Prenatal Diagnosis Research Articles

Factors of poor prognosis in newborns with a prenatal diagnosis of gastroschisis in Bogota, Colombia.

To identify factors associated with poor prognoses in newborns with a prenatal diagnosis of gastroschisis in eight hospitals in Bogota, Colombia, from 2011 to 2022. A multi-center retrospective case-control study was conducted on newborns with gastroschisis in eight hospitals in Bogota, Colombia. Poor prognosis was defined as the presence of sepsis, intestinal complications, or death. The study included 101 patients. Preterm newborns under 32weeks had a poor neonatal prognosis (OR 6.78 95 % CI 0.75-319). Oligohydramnios (OR 4.95 95 % CI 1.15-21.32) and staged closure with silo (OR 3.48; 95 % CI 1.10-10.96) were risk factors for neonatal death, and intra-abdominal bowel dilation of 20-25 mm was a factor for the development of intestinal complications (OR 3.22 95 % CI 1.26-8.23). Intra-abdominal bowel dilation between 20 and 25 mm was associated with intestinal complications, while oligohydramnios was associated with the risk of perinatal death, requiring increased antenatal surveillance of fetal wellbeing. Management with primary reduction when technically feasible is recommended in these infants, considering that the use of silos was associated with higher mortality.

Creatine Kinase-MM/Proto-oncogene Tyrosine-Protein Kinase Receptor as a Sensitive Indicator for Duchenne Muscular Dystrophy Carriers.

Duchenne muscular dystrophy (DMD), a lethal X-linked recessive genetic disease, is characterized by progressive muscle wasting which will lead to premature death by cardiorespiratory complications in their late twenties. And 2.5-19% DMD carriers that also suffer from skeletal muscle damage or dilated cardiomyopathy when diagnosed as soon as possible is meaningful for prenatal diagnosis and advance warning for self-health. The current DMD carrier screening mainly relies on detecting serum creatine kinase activity, covering only 50-70% DMD carriers which will cause many false negatives and require the discovery of highly effective biomarker and simple detection procedure for DMD carriers. In this article, we have compiled a comprehensive summary of all documented biomarkers associated with DMD and categorized them based on their expression patterns. We specifically pinpointed novel DMD biomarkers, previously unreported in DMD carriers, and conducted further investigations to explore their potential. Compared to creatine kinase activity alone in DMD carriers, creatine kinase-MM can improve the specificity from 73 to 81%. And our investigation revealed another promising protein: proto-oncogene tyrosine-protein kinase receptor (RET). When combined with creatine kinase-MM (creatine kinase-MM/RET ratio), it significantly enhances the specificity (from 81 to 83%) and sensitivity (from71.4 to 93%) of detecting DMD carriers in serum. Moreover, we successfully devised an efficient method for extracting RET from dried blood spots. This breakthrough allowed us to detect both creatine kinase-MM and RET using dried blood spots without compromising the detection rate.

Agenesis of the ductus venosus and fetal growth restriction: Is there a relation? A tertiary care center experience and systematic review of the literature.

An update on the antenatal diagnosis of agenesis of ductus venosus (ADV) by differentiating the various possible types of shunts, focusing on the associated fetal anomalies, and predicting neonatal outcomes. This study reviewed the experience of two tertiary referral centers and literature. An unfavorable outcome was detected in preterm fetuses (p = 0.017), fetuses with a genetic anomaly (p = 0.046) or other associated malformations (p < 0.001). 71% of ADVs with other anomalies had an extrahepatic ADV (p = 0.002). 76% of fetuses with Fetal Growth Restriction (FGR) had an extrahepatic ADV (p = 0.025). ADV may negatively influence fetal growth in cases with extrahepatic vein drainage.

Large regions of homozygosity in prenatal diagnosis.

Chromosomal microarrays (CMA) incorporate single nucleotide polymorphisms to enable the detection of regions of homozygosity (ROH). Here, we retrospectively analyzed 6288 prenatal cases who performed CMA to explored the clinical implications of large ROH in prenatal diagnosis. We analyzed cases with ROH larger than 10 megabases and reviewed the ultrasound findings; karyotype results and pregnancy follow-up data. Cases with possible imprinting disorders were assessed by methylation-specific multiplex ligation-dependent probe amplification. In total, we identified 50 cases with large ROH and chromosomes 1 and 2 were the most affected. About 59.18% of the ROH cases had ultrasound abnormalities, with the most common findings being ultrasound soft-marker abnormalities. There were seven fetuses had ROH which covered almost the entire chromosome and four had terminal ROH that involved almost the entire long arm of the chromosomes, which indicated uniparental disomy (UPD), of which 70% showed abnormal ultrasound findings. Ten cases with multiple ROH on different chromosomes indicated the third to fifth degree of consanguinity. In this study, we highlighted the clinical relevance of large ROH related to UPD. The analysis of ROH allowed us to gain further understanding of complex cytogenetic and disease mechanisms in prenatal diagnosis.

Prenatal diagnosis of Silver–Russell syndrome with 8q12 deletion including the PLAG1 gene: a case report and review

Prenatal diagnosis of Silver–Russell syndrome with 8q12 deletion including the PLAG1 gene: a case report and review

Investigation of health inequities in maternal and neonatal outcomes of patients with placenta accreta spectrum: a multicenter study.

Placenta accreta spectrum (PAS) is associated with significant maternal and neonatal morbidity and mortality. There is limited established data on healthcare inequities in outcomes of patients with PAS. To investigate health inequities in maternal and neonatal outcomes of pregnancies with PAS. This multicentered retrospective cohort study included patients with histopathological diagnosis of PAS at four regional perinatal centers between 1/1/2013 - 6/30/2022. Maternal race and/or ethnicity were categorized as either Hispanic, non-Hispanic Black, non-Hispanic White, or Asian or Pacific Islander. Primary outcome was a composite adverse maternal outcome: transfusion of 4+ units of packed red blood cells, vasopressor use, mechanical ventilation, bowel or bladder injury or mortality. Secondary outcomes were composite adverse neonatal outcome (APGAR < 7 at 1-minute, morbidity, or mortality), gestational age at PAS diagnosis, and planned delivery by a multidisciplinary team. Multivariable logistic regression was used to estimate the associations of race/ethnicity with maternal and neonatal outcomes. 408 pregnancies with PAS were included. In 218 patients (53%), the diagnosis of PAS was made antenatally. Patients predominantly self-identified as non-Hispanic White (31.6%) or non-Hispanic Black (24.5%). After adjusting for institution, age, BMI, income and parity, there was no difference in composite adverse maternal outcome among racial and ethnic groups. Similarly, adverse neonatal outcomes, gestational age at prenatal diagnosis, rate of planned delivery by a multidisciplinary team and cesarean hysterectomy were similar between groups. In our multicenter PAS cohort, race and/or ethnicity were not associated with inequities in composite maternal or neonatal morbidity, timing of diagnosis and planned multi-disciplinary care. We hypothesize that comparable incidence of individual risk factors for perinatal morbidity as well as geographic proximity reduce potential inequities that may exist in the larger population.

Clinical and radiological evaluation of caudal regression syndrome.

Caudal regression syndrome is a form of segmental spinal dysgenesis involving the caudal spinal column, ranging from segmental coccygeal agenesis to extensive thoracolumbar agenesis with varying degrees of spinal cord dysgenesis. A majority of caudal regression cases are sporadic but maternal pre-gestational diabetes mellitus is an important risk factor. Imaging is an integral part of management of caudal regression syndrome. Antenatal diagnosis on obstetric ultrasound and evaluation with fetal MRI is ideal. Early postnatal diagnosis and/or detailed evaluation with MRI is essential for early management to improve outcomes. Pang classification categorizes caudal regression syndrome into two categories based on the position of the conus while Renshaw classification is based on the degree of vertebral column agenesis. Caudal regression syndrome may be associated with several additional anomalies, both spinal and extraspinal. A number of genitourinary and gastrointestinal anomalies have been described in association with caudal regression syndrome. The field of view of MRI of the lumbosacral spine in caudal regression syndrome needs to be extended to visualize the retroperitoneal structures without the use of a saturation band. Syndromic associations may be suspected, and additional imaging performed, based on findings of extended field of view MRI of the spine. Associated sacral masses and filar abnormalities need to be identified and may also require surgical treatment. The multisystem nature of this disease necessitates a multimodality approach to the evaluation and management of caudal regression syndrome with close cooperation between pediatric neuroradiologists and body radiologists as well as multiple clinical teams. Appropriate early management with surgical correction as necessary can significantly improve prognosis and survival in caudal regression syndrome.

Prenatal diagnosis of fetal neck mass.

Prenatal diagnosis of fetal neck mass.

Images of Extremely Rare Cantrell Phenomenon

We present a case of a neonate born with prenatal diagnosis of Cantrell syndrome and ectopia cordis. This extremely rare congenital disorder underscores the significant need for multimodality imaging to plan further management. The aim of the study was to present the thoracoabdominal syndrome using a three-dimensional computed tomography angiography. The CT scans confirmed complex intracardiac defects consisting of tetralogy of Fallot, total anomalous pulmonary venous return and persistent left superior vena cava. In conclusion, Cantrell syndrome necessitates a multidisciplinary approach, from the onset of the prenatal diagnosis followed by prompt medical imaging and surgical interventions after birth. The thoracoabdominal wall defect including complete ectopia cordis is an extremely rare disorder with a fatal outcome.

Expectant management for umbilical artery thrombosis in the third trimester of pregnancy: a case report

BackgroundUmbilical artery thrombosis (UAT) is a rare complication of pregnancy and is associated with adverse pregnancy outcomes, including fetal intrauterine distress, intrauterine growth restriction, and still birth. UAT is unpredictable, and prenatal diagnosis is challenging. There is no consensus on the treatment strategy of UAT, especially for patients with prenatal detection of one of the umbilical artery embolisms. In most previous cases, an emergency cesarean section was performed, or intrauterine fetal death occurred at the time of UAT diagnosis.Case presentationIn this report, we describe a case of thrombosis in one of the umbilical arteries detected by routine ultrasonography at 31+3 weeks of gestation in a 34-year-old woman. Following expectant management with intensive monitoring for 4 four days, an emergency cesarean section was performed because of abnormal fetal umbilical cord blood flow and middle cerebral artery blood flow; the newborn was in good condition at birth. The final umbilical cord histopathology revealed thrombosis in one of the umbilical arteries. Both mother and newborn described in this case underwent long-term follow-up for nearly 2 two years and are currently in good health without any complications.ConclusionsBased on our experience, obstetricians should comprehensively consider the current gestational age and fetal intrauterine status when UAT is suspected to determine the best delivery time. The appropriate gestational age should be prolonged as long as the mother and fetus are stable when the fetus is immature, trying our best to complete the corticosteroid treatment to promote fetal lung maturity and magnesium sulfate to protect fetal brain. During expectant management, ultrasound monitoring, electronic fetal heart monitoring, and fetal movement counting should be strengthened. Clinicians should ensure that the patients and their families are informed about all potential risks of expectant management for UAT.

Truncus arteriosus from prenatal diagnosis to clinical outcome: a single-centre experience.

The aim of this study was to review our institution's experience with truncus arteriosus from prenatal diagnosis to clinical outcome. and results: We conducted a single-centre retrospective cohort study for the years 2005-2020. Truncus arteriosus antenatal echocardiographic diagnostic accuracy within our institution was 92.3%. After antenatal diagnosis, five parents (31%) decided to terminate the pregnancy. After inclusion from referring hospitals, 16 patients were offered surgery and were available for follow-up. Right ventricle-to-pulmonary artery continuity was preferably established without the use of a valve (direct connection), which was possible in 14 patients (88%). There was no early or late mortality. Reinterventions were performed in half of the patients at latest follow-up (median follow-up of 5.4 years). At a median age of 5.5 years, 13 out of 14 patients were still without right ventricle-to-pulmonary artery valve, which was well tolerated without signs of right heart failure. The right ventricle demonstrated preserved systolic function as expressed by tricuspid annular plane systolic excursion z-score (-1.4 ± 1.7) and fractional area change (44 ± 12%). The dimensions and function of the left ventricle were normal at latest follow-up (ejection fraction 64.4 ± 6.2%, fractional shortening 34.3 ± 4.3%). This study demonstrates good prenatal diagnostic accuracy of truncus arteriosus. There was no mortality and favourable clinical outcomes at mid-term follow-up, with little interventions on the right ventricle-to-pulmonary artery connection and no right ventricle deterioration. This supports the notion that current perspectives of patients with truncus arteriosus are good, in contrast to the poor historic outcome series. This insight can be used in counselling and surgical decision-making.

Introduction: A Practical Guide to Central Nervous System Malformations—From Genetics, to Diagnosis and Treatment

AbstractCentral nervous system (CNS) malformations encompass diverse congenital anomalies impacting brain and spinal cord development, profoundly affecting neurological function. They arise from disruptions in embryonic neural tube formation, neuronal migration, and cortical organization. This abstract provides a comprehensive overview of CNS malformations, covering classification, etiology, clinical manifestations, and diagnostic challenges. CNS malformations fall into distinct groups: neural tube defects (e.g., anencephaly, spina bifida), resulting from incomplete neural tube closure; malformations of cortical development (e.g., lissencephaly, polymicrogyria), featuring irregularities in cortical folding; and anomalies affecting structures like the corpus callosum, cerebellum, and CNS vasculature, alongside conditions such as hydrocephalus and Chiari malformations. Genetic factors, including mutations in LIS1, DCX, and RELN, contribute significantly, while environmental factors like maternal folic acid deficiency also play a role. Some malformations occur in genetic syndromes (e.g., tuberous sclerosis, neurofibromatosis). Clinical presentations vary, with neural tube defects typically presenting severe deficits at birth, while cortical malformations manifest as intellectual disabilities, seizures, and motor deficits. Hydrocephalus elevates intracranial pressure, and Chiari malformations cause headaches and neurological symptoms. Diagnosis necessitates a multidisciplinary approach involving clinical evaluation, neuroimaging, genetic testing, and histopathological analysis. Prenatal diagnosis via ultrasound and magnetic resonance imaging is crucial for planning interventions, while postnatal diagnosis relies on clinical and imaging findings.Understanding CNS malformations is vital for early detection, intervention, and comprehensive care provision. Advances in genetics and neuroimaging offer hope for improved outcomes and better quality of life for affected individuals.

Insight into the research history and trends of total anomalous pulmonary venous connection: a bibliometric analysis

BackgroundTotal anomalous pulmonary venous connection (TAPVC) is a rare congenital heart disease characterized by the inability of all pulmonary veins to connect to the left atrium. Our previous bibliometric article summarized the characteristics of only the 100 most cited papers in TAPVC research. The purpose of this study was to use comprehensive bibliometric analysis to examine the development history, current status, and future trends in the field of TAPVC.MethodsAll publications on TAPVC published between 2000 and 2023 were collected from the Web of Science Core Collection. The publication and citation data were quantitatively analyzed by publication year, country, institution, author, and journal. Co-authorship and co-occurrence analyses were performed using VOSviewer, and keyword and reference bursts were identified using CiteSpace. Pearson’s test was used to examine the correlations between two continuous variables.ResultsAs of July 20, 2023, we identified 368 publications with 3320 citations. These publications were published in 132 journals and authored by 1835 researchers from 457 institutions in 47 countries. For the number of publications, the top country, top institution, top author, and top journals were the United States (n = 82), Shanghai Jiao Tong University (n = 13), Huiwen Chen (n = 9), and Annals of Thoracic Surgery and Pediatric Cardiology (n = 29 each), respectively. For the number of citations, the top country, top affiliation, top author, and top journal were the United States (n = 1348), University of Toronto (n = 250), Christopher A. Caldarone (n = 315), and Annals of Thoracic Surgery (n = 746), respectively. The number of national publications significantly correlated with GDP (R = 0.887, P < 0.001), research & development (R&D) expenditure (R = 0.375, P = 0.013), population (R = 0.694, P < 0.001), and journals (R = 0.751, P < 0.001). The number of national citations significantly correlated with GDP (R = 0.881, P < 0.001), R&D expenditure (R = 0.446, P = 0.003), population (R = 0.305, P = 0.037), and journals (R = 0.917, P < 0.001). International collaboration in the field of TAPVC was not well developed. The most commonly cited publication discussed era changes in mortality and reoperation rate in TAPVC patients. The most common keywords were “total anomalous pulmonary venous connection” and “congenital heart disease”. The keyword “case report” appeared most recently, with an average occurrence year of 2021.8. The co-occurrence analysis grouped 26 keywords into six themes: surgical repair of TAPVC, postoperative pulmonary vein stenosis, surgical repair of TAPVC patients with heterotaxy, application of echocardiography in diagnosing TAPVC, application of echocardiography in the prenatal diagnosis of TAPVC, and application of the sutureless technique in the surgical repair of TAPVC patients with right atrial isomerism or a single ventricle. Citation burst detection identified 32 references with citation bursts, seven of which had ongoing citation bursts until 2023.ConclusionsThis study conducted a bibliometric analysis to provide a comprehensive overview of TAPVC research. We hope to offer new ideas for promoting development in the field of TAPVC.

Genetic analysis of a fetus with cryptophthalmos due to variants of FREM2 gene

To explore the genetic etiology of a fetus with cryptophthalmos detected by prenatal ultrasonography. A fetus undergoing induced labor at 32nd gestational week due to absence of bilateral eye fissures detected by prenatal ultrasonography in January 2017 was selected as the study subject. Umbilical cord blood sample from the fetus and peripheral blood samples from its parents were collected for the extraction of genomic DNA. Pathogenic variants were screened through whole exome sequencing (WES) and verified by Sanger sequencing. Pathogenicity of candidate variants was verified by bioinformatic analysis and protein structure simulation. Based on the results of genetic testing, prenatal diagnosis was provided to the couple upon their subsequent pregnancy. The couple had four adverse pregnancies previously. The aborted fetus was the fifth, with fused bilateral upper and lower eyelids, poorly developed eyeballs, adhesion of the cornea with the upper eyelid, low-set ears, and abnormal plantar creases, and was diagnosed with cryptophthalmos. WES and Sanger sequencing revealed that the fetus has harbored compound heterozygous variants of the FREM2 gene, namely c.4537G>A (p.D1513N) and c.7292C>T (p.T2431M). Both variants were unreported associated with cryptophthalmos previously. Protein structure simulation showed that they may lead to loss of hydrogen bonds in the protein product. Based on the guidelines from the American College of Medical Genetics and Genomics (ACMG), both variants were predicted to be likely pathogenic (PM1_Supporting+PM2_Supporting+PM5+PP3+PP4; PM2_Supporting+PM3+PP3+PP4). The mother was performed prenatal diagnosis in her sixth pregnancy based on the variants detected in this family, and delivered a daughter with normal phenotype. The FREM2: c.4537G>A and c.7292C>T compound heterozygous variants probably underlay the pathogenesis of cryptophthalmos in this fetus. Above finding has enriched the mutational spectrum of the FREM2 gene.

Prenatal diagnosis of a fetus with 1p36 deletion syndrome and 3p26.3p25.2 duplication

To explore the characteristics of a fetus with chromosome 1p36 deletion syndrome and 3p26.3p25.2 duplication. A pregnant woman who had attended the Genetic Counseling Clinic of Linyi People's Hospital on February 22, 2022 and her fetus were selected as the study subjects. Clinical data were collected. Chromosomal karyotyping, fluorescence in situ hybridization (FISH) and chromosomal microarray analysis (CMA) were carried out for the prenatal diagnosis. Ultrasonography at 24th gestational week revealed that the fetus had ventricular septal defect, single umbilical artery, and slight widening of left lateral ventricle (12 mm). The woman was found to have a karyotype of 46,XX,t(1;3)(p36.22;p25.2), and the result of FISH was t(1;3)(3pter+,1qter+;1pter+,3qter+). The fetus was found to have a karyotype of 46,X?,add(1)(p36), and CMA confirmed that it has a 9.0 Mb deletion at 1p36.33p36.22 and a 12.6 Mb duplication at 3p26.3p25.2. Combining the maternal karyotype, the molecular karyotype of the fetus was determined as 46,X?,der(1)t(1;3)(p36.22;p25.2)mat.arr[hg19]1p36.33p36.22(849467_9882666)×1, 3p26.3p25.2(61892_12699607)×3, with the former known to be associated with 1p36 deletion syndrome. The fetus was diagnosed with 1p36 deletion syndrome, and its 1p36.33p36.22 deletion and 3p26.3p25.2 duplication had both derived from the balanced translocation carried by its mother.

Preimplantation genetic testing for a Chinese pedigree affected with Rett syndrome

To carry out preimplantation genetic testing (PGT) for a Chinese pedigree affected with Rett syndrome (RTT). A pedigree affected with RTT who had presented at the First Hospital of Jilin University on June 4, 2021 was selected as the study subject. Variant of the MECP2 gene was analyzed by next generation sequencing (NGS) and Sanger sequencing. Direct sequencing was also used to determine the carrier status for the c.925C>T variant of the MECP2 gene in the blastocysts, and Sanger sequencing was used to validate the results. The MECP2 gene and 168 effective single nucleotide polymorphism (SNP) loci within 2 Mb ranges up- and downstream of the gene were used to construct a haplotype for analyzing the variant site in the embryos, and embryos without the variant were subjected to the analysis for chromosomal aneuploidies. PGT analysis revealed that five out of seven blastocysts did not harbor the pathogenic variant. The results of aneuploidy analysis indicated that two out of five blastocysts without the variant were euploid. Following genetic counselling, the couple had opted to transplant the optimal blastocyst. Following clinical pregnancy, prenatal diagnosis showed that the fetus has a normal chromosomal karyotype, and the c.925C>T variant was not detected in the amniotic fluid sample. A healthy girl was born by Cesarean section at full term. NGS can attain efficient PGT detection and reduce the risk of disease recurrence in families affected with RTT.

Genetic analysis of a fetus with Pitt-Hopkins syndrome due to a 18q21.2q21.31 microdeletion

To carry out invasive prenatal diagnosis for a fetus with ultrasound-indicated agenesis of corpus callosum and explore its genetic etiology. A pregnant woman presented at the Affiliated Hospital of Putian College on December 16, 2022 was selected as the study subject. Amniotic fluid and peripheral blood samples from the fetus and the couple were collected. Conventional G-banded chromosomal karyotyping was carried out, and whole-genome copy number variation analysis was performed using single nucleotide polymorphism microarray (SNP-array). The karyotypes of the fetus and the couple were normal by the G-banding analysis. SNP-array analysis of the amniotic fluid sample revealed a 4.5 Mb microdeletion in the 18q21.2q21.31 region of the fetus. SNP-array analysis of peripheral blood samples from the couple did not find any abnormality. Through G-banded chromosomal karyotyping and SNP-array analysis, a fetus with 18q21.2q21.31 microdeletion was identified, which has conformed to the diagnosis of Pitt-Hopkins syndrome. Above finding has provided a basis for genetic counseling for the couple.

Prenatal echocardiography diagnosis of a novel combination of bilateral ductus arteriosus and cardiovascular anomalies: a case report and literature review

BackgroundBilateral ductus arteriosus (BDA) is a relatively rare vascular malformation. According to the double arch theory, BDA is formed when the distal ends of the sixth pairs of primitive arches on the left and right sides have not regressed. We describe a fetus with prenatal echocardiographic findings of BDA and right aortic arch mirror-image branching (RAA-MIB) combined with congenital heart disease. Furthermore, to gain a deeper understanding of the embryological mechanism of BDA, we review the literature on all combinations of BDA present in 40 fetuses/infants.Case summaryA 22-year-old female patient underwent fetal echocardiography at 23 weeks of gestation. Both the two-dimensional (2D) grayscale image and color Doppler flow imaging (CDFI) revealed dextro-transposition of the great arteries combined with a ventricular septal defect and RAA-MIB. The following scan revealed a rare vascular ring, which was identified as BDA extending from the confluent of the left pulmonary artery and right pulmonary artery, completely encircling the trachea to form an “O”-shaped vascular ring before finally converging into the descending aorta. A persistent left superior vena cava was also observed. We subsequently used four-dimensional (4D) color Doppler imaging with the spatiotemporal image correlation (STIC) HD live flow and STIC HD live flow silhouette mode to clearly display ventricular arterial connectivity and the direction of vessel travel. Adjusting the image quality and display angle is very important when applying STIC. The 4D images confirmed our diagnosis. After multidisciplinary counseling and discussion with her family, this female patient decided to terminate the pregnancy.ConclusionOur review of the literature summarized nine combinations classified into three types of BDA and aortic arch pathology. However, our case differs because it is a novel combination of intracardiac structural abnormalities and vascular rings in a fetus. Prenatal ultrasound diagnosis of BDA is important and requires a combination of 2D grayscale, CDFI, and STIC images to assist in scanning.

Prenatal diagnosis and pregnancy outcomes in fetuses with ventriculomegaly

ObjectiveGenetic etiology plays a critical role in fetal ventriculomegaly (VM). However, the studies on chromosomal copy number variants (CNVs) in fetal VM are limited. This study aimed to investigate the chromosomal CNVs in fetuses with mild to moderate VM, and explore its genotype-phenotype correlation.MethodsA total of 242 fetuses with mild to moderate VM detected by prenatal ultrasound were enrolled in our study from October 2018 to October 2022. All cases underwent chromosomal microarray analysis (CMA) and G-banding simultaneously. All VM cases were classified different subgroups according to the maternal age, severity, VM distribution and presence/absence of other ultrasound abnormalities. The pregnancy outcomes and health conditions after birth were followed up. We also performed a pooled analysis regarding likely pathogenic and pathogenic CNVs (LP/P CNVs) for VM.ResultsThe detection rate of chromosomal abnormalities by karyotyping was 9.1% (22/242), whereas it was 16.5% (40/242) when CMA was conducted (P &amp;lt; 0.05). The total detection rate of chromosomal abnormalities by karyotyping and CMA was 21.1% (51/242). A 12.0% incremental yield of CMA over karyotyping was observed. The detection rate of total genetic variants in fetuses with bilateral VM was significantly higher than in fetuses with unilateral VM (30.0% vs. 16.7%, P = 0.017). No significant differences were discovered between isolated VM and non-isolated VM, or between mild and moderate VM, or between advanced maternal age (AMA) and non-AMA (all P &amp;gt; 0.05). 28 fetuses with VM were terminated and 214 fetuses were delivered: one presented developmental delay and one presented congenital heart disease. The VM cases with both positive CMA and karyotypic results had a higher rate of termination of pregnancy than those with either a positive CMA or karyotypic result, or both negative testing results (P &amp;lt; 0.001).ConclusionThe combination of CMA and karyotyping should be adopted to improve the positive detection rate of chromosomal abnormalities for VM. The total genetic abnormalities detected using both techniques would affect the final pregnancy outcomes. LP/P CNVs at 16p11.2, 17p13, and 22q11.21 were identified as the top three chromosomal hotspots associated with VM, which would enable genetic counselors to provide more precise genetic counseling for VM pregnancies.

Machine Learning to Predict Outcomes of Fetal Cardiac Disease: A Pilot Study.

Prediction of outcomes following a prenatal diagnosis of congenital heart disease (CHD) is challenging. Machine learning (ML) algorithms may be used to reduce clinical uncertainty and improve prognostic accuracy. We performed a pilot study to train ML algorithms to predict postnatal outcomes based on clinical data. Specific objectives were to predict (1) in utero or neonatal death, (2) high-acuity neonatal care and (3) favorable outcomes. We included all fetuses with cardiac disease at Sunnybrook Health Sciences Centre, Toronto, Canada, from 2012 to 2021. Prediction models were created using the XgBoost algorithm (tree-based) with fivefold cross-validation. Among 211 cases of fetal cardiac disease, 61 were excluded (39 terminations, 21 lost to follow-up, 1 isolated arrhythmia), leaving a cohort of 150 fetuses. Fifteen (10%) demised (10 neonates) and 65 (48%) of live births required high acuity neonatal care. Of those with clinical follow-up, 60/87 (69%) had a favorable outcome. Prediction models for fetal or neonatal death, high acuity neonatal care and favorable outcome had AUCs of 0.76, 0.84 and 0.73, respectively. The most important predictors for death were the presence of non-cardiac abnormalities combined with more severe CHD. High acuity of postnatal care was predicted by anti Ro antibody and more severe CHD. Favorable outcome was most predicted by no right heart disease combined with genetic abnormalities, and maternal medications. Prediction models using ML provide good discrimination of key prenatal and postnatal outcomes among fetuses with congenital heart disease.