Prenatal Diagnosis Center Research Articles

Prenatal diagnosis and outcomes in 320 fetuses with nasal bone anomalies.

Object: To investigate the chromosome abnormalities associated with absent or hypoplastic fetal nasal bone. Methods: Patients with fetal nasal bone anomalies (NBA) referred to our center for prenatal diagnosis between 2017 and 2021 were retrospectively evaluated. All these patients underwent chromosomal microarray and/or karyotyping and received genetic counseling before and after testing. Results: Among 320 fetuses with NBA, chromosomal abnormalities were diagnosed in 89 (27.8%) cases, including 53 cases of trisomy 21, which was the most common type of chromosomal aneuploidy, accounting for 59.6% of all detected abnormalities. In addition to aneuploidies, 29 cases of copy number variants (CNVs) were detected. In cases of isolated NBA with low-risk screening results and without other risk factors, the incidence of fetal chromosomal aneuploidies and pathogenic CNVs is 5.3% (7 in 132 cases). Conclusion: This study suggests that parents of fetuses should be informed about the possibility of fetal aneuploidy and pathogenic CNVs and that discussion with the parents is also recommended, providing data support and reference for clinical counseling.

Clinical phenotype and genetic analysis of a patient with a heterozygous 6p25.3 deletion and partial trisomy 15q

To investigate the clinical phenotype and genetic characteristics of a patient with a heterozygous 6p25.3 deletion and partial trisomy 15q. A patient who had presented at the Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University on May 14, 2021 was selected as the study subject. Clinical data of the patient was collected, and G-banded chromosomal karyotyping and copy number variation sequencing (CNV-seq) were carried out. The patient's main clinical features have included complete uterine septum, vaginal septum, atrophy of left eyeball, abnormal fingers and toes, and mental retardation. The karyotype of the patient was 46,XX,der(6)t(6;15)(p25.3;q26.1). CNV-seq result has indicated a 1.20 Mb heterozygous deletion in the 6p25.3 region and a 10.20 Mb duplication in the 15q26.1q26.3 region. The deletion segment has included the FOXQ1 gene, which may be related with the abnormal development of the left eye. The duplication segment has a 96.16% overlap with the region associated with 15q26 overgrowth syndrome (including the IGF1R gene), which may be related to the patient' s abnormal development of the Müllerian duct, abnormal fingers and toes, and mental developmental delay. The heterozygous deletion of the 6p25.3 region and duplication of the 15q26.1q26.3 region probably underlay the abnormal clinical phenotype in this patient.

The role of pediatric oncologist in prenatal diagnosis: A 10-year retrospective study at Assistance Publique Hôpitaux de Marseille (AP-HM)

Solid tumors or predisposition syndromes are increasingly suspected before birth. However optimal management and outcomes remain unclear. We have performed a ten-year retrospective study of oncologic indications of prenatal diagnosis in public hospitals in Marseille. Data were obtained from prenatal diagnosis center and hospital imaging databases and pediatric oncology department files. Fifty-one cases were identified, 40 with mass: adrenal 17, sacrococcygeal 9, cardiac 7, abdominal 4, ovarian 1, cervical 2; 8 with developmental abnormalities (omphalocele 4, macroglossia 4), 3 WITH familial predisposition syndromes (familial rhabdoid 2, Li-Fraumeni 1). Median detection time was 30 week. Termination of pregnancy was decided for 9 fetuses (4 cardiac lesions and suspected tuberous sclerosis, 2 sacrococcygeal tumors, 1 Beckwith–Wiedemann Syndrome, 2 SMARCB1 mutations. Preterm birth occurred in 8 cases. Eleven newborns (26,1%) required intensive care (8 for mechanical complications). Of of 17 adrenal mass ES, 4 disappeared before birth and 5 before one year. Seventeen newborns underwent surgery: 13 masses (teratoma 7, myelomeningocele 2, cystic nephroma 1, neuroblastoma 2), 4 omphaloceles, one biopsy. Surgery performed after one year for incomplete regression identified 1 neuroblastoma, 2 bronchogenic cysts and 2 nonmalignant masses. Three newborns received chemotherapy. Except one patient with BWS who died of obstructive apnea, all children are alive disease free with a median follow-up of 60 months [9–131 months]. Twelve have sequelae. Various solid tumors and cancer predisposition syndromes can be detected before birth. A multidisciplinary collaboration is strongly recommended for optimal management before and after birth.

Genetic basis of ß-thalassemia in families of pashtun ethnicity in Dera Ismail Khan district of Khyber Pakhtun-Khwa province, Pakistan

ABSTRACT Objectives The objective of current genetic research was to verify the genetic basis of ß-thalassemia and its pattern of inheritance in families of Pashtun ethnicity in District Dera Ismail Khan, Pakistan. Methodology Blood samples from clinically diagnosed five unrelated ß-thalassemia families were collected and target Sanger Sequencing of HBB gene was done. Moreover, in silico analysis including protein modeling and Protein-Protein docking was aslo performed. Results and Discussion Clinical analysis of patients from family 1,2, 4, and 5 revealed Thalassemia Intermedia, while patient from family 3 was suffering from thalassemia major. The average Hb concentrations between the cases that were severe were found to be a little lower (6.3 mg/dl) than the patients with milder clinical manifestations (7.6 ± 1.4). Genetic analysis in family 1 identified compound heterozygous mutation of HBB (NM_000518) i.e. c.20A>T +c.92 G>A, in family 2 and 4 compound heterozygous mutations c.20A>T + c.27_28insG, in family 3 homozygous mutation c.27_28insG, while in family 5 we identified homozygous mutation c.92 + 5 G>C (IVS-1 + 5 G>C). Conclusion This study offers an effective incentive to establish a mutation detection as well as prenatal diagnosis (PND) centers at a larger scale in the Pashtun ethnicity residing in District Dera Ismail Khan, Pakistan.

Optical genome mapping analysis of a Chinese pedigree with a rare chromosome 17 paracentric inversion insertion

To carry out optical genome mapping (OGM) for a Chinese pedigree with a rare paracentric reverse insertion of chromosome 17. A high-risk pregnant woman identified at the Prenatal Diagnosis Center of Hangzhou Women's Hospital in October 2021 and her family members were selected as the study subjects. Chromosome G banding analysis, fluorescence in situ hybridization (FISH), single nucleotide polymorphism array (SNP array) and OGM were applied to verify the balanced structural abnormality of chromosome 17 in the pedigree. Chromosomal karyotyping analysis and SNP array assay have identified a duplication of 17q23q25 in the fetus. Karyotyping analysis of the pregnant woman showed that the structure of chromosome 17 was abnormal, whilst SNP array has detected no abnormality. OGM revealed that the woman has carried a paracentric reverse insertion, which was confirmed by FISH. The karyotype of her husband was normal. The duplication of 17q23q25 in the fetus has derived from a paracentric reverse insertion of chromosome 17 in its mother. OGM has the advantage for delineating balanced chromosome structural abnormalities.

Prenatal diagnosis and pregnancy outcome of fetuses with rare autosomal trisomies indicated by non-invasive prenatal testing

To analyze the result of prenatal diagnosis and outcome of pregnancy for fetuses with rare autosomal trisomies (RATs) suggested by non-invasive prenatal testing (NIPT). A total of 69 608 pregnant women who underwent NIPT at Genetics and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from January 2016 to December 2020 were selected as study subjects. The result of prenatal diagnosis and outcome of pregnancy for those with a high risk for RATs were retrospectively analyzed. Among the 69 608 pregnant women, the positive rate of NIPT for high-risk RATs was 0.23% (161/69 608), with trisomy 7 (17.4%, 28/161) and trisomy 8 (12.4%, 20/161) being the most common, and trisomy 17 (0.6%, 1/161) being the rarest. For 98 women who had accepted invasive prenatal diagnosis, 12 fetal chromosomal abnormalities were confirmed, and in 5 cases the results were consistent with those of NIPT, which yielded a positive predictive value of 5.26%. Among the 161 women with a high risk for RATs, 153 (95%) were successfully followed up. 139 fetuses were ultimately born, with only one being clinically abnormal. Most women with a high risk for RATs by NIPT have good pregnancy outcomes. Invasive prenatal diagnosis or serial ultrasonography to monitor fetal growth, instead of direct termination of pregnancy, is recommended.

The value of chromosomal microarray analysis and fluorescence in situ hybridization for the prenatal diagnosis of chromosomal mosaicisms

To assess the value of chromosomal microarray analysis (CMA) and fluorescence in situ hybridization (FISH) for the prenatal diagnosis of chromosomal mosaicisms. A total of 775 pregnant women who had visited the Prenatal Diagnosis Center of Yancheng Maternal and Child Health Care Hospital from January 2018 to December 2020 were selected as study subjects. Chromosome karyotyping analysis and CMA were carried out for all women, and FISH was used to validate the suspected mosaicism cases. Among the 775 amniotic fluid samples, karyotyping has identified 13 mosaicism cases, which yielded a detection rate of 1.55%. Respectively, there were 4, 3, 4 and 2 cases for sex chromosome number mosaicisms, abnormal sex chromosome structure mosaicisms, abnormal autosomal number mosaicisms and abnormal autosomal structure mosaicisms. CMA has only detected only 6 of the 13 cases. Among 3 cases verified by FISH, 2 cases were consistent with the karyotyping and CMA results, and clearly showed low proportion mosaicism, and 1 case was consistent with the result of karyotyping but with a normal result by CMA. Eight pregnant women had chosen to terminate the pregnancy (5 with sex chromosome mosaicisms and 3 with autosomal mosaicisms). For fetuses suspected for chromosomal mosaicisms, CMA, FISH and G-banding karyotyping should be combined to determine the type and proportion of mosaicisms more precisely in order to provide more information for genetic counseling.

Fetal Neurology Practice Survey: Current Practice and the Future Directions

BackgroundFetal neurology is a rapidly evolving field. Consultations aim to diagnose, prognosticate, and coordinate prenatal and perinatal management along with other specialists and counsel expectant parents. Practice parameters and guidelines are limited. MethodsA 48-question online survey was administered to child neurologists. Questions targeted current care practices and perceived priorities for the field. ResultsRepresentatives from 43 institutions in the United States responded; 83% had prenatal diagnosis centers, and the majority performed on-site neuroimaging. The earliest gestational age for fetal magnetic resonance imaging was variable. Annual consultations ranged from <20 to >100 patients. Fewer than half (n = 17.40%) were subspecialty trained. Most respondents (n = 39.91%) were interested in participating in a collaborative registry and educational initiatives. ConclusionsThe survey highlights heterogeneity in clinical practice. Large multisite and multidisciplinary collaborations are essential to gather data that inform outcomes for fetuses evaluated across institutions through registries as well as creation of guidelines and educational material.

Global Policy and Practice for Intrauterine Fetal Resuscitation During Fetal Surgery for Open Spina Bifida Repair

Globally accepted recommendations suggest that a woman should be between 19 weeks and 25 weeks plus 6 days of pregnancy to be considered eligible for fetal closure of open spina bifida. A fetus requiring emergency delivery during surgery is therefore potentially considered viable and thus eligible for resuscitation. There is little evidence, however, to support how this scenario is addressed in clinical practice. To explore current policy and practice for fetal resuscitation during fetal surgery for open spina bifida in centers undertaking fetal surgery. An online survey was designed to identify current policies and practices in place to support fetal surgery for open spina bifida, exploring experiences and management of emergency fetal delivery and fetal death during surgery. The survey was emailed to 47 fetal surgery centers in 11 countries where fetal spina bifida repair is currently performed. These centers were identified through the literature, the International Society for Prenatal Diagnosis center repository, and an internet search. Centers were contacted between January 15 and May 31, 2021. Individuals volunteered participation through choosing to complete the survey. The survey comprised 33 questions of mixed multiple choice, option selection, and open-ended formats. Questions explored policy and practice supporting fetal and neonatal resuscitation during fetal surgery for open spina bifida. Responses were obtained from 28 of 47 centers (60%) in 11 countries. Twenty cases of fetal resuscitation during fetal surgery during the last 5 years were reported across 10 centers. Four cases of emergency delivery during fetal surgery after maternal and/or fetal complications during the last 5 years were reported across 3 centers. Fewer than half the 28 centers (n = 12 [43%]) had policies in place to support practice in the event of either imminent fetal death (during or after fetal surgery) or the need for emergency fetal delivery during fetal surgery. Twenty of 24 centers (83%) reported preoperative parental counseling on the potential need for fetal resuscitation prior to fetal surgery. The gestational age at which centers would attempt neonatal resuscitation after emergency delivery varied from 22 weeks and 0 days to more than 28 weeks. In this global survey study of 28 fetal surgical centers, there was no standard practice about how fetal resuscitation or subsequent neonatal resuscitation was managed during open spina bifida repair. Further collaboration between professionals and parents is required to ensure sharing of information to support knowledge development in this area.

Analysis of genetic etiology and related factors in 1 065 women with spontaneous abortions

To explore the genetic etiology and related factors in 1 065 women with spontaneous abortions. All patients have presented at the Center of Prenatal Diagnosis of Nanjing Drum Tower Hospital from January 2018 to December 2021. Chorionic villi and fetal skin samples were collected, and the genomic DNA was assayed by chromosomal microarray analysis (CMA). For 10 couples with recurrent spontaneous abortions but normal CMA results for abortive tissues, non-in vitro fertilization-embryo transfer (IVF-ET) pregnancies and no previous history of live births and no structural abnormalities of the uterus, peripheral venous blood samples were collected. Genomic DNA was subjected to trio-whole exome sequencing (trio-WES). Candidate variants were verified by Sanger sequencing and bioinformatics analysis. Multifactorial unconditional logistic regression analysis was carried out to analyze the factors that may affect chromosomal abnormality in spontaneous abortions, such as the age of the couple, number of previous spontaneous abortions, IVF-ET pregnancy and history of live birth. The incidence of chromosomal aneuploidies in spontaneous abortions during the first trimester was compared in young or advanced-aged patients by chi-square test for liner trend. Among the 1 065 spontaneous abortion patients, 570 cases (53.5%) of chromosomal abnormalities were detected in spontaneous abortion tissues, which included 489 cases (45.9%) of chromosomal aneuploidies and 36 cases (3.4%) of pathogenic/likely pathogenic copy number variations (CNVs). Trio-WES results have revealed one homozygote variant and one compound heterozygote variants in two pedigrees, both of which were inherited from the parents. One likely pathogenic variant was detected in the patient from two pedigrees. Multifactorial unconditional Logistic regression analysis suggested that age of patient was an independent risk factor of chromosome abnormalities (OR = 1.122, 95%CI: 1.069-1.177, P < 0.001), the number of previous abortions and IVF-ET pregnancy were independent protective factors for chromosomal abnormalities (OR = 0.791, 0.648; 95%CI: 0.682-0.916, 0.500-0.840; P = 0.002, 0.001), whilst the age of husband and history of live birth were not (P > 0.05). The incidence of aneuploidies in the abortive tissues has decreased with the number of previous spontaneous abortions in young patients (χ² = 18.051, P < 0.001), but was not significantly correlated with the number of previous spontaneous abortions in advanced-aged patients with spontaneous abortions (P > 0.05). Chromosomal aneuploidy is the main genetic factor for spontaneous abortion, though CNVs and genetic variants may also underlie its genetic etiology. The age of patients, number of previous abortions and IVF-ET pregnancy are closely associated with chromosome abnormalities in abortive tissues.

Follow-up of fetuses with de novo copy number variations of unknown significance detected by chromosomal microarray analysis

To analyze the prognosis of fetuses identified with de novo variants of unknown significance (VOUS) by chromosome microarray analysis (CMA). A total of 6 826 fetuses who underwent prenatal CMA detection at the Prenatal Diagnosis Center of Drum Tower Hospital from July 2017 to December 2021 were selected as the study subjects. The results of prenatal diagnosis, and outcome of fetuses identified with VOUS of de novo origin were followed up. Among the 6 826 fetuses, 506 have carried VOUS, of which 237 were detected for the parent-of-origin and 24 were found to be de novo. Among the latters, 20 were followed up for 4 to 24 months. Four couples had opted elective abortion, 4 had developed clinical phenotypes after birth, and 12 were normal. Fetuses with VOUS should be continuously follow-up, in particular those carrying de novo VOUS, in order to clarify their clinical significance.

Value of chromosomal microarray analysis for the diagnosis of fetuses with anomalies of central nervous system

To assess the value of chromosomal microarray analysis (CMA) for the diagnosis of fetuses with anomalies of the central nervous system (CNS) and summarize the outcome of the pregnancies and follow-up. A total of 636 fetuses from June 2014 to December 2020 who were referred to the Prenatal Diagnosis Center of Nanjing Drum Tower Hospital due to abnormal CNS prompted by ultrasound were selected as the research subjects. Based on the ultrasound findings, the fetuses were divided into ventricular dilatation group (n = 441), choroid plexus cyst group (n = 41), enlarged posterior fossa group (n = 42), holoprosencephaly group (n = 15), corpus callosum hypoplasia group (n = 22), and other anomaly group (n = 75). Meanwhile, they were also divided into isolated (n = 504) and non-isolated (n = 132) groups based on the presence of additional abnormalities. Prenatal samples (amniotic fluid/chorionic villi/umbilical cord blood) or abortus tissue were collected for the extraction of genomic DNA and CMA assay. Outcome of the pregnancies and postnatal follow-up were summarized and subjected to statistical analysis. In total 636 fetuses with CNS anomalies (including 89 abortus tissues) were included, and 547 cases were followed up. The overall detection rate of CMA was 11.48% (73/636). The detection rates for the holoprosencephaly group, ACC group, choroid plexus cyst group, enlarged posterior fossa group, ventricular dilatation group and other anomaly group were 80% (12/15), 31.82% (7/22), 19.51% (8/41), 14.29% (6/42), 7.48% (33/441) and 9.33% (7/75), respectively. Compared with the isolated CNS anomaly group, the detection rate for the non-isolated CNS anomaly group was significantly higher (6.35% vs. 31.06%) (32/504 vs. 41/132) (χ² = 62.867, P < 0.001). Follow up showed that, for 52 fetuses with abnormal CMA results, 51 couples have opted induced labor, whilst 1 was delivered at full term with normal growth and development. Of the 434 fetuses with normal CMA results, 377 were delivered at full term (6 had developmental delay), and 57 couples had opted induced labor. The rate of adverse pregnancy outcome for non-isolated CNS abnormal fetuses was significantly higher than that of isolated CNS abnormal fetuses (26.56% vs. 10.54%) (17/64 vs. 39/370) (χ² = 12.463, P < 0.001). Fetuses with CNS anomaly should be tested with CMA to determine the genetic cause. Most fetuses with negative CMA result have a good prognosis, but there is still a possibility for a abnormal neurological phenotype. Fetuses with CNS abnormalities in conjunct with other structural abnormalities are at increased risk for adverse pregnancy outcomes.

Molecular genetic characteristics of a family which coinheritance of rare-88 C>G (HBB:c.-138 C>G) β-thalassemia mutation with α-thalassemia and review of the literature

The molecular genetic characteristics of a family with rare -88 C>G (HBB: c.-138 C>G) β-thalassemia gene mutation were studied using cohort study. The cohort study was conducted from June to August 2022 by Prenatal Diagnosis Center of Sanya Women and Children's Hospital Managed by Shanghai Children's Medical Center. The phenotype and genotype were analyzed by hematological cytoanalyzer, automatic electrophoretic analysis system, and next-generation sequencing (NGS). And then, Sanger sequencing was used to verify the rare gene results. The results showed that the proband, her father, her uncle and her younger male cousin had discrete microcytosis (MCV 70.1 fl, 71.9 fl, 73.1 fl and 76.6 fl, respectively) and hypochromia (MCH 21.5 pg,22.0 pg,22.6 pg and 23.5 pg, respectively), elevated hemoglobin A2 level (5.3%, 5.4%, 5.4% and 5.5%, respectively), slightly elevated or normal fetal hemoglobin (Hb F), but no anemia. The proband was identified to have co-inherited ɑ-thalassemia (Hb Westmead gene heterozygous mutation, ɑwsɑ/ɑɑ) and β-thalassemia with a rare -88 C>G (HBB: c.-138 C>G) heterozygous mutation (β-88 C>G/βN). Her mother had the same α-thalassemia as the proband. Her father, her uncle and her younger male cousin had the same rare -88 C>G heterozygous mutations as the proband. While her grandmother and younger brother were not carrier of thalassemia. In conclusion, 4 cases of rare -88 C>G(HBB:c.-138 C>G) heterozygous mutation had been detected in a Chinese family. Carriers of this beta-thalassemia are clinically asymptomatic. This study enriches the knowledge of the thalassemia mutation spectrum in Chinese people and provides valuable information for genetic counseling, prenatal diagnosis, and prevention of thalassemia, providing a scientific basis for improving the quality of birth population and preventing birth defects.

Applying and assessing the PEERS model on genetic counseling training in China: A mixed-method approach.

Due to the changing medical demands in the healthcare system, there is a need for a standardized and professionalized curriculum for genetic counselors. This mixed-method study will observe and evaluate the first Peer Experiential and Reciprocal Supervision (PEERS) training program on genetic counseling among medical practitioners in China; to provide feedback and recommendation for future training and practices. A genetic counselor training program was held from December 10-11, 2016 in a fetal medicine unit and prenatal diagnosis center in Shanghai with 59 participants from clinical centers, hospitals, and organizations in China. An ethnographic reflexive assessment with a structured questionnaire were used to provide insights and feedback on the training experience. Results indicate an inadequate mastery of genetic and fetal knowledge; lack of empathetic understanding and cultural sensitivity; difficulties in adopting a non-directive counseling approach; distance between reality and fictionality in the training; overall training's helpfulness. The professionalization of genetic counseling in China is in the making with the soaring demands for genetic counseling services; this first experiment of PEERS training turned out to be needed, worth to be adapted toward medical centers across China, to better understand and face the challenges rising from genetic counseling practice.

Relevance of Fetal Brain Magnetic Resonance Imaging Compared to Ultrasound for Detecting Cerebral Anomalies in Fetuses with Cleft Lip and/or Palate: A Cohort Study

Introduction: Relevance of fetal brain magnetic resonance imaging (MRI) in cases of cleft lip and/or palate (CL/P) is still discussed to date. The aim of our study was to review the contribution of fetal brain MRI for detecting cerebral anomalies in cases of CL/P comparing antenatal data with neonatal outcomes. Methods: A retrospective multicenter study was conducted from January 2010 to October 2020 in two multidisciplinary prenatal diagnosis centers among women with a fetal ultrasound (US) diagnosis of CL/P. Prenatal imaging and genetic analysis data were collected, as well as postnatal data, including outcomes of children who had an abnormal prenatal MRI. Results: Among the 202 fetuses with a US diagnosis of CL/P, 96 underwent US and fetal brain MRI. 19 brain MRIs were found to be abnormal: 14 (73.7%) involved CL/P associated with other US abnormalities and five (26.3%) involved isolated clefts, of which four were cleft lip and alveolus and secondary palate (CLP). MRI identified severe abnormalities that changed the prognoses of 3 cases of clefts associated with other US abnormalities. In contrast, MRI found only minor abnormalities for the five isolated clefts, with no postnatal disorders found in these children. Conclusion: Fetal brain MRI should be proposed in cases of clefts associated with other anomalies or if US examination is limited by local conditions. MRI could also be discussed in cases of isolated CLP but should not be performed in cases of isolated cleft lip.

Retrospective analysis for 424 330 first-line screening results of non-invasive prenatal testing in Hebei province

Objective: To evaluate the effect of noninvasive prenatal testing (NIPT) as first-line screening in fetal chromosome aneuploidy screening practice, and to provide evidence for the prevention and control strategy of birth defects. Methods: Since July 2019, Hebei province had carried out the NIPT project providing first-line screening for eligible pregnant women in the area (except for those who were not applicable). Pregnant women with high risk received genetic counseling, prenatal diagnosis and intervention guidance. Low risk and false-positive ones received continuous detection and moved to prenatal diagnosis center for counseling and diagnosis if abnormities were discovered. All pregnant women were followed up to learn about pregnancy outcomes and newborn health status. Detection results and clinical data of pregnant women participating the NIPT project from July 2019 to July 2020 were collected. The detection results and effect of NIPT were analyzed. Results: (1) Basic information of the screened population: A total of 424 330 pregnant women were screened, and 423 596 were successfully detected, with a success rate of 99.83% (423 596/424 330). The age of pregnant women was (28.8±4.5) years old; the gestational age of screening was (16.6±2.3) weeks; the proportion of advanced-age pregnant women (≥35 years old) was 10.18% (43 132/423 596); in vitro fertilization-embryo transfer (IVF-ET) rate was 1.58% (6 713/423 596); the twin rate was 1.38% (5 849/423 596); the proportion of primipara was 34.23% (144 977/423 596). (2) Screening results and detection performance: totally, 325, 73 and 20 pregnant women were diagnosed with trisomy 21, 18 and 13; the sensitivity were 99.39%, 100.00% and 100.00%; the specificity were 99.98%, 99.99% and 99.98%; the positive predictive value were 75.76%, 68.87% and 21.51%, respectively. Besides, 249 190 pregnant women were received supplementary reports as well, and 255, 10 and 9 were confirmed for sex chromosome aneuploidy, other autosomal aneuploidy and deletion/duplication syndrome; the positive predictive value were 37.78%, 6.06% and 32.14%, respectively. The sensitivity of NIPT for target trisomy (trisomy 21, 18 and 13) screening in advanced-age, IVF-ET and twin pregnant women were 99.29%, 100.00% and 90.00%, respectively; the specificity were 99.93% for all; the positive predictive value were 82.25%, 61.54% and 69.23%, respectively. Conclusions: NIPT has a significant effect and good performance in the first-line screening of fetal chromosome aneuploidy in the whole population, which might provide reference for the improvement of birth defect prevention and control strategy.

Fetal Megacystis in the first trimester: Comparing management and outcomes between longitudinal bladder length groups

Fetal megacystis is a sonographic sign, defined in first trimester as a longitudinal bladder length (LBD)>7 mm. Different causes may be associated with megacystis and outcomes vary with many factors. There are no international guidelines on how to manage megacystis cases, and invasive testing is controversial when no other abnormalities are found. The main objective of this study is to compare etiologies, management and outcomes of fetuses with first trimester megacystis, specifically between groups of LBD≤15 mm and >15 mm. This is a retrospective cohort study of megacystis cases managed in a Prenatal Diagnosis Center, between January 2009 and September 2020. Descriptive and bivariate analysis were performed. We studied 43 fetuses: 67.4% with LBD≤15 mm and 32.6% with LBD>15 mm. We found an association between LBD and isolated Low Urinary Tract Obstruction (LUTO) (3.4% vs 64.3%; p<0.001) and with isolated megacystis (44.8% vs 0.0%; p = 0.001). No differences were seen regarding the presence of aneuploidies (31.0% vs 14.3%; p = 0.213). Invasive testing was performed in 93.0% of cases. Overall, we report 41.9% of live births, 39.5% of pregnancy termination and 18.6% of intrauterine fetal demise. We found a higher rate of live births in fetuses with LBD≤15 mm (55.2% vs 14.3%; p = 0.011). For a mean follow-up time of 20.6 months, we report one neonatal death and one case of renal insufficiency. In conclusion, isolated LUTO is more frequent if LBD>15 mm whereas isolated megacystis is more frequently found if LBD≤15 mm. If LBD≤15 mm, live birth rates and long-term outcomes seem to be enhanced.

Perinatal outcomes of prenatal cases testing positive for trisomy 9 by noninvasive prenatal testing

ObjectivesTo evaluate the performance of non-invasive prenatal testing (NIPT) for the detection of fetal trisomy 9 in prenatal screening and to investigate the prenatal appearances and genetic counseling of trisomy 9 fetuses. Materials and methodsThe ultrasonography information, laboratory detection and pregnancy outcome of 16 cases of single pregnancy with trisomy 9 identified by NIPT who received amniocentesis in our prenatal diagnosis center from January 2018 to December 2020 were retrospectively analyzed. ResultsAmong the 16 cases, 2 cases of trisomy 9, 3 cases of trisomy 9 mosaicism, 2 cases reporting of regions of homozygosity and 9 cases of false positive were diagnosed. Among the true positive cases, 4 cases showed abnormal ultrasonic finding: 3 cases terminated pregnancy and 1 case was lost to follow-up. Another 1 case was in utero fetal demise in the second trimester without structural abnormality, and 2 cases were normal live birth without developmental abnormalities. In the 9 cases with normal kayrotyping, 1 case had termination of pregnancy and 1 case with mental retardation and poor cognitive ability, other 7 had good pregnancy outcomes. ConclusionOur results may be helpful for the selection of prenatal diagnostic strategies and genetic counseling for pregnant women with trisomy 9 revealed by NIPT.

Prenatal diagnosis of Bardet‑Biedl syndrome due to novel variants in the BBS10 gene in a fetus with multiple anomalies: A case report

Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by obesity, mental retardation, retinal dystrophy, hypogenitalism and renal and polydactyly malformations. The last two malformations may be observed antenatally and are highly variable, making the prenatal diagnosis of BBS challenging. The present study investigated the molecular etiology of BBS and validated a method for prenatal diagnosis. A Chinese couple who had conceived two fetuses with multiple malformations, including hyperechogenic kidneys, polydactyly, cardiac malformation and abdominal abnormalities, presented at the Prenatal Diagnosis Center of Boai Hospital of Zhongshan Affiliated to Southern Medical University (Zhongshan, China) in November 2018. BBS was suspected and whole-exome sequencing was performed for the second fetus. Two novel compound heterozygous variants were detected in the BBS10 gene, c.784_785delGA from the father and c.1812dupT from the mother, which are probably causative of the pathogenesis of BBS. This finding provided a basis for genetic counseling and prenatal diagnosis for the couple and enriched the variation spectrum of the BBS10 gene. The ultrasonic findings of the fetal abdomen are the first reported in fetuses with BBS, expanding the antenatal phenotypes of BBS.

Should prenatal chromosomal microarray analysis be offered for isolated ventricular septal defect? A single-center retrospective study from China.

ObjectiveTo evaluate the utility of chromosomal microarray analysis (CMA) in fetuses with isolated ventricular septal defect (VSD) and to explore the favorable factors for predicting spontaneous closure of defects.MethodsThe study included 436 singleton pregnancies seen at a referral prenatal diagnosis center, between January 2016 and May 2020, of which 168 fetuses with isolated VSD were diagnosed in the prenatal setting. VSD was classified as an isolated VSD whether it had ultrasound soft markers or not. All patients underwent testing employing quantitative fluorescent polymerase chain reaction (QF-PCR) and CMA as the first-line genetic detection strategies, mainly in amniotic fluid and umbilical blood samples. Rates of chromosomal abnormalities were compared by subgroups of isolated VSD (muscular or perimembranous). Binary logistic regression analysis was performed to predict the independent determinants of spontaneous closure by 2 years.ResultsOverall, the CMA identified clinically significant copy number variations (CNVs) in 7/168 (4.2%) fetuses and variants of unknown significance (VOUS) in 15/168 (8.9%). Muscular and perimembranous VSDs were found in 53.6 and 46.4%, respectively. Clinically significant relevant subchromosomal aberrations were revealed in seven (9.0%) perimembranous VSDs compared with none in 90 muscular defects (P < 0.01). The median initial size of the defect in the muscular VSDs was 2.2(1.8–2.7) mm, as compared to that of 2.8 (2.2–3.2) mm in the perimembranous VSDs group (p = 0.000). In muscular vs. perimembranous VSDs, spontaneous closure occurred more frequently and earlier [40.0 vs. 15.4% in utero (p = 0.000), 61.1 vs. 30.8% at 1-year (p = 0.000), and 75.6 vs. 42.3% at 2-year (P = 0.000)]. Postnatal surgical closure was warranted in 4/90 (4.4%) of the infants with muscular VSDs, as compared to 29/71 (40.8%) with perimembranous defects (p = 0.000). Furthermore, isolated muscular type VSD, smaller defect size, and maternal age of less than 35 years are all positive predictors of spontaneous closure of the defects.ConclusionThis study highlighted the value of microarray for unbalanced subchromosomal abnormalities in fetuses with isolated VSD, particularly in the perimembranous defects. The detection of an isolated muscular VSD prenatally may be considered a benign or likely benign finding; in contrast, for perimembranous VSD, a prenatal CMA should be offered.