrasound manifestations and molecular and cytogenetic results of five PKS foetuses. Samples of amniotic fluid and/or cord blood, skin biopsy and placenta were collected. Conventional karyotyping and single nucleotide polymorphism array (SNP array) were performed on all the amniotic fluid or cord blood samples. Copy number variants sequencing (CNV-seq) and fluorescence in situ hybridization (FISH) were also used for the validation for one foetus. All the five foetuses were from pregnancies with advanced parental age. Two foetuses involved structural abnormalities and one foetus had only soft markers, all of which included increased nuchal translucency. The rest two foetuses had normal ultrasounds in the second trimester, which has rarely been reported before. The karyotype revealed typical i(12p) in four cases and a small supernumerary marker chromosome consisting of 12p and 20p in the remaining one case. The proportion of cells with i(12p) ranged from 0 to 100% in cultural cells, while SNP array results suggested 2-4 copies of 12p. For one foetus, metaphase FISH showed normal results, but the interphase FISH suggested cell lines with two, three and four copies of 12p in the amniotic fluid. Advanced parental age may be an important risk factor for PKS, and there were no typical ultrasound manifestations related to PKS. A combination of karyotype analysis and molecular diagnosis is an effective method for the diagnosis of PKS.

Chromosomal microarray analysis for pregnancies with abnormal maternal serum screening who undergo invasive prenatal testing.

Recently, chromosomal microarray analysis (CMA) has been implemented as a first-tier test in pregnancies with ultrasound anomalies. However, its application for pregnancies with abnormal maternal serum screening (AMSS) only is not widespread. This study evaluated the value of CMA compared to traditional karyotyping in pregnancies with increased risk following first- or second-trimester maternal serum screening. Data from 3973 pregnancies with referral for invasive prenatal testing following AMSS were obtained from April 2016 to May 2020. Routine karyotyping was performed and single nucleotide polymorphism array was recommended. The foetuses were categorized according to the indications as AMSS only (group A) and AMSS with ultrasound anomalies (group B). CMA was performed on 713 prenatal samples. The proportion of women opting for CMA testing in both groups increased over the years. The incremental yield of clinically significant findings for pregnancies with high risk of screening results was similar to that for the foetuses with ultrasound soft markers (P > 0.05), but significantly lower than that for the foetuses with structural anomalies (P < 0.05). The total frequencies of variants of unknown significance in groups A and B showed no significant difference (P > 0.05). CMA should be performed for pregnant women undergoing prenatal invasive testing due to AMSS, especially with high-risk results, regardless of ultrasound findings.

[Prenatal ultrasonic characteristics and genetic analysis of fetuses with chromosome 22q11 microdeletion syndrome].

OBJECTIVE: To analyze the prenatal ultrasonic characteristics and genetic features of 14 fetuses with chromosome 22q11 microdeletion syndrome (22q11DS). METHODS: 4989 fetuses were analyzed by using single nucleotide polymorphism array (SNP array) in the Fujian Maternal and Child Health Hospital from November 2016 to November 2019. RESULTS: SNP array showed that 11 fetuses had classic 3 Mb microdeletion in 22q11 region, one fetus had 2.0 Mb microdeletion, and two fetuses had 1.0 Mb microdeletion. The 1.0 Mb microdeletion in 22q11 region contains SNAP29 and CRKL genes, which may increase the risk of congenital renal malformation and cardiovascular malformation. CONCLUSION: Prenatal ultrasonic characteristics of fetuses with 22q11 microdeletion syndrome vary, and SNP array is a powerful tool to diagnose such diseases, which can provide accurate genetic diagnosis and enable prenatal diagnosis.

Prenatal diagnosis of 22q11.2 copy number abnormalities in fetuses via single nucleotide polymorphism array.

The q11.2 region on chromosome 22 contains numerous low-copy repeats that lead to deleted or duplicated regions in the chromosome, thereby resulting in different syndromes characterized by intellectual disabilities or congenital anomalies. The association between patient phenotypes and 22q11.2 copy number abnormalities has been previously described in postnatal cases; however, these features have not been systematically evaluated in prenatal cases because of limitations in phenotypic identification in prenatal testing. In this study, we investigated the detection rate of 22q11.2 copy number abnormalities in 2500 fetuses using single nucleotide polymorphism (SNP) array and determined the common abnormal ultrasound findings in fetuses carrying the 22q11.2 copy number abnormalities. The 22q11.2 copy number abnormalities were identified in 13 fetuses with cardiovascular malformations (6/13), kidney malformations (3/13), isolated ultrasound markers (3/13), or high-risk Down syndrome based on maternal serum screening (1/13). Approximately 0.5% (13/2500) of the fetuses harbored 22q11.2 copy number abnormalities. The most frequent ultrasound findings in fetuses with these abnormalities were cardiovascular malformations, followed by kidney malformations and isolated ultrasound markers. Prenatal diagnosis of these genetic abnormalities allows for the delineation of differential diagnoses, characterization of a wide spectrum of associated malformations, and determination of associations that exist between prenatal diagnosis and obstetrical outcomes.

Detection of copy number disorders associated with congenital anomalies of the kidney and urinary tract in fetuses via single nucleotide polymorphism arrays.

BACKGROUND: While congenital anomalies of the kidney and urinary tract (CAKUT) constitute one-third of all congenital malformations, the mechanisms underlying their development are poorly understood. Some studies have reported an association between CAKUT and copy number variations (CNVs) in children and adults, but few have focused on chromosomal microarray analysis (CMA) findings in fetuses with CAKUT. Therefore, we aimed to perform a CMA on fetuses with CAKUT and normal karyotypes in the presence and absence of other structural anomalies. METHOD: The study was conducted in 147 fetuses with CAKUT and normal karyotypes between January 2016 and January 2019 in the Fujian Provincial Maternal and Child Health Hospital. Single nucleotide polymorphism (SNP) analysis was performed using the Affymetrix CytoScan HD platform. RESULTS: The SNP array identified abnormal CNVs in 13 cases (8.8%): Six were pathogenic, and seven were variations of uncertain clinical significance (VOUS). The detection rate of abnormal CNVs in non-isolated CAKUT was higher than that in isolated CAKUT (22.7% vs 6.4%, P = .038). Within the abnormal CNV groups, the highest frequency of CNVs was identified in fetuses with polycystic kidney dysplasia (13.5%), followed by those with renal agenesis (10.5%). CONCLUSION: SNP array is effective for identifying chromosomal abnormalities in CNVs in fetuses with CAKUT and normal karyotypes, and help counseling.

Chromosomal microarray analysis for pregnancies with or without ultrasound abnormalities in women of advanced maternal age.

BACKGROUND: Chromosomal microarray analysis (CMA) has been suggested to be routinely conducted for fetuses with ultrasound abnormalities (UA), especially with ultrasound structural anomalies (USA). Whether to routinely offer CMA to women of advanced maternal age (AMA) without UA when undergoing invasive prenatal testing is inconclusive. OBJECTIVE: This study aimed to evaluate the efficiency of CMA in detecting clinically significant chromosomal abnormalities in fetuses, with or without UA, of women with AMA. METHODS: Data from singleton pregnancies referred for prenatal CMA due to AMA, with or without UA were obtained. The enrolled cases were divided into AMA group (group A) and AMA accompanied by UA group (group B). Single nucleotide polymorphism (SNP) array technology and conventional karyotyping were performed simultaneously. RESULTS: A total of 703 cases were enrolled and divided into group A (N = 437) and group B (N = 266). Clinically significant abnormalities were detected by CMA in 52 cases (7.4%, 52/703; the value in group A was significantly lower than that in group B (3.9% vs 13.2%, P < .05); no statistic difference was observed with respect to submicroscopic variants of clinical significance between the two groups (0.9% vs 2.6%, P > .05). CONCLUSIONS: Chromosomal microarray analysis should be available to all women with AMA undergoing invasive prenatal testing, regardless of ultrasound findings.

[Prenatal diagnosis of 22q11 microdeletion syndrome].

OBJECTIVE: To establish a method for the prenatal diagnosis of 22q11 microdeletion syndrome. METHODS: BACs-on-Beads (BoBs) and fluorescence in situ hybridization (FISH) were performed on a fetus for whom amniotic chromosomal culturing has failed and a pair of twin fetuses suspected for 22q11 deletion syndrome. RESULTS: 22q11 microdeletion was detected in all 3 fetuses by prenatal BoBs as well as FISH, with only one red signal detected at the DiGeorge/VCFS N25 site and two green signals on the 22q13.3 ARSA site. CONCLUSION: The combination of prenatal BoBs and FISH can provide a method for the prenatal diagnosis of 22q11 microdeletion.

Genetic evaluation for twin pregnancies using karyotyping and single nucleotide polymorphism array analysis.

The study aimed to assess chromosomal abnormalities in twin pregnancies using karyotyping and SNP array analysis. The research involved 530 twin pregnancies from two prenatal diagnosis centers between October 2012 and October 2022. Two types of twin pregnancies were considered: monochorionic diamniotic (MCDA) and dichorionic diamniotic (DCDA), with a total of 177 MCDA and 353 DCDA cases. Chromosomal abnormalities were examined based on chorionic and amniotic sac properties and clinical indications. Among 42 twin pregnancies, 50 fetuses showed chromosomal abnormalities by karyotyping, with 35 cases of aneuploidy in DCDA and 10 in MCDA. Trisomy 21 was the most common aberration, affecting 15 fetuses in DCDA and 4 in MCDA. The rate of discordant karyotypes in MCDA and DCDA groups was 1.1% and 8.8%, respectively. Ultrasound abnormalities and advanced maternal age were frequent indications (55.3% and 39.2%, respectively). Aneuploidy frequencies in DCDA and MCDA pregnancies with advanced maternal age were 10.6% and 4.5%. Cardiac defects and increased nuchal translucency were common anomalies, with higher incidences of chromosomal abnormalities in DCDA (12.5% and 6.9%) and MCDA groups (23.5% and 3.7%). SNP array identified 1.6% clinically significant copy number variants in DCDA fetuses with ultrasound abnormalities, while no significant CNVs were found in MCDA pregnancies. Chromosomal aneuploidies were the primary abnormalities in twin pregnancies, with detectable abnormalities and clinically significant CNVs more likely in DCDA pregnancies, especially those with ultrasound abnormalities.

Prenatal diagnosis and genetic etiology analysis of talipes equinovarus by chromosomal microarray analysis.

BACKGROUND: With the advancement of molecular technology, fetal talipes equinovarus (TE) is believed to be not only associated with chromosome aneuploidy, but also related to chromosomal microdeletion and microduplication. The study aimed to explore the molecular etiology of fetal TE and provide more information for the clinical screening and genetic counseling of TE by Chromosomal Microarray Analysis (CMA). METHODS: This retrospectively study included 131 fetuses with TE identified by ultrasonography. Conventional karyotyping and SNP array analysis were performed for all the subjects. They were divided into isolated TE group (n = 55) and complex group (n = 76) according to structural anomalies. RESULTS: Among the total of 131 fetuses, karyotype analysis found 12(9.2%) abnormal results, while SNP array found 27 (20.6%) cases. Trisomy 18 was detected most frequently among abnormal karyotypes. The detection rate of SNP array was significantly higher than that of traditional chromosome karyotype analysis (P < 0.05). SNP array detected 15 (11.5%) cases of submicroscopic abnormalities that karyotype analysis did not find. The most common CNV was the 22q11.2 microdeletion. For both analyses, the overall detection rates were significantly higher in the complex TE group than in the isolated TE group (karyotype: P < 0.05; SNP array: P < 0.05). The incremental yield of chromosomal abnormalities in fetuses with unilateral TE (22.0%) was higher than in fetuses with bilateral TE (19.8%), but this difference was not statistically significant (P > 0.05). Abnormal chromosomes were most frequently detected in fetuses with TE plus cardiovascular system abnormalities. CONCLUSION: Fetal TE is related to chromosomal microdeletion or microduplication. Prenatal diagnosis is recommended for fetuses with TE, and CMA testing is preferred. CMA can improve the detection rate of chromosomal abnormalities associated with fetal TE, especially in pregnancies with complex TE.

Using single nucleotide polymorphism array for prenatal diagnosis in a large multicenter study in Southern China.

Numerous studies have evaluated the use of single nucleotide polymorphism array (SNP-array) in prenatal diagnostics, but very few have evaluated its application under different risk conditions. Here, SNP-array was used for the retrospective analysis of 8386 pregnancies and the cases were categorized into seven groups. Pathogenic copy number variations (pCNVs) were found in 699 (8.3%, 699/8386) cases. Among the seven different risk factor groups, the non-invasive prenatal testing-positive group had the highest pCNVs rate (35.3%), followed by the abnormal ultrasound structure group (12.8%), and then the chromosomal abnormalities in the couples group (9.5%). Notably the adverse pregnancy history group presented with the lowest pCNVs rate (2.8%). Further evaluation of the 1495 cases with ultrasound abnormalities revealed that the highest pCNV rates were recorded in those cases with multiple system structure abnormalities (22.6%), followed by the groups with skeletal system (11.6%) and urinary system abnormalities (11.2%). A total of 3424 fetuses with ultrasonic soft markers were classified as having one, two, or three ultrasonic soft markers. The different pCNV rates in the three groups were statistically significant. There was little correlation between pCNVs and a previous history of adverse pregnancy outcomes, suggesting that genetic screening under these conditions should be evaluated on a case-by-case basis.

Erythrocyte Indices and Hemoglobin Analysis for α-Thalassemia Screening in an Area with High Carrying Rate.

Carriers of α-thalassemia exhibit hypochromic microcytosis with mean corpuscular volume (MCV) < 80 fL, mean corpuscular hemoglobin (MCH) < 27 pg, and reduced hemoglobin A2 (HbA2). We studied the distribution and diagnostic efficiencies of these indicators and their combinations in patients with and without alpha-thalassemia. Based on genetic diagnosis, 10,883 participants were divided into alpha-thalassemia group (n = 1655) and negative-for-alpha-thalassemia group (n = 9228). Erythrocyte parameters and hemoglobin analysis of the groups were analyzed. Moreover, we compared the four screening schemes (MCV/MCH, MCV/MCH/HbA2, MCV + MCH, MCV + MCH + HbA2) to find the best for α-thalassemia screening. The genotypes of --SEA/αα, and -α3.7/αα are the most prevalent with 54.9% and 27.6% in Fujian Province, China. There were significant differences in the distribution of MCV, MCH, and HbA2 in the two groups. Among the three, MCH exhibited the highest sensitivity, specificity, positive predictive value, negative predictive value, and diagnostic accuracy. Although the four screening schemes have their advantages, there are significant differences in their sensitivity and specificity. MCV + MCH had the best diagnostic performance (72.6% sensitivity, 89.0% specificity) as well as the highest Youden index (61.59%). Our results showed that MCH could be used to screen α-thalassemia instead of MCV and HbA2. However, it is recommended that MCV/MCH/HbA2 screening be used in areas with high α-thalassemia incidence to increased sensitivity.

Chromosomal Abnormalities and Pregnancy Outcomes for Fetuses With Gastrointestinal Tract Obstructions.

Fetal gastrointestinal tract obstruction (GITO) is the most frequently encountered gastrointestinal defect in the prenatal period. This study aimed to investigate the genetic disorders and pregnancy outcomes of fetal GITO. We reviewed data from 70 pregnancies that were referred for invasive prenatal testing because of fetal GITO. According to the level of obstruction, they were classified into esophageal atresia/stenosis, duodenal atresia/stenosis, jejunal or ileal atresia/stenosis, or anal atresia. Traditional karyotyping was performed on all the 70 pregnancies, and chromosomal microarray analysis (CMA) was performed on 32 of them in parallel. Traditional karyotyping revealed twelve (17.1%) chromosomal abnormalities, including 11 cases of trisomy 21 (Down syndrome), and one case of a supernumerary marker chromosome related to Cat eye syndrome. According to the absence or presence of other ultrasound anomalies, they were categorized into isolated GITO (n = 36) and non-isolated GITO (n = 34). The rate of chromosomal abnormalities in the non-isolated GITO pregnancies was significantly higher than that in the isolated GITO pregnancies (29.4 vs. 5.5%, p < 0.05); the survival rate in the isolated group was significantly higher than that in the non-isolated group (67.6 vs. 34.4%, p < 0.05). Among the 32 cases where CMA was performed, an additional one (3.1%) copy number variant with clinical significance was noted in a fetus with normal karyotype. The microduplication on 7q12 was considered to be the genetic etiology of duodenal stenosis, although it was inherited from a phenotypically normal mother. Our study supports the strong association between Down syndrome and fetal GITO, especially duodenal stenosis. Our findings suggested that the risk of chromosomal abnormalities was increased when GITO was accompanied by other ultrasound anomalies; thus, chromosomal abnormalities and fetal anatomy should be carefully evaluated for pregnancy management of fetal GITO.

Evaluation of genetic variants using chromosomal microarray analysis for fetuses with polyhydramnios.

BACKGROUND: Polyhydramnios, the excessive accumulation of amniotic fluid, is associated with an elevated risk of abnormal karyotype, particularly aneuploidy. Studies focusing on chromosomal microarray analysis (CMA) in pregnancies with polyhydramnios are limited. The aim of this study is to evaluate the implications of pregnancy with polyhydramnios by CMA testing and routine karyotyping. METHODS: Data from 131 singleton and 17 twin pregnancies that underwent prenatal CMA testing due to polyhydramnios between May 2017 and May 2021 were reviewed. Enrolled cases were grouped into isolated polyhydramnios (N = 39) and non-isolated polyhydramnios (N = 111). Non-isolated group was further categorized as subgroup of soft markers (n = 59) and non-soft markers (n = 52). RESULTS: CMA revealed an additional 10 (6.7%) chromosomal aberrations with clinical significance in 9 fetuses from singleton pregnancies and 1 from a twin pregnancy. Six microdeletion/microduplication syndromes were observed, of which 4 were located on chromosome 17. The incremental yields of clinically significant CMA findings in non-isolated polyhydramnios was 8.1%, and the values in fetuses along with soft markers and non-soft markers were 5.1% and 11.5% (p > 0.05), respectively. Only one incidental finding related to neuropathy with liability to pressure palsies was detected from 39 fetuses with isolated polyhydramnios. CONCLUSIONS: Non-isolated polyhydramnios is associated with several microdeletion/microduplication syndromes, regardless of singleton or twin pregnancies. Our results suggest insufficient evidence to recommend CMA in pregnancies with isolated polyhydramnios.

Corrigendum: Chromosomal abnormalities and pregnancy outcomes for fetuses with gastrointestinal tract obstructions.

[This corrects the article DOI: 10.3389/fped.2022.918130.].