Prenatal Diagnosis Center Research Articles

Application of Combined Ultrasound and Maternal Serum Biochemical Indexes in the Detection of Fetal Structural Abnormalities and Chromosomal Abnormalities

By exploring different prenatal diagnosis indications of fetal chromosomal abnormalities, it can provide a theoretical basis and reference value for clinical consultation of pregnant women with similar high-risk factors. In this paper, 1800 pregnant women undergoing amniotic fluid aspiration chromosomal examination in the prenatal diagnosis center were selected as the object of this study. Amniocentesis, fetal cell culture, and karyotype analysis were performed on pregnant women who were 14-20 weeks pregnant and had signed an informed consent. After amniocentesis fetal chromosome analysis, the type of fetal chromosomal abnormality was determined, and the detection rate of chromosomal abnormality was statistically described. Chi-square test was used for comparison between groups, P < 0.05. This study shows that the use of ultrasound screening combined with maternal serum indicators is effective in screening fetal structural abnormalities and chromosomal abnormalities in early pregnancy, and significantly improves the detection rate of chromosomal abnormalities. The detection of fetal structural malformations is also very high, but it should be combined with ultrasound screening of mid-to-late pregnancy. The tricuspid regurgitation and umbilical vein a-wave reversal in the soft ultrasound index can be used as predictors of fetal congenital heart disease in early pregnancy.

Application of intelligent algorithms in Down syndrome screening during second trimester pregnancy.

BACKGROUNDDown syndrome (DS) is one of the most common chromosomal aneuploidy diseases. Prenatal screening and diagnostic tests can aid the early diagnosis, appropriate management of these fetuses, and give parents an informed choice about whether or not to terminate a pregnancy. In recent years, investigations have been conducted to achieve a high detection rate (DR) and reduce the false positive rate (FPR). Hospitals have accumulated large numbers of screened cases. However, artificial intelligence methods are rarely used in the risk assessment of prenatal screening for DS.AIMTo use a support vector machine algorithm, classification and regression tree algorithm, and AdaBoost algorithm in machine learning for modeling and analysis of prenatal DS screening.METHODSThe dataset was from the Center for Prenatal Diagnosis at the First Hospital of Jilin University. We designed and developed intelligent algorithms based on the synthetic minority over-sampling technique (SMOTE)-Tomek and adaptive synthetic sampling over-sampling techniques to preprocess the dataset of prenatal screening information. The machine learning model was then established. Finally, the feasibility of artificial intelligence algorithms in DS screening evaluation is discussed.RESULTSThe database contained 31 DS diagnosed cases, accounting for 0.03% of all patients. The dataset showed a large difference between the numbers of DS affected and non-affected cases. A combination of over-sampling and under-sampling techniques can greatly increase the performance of the algorithm at processing non-balanced datasets. As the number of iterations increases, the combination of the classification and regression tree algorithm and the SMOTE-Tomek over-sampling technique can obtain a high DR while keeping the FPR to a minimum. CONCLUSIONThe support vector machine algorithm and the classification and regression tree algorithm achieved good results on the DS screening dataset. When the T21 risk cutoff value was set to 270, machine learning methods had a higher DR and a lower FPR than statistical methods.

An assessment of the analytical performance of non-invasive prenatal testing (NIPT) in detecting sex chromosome aneuploidies: 34,717-patient sample in a single prenatal diagnosis Centre in China.

The present study aimed to evaluate the efficacy of a non-invasive prenatal test (NIPT) in the detection of the sex chromosome aneuploidies (SCAs) at our prenatal diagnosis centre. Among a cohort of 34,717 pregnancies, maternal plasma samples from our prenatal diagnosis centre were subject to analysis of SCAs using NIPT detection. Pregnant women with NIPT positive results of SCAs were recommended to undergo an invasive prenatal diagnosis (i.e. karyotyping and fluorescence in situ hybridization) to validate the prediction value of NIPT. From 34,717 clinical pregnancies, 229 (0.66%) pregnancies were identified with SCAs. Of these, 78 (34.1%) cases were positive for 45,X and 151 (65.9%) cases comprised a sex chromosome trisomy. Of the 229 positive NIPT results, 193 (84.3%) cases had accepted an invasive diagnosis involving karyotyping analysis of the amniotic fluid, which confirmed 67 cases (34.7%) as true positive, as well as 126 cases (65.3%) as false positive. The positive predictive values were 23.07%, 50%, 36% and 27.27% respectively. The remaining 36 (15.7%) cases declined a prenatal diagnosis. The termination rates of 45,X, 47,XXY, 47,XXX and 47,XYY were 20.5%,46%,12.9% and 11.5% respectively. NIPT demonstrated a lower accuracy in predicting monosomy X than sex chromosome trisomies. After invasive testing, the fetal chromosome with 45,X and 47,XXY were terminated more often than those with 47,XXX, 47,XYY. Because NIPT is a screening test, false positive/negative cases exist, and pre- and post-test counselling is essential for informing patients about the benefits and limitations of the test. Confirmatory testing of abnormal results is recommended prenatally or after birth, and the importance of confirmatory testing and benefits of early diagnosis should be addressed.

Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type

BackgroundCombined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.Methods248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Prenatal data of Hcy levels determined by enzymatic cycling assay, acylcarnitine analysis using liquid chromatography tandem mass spectrometry, organic acid analysis using gas chromatography mass spectrometry, and genetic analysis by direct sequencing of 248 at-risk fetuses were retrospectively reviewed.ResultsFor 2.0 and 16.0 μmol/L levels of Hcy AF samples, the relative errors were − 2.5% and 2.8%, respectively. The respective measurement uncertainties were 13.07% and 14.20%. For the 248 at-risk fetuses, 63 fetuses were affected and 185 fetuses were unaffected. Hcy level of 13.20 (6.62–43.30) μmol/L in 63 affected fetuses was significantly higher than that in 185 unaffected fetuses of 2.70 (0.00–5.80) μmol/L, and there was no overlap between the affected and unaffected groups. The diagnostic sensitivity and specificity of Hcy were 100% and 92.05%, respectively. The positive and negative predictive values of the combination of Hcy, propionylcarnitine (C3), ratio of C3 to acetylcarnitine (C2; C3/C2), methylmalonic acid (MMA), and methylcitric acid (MCA) were both 100%. Sixteen fetuses displayed inconclusive genetic results of MMACHC variants, in which seven fetuses were determined to be affected with elevated levels of Hcy, C3, C3/C2 and MMA, and their levels were 18.50 (6.70–43.30) μmol/L, 8.53(5.02–11.91) μmol/L, 0.77 (0.52–0.97), 8.96 (6.55–40.32) mmol/mol Cr, respectively. The remaining nine fetuses were considered unaffected based on a normal amniotic fluid metabolite profile.ConclusionsHcy appears to be another characteristic biomarker for the prenatal diagnosis of cblC defect. The combination of Hcy assay with acylcarnitine and organic acid analysis is a fast, sensitive, and reliable prenatal diagnostic biochemical approach. This approach could overcome the challenge of the lack of genetic analysis for families with at-risk cblC defect fetuses.

Variation analysis of genes associated with Usher syndrome type 1 in 136 Chinese deafness families

Objective: To investigate the variation of genes associated with Usher syndrome type 1(USH1)in 136 Chinese deafness families from Henan province. Methods: The data of 136 deafness families tested by next-generation sequencing(NGS) which identified in the center of genetics and prenatal diagnosis of the First Affiliated Hospital of Zhengzhou University from November 2016 to December 2019 were analysized and the variation frequency of six genes related to Usher syndrome type 1(MYO7A, USH1C, CDH23, PCDH15, USH1G, CIB2) were summarized. Results: Five deafness families were detected nine pathogenic or likely pathogenic variations in two genes, accounting for 3.7% of all families. Among them, four families were caused by MYO7A variations and one family was caused by CDH23 variation. Meanwhile, seven variations of two genes were reported for the first time. They were c.313delG, c.5257dupA, c.5435A>T, c.5636G>C, c.5722T>G of MYO7A, and c.155_166del, c.4802delA of CDH23. The patients' vision of family 2 and family 3 had no obvious abnormality at present, but according to genetic diagnosis and walking dealy, they were considered to be USH1. Conclusions: MYO7A is the most common caustive gene associated with USH1 in Henan deafness patients, the application of next-generation sequencing technology can make USH1 patients diagnosed earlier before the visual symptoms appear.

Termination of pregnancy for foetal indication in the French context analysis of decision-making in a Multidisciplinary Centre For Prenatal Diagnosis

ObjectiveIn France, termination of pregnancy (TOP) for medical reasons is legal, regardless of the term, after authorisation by a Multidisciplinary Centre for Prenatal Diagnosis (MCPD). This study analyses the elements supporting the TOP decision-making process faced with a foetal pathology. Study designMedical records of one MCPD were analysed for the period 2013 and 2014 and semi-structured interviews with MCPD members were conducted. ResultsOut of 265 files concerning foetal indications, all but one resulted in a decision for TOP. The main indications in number for TOP were malformations and chromosomal abnormalities. For indications such as trisomy 21, authorisations are generally given without discussion. Our results underline the importance that professionals attach to the collegiality of decisions, particularly in situations of uncertainty. ConclusionThis study provides information about the activity of MCPDs within the field of prenatal diagnosis and shows the importance of these structures in supporting women and couples whilst respecting their autonomy. At present, the role of the MCPD is in the process of evolving and could become an information and advisory board for women, based on collegial expertise to guide their decision-making.

SNP Array as a Tool for Prenatal Diagnosis of Congenital Heart Disease Screened by Echocardiography: Implications for Precision Assessment of Fetal Prognosis.

ObjectiveThis study aimed to examine the effectiveness of the SNP array for the prenatal diagnosis of congenital heart disease (CHD) screened by echocardiography.Patients and MethodsA total of 356 pregnant women with fetal congenital heart malformations revealed by echocardiography at the Center for Prenatal Diagnosis of Fujian Maternal and Children Hospital during the period from November 2016 through July 2019 were recruited. The fetuses were assigned into three cohorts, including 142 with a single cardiac malformation, 106 with multiple cardiac malformations and 108 with cardiac and extracardiac malformations. All fetuses underwent chromosomal karyotyping and SNP array simultaneously, and the effectiveness of the SNP array for the prenatal diagnosis of CHD was evaluated.ResultsThe overall prevalence of abnormal karyotypes was 9.3% among the 356 fetuses with CHD, and a higher proportion was found in fetuses with cardiac and extracardiac malformations (18.5%) than in those with single (5.6%) or multiple cardiac malformations (4.7%) (P<0.05). Consistent with karyotype analysis, SNP array detected an additional 25 fetuses with pathogenic copy number variations (CNVs), seven with variant of unknown significance (VOUS) and seven with benign CNVs, and a lower proportion of abnormal CNV was found in fetuses with a single cardiac malformation (4.2%) than in those with multiple cardiac malformations (9.4%) or cardiac and extracardiac malformations (14.8%) (P<0.05). Among the 33 fetuses with chromosomal abnormality, postnatal follow-up showed termination of pregnancy in 25 with pathogenic CNVs, one with VOUS, and six with normal karyotypes and SNP array findings but severe multiple malformations by ultrasonography.ConclusionSNP array increases the overall detection of abnormal CNVs by 9%, which improves the detection of CNVs associated with CHD. SNP array may serve as a tool for prenatal diagnosis of CHD that facilitates the discovery of pathogenic genes associated with CHD and provide valuable insights into the precision assessment of fetal prognosis during the prenatal counseling.

Aberran sağ subklavyen arter: Down sendromu ve konjenital kalp hastalığı için güçlü bir belirteç midir?

Amac: Fetal aberran sag subklavyen arter (ARSA) ile Down sendromu arasindaki iliski uzun zamandir bilinmektedir. Calismamizin amaci populasyonumuzdaki ARSA insidansini ve Down sendromu ve konjenital kalp hastaliklari (KKH) ile iliskisini belirlemektir. Gerec ve Yontem: 2015-2018 yillari arasinda ucuncu basamak merkezde prenatal tani icin 3150 gebeye fetal ekokardiyografi yapildi. ARSA varligi, fetal ekokardiyografi sirasinda transvers 3 damar trakea planinda renkli Doppler sonografide goruntulenmesi ile dogrulandi. Calismamizda ARSA'nin sikligi ve Down sendromu ile korelasyonu arastirildi. Bulgular: 3150 hasta arasinda 42 fetuste (% 1.3) ARSA, 36 fetuste (% 1.14) izole ARSA saptandi. Down sendromlu dokuz fetusten iki hastada (% 22.2) ARSA pozitifti. ARSA, KKH olan fetuslerden sadece birinde pozitifti (% 4.1). Izole ARSA'nin Down sendromu ve CHD icin pozitif olasilik oranlari sirasiyla 0.73 ve 3.81 idi. Sonuc: Olgu serimizde, prenatal ARSA'nin saptanmasi Down sendromu icin tek basina guclu bir marker gibi gorunmemektedir ve izole ARSA, KKH ile zayif bir iliski gostermektedir.

Interruptions médicales de grossesse pour indications maternelles : analyse rétrospective en Normandie Occidentale (2010–2019)

IntroductionTermination of pregnancy for maternal reasons (MTOP) are authorized in France without limit of term when “the continuation of the pregnancy puts in serious danger the health of the woman”. The literature on the subject is rare and we wanted to make an inventory in our region. MethodsRetrospective observational study between 2010 and 2019 at the multidisciplinary center for prenatal diagnosis in Western Normandy. ResultsThirty-one cases of MTOP were included (2.5% of all TOP). At the CHU de Caen, they represented one in 1200 births. Twenty-three percent of MTOP had a psychosocial or psychiatric indication (average term=22 SA) and 29% an obstetric indication due to severe preeclampsia (23 SA). Finally, 48% were linked to a non-obstetric somatic disorder including 46% pre-existing pathologies (average term=11 SA), most often cardiological or nephrological and 54% diagnosed during pregnancy (17 SA) dominated by neoplasias. They were more often (68%) performed in the second trimester. Vaginal births were more frequent (74% against 26% of endouterine aspirations). ConclusionStrict medical contraindications to pregnancy are exceptional. Recourse to the medical termination of pregnancy within the framework of a preexisting pathology must remain rare, by systematizing of the preconception consultation.

Analysis of MYO15A variation in children with DFNB3

Objective: To analyze the genetic and clinical characteristics of MYO15A variants associated non-syndromic autosomal recessive deafness3 (DFNB3). Methods: The hearing test and high-throughput sequencing data of 108 families with non-syndromic hearing loss, who visited the Center of Genetics and Prenatal Diagnosis in the First Affiliated Hospital of Zhengzhou University from November 2016 to February 2019, were retrospectively analyzed to investigate the characteristics of MYO15A variation. Results: Compound heterozygous MYO15A variations were detected in nine patients from eight families, accounting for 7.4% of all 108 families. The variants were c.5910+1G>A/c.9417_9418insTA, c.4234T>G/c.8324G>T, c.3926A>T/c.5002delC, c.9690+1G>A/c.10257_10259delCTT, c.8324G>T/c.10419_10423delCAGCT, c.4519C>T/c.6454G>C, c.6177+1G>T/c.10257_10259delCTT and c.5692C>T/c.7396-1G>A. All patients had severe to profound hearing loss. Among the 14 variations, 12 variations were located in the main structural domains, including 5 in motor domain, 3 in FERM domain, 3 in MyTH4 domain and 1 in IQ motif. The c.3926A>T, c.4234T>G, c.4519C>T, c.5002delC, c.6454G>C, c.8324G>T, c.9417_9418insTA and c.10419_10423delCAGCT had not been reported in the Human Gene Mutation Database up to February 2020. According to the guidelines of the American College of Medical Genetics and Genomics (ACMG), 6 reported variants and the first reported c.4519C>T, c.5002delC, c.9417_9418insTA and c.10419_10423delCAGCT were identified as pathogenic variants, while c.8324G>T was likely pathogenic variant, and c.3926A>T, c.4234T>G and c.6454G>C were variants of uncertain significance. Conclusions: The variations of MYO15A in patients with DFNB3 are mainly complex heterozygous. The clinical phenotypes are mostly severe to profound hearing loss, and the mutation loci are mainly in the motor, FERM and MyTH4 domains.

The prenatal ultrasonic character and postnatal follow-up of 227 microcystic and macrocystic congenital cystic adenomatoid malformations

The objective of our study was to compare microcystic and macrocystic congenital cystic adenomatoid malformation (CCAMs) through prenatal characteristics, perinatal outcome, postnatal management and development after consultation in our prenatal diagnosis centre. We conducted a retrospective cohort study of 227 cases prenatally diagnosed as CCAM in our hospital within three years. One hundred and eighty-one cases continued their pregnancy and 46 pregnancies were terminated. One hundred and fifteen of 227 cases were microcystic and 112 were macrocystic. The prenatal ultrasound characteristics of two types showed no statistically significant differences, despite that CVR of macrocystic CCAMs was mildly greater than microcystic. None of recorded cases received surgical intervention in utero. Compared with healthy foetuses, CCAMs presented with higher percentage of polyhydramnios and male foetuses, larger amount of postpartum blood loss and longer duration of NICU hospitalisation. Compared with 46 legal abortions, continued pregnancy cases had a smaller CVR, less polyhydramnios, cardiac shift and hydrops. One hundred and seventy-nine cases were followed up after birth and 174 babies were asymptomatic. Thirty one cases received successful surgical resection. In conclusion, the prenatally diagnosed CCAMs have a good short-term prognosis and conservative management is a reasonable option in asymptomatic fetuses. Microcystic and macrocystic CCAMs both presented similar prenatal courses and perinatal prognoses. Conservative management, prenatally and postnatally, could be accepted in selected cases. Impact statement What is already known on this subject? Congenital cystic adenomatoid malformation is a well-known developmental abnormality of the lung. The prognosis for most CCAMs is good, but the prenatal and postnatal management remains controversial. What do the results of this study add? This study is one of the largest case cohorts to conclude that microcystic and macrocystic CCAMs both presented similar prenatal courses and perinatal prognoses. Conservative management is a reasonable option in asymptomatic babies. What are the implications of these findings for clinical practice and/or further research? A comprehensive assessment by an experienced multidisciplinary team is necessary to forbid blinding abortions of CCAMs. Conservative management prenatally and postnatally could be accepted in most asymptomatic cases.

Impact of simulation-based prenatal invasive procedure training on professional practice, a preliminary study

IntroductionAmniocentesis and chorionic villus sampling remain the cornerstone of prenatal diagnosis. These procedures are associated with a risk of miscarriage estimated at approximately 0.5 %. Our team has developed a training model for performing simulation-based prenatal invasive procedures. Several simulation sessions are offered each year to obstetricians-gynecologists involved in fetal medicine in France and abroad. This simulation-based learning has already been conclusively evaluated according to levels I and II of the Kirkpatrick model. Here, we carried out a preliminary study according to level III: does participation in training in prenatal invasive procedures through simulation have an influence on professional practice? MethodsAn anonymous online survey was sent to 82 obstetricians-gynecologists who participated in the training in prenatal invasive procedures at the Antoine Béclère maternity hospital between January 1st, 2014 and December 31, 2018. This questionnaire, entitled "Evaluation of the professional impact of training in invasive procedures through simulation", included 20 quantitative and qualitative items. Results48 (59 %) obstetricians-gynecologists responded to the questionnaire. 98 % of the participants considered that participation in the training had a significant impact on their professional practice. Half considered this impact to be major. 60 % of the former participants are now attached to a Multidisciplinary Center for Prenatal Diagnosis. ConclusionParticipation in training is considered by former participants to have a significant impact on their professional practice. In order to finalize the evaluation of this learning, a study of the benefits for patients and their pregnancy should be discussed.

A retrospective analysis the clinic data and follow-up of non-invasive prenatal test in detection of fetal chromosomal aneuploidy in more than 40,000 cases in a single prenatal diagnosis center

ObjectiveTo evaluate the efficacy of non-invasive prenatal test (NIPT) in the detection of chromosomal aneuploidy according to the follow-up information from a single prenatal diagnosis center. MethodsA total of 40,311 cases were retrospectively reviewed. The screening was performed using a BGI protocol, pre-test and post-test genetic counseling was provided, and the pregnancy outcomes were recorded. The results of NIPT and clinical follow-up data were analyzed together with the pregnancy outcomes, confirmatory testing results, and ultrasound findings. ResultsOf the 40,311cases were includes in the study, successful follow-up was conducted in 468 (1.16%) cases with high risk, 225 (0.56%) cases with rare autosomal trisomy (RAT) and copy number variation (CNV). 39,572 (98.17%) cases with low risk and 623 (1.57%) cases of which were confirmed with adverse pregnancy outcomes. 46 (0.1%) cases with failed tests. Among them, 398 (84.7%) cases with high-risk results chose invasive testing, revealing 198 true positive cases. In cases with RAT and CNV results, 189 cases underwent invasive testing, revealing 5 cases RAT and 4 pathogenic CNVs. ConclusionsNIPT appears to be effective in detecting the fetal chromosomal aneuploidies T21, T18 and SCAs, but it exist false positive/negative cases, unconfirmed high-risk cfDNA results, and the high false positive rate in cases with RAT and CNV results implied the limitations of this screening method. Our study showed the importance to associate cfDNA screening results with clinical follow-up data and provided information that may help with result interpretation, genetic counseling and the decision making in clinic.

Moderate and severe fetal pyelectasis: Correlation between prenatal aspects and postnatal outcome.

Renal pelvic dilatation (RPD) is a frequent finding in fetal ultrasound. The aim of the study is to correlate the prenatally detected moderate and severe pyelectasis with the postnatal outcome. A retrospective analysis involving 90 cases of prenatally detected moderate and severe RPD referred to our prenatal diagnosis centre with 18 months of urological follow-up. Prenatal ultrasound was correlated with postnatal renal function, assessed by plasmatic creatinine and/or renal scintigraphy performed before surgery. Cases were divided between two groups according to postnatal management: group A including 35 newborns (38.9%) that needed surgical treatment and group B with 55 patients (61.1%) who were managed conservatively. The group A presented higher median RPD (18 mm, IQR 12-25 mm) compared to the group B (11 mm, IQR 10-14 mm). The most common anomaly detected within group A was pelvi-ureteric junction (PUI) obstruction (43%). Within group B 32 cases (58%) showed spontaneous resolution of hydronephrosis during postnatal follow up. In case of moderate pyelectasis the risk of postnatal surgery was 25% and raised to 60% for severe RPD. In our study, 29 newborns showed pathologic scintigraphies: 25 required surgery while 4 did not find indication for surgery due to ipsilateral renal function irreversible damage. 6 patients had high creatinine level (>0.6 mg/dl). 35 cases out of 90 (39%) developed monolateral irreversible renal function impairment. Moderate and severe RPD are often correlated with postnatal renal damage, therefore a close multidisciplinary follow-up is required. Prenatal scanning is highly predictive of postnatal outcome and can address properly the prenatal counseling.

Mutational analysis and prenatal diagnosis of TMPRSS3 gene in two Chinese families affected with deafness

Objective: To detect potential mutations in two Chinese families affected with deafness, so as provide prenatal diagnosis for them. Methods: Two Chinese families affected with deafness were identified at the genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from March 2018 to December 2018.Mutation analyses were carried out by next generation sequencing (NGS),suspected mutations were verified by Sanger sequencing in the probands, unaffected relatives. Prenatal diagnosis for high-risk fetus were carried out through Sanger sequencing. Results: The proband of family 1 carried a c.432delA and a c.617-2_617-1insTC mutation of the TMPRSS3 gene, the proband of family 2 carried a c.271C>T(p.R91X) and a c.147dupTmutation ofthe TMPRSS3 gene, both parents of the two probands were carriers of heterozygous variants. Conclusions: Mutations in the TMPRSS3 gene are the suspected cause of deafness in two families. Application of next generation sequencing technologies make gene diagnosis of deafness efficiently and accurately and the molecular findings increase our understanding of the function of TMPRSS3 gene and enrich the human gene mutation database. It is helpful for recurrent genetic counseling and prenatal diagnosis for these families.

Analysis of genetic variation in patients with Waardenburg syndrome type Ⅱ by next generation sequencing

Objective: To detect gene mutation sassociated with deafness in four Waardenburg syndrome (WS) type Ⅱ patients, and to explore the possible mechanism of molecular genetics. Methods: All patients with WS were identified at the genetic and prenatal diagnosis center of the First Affiliated Hospital of Zhengzhou University from August 2015 to December 2018.Clinical materials and peripheral blood were collected from patients and family members. The genes associated with deafness of the patients were tested by next generation sequencing(NGS). And suspected mutations were verified by Sanger sequencing. Results: All patients carried heterozygous mutations in SOX10, they were c.355_356insTCAGGCAGCGC, c.1106_1107insTGGGGCCCCCCACACTA, c.511T>C (p.Y171H), c.91_100del. According to the guidelines for genetic variation of the Amercian College of Medical Genetics and Genomics (ACMG), three frameshift mutations were pathogenic mutations, one missense mutation was likely pathogenic mutation. Conclusion: Application of next generation sequencing technologies make gene diagnosis of Waardenburg syndrome efficiently and accurately.

First-trimester sonographic diagnosis of sirenomelia: A multicenter series of 12 cases and review of the literature.

To determine the key sonographic features for the diagnosis of sirenomelia in the first trimester of pregnancy. Cases of sirenomelia from several prenatal diagnosis centers were retrospectively identified and reviewed. The diagnosis was established through the detection of fused lower limbs. Additional sonographic findings were also noted. A total of 12 cases were collected. The most striking sonographic finding was the detection of malformed lower limbs, which appeared to be fused and in an atypical position. Nuchal translucency thickness was mildly increased in three cases (25%). An abdominal cyst, representing the dilated blind-ending bowel, was noted in seven cases (58%). Color flow imaging detected a single umbilical artery in six cases (50%) and the associated intra-abdominal vascular anomalies in three cases (25%). No cases of aneuploidy were detected. The pregnancy was terminated in nine cases (75%) and intrauterine demise occurred in the remaining three cases (25%). The sonographic detection of abnormal lower limbs or an intra-abdominal cyst located laterally during the first-trimester scan may be warning signs of sirenomelia. This should prompt a detailed examination of the fetal lower body and intra-abdominal anatomy, including the main abdominal vessels, in order to look for additional confirmatory findings.

Perinatal grief following neonatal comfort care for lethal fetal condition.

The objective of the study was to assess perinatal grief experienced after continuing pregnancy and comfort care in women diagnosed with lethal fetal condition compared with termination of pregnancy for fetal anomaly (TOPFA). This was a retrospective observational study which included women who chose to continue their pregnancy after the diagnosis of lethal fetal condition with comfort care support at birth at the Prenatal Diagnosis Center of Rennes Hospital from January 2007 to January 2017. Women were matched with controls who underwent TOPFA for the same type of fetal anomaly, gestational age at diagnosis and year. Women were evaluated by a questionnaire including the Perinatal Grief Scale. There were 28 patients in the continuing pregnancy group matched with 56 patients in the TOPFA group. Interval between fetal loss and completion of questionnaire was 6±3 years. Perinatal grief score was similar at 61±22 vs 58±18 (p = 0.729) in the continuing pregnancy and TOPFA groups, respectively. Women in the TOPFA group expressed more guilt. The cesarean-section rate in the continuing pregnancy group was 25%. Perinatal grief experienced by women opting for continuing pregnancy and comfort care after diagnosis of a potentially lethal fetal anomaly is not more severe than for those choosing TOPFA.

Chromosomal microarray analysis for the detection of chromosome abnormalities in fetuses with echogenic intracardiac focus in women without high-risk factors.

To investigate the association between pathogenic copy number variants (p-CNVs) and abnormal karyotypes detected by chromosomal microarray analysis (CMA) and echogenic intracardiac focus (EIF).This was a retrospective study of fetuses with EIF with CMA data at the Prenatal Diagnosis Center of the West China Second University Hospital of Sichuan University between September 2014 and May 2017. Fetuses were assigned to the isolated EIF and non-isolated EIF groups according to the presence of other ultrasound abnormalities.Among 244 pregnant women, there were 143 cases of isolated EIF and 101 of non-isolated EIF. CMA revealed chromosome abnormality (n = 9 (3.7%): trisomy 21, n = 4; sexual trisomy, n = 2; and p-CNV, n = 3), variants of unknown significance (VOUS, n = 19), and benign CNV (b-CNV, n = 216). Among the fetuses with isolated EIF, 5 had chromosomal abnormalities (3.5%). Among the fetuses with non-isolated EIF, four had chromosomal abnormalities (4.0%). All fetuses with trisomy 21 were in the non-isolated group. The frequency of labor induction was 66.7% (6/9) among the fetuses with chromosome abnormality and 21.1% (4/19) among those with VOUS. Among those with chromosomal abnormalities, one (11.1%) had congenital heart disease.In pregnant women without high-risk factors for chromosomal abnormalities, ultrasound abnormalities, including EIF, could be an indication for CMA. Ultrasound abnormalities (including EIF) and chromosome abnormality could indicate a high risk of CHD. The presence of EIF and at least another ultrasound abnormality could indicate a high risk of trisomy 21.

Analysis of 21 723 Pregnant Women's First Trimester Screening for Down Syndrome in Sichuan Province

To compare the effect of different first-trimester screening programmes for Down syndrome in Sichuan Province. We retrospectively collected the data of singleton pregnancies that were screened by serum biochemistry markers combined with nuchal translucency screening tests in the first trimester in Prenatal Diagnosis Center of West China Second University Hospital of Sichuan University from January 2011 to December 2017. The fetal chromosome results were obtained by amniocentesis or by telephone follow-up. The screening effect of maternal age, nuchal translucency thickness, maternal serum biochemistry markers and combined screening in the first trimester were analyzed. Among the 21 723 singleton pregnancies, 33 cases were diagnosed as Down syndrome, and 19 cases were diagnosed as trisomy 18 sex chromosome abnormalities were found in 4 cases, and other chromosome abnormalities were found in 8 cases. For the combined screening, the detection rate of Down syndrome was 72.73%, and the false positive rate was 2.49%; the detection rate of trisomy 18 syndrome was 73.68% with the false positive rate of 0.39%. With a 5% false positive rate, maternal age, nuchal translucency thickness, serum biochemistry markers and combined screening would respectively detect 15.15%, 57.58%, 60.61% and 87.88% of Down syndrome fetuses. Compared with the other three screening programmes, the combined screening can effectively screen fetuses with Down syndrome and other chromosomal abnormalities.