Fetal Ultrasound Abnormalities Research Articles

The yield of SNP microarray analysis for fetal ultrasound cardiac abnormalities.

Chromosomal microarray analysis (CMA) has emerged as a critical instrument in prenatal diagnostic procedures, notably in assessing congenital heart diseases (CHD). Nonetheless, current research focuses solely on CHD, overlooking the necessity for thorough comparative investigations encompassing fetuses with varied structural abnormalities or those without apparent structural anomalies. This study sought to assess the relation of single nucleotide polymorphism-based chromosomal microarray analysis (SNP-based CMA) in identifying the underlying causes of fetal cardiac ultrasound abnormalities. A total of 2092 pregnant women who underwent prenatal diagnosis from 2017 to 2022 were included in the study and divided into four groups based on the presence of ultrasound structural abnormalities and the specific type of abnormality. The results of the SNP-Array test conducted on amniotic fluid samples from these groups were analyzed. Findings from the study revealed that the non-isolated CHD group exhibited the highest incidence of aneuploidy, overall chromosomal abnormalities, and trisomy 18, demonstrating statistically significant differences from the other groups (p < 0.001). Regarding the distribution frequency of copy number variation (CNV) segment size, no statistically significant distinctions were observed between the isolated CHD group and the non-isolated CHD group (p > 0.05). The occurrence rates of 22q11.2 and 15q11.2 were also not statistically different between the isolated CHD group and the non-isolated congenital heart defect group (p > 0.05). SNP-based CMA enhances the capacity to detect abnormal CNVs in CHD fetuses, offering valuable insights for diagnosing chromosomal etiology and facilitating genetic counseling. This research contributes to the broader understanding of the utility of SNP-based CMA in the context of fetal cardiac ultrasound abnormalities.

Whole-exome sequencing in deceased fetuses with ultrasound anomalies: a retrospective analysis

BackgroundWhole-exome sequencing (WES) is an effective method in the prenatal setting for identification of the underlying genetic etiology of fetal ultrasound abnormalities. To investigate the diagnostic value of WES in fetuses with ultrasound abnormalities that resulted in fetal demise or pregnancy termination.Methods61 deceased fetuses with ultrasound abnormalities and normal copy number variation Sequencing were retrospectively collected. Proband-only or trio-WES were performed on the products of conception.ResultCollectively, 28 cases were positive with 39 variants (10 pathogenic, 22 likely pathogenic and 7 variants of uncertain significance) of 18 genes, and the overall diagnostic rate was 45.9% (28/61), of which 39.2% (11/28) were de novo variants. In addition, 21 variants in 11 genes among the positive cases had not been previously reported. The diagnostic yield for definitive findings for trio analysis was 55.9% (19/34) compared to 33.3% (9/27) for singletons. The most common ultrasound abnormalities were skeletal system abnormalities 39.2% (11/28), followed by multiple system abnormalities (17.9%, 5/28) and genitourinary abnormalities (17.9%, 5/28).ConclusionOur results support the use of WES to identify genetic etiologies of ultrasound abnormalities and improve understanding of pathogenic variants. The identification of disease-related variants provided information for subsequent genetic counseling of recurrence risk and management of subsequent pregnancies.

Fetal Ultrasound and Magnetic Resonance Imaging Abnormalities in Congenital Cytomegalovirus Infection Associated with and without Fetal Growth Restriction.

Congenital cytomegalovirus infection (cCMV) can cause fetal growth restriction (FGR) and severe sequelae in affected infants. Clinicians generally suspect cCMV based on multiple ultrasound (US) findings associated with cCMV. However, no studies have assessed the diagnostic accuracy of fetal US for cCMV-associated abnormalities in FGR. Eight FGR and 10 non-FGR fetuses prenatally diagnosed with cCMV were examined by undergoing periodic detailed US examinations, as well as postnatal physical and imaging examinations. The diagnostic accuracy of prenatal US for cCMV-associated abnormalities was compared between FGR and non-FGR fetuses with cCMV. The diagnostic sensitivity rates of fetal US for cCMV-related abnormalities in FGR vs. non-FGR fetuses were as follows: ventriculomegaly, 66.7% vs. 88.9%; intracranial calcification, 20.0% vs. 20.0%; cysts and pseudocysts in the brain, 0% vs. 0%; ascites, 100.0% vs. 100.0%; hepatomegaly, 40.0% vs. 100.0%; splenomegaly, 0% vs. 0%. The diagnostic sensitivity of fetal US for hepatomegaly and ventriculomegaly in FGR fetuses with cCMV was lower than that in non-FGR fetuses with cCMV. The prevalence of severe long-term sequelae (e.g., bilateral hearing impairment, epilepsy, cerebral palsy, and severe developmental delay) in the CMV-infected fetuses with FGR was higher, albeit non-significantly. Clinicians should keep in mind the possibility of overlooking the symptoms of cCMV in assessing fetuses with FGR.

Application of Complete Prenatal Diagnosis in Fetal Ultrasound Abnormalities.

To investigate the value of prenatal diagnosis in fetal ultrasound abnormalities. Amniotic fluid samples of pregnant women who underwent invasive amniocentesis for ultrasound examination suggestive of fetal ultrasound structural abnormalities and soft markers of abnormalities during pregnancy from January 2016 to June 2021 at the Prenatal Diagnostic Center of Putian College Hospital were collected for amniotic fluid cell culture and G manifest band karyotype analysis. (1) Most pregnant women with ultrasound abnormalities were delivered at the age of 23 to 32 years. (2) There were 66 cases of abnormal karyotype with an abnormal incidence of 9.64% (66/685), with chromosomal number abnormalities predominating. (3) Fetal ultrasound abnormalities are mainly soft markers of abnormalities. (4) The comparison of ultrasound abnormalities in the low and high maternal-fetal age groups was not statis-tically significant. (1) Fetal ultrasound abnormalities are mainly soft markers of abnormalities. (2) The rate of fetal chromosomal abnormalities was the highest among the soft ultrasound indicators with NT thickening. (3) The incidence of fetal ultrasound abnormalities did not increase with increasing age. There was no statistical difference in the incidence of chromosomal abnormalities between the low age group and the high age group. (4) Fetal ultrasound testing provides a scientific and accurate basis for clinical heritage counseling and rebirth counseling, especially for chromosomal aneuploidy number abnormalities.

Residual risk of noninvasive prenatal screening in pregnancies with ultrasound anomalies

ObjectivesTo discuss the residual risk (RR) of noninvasive prenatal screening (NIPS) for the mothers with fetal ultrasound abnormalities. Methods880 pregnant women with fetal ultrasound abnormalities accepted prenatal diagnosis by chromosomal microarray analysis (CMA) after amniocentesis. Furthermore, the detection efficiency of NIPS was evaluated and calculated based on our previous studies and other literatures. The RR of the chromosome abnormality results was then analyzed. ResultsA total of 103 cases were confirmed as fetal chromosome abnormalities, including 65 (63.1%) of aneuploidies and 38 (36.9%) of clinical significant copy number variations (CNVs). Of which, based on the estimated NIPS efficacy, 87 cases could also be detected by NIPS. The detection rate (DR) was 84.5%, while 16 cases would be missed. The total of RR of NIPS in the fetuses with ultrasound anomalies was 2.0% (16/793), approximately one in 51. The top three RR of fetal ultrasound abnormalities were echogenic bowel (5.9%), multiple systems of structural anomalies (4.5%), and nervous system anomalies (4.2%). ConclusionThe overall residual risk of NIPS in the fetuses with ultrasound anomalies was approximately 2.0%, especially in echogenic bowel, multiple systems of structural anomalies and nervous system anomalies.

Prenatal detection of pure proximal 6q14.1 microduplication encompassing LCA5 gene: A variant of likely benign.

Trisomy 6q is a recognizable syndrome which exhibits psychomotor/growth retardation, developmental/intellectual disabilities, feeding difficulties, facial dysmorphism, hearing loss, brain and heart malformations. The purpose of this study was to delineate the prenatal features of proximal 6q14.1 duplication in fetal period, which was rarely reported in clinic. Eight pregnant women who opted for amniocentesis due to the fetal ultrasound abnormalities, maternal serum screening or other indications for prenatal diagnosis between 2019 and 2020. Chromosomal microarray analysis and G-banding analysis were offered after informed consents were obtained. Cytogenetic prenatal investigation showed all fetuses presented normal karyotypes except case 4 exhibiting a balanced chromosomal translocation 46,XX,t (4;8)(p16;q24). The chromosomal microarray analysis detected 0.211–0.242 Mb duplications of 6q14.1 (chr6: 80109532–80351666, hg19) in all 8 cases, encompassing the morbid gene LCA5 in common. Seven pregnant women (P1-P7) continued their pregnancies and delivered healthy infants at term while the parents of case 8 opted for termination of pregnancy for severe abnormal ultrasound findings. Overall, all neonates were in a good healthy condition with no evident anomalies, ranging from 2 m to 16 m. It is proposed that 6q14.1 duplication involving LCA5 gene detected in our study might be variants of likely benign. However, further large-scale studies should be gathered to assess its pathogenicity. To our knowledge, our study is the first report focusing on prenatally detected proximal 6q14.1 duplication, accompanied by detailed clinic phenotypes. Diverse ultrasound findings were observed in these cases, ranging from normal to abnormal. More evidence should be gathered to interpret the prenatal genotype-phenotype correlation of 6q14.1 duplication. For these cases with 6q14.1 microduplication, long term follow up should be carried out in case abnormal clinical symptoms or developmental-behavioral disorders emerge.

Trio exome sequencing is highly relevant in prenatal diagnostics.

ObjectiveAbout 3% of newborns show malformations, with about 20% of the affected having genetic causes. Clarification of genetic diseases in postnatal diagnostics was significantly improved with high‐throughput sequencing, in particular through whole exome sequencing covering all protein‐coding regions. Here, we aim to extend the use of this technology to prenatal diagnostics.MethodBetween 07/2018 and 10/2020, 500 pregnancies with fetal ultrasound abnormalities were analyzed after genetic counseling as part of prenatal diagnostics using WES of the fetus and parents.ResultsMolecular genetic findings could explain ultrasound abnormalities in 38% of affected fetuses. In 47% of these, disease‐causing de novo variants were found. Pathogenic variants in genes with autosomal recessive or X‐linked inheritance were detected in more than one‐third (70/189 = 37%). The latter are associated with increased probability of recurrence, making their detection important for further pregnancies. Average time from sample receipt to report was 12 days in the recent cases.ConclusionTrio exome sequencing is a useful addition to prenatal diagnostics due to its high diagnostic yield and short processing time (comparable to chromosome analysis). It covers a wide spectrum of genetic changes. Comprehensive interdisciplinary counseling before and after diagnostics is indispensable.

A systematic review of maternal TORCH serology as a screen for suspected fetal infection.

The acronym 'TORCH' refers to well-recognised causes of perinatal infections: toxoplasmosis, rubella, cytomegalovirus (CMV) and herpes simplex virus (HSV). A TORCH serology panel is often used to test for maternal primary infection following detection of ultrasound abnormalities in pregnancy. This review aims to estimate the diagnostic yield of maternal TORCH serology in pregnancy following fetal ultrasound abnormalities. Primary studies published since 2000 that assessed maternal TORCH serology for suspected fetal infection and included information on indications for testing, definition of positive TORCH serology results, and perinatal outcomes were included. Eight studies with a total of 2538 pregnancies were included. The main indications for testing were polyhydramnios, fetal growth restriction and hyperechogenic bowel. There were 26 confirmed cases of congenital CMV, of which 15 had multiple ultrasound abnormalities. There were no cases of congenital toxoplasmosis, rubella or HSV confirmed in any of the eight studies. The clinical utility of TORCH serology for non-specific ultrasound abnormalities such as isolated fetal growth restriction or isolated polyhydramnios is low. It is time to retire the TORCH acronym and the reflex ordering of 'TORCH' panels, as their continued use obscures, rather than illuminates, appropriate investigation for fetal ultrasound abnormalities.

Cell-free DNA test for pathogenic copy number variations: A retrospective study

ObjectiveTo evaluate the detection rate (DR) by prenatal cell-free DNA test for pathogenic copy number variations (CNVs)＞2 Mb among pregnancies with fetal ultrasound abnormalities. Materials and methodsThis was a retrospective study on 29 pregnant women with fetuses diagnosed as microdeletion/microduplication syndromes by prenatal chromosome microarray analysis (CMA). Cell-free DNA from the maternal plasma was sequenced on the NextSeq CN500 sequencer. The quality standard of unique map reads in a single sample was greater than 10 M and only gains and losses of more than 2 Mb were reported. ResultsA total of 24 CNVs were identified by cell-free DNA test among the 21 fetuses with pathogenic CNVs identified by prenatal CMA, including 20 consistent CNVs and 4 inconsistent CNVs. Overall, the DR of cell-free DNA test for pathogenic CNVs ＞2 Mb was 69%. Microdeletions or microduplications at 22q11.2 were the most common CNVs, with a DR of 4/5 (80%) and 3/4 (75%) respectively. ConclusionCell-free DNA test exhibited a moderate DR for pathogenic CNVs ＞2 Mb among fetuses with ultrasound abnormalities. Cell-free DNA test could provide an opportunity for early screening before the appearance of abnormalities on fetal ultrasound, while further clinical data and cost-effectiveness assessment are needed.

The Value of Prenatal Systematic Ultrasonic Examination of Fetal Structural Abnormality in Diagnosing Fetal Structural Abnormality

In order to explore the value of prenatal systematic ultrasound examination of fetal structural abnormality in the diagnosis of fetal structural abnormality, this paper retrospectively analyzed 200 cases of fetal abnormality referrals from December 2017 to December 2019 in the prenatal systematic ultrasound examination of the designated hospital in this study of pregnant women. By sorting, summarizing and summarizing the actual conditions of the systematic ultrasound examination of each prenatal fetal abnormal section, this study calculated, recorded and analyzed the detection rate, missed diagnosis rate, sensitivity, and specificity of the systematic ultrasound examination of structural abnormality, and then discussed the value of prenatal systematic ultrasound in the diagnosis of fetal structural abnormality. The results showed that, 185 cases were detected out of 200 fetal abnormality with the detection rate of 92.5%; missed diagnosis rate is 7.3%; detection sensitivity is 87.43%; and specificity is 76.58%. Among them, the detection rate of malformations of different diseases from high to low is cardiovascular system (97.54%), nervous system (93.16%), respiratory system (90.62%), facial system (87.54%), and urinary system (85.47%). Therefore, the prenatal systematic ultrasound fetal structural abnormality examination for pregnant women can achieve good diagnostic results, can provide pregnant women with fetal structural abnormality the opportunity to terminate pregnancy early, and effectively reduce the birth of structural abnormal fetuses and the burden of family and society, having important clinical significance and reducing.

Application of chromosome microarray analysis in prenatal diagnosis

BackgroundTo explore the application value of chromosomal microarray analysis (CMA) in prenatal diagnosis.MethodsThe results of chromosome karyotype analysis and CMA of 477 cases undergoing amniocentesis were analyzed. The results of the no ultrasound abnormality group and the ultrasound abnormality group were compared separately. Within the ultrasound abnormality group, the results of the ultrasound structural malformation group, the ultrasound soft index abnormality group, and other ultrasound abnormality (including abnormal amniotic fluid volume and fetal growth restriction) groups were compared.ResultsAbnormal chromosome and CMA results were found in a total of 71 cases (15.88%, 71/447), which can be broken down into a total of 23 karyotype abnormalities (5.15%, 23/447), consisting of 18 cases of aneuploidy (4.03%, 18/447), 2 cases of unbalanced chromosome rearrangements (0.44%, 2/447), and 3 cases of chimerism (0.67%, 3/447); 17 cases with detection of pathogenic copy number variations (pCNVs) (3.80%, 17/447); and 31 cases of detection of clinical variants of unknown significance (VOUS) (6.93%, 31/447). CMA detected 3.8% more genetic abnormalities than karyotype analysis (in addition to the abnormalities detected simultaneously by karyotype analysis). Between the no ultrasound abnormality group and the ultrasound abnormality group, there was an extremely significant difference in the detection rate of an abnormal chromosomal karyotype (P < 0.01) and of VOUS (P < 0.01), but there was no significant difference in the detection rate of pCNV (P > 0.05). Comparing the ultrasound structural malformation group, the ultrasound soft index abnormality group, and the other ultrasound abnormality group, there were no significant differences in the detection rate of abnormal chromosomal karyotypes (P > 0.05), pCNV (P > 0.05) or VOUS (P > 0.05).ConclusionsThe detection rate of chromosomal karyotype abnormalities in prenatal diagnosis in cases with no ultrasound abnormalities was higher. For cases with fetal ultrasound structural abnormalities, when compared with traditional karyotype analysis, CMA can improve the detection rate of fetal genetic abnormalities. However, the no ultrasound abnormality group also had a high VOUS abnormality detection rate, so it is necessary to strictly define the CMA indications.

Clinical and ultrasound features associated with congenital cytomegalovirus infection as potential predictors for targeted newborn screening in high-risk pregnancies

This prospective cohort study aimed to determine clinical factors associated with congenital cytomegalovirus (CMV) infection in pregnancy. Newborns born at a perinatal medical center received PCR analyses for CMV-DNA in their urine with informed consent. Clinical data, including age, maternal fever or flu-like symptoms, complications, ultrasound fetal abnormality, gestational weeks at delivery, and birth weight, were collected. Logistic regression analyses determined clinical findings associated with congenital CMV infection (cCMV). cCMV was diagnosed in 32 of 4380 pregnancies. Univariate and multivariable analyses revealed that age < 25 years old (OR 2.7, 95% CI 1.1–6.6; p < 0.05), the presence of maternal fever or flu-like symptoms (5.4, 2.6–11.2; p < 0.01), ultrasound fetal abnormalities (12.7, 5.8–27.7; p < 0.01), and preterm delivery at less than 34 gestational weeks (2.6, 1.1–6.0; p < 0.05) were independent clinical findings associated with cCMV. A combination of maternal fever/flu-like symptoms, ultrasound fetal abnormalities, or preterm delivery at less than 34 gestational weeks as optimal predictive factors showed 90.6% sensitivity, 66.4% specificity, and a maximum Youden index of 0.57. CMV-DNA tests in the urine of newborns born to mothers with these clinical manifestations may be an effective method in detecting cCMV as a targeted screening with a high sensitivity.

Copy number variations in ultrasonically abnormal late pregnancy fetuses with normal karyotypes

Many fetuses are found to have ultrasonic abnormalities in the late pregnancy. The association of fetal ultrasound abnormalities in late pregnancy with copy number variations (CNVs) is unclear. We attempted to explore the relationship between types of ultrasonically abnormal late pregnancy fetuses and CNVs. Fetuses (n = 713) with ultrasound-detected abnormalities in late pregnancy and normal karyotypes were analyzed. Of these, 237 showed fetal sonographic structural malformations and 476 showed fetal non-structural abnormalities. Single nucleotide polymorphism (SNP)-based chromosomal microarray (CMA) was performed on the Affymetrix CytoScan HD platform. Using the SNP array, abnormal CNVs were detected in 8.0% (57/713) of the cases, with pathogenic CNVs in 32 cases and variants of uncertain clinical significance (VUS) in 25 cases. The detection rate of abnormal CNVs in fetuses with sonographic structural malformations (12.7%, 30/237) was significantly higher (P = 0.001) than that in the fetuses with non-structural abnormalities (5.7%, 27/476). Overall, we observed that when fetal sonographic structural malformations or non-structural abnormalities occurred in the third trimester of pregnancy, the use of SNP analysis could improve the accuracy of prenatal diagnosis and reduce the rate of pregnancy termination.

Segmental aneuploidies in fetuses with isolated echogenic intracardiac focus among women younger than 35\xa0years

Studies on the occurrence of segmental aneuploidoidy in fetuses with isolated echogenic intracardiac focus (EIF) are scarce. The aim of this study was to analyze whether there is an association between abnormal segmental aneuploidies and isolated EIF. This was a prospective case–control study. The study participants in the case group were fetuses that were diagnosed with isolated EIF. Samples without fetal ultrasound abnormalities but received prenatal diagnosis for other reasons (serological screening high-risk, voluntary request) were set as controls. All pregnant women were younger than 35 years old at the expected date of childbirth. Copy number variation sequencing (CNV-seq) was performed for all samples. The case group and control group successfully underwent CNV-seq analysis and exhibited 1,099 and 5,616 amniotic fluid samples, respectively. The detection rates of abnormal segmental aneuploidies in the case group and control group were 0.6% (7/1,099) and 1.1% (64/5,616), respectively; no statistically significant difference was found between the two groups (x2 = 2.220, P = 0.136). Isolated EIF did not increase the risk of fetal segmental aneuploidies.

Neurological outcomes of congenital Zika syndrome in toddlers and preschoolers: a case series

Congenital Zika syndrome causes a spectrum of neurological symptoms with varying effects on function that require different therapeutic strategies. To date, this spectrum of effects and its clinical implications have not been completely described. We describe the neurological examination findings in toddlers and preschoolers, including predominant symptom complexes and comorbidities. This study is a case-series neurological evaluation of 75 children with congenital Zika syndrome in Campina Grande, Brazil. The study is part of a cohort of children with congenital Zika syndrome that started in 2015 and is still ongoing. Children with Zika virus infection detected during pregnancy (mothers exhibited rash and were followed and diagnosed by fetal ultrasound abnormalities or RT-PCR) or through microcephaly screening after birth, using Intergrowth 21 guidelines, were selected by laboratory and radiological criteria. Children were examined during a 10-day period in September, 2018, and underwent neurological interview, examination, and assessment of functional outcomes and comorbidities. Children were divided in groups of predominant corticospinal or neuromuscular clinical signs and the associations between these groups and clinical comorbidities were assessed. All of the children recruited to the study from Nov 29, 2015 to Nov 30, 2017 had imaging correlates of congenital Zika syndrome. Children were assigned to groups depending on the signs exhibited, either corticospinal or neuromuscular, with or without dyskinetic signs. 75 children completed the evaluation, 38 (51%) girls and 37 (49%) boys. Median age was 33 months (range 26-40 months; IQR 29-34). Microcephaly was present at birth in 56 (75%) children, and 19 (25%) children were born with normal head circumference, 15 of whom later developed microcephaly. Neurological examination grouped four children as having isolated dyskinetic signs, 48 children were assigned to the corticospinal group and 23 into the neuromuscular group. Dyskinetic findings were present in 30 (40%) children, either alone (four [5%]) or combined with corticospinal (19 [40%] of 48) or neuromuscular (seven [30%] of 23) findings. Comorbidities were highly prevalent, and the neuromuscular group had worse functional outcomes, evaluated by gross motor function (p=0·026), manual abilities (p=0·0013), and communication function (p<0·0005) classification scales, than the corticospinal group, whereas pneumonia (p<0·0005) and urinary tract infections (p<0·0005) were more frequent in the corticospinal group. Cortical hyperexcitability was supported by several clinical correlates, such as early onset epilepsy, persistence of primitive reflexes, and dystonia. We describe distinct neurological profiles in the congenital Zika syndrome spectrum, with functional outcomes tending to correlate with these groups. The clinical division of children based on the disease signs proposed here is supported by the literature on central and peripheral nervous system pathology in congenital Zika syndrome. The high prevalence of dyskinetic symptoms merits special attention. Brazilian National Council for Scientific and Technological Development and by the Coordination for the Improvement of Higher Education Personnel.

Evaluation of Diagnostic Yield in Fetal Whole-Exome Sequencing: A Report on 45 Consecutive Families.

Prenatal ultrasound (US) abnormalities often pose a clinical dilemma and necessitate facilitated investigations in the search of diagnosis. The strategy of pursuing fetal whole-exome sequencing (WES) for pregnancies complicated by abnormal US findings is gaining attention, but the reported diagnostic yield is variable. In this study, we describe a tertiary center’s experience with fetal WES from both terminated and ongoing pregnancies, and examine the clinical factors affecting the diagnostic rate. A total of 45 consecutive families of Jewish descent were included in the analysis, for which clinical fetal WES was performed under either single (fetus only), trio (fetus and parents) or quatro (two fetuses and parents) design. Except one, all families were non-consanguineous. In 41 of the 45 families, WES was sought following abnormal fetal US findings, and 18 of them had positive relevant family history (two or more fetuses with US abnormalities, or single fetus with US abnormalities and an affected parent). The overall diagnostic yield was 28.9% (13/45 families), and 31.7% among families with fetal US abnormalities (13/41). It was significantly higher in families with prenatal US abnormalities and relevant family history (10/18, 55.6%), compared to families with prenatal US abnormal findings and lack of such history (3/23, 13%) (p = 0.004). WES yield was relatively high (42.9–60%) among families with involvement of brain, renal or musculoskeletal US findings. Taken together, our results in a real-world setting of genetic counseling demonstrates that fetal WES is especially indicated in families with positive family history, as well as in fetuses with specific types of congenital malformation.

Performance of a Multiplex Nested Polymerase Chain Reaction in Detecting 7 Pathogens Containing DNA in Their Genomes Associated With Congenital Infections.

Infections are the leading cause of perinatal and infant mortality in low-income and low-resource countries, which have a higher prevalence of infections. Definitive diagnosis of congenital and perinatal infections is largely dependent upon the results of laboratory tests. To develop a multiplex nested polymerase chain reaction (PCR) technique for the simultaneous detection of 7 pathogens containing DNA in their genomes in suspected cases of congenital infection. Eligible participants were pregnant women with positive immunoglobulin M antibodies raised to one of the pathogens in the prenatal serologic screening, associated or not with fetal ultrasound abnormalities or positive fetal serology. Neonates whose mothers did not attend prenatal care were included when they presented with symptomatology and laboratory parameters suggestive of infection. The detection rate of the multiplex nested PCR was compared with maternal, fetal, and neonatal serology, as well as placental immunohistochemistry and noncommercial amplifications. Of 161 suspected cases, the multiplex nested PCR detected 60 (37.3%), whereas the tests available in hospital laboratories detected 13 of 60 (21.7%) of the cases detected by the multiplex nested PCR, demonstrating a 4.6 times higher detection rate for the multiplex nested PCR (Fisher exact test, P < .001). Positive amplifications were to Toxoplasma gondii (32 cases), cytomegalovirus (14 cases), parvovirus B19 (5 cases), and adenovirus (5 cases). In 4 cases, 2 pathogens were simultaneously detected. All types of biological matrices were suitable for amplification. Sequencing of multiplex nested PCR products confirmed the molecular findings. The multiplex nested PCR significantly increased the number of diagnosed congenital infections. Given the scarcity of DNA recovered from amniotic fluid and some neonatal samples, this multiplex nested PCR allows the simultaneous detection of 7 pathogens associated with congenital infections in a reliable, faster, cost-effective, and more sensitive way.

Prenatal diagnosis: the clinical usefulness of array comparative genomic hybridization.

Background:Array comparative genomic hybridization (aCGH) has been replacing karyotype in neurodevelopment diseases or intellectual disability cases. Regarding prenatal diagnosis (PND) karyotyping is still the criterion standard technique; nevertheless, the application of aCGH in this field has been increasing dramatically and some groups recommended it as the first-tier prenatal genetic test in cases of fetal ultrasound abnormalities. Despite aCGH greater resolution, the detection of variants of unknown significance (VOUS) is not desirable, so it's need some reflexion before generalized application on PND.Objective:The aim of this study was to analyze the prevalence and type of copy number variants (CNVs) detected in the 55 PND samples collected from pregnancies with indication to perform aCGH.Methods:aCGH was performed using Agilent 4 × 180K microarrays and results were analyzed using CytoGenomics software.Results and conclusion:Eight (14.5%) cases had pathogenic or likely pathogenic CNVs. VOUS were found in 21.8% of the cases, but this frequency could be minimized if only large CNVs above 1 million base pairs that are outside the clinically curated targeted regions were considered.

Analyse de l’ADN fœtal dans le sang maternel comme test de dépistage pour la trisomie 21 pour les grossesses gémellaires

ObjectivesTo evaluate the performance of noninvasive prenatal testing by cell-free circulating fetal DNA in maternal blood (cfDNA) in screening for trisomies 21 in twin pregnancies. MethodsCfDNA was performed in 492 patients with twin pregnancies without ultrasound anomalies in the first trimester as a first-line screening test or after serum screening. Data were collected prospectively and a retrospective analysis was done. CfDNA was executed by massive parallel technique. The fetal fraction threshold for test evaluation was 8%. Regression analysis was performed to evaluate the effect of different parameters on the test failure rate. Performance of the test was also considered. ResultsIn 377 patients, the test was prescribed first line and in 115 after standard serum screening. Twelve tests (2.9%) have initially failed on the 420 pregnancies with available outcomes and regression analysis found only maternal weight as a significant independent factor of test failure. A second test was performed on 10 patients, all of them had an available result. cfDNA identified all 3 cases of trisomy 21. The sensitivity was 100.0% (95% CI [29.2–100.0%]) and specificity was 99.8% (95% CI [98.7–100.0%]). There was no significant difference between spontaneous pregnancies and those induced by assisted reproductive technologies (ART), in terms of fetal fraction percentage, no-call results for cfDNA screening, maternal weight, or test performance between the two groups. ConclusionIn twin pregnancies without fetal ultrasound abnormalities, the performance and success rate of the cfDNA are excellent. Therefore, cfDNA could be offered in routine practice as a first-line screening test in this population.

Prenatal Diagnosis of a 20 Mb Terminal Fetal 4q-Deletion in the Cytoband q33q35.2 Inherited from the Mother

AbstractThe authors present a case of prenatally diagnosed fetal terminal 4q deletion in the cytoband 4q33q35.2, inherited from the mother. The index pregnancy was referred at 28+2 weeks of gestation for polyhdramnios. Prior to performing the scan, distinctive facial features were noted in the mother. Target scan confirmed polyhdramnios, and revealed fetal retrognathia. The fetal karyotype reported a terminal 4q33&gt;ter deletion, which was further delineated by chromosomal microarray analysis. Subsequently, maternal karyotype revealed identical deletion. Subtle fetal ultrasound abnormalities should receive meticulous assessment, and evaluation using the currently available wide range of cytogenetic and molecular gene tests.