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Archivos Argentinos de Pediatria Apr 2020Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, longterm morbidity and mortality. The... (Review)
Review
Among congenital malformations, heart defects are the most common type of anomaly, and these are associated with a high perinatal, longterm morbidity and mortality. The objective of this update was to review the rate of prenatal detection, screening characteristics throughout the pregnancy, in both the first and second trimesters, indications for advanced echocardiography, and to establish a management algorithm in case of prenatal diagnosis of a congenital heart disease. Potential invasive and non-invasive tests and obstetric follow-up will be discussed here. Finally, the main characteristics of fetal therapy in heart anomalies will be reviewed, both cardiac interventions and intrauterine treatment of arrhythmias.
Topics: Female; Fetal Therapies; Heart Defects, Congenital; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 32199055
DOI: 10.5546/aap.2020.eng.e149 -
Obstetrics and Gynecology Clinics of... Jun 2017The American Congress of Obstetricians and Gynecologists recommends that all pregnant women be offered aneuploidy screening or diagnostic testing. A myriad of screening... (Review)
Review
The American Congress of Obstetricians and Gynecologists recommends that all pregnant women be offered aneuploidy screening or diagnostic testing. A myriad of screening and testing options are available to patients based on their risk profile and gestational age. Screening options include traditional serum analyte screening, such as first-trimester screening or quadruple screening, and more recently, cell-free DNA. Diagnostic testing choices include chorionic villus sampling and amniocentesis. The number of screening and diagnostic modalities complicates prenatal counseling for physicians and can be difficult for patients to grasp. Appropriate pretest and posttest counseling is important to ensure adequate understanding of results and ensure testing strategy is concordant with patient goals.
Topics: Amniocentesis; Aneuploidy; Chorionic Villi Sampling; Counseling; Female; Genetic Testing; Humans; Mass Screening; Pregnancy; Prenatal Diagnosis
PubMed: 28499534
DOI: 10.1016/j.ogc.2017.02.004 -
Australian Family Physician Oct 2017Non-invasive prenatal testing (NIPT), also known as cell-free DNA testing and non-invasive prenatal screening (NIPS), is an important addition to the range of screening...
BACKGROUND
Non-invasive prenatal testing (NIPT), also known as cell-free DNA testing and non-invasive prenatal screening (NIPS), is an important addition to the range of screening tests for fetal chromosomal abnormalities. For trisomy 21 in particular, NIPT is superior to other screening modalities. However, NIPT has limitations and complexities that requesting clinicians and their patients should understand.
OBJECTIVE
This review article will briefly describe the technical basis of NIPT assays and compare the performance characteristics of NIPT with existing screening tests. The clinical use of NIPT will also be discussed.
DISCUSSION
NIPT is now an established option for antenatal screening for trisomy 21, 18, 13 and other selected chromosomal abnormalities. If used appropriately, it increases the detection rate for fetal chromosomal abnormalities, while decreasing the number of invasive tests required. An understanding of the scientific basis of NIPT, and the appropriate clinical use and limitations, will enable medical practitioners to provide optimal antenatal screening.
Topics: Adult; Cell-Free Nucleic Acids; Down Syndrome; Female; Genetic Testing; Humans; Pregnancy; Prenatal Diagnosis; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 29036772
DOI: No ID Found -
Ultrasound in Obstetrics & Gynecology :... Aug 2020
Topics: Adult; Biometry; Female; Fetal Development; Fetal Growth Retardation; Humans; Infant, Newborn; Infant, Small for Gestational Age; Obstetrics; Pregnancy; Prenatal Diagnosis
PubMed: 32738107
DOI: 10.1002/uog.22134 -
Genome Medicine Oct 2022Exome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain...
BACKGROUND
Exome sequencing (ES) is becoming more widely available in prenatal diagnosis. However, data on its clinical utility and integration into clinical management remain limited in practice. Herein, we report our experience implementing prenatal ES (pES) in a large cohort of fetuses with anomalies detected by ultrasonography using a hospital-based in-house multidisciplinary team (MDT) facilitated by a three-step genotype-driven followed by phenotype-driven analysis framework.
METHODS
We performed pES in 1618 fetal cases with positive ultrasound findings but negative for karyotyping and chromosome microarray analysis between January 2014 and October 2021, including both retrospective (n=565) and prospective (n=1053) cohorts. The diagnostic efficiency and its correlation to organ systems involved, phenotypic spectrum, and the clinical impacts of pES results on pregnancy outcomes were analyzed.
RESULTS
A genotype-driven followed by phenotype-driven three-step approach was carried out in all trio pES. Step 1, a genotype-driven analysis resulted in a diagnostic rate of 11.6% (187/1618). Step 2, a phenotype-driven comprehensive analysis yielded additional diagnostic findings for another 28 cases (1.7%; 28/1618). In the final step 3, data reanalyses based on new phenotypes and/or clinical requests found molecular diagnosis in 14 additional cases (0.9%; 14/1618). Altogether, 229 fetal cases (14.2%) received a molecular diagnosis, with a higher positive rate in the retrospective than the prospective cohort (17.3% vs. 12.4%, p<0.01). The diagnostic rates were highest in fetuses with skeletal anomalies (30.4%) and multiple organ involvements (25.9%), and lowest in fetuses with chest anomalies (0%). In addition, incidental and secondary findings with childhood-onset disorders were detected in 11 (0.7%) cases. Furthermore, we described the prenatal phenotypes for the first time for 27 gene-associated conditions (20.0%, 27/135) upon a systematic analysis of the diagnosed cases and expanded the phenotype spectrum for 26 (19.3%) genes where limited fetal phenotypic information was available. In the prospective cohort, the combined prenatal ultrasound and pES results had significantly impacted the clinical decisions (61.5%, 648/1053).
CONCLUSIONS
The genotype-driven approach could identify about 81.7% positive cases (11.6% of the total cohort) with the initial limited fetal phenotype information considered. The following two steps of phenotype-driven analysis and data reanalyses helped us find the causative variants in an additional 2.6% of the entire cohort (18.3% of all positive findings). Our extensive phenotype analysis on a large number of molecularly confirmed prenatal cases had greatly enriched our current knowledge on fetal phenotype-genotype correlation, which may guide more focused prenatal ultrasound in the future. This is by far the largest pES cohort study that combines a robust trio sequence data analysis, systematic phenotype-genotype correlation, and well-established MDT in a single prenatal clinical setting. This work underlines the value of pES as an essential component in prenatal diagnosis in guiding medical management and parental decision making.
Topics: Pregnancy; Female; Humans; Exome; Retrospective Studies; Cohort Studies; Prospective Studies; Ultrasonography, Prenatal; Prenatal Diagnosis; Fetus
PubMed: 36307859
DOI: 10.1186/s13073-022-01130-x -
Prenatal Diagnosis May 2022We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
We conducted a systematic review and meta-analysis to determine the diagnostic yield of exome sequencing (ES) for prenatal diagnosis of fetal structural anomalies, where karyotype/chromosomal microarray (CMA) is normal.
METHODS
Following electronic searches of four databases, we included studies with ≥10 structurally abnormal fetuses undergoing ES or whole genome sequencing. The incremental diagnostic yield of ES over CMA/karyotype was calculated and pooled in a meta-analysis. Sub-group analyses investigated effects of case selection and fetal phenotype on diagnostic yield.
RESULTS
We identified 72 reports from 66 studies, representing 4350 fetuses. The pooled incremental yield of ES was 31% (95% confidence interval (CI) 26%-36%, p < 0.0001). Diagnostic yield was significantly higher for cases pre-selected for likelihood of monogenic aetiology compared to unselected cases (42% vs. 15%, p < 0.0001). Diagnostic yield differed significantly between phenotypic sub-groups, ranging from 53% (95% CI 42%-63%, p < 0.0001) for isolated skeletal abnormalities, to 2% (95% CI 0%-5%, p = 0.04) for isolated increased nuchal translucency.
CONCLUSION
Prenatal ES provides a diagnosis in an additional 31% of structurally abnormal fetuses when CMA/karyotype is non-diagnostic. The expected diagnostic yield depends on the body system(s) affected and can be optimised by pre-selection of cases following multi-disciplinary review to determine that a monogenic cause is likely.
Topics: Exome; Female; Humans; Pregnancy; Pregnancy Trimester, First; Prenatal Diagnosis; Ultrasonography, Prenatal; Exome Sequencing
PubMed: 35170059
DOI: 10.1002/pd.6115 -
The Journal of Maternal-fetal &... Dec 202315q11.2 microdeletion can lead to syndromes affecting the nervous system. However, 15q11.2 microdeletion has large phenotypic differences and incomplete penetrance,... (Review)
Review Meta-Analysis
OBJECTIVE
15q11.2 microdeletion can lead to syndromes affecting the nervous system. However, 15q11.2 microdeletion has large phenotypic differences and incomplete penetrance, which brings challenges to prenatal diagnosis. We reported 21 cases of 15q11.2 microdeletion fetuses in Eastern China and reviewed literature on the prenatal clinical characteristics related to the deletion variants to provide a basis for prenatal genetic counseling.
METHODS
The clinical data of 21 cases of 15q11.2 microdeletion fetuses collected from June 2018 to September 2021 were retrospectively analyzed, and chromosomal microarray analysis was performed. The reported prenatal clinical features of 15q11.2 microdeletion fetuses were reviewed and summarized. A meta-analysis of 20 studies was performed to test heterogeneity, data integration, and sensitivity on the correlation between 15q11.2 microdeletion and neuropsychiatric diseases.
RESULTS
The median age of the women was 29.5 years. The median gestational age at interventional examination was 24 weeks. All fetuses showed deletion variants of the 15q11.2 fragment, and the median deletion range was approximately 0.48 MB. Ultrasound of five cases showed no abnormalities; however, four of them showed a high risk of Down's syndrome (risk values were 1/184, 1/128, 1/47, and 1/54, respectively). The remaining 16 fetuses showed congenital heart disease (7/16), elevated nuchal translucency (5/16), abnormal brain structure (2/16) and renal disease (2/16). In a literature review of 82 prenatal cases, 44% (36/82) had abnormal ultrasound features, 31% (11/36) showed abnormal nuchal translucency, approximately 28% (10/36) showed abnormal cardiac structure, and 14% (5/36) had brain structural abnormalities. The meta-analysis revealed that the frequency of the 15q11.2 microdeletion mutation in patients with schizophrenia and epilepsy was significantly higher (odds ratio 2.04, 95% confidence interval: 1.78-2.33, < 0.00001; odds ratio 5.23, 95% confidence interval: 2.83-9.67, < 0.00001) than that in normal individuals.
CONCLUSION
More than half of the 15q11.2 microdeletion cases presented no abnormalities in prenatal ultrasound examination. The cases with ultrasound features mainly showed isolated malformations such as elevated nuchal translucency, congenital heart disease, and brain structural abnormalities. Postpartum 15q11.2 microdeletion patients are at an increased risk of suffering from schizophrenia, epilepsy, and other neurological and mental diseases from 15q11.2 microdeletion. Therefore, prenatal diagnosis of 15q11.2 microdeletion not only depends on molecular diagnostic techniques but also requires cautious genetic counseling.
Topics: Adult; Female; Humans; Pregnancy; Fetus; Heart Defects, Congenital; Nuchal Translucency Measurement; Prenatal Diagnosis; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 37770195
DOI: 10.1080/14767058.2023.2262700 -
Ultrasound in Obstetrics & Gynecology :... Aug 2022Outcome of common arterial trunk (CAT) depends mainly on truncal valve function, presence of coronary artery abnormalities and presence of interrupted aortic arch. The...
OBJECTIVES
Outcome of common arterial trunk (CAT) depends mainly on truncal valve function, presence of coronary artery abnormalities and presence of interrupted aortic arch. The main objective of this study was to evaluate the accuracy of prenatal diagnosis of CAT by analyzing prenatal vs postnatal assessment of: (1) anatomic subtypes and (2) truncal valve function. The secondary objective was to assess the potential impact of prenatal diagnosis of CAT on postnatal mortality and morbidity by comparing prenatally vs postnatally diagnosed patients.
METHODS
This was a retrospective analysis of all CAT patients diagnosed either prenatally, with postnatal or fetopsy confirmation, or postnatally, from 2011 to 2019 in a single tertiary center. Cohen's kappa statistic was used to evaluate agreement between pre- and postnatal assessment of anatomic subtypes according to Van Praagh and of truncal valve function. Mortality and morbidity variables were compared between prenatally vs postnatally diagnosed CAT patients.
RESULTS
A total of 84 patients (62 liveborn with prenatal diagnosis, 16 liveborn with postnatal diagnosis and six terminations of pregnancy with fetopsy) met the inclusion criteria. The accuracy of prenatal diagnosis of CAT anatomic subtype was 80.3%, and prenatal and postnatal concordance for subtype diagnosis was only moderate (κ = 0.43), with no patient with CAT Type A3 (0/4) and only half of patients with CAT Type A4 (8/17) being diagnosed prenatally. Fetal evaluation of truncal valve function underestimated the presence (no agreement; κ = 0.09) and severity (slight agreement; κ = 0.19) of insufficiency. However, four of five cases of postnatally confirmed significant truncal valve stenosis were diagnosed prenatally, with fair agreement for both presence and severity of stenosis (κ = 0.38 and 0.24, respectively). Mortality was comparable in patients with and those without prenatal diagnosis (log-rank P = 0.87). CAT patients with fetal diagnosis underwent earlier intervention (P < 0.001), had shorter intubation time (P = 0.047) and shorter global hospital stay (P = 0.01).
CONCLUSIONS
The accuracy of prenatal diagnosis of CAT is insufficient to tailor neonatal management and to predict outcome. Fetal assessment of truncal valve dysfunction appears unreliable due to perinatal transition. Improvement is necessary in the fetal diagnosis of anatomic subtypes of CAT requiring postnatal prostaglandin infusion. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Constriction, Pathologic; Female; Heart Defects, Congenital; Humans; Pregnancy; Prenatal Diagnosis; Retrospective Studies; Truncus Arteriosus, Persistent; Ultrasonography, Prenatal
PubMed: 35118719
DOI: 10.1002/uog.24873 -
Taiwanese Journal of Obstetrics &... Jan 2021Abdominal lymphatic malformations (LM) are rare congenital malformations of the lymphatic system, representing only 2% of all LM in newborns. They may arise from... (Review)
Review
Abdominal lymphatic malformations (LM) are rare congenital malformations of the lymphatic system, representing only 2% of all LM in newborns. They may arise from intra-abdominal solid organs (such as the liver, pancreas, kidneys, spleen, adrenal glands, and gastrointestinal tract), mesentery, omentum, and retroperitoneum. Mesenteric LM are the most commonly seen, with retroperitoneal LM being the second most common. Fetal abdominal LM could be associated with karyotypic or other abnormalities, including skin edema, hydrops fetalis, and polyhydramnios, and prenatal diagnosis and perinatal counseling for these LM are important. Prenatal ultrasound (US) and magnetic resonance imaging (MRI) have led to an increased diagnosis of abdominal LM and improved monitoring and intervention postnatally. This article provides an overview of fetal abdominal LM, including the prenatal diagnoses, differential diagnoses, comprehensive illustrations of the imaging findings, treatments, and fetal outcomes.
Topics: Abdomen; Diagnosis, Differential; Female; Humans; Lymphatic Abnormalities; Magnetic Resonance Imaging; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 33494985
DOI: 10.1016/j.tjog.2020.11.003 -
BMC Pregnancy and Childbirth May 2023In terms of embryonic origin, vascular ring is a congenital anomaly in which the aortic arch and its branches completely or incompletely encircle and compress the...
BACKGROUND
In terms of embryonic origin, vascular ring is a congenital anomaly in which the aortic arch and its branches completely or incompletely encircle and compress the trachea or esophagus. Early and accurate diagnosis of a vascular ring is the key to treatment. Prenatal diagnosis mainly relies on fetal echocardiography, but the rate of missed diagnosis and misdiagnosis is still very high, and the prognosis has not been evaluated. The aim of this study was to investigate the accuracy of prenatal diagnosis and to evaluate the prognosis semi-quantitatively according to the shape of the ring and the distance between the vessel and the trachea.
METHODS
From 2019 to 2021, 37,875 fetuses underwent prenatal ultrasound examination in our center. All fetal cardiac examinations were performed using the fetal echocardiography method proposed by the American Institute of Ultrasound in Medicine (AIUM) combined with dynamic sequential cross-sectional observation (SCS). For SCS, the standard abdominal section was taken as the initial section, and the probe was moved cephalically along the long axis of the body until the superior mediastinum had disappeared. If a vascular ring was found, the shape of the ring and the distance of the branch to the airway were observed. The distance relationship with the airway was divided into three grades: I-III; the closer the distance, the lower the grade. The vascular rings were monitored every 4 weeks before birth. All were monitored before surgery or 1 year after birth.
RESULTS
A total of 418 cases of vascular rings were detected. There was no missed diagnoses or misdiagnoses by SCS. The vessels formed different shaped rings according to their origin and route. Grade I, "" and "O" rings have a poor prognosis and are associated with the highest risk of respiratory symptoms.
CONCLUSIONS
SCS can accurately diagnose vascular rings before delivery, evaluate the shape and size of the rings to conduct prenatal monitoring of children until birth, which plays a guiding role in airway compression after birth.
Topics: Female; Humans; Pregnancy; Cross-Sectional Studies; Prenatal Diagnosis; Prognosis; Ultrasonography, Prenatal; Vascular Ring
PubMed: 37131147
DOI: 10.1186/s12884-023-05637-y