-
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 -
BMJ Open Jul 2019To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence...
OBJECTIVES
To assess international trends and patterns of prenatal diagnosis of critical congenital heart defects (CCHDs) and their relation to total and live birth CCHD prevalence and mortality.
SETTING
Fifteen birth defect surveillance programmes that participate in the International Clearinghouse for Birth Defects Surveillance and Research from 12 countries in Europe, North and South America and Asia.
PARTICIPANTS
Live births, stillbirths and elective terminations of pregnancy for fetal anomaly diagnosed with 1 of 12 selected CCHD, ascertained by the 15 programmes for delivery years 2000 to 2014.
RESULTS
18 243 CCHD cases were reported among 8 847 081 births. The median total prevalence was 19.1 per 10 000 births but varied threefold between programmes from 10.1 to 31.0 per 10 000. CCHD were prenatally detected for at least 50% of the cases in one-third of the programmes. However, prenatal detection varied from 13% in Slovak Republic to 87% in some areas in France. Prenatal detection was consistently high for hypoplastic left heart syndrome (64% overall) and was lowest for total anomalous pulmonary venous return (28% overall). Surveillance programmes in countries that do not legally permit terminations of pregnancy tended to have higher live birth prevalence of CCHD. Most programmes showed an increasing trend in prenatally diagnosed CCHD cases.
DISCUSSION AND CONCLUSIONS
Prenatal detection already accounts for 50% or more of CCHD detected in many programmes and is increasing. Local policies and access likely account for the wide variability of reported occurrence and prenatal diagnosis. Detection rates are high especially for CCHD that are more easily diagnosed on a standard obstetric four-chamber ultrasound or for fetuses that have extracardiac anomalies. These ongoing trends in prenatal diagnosis, potentially in combination with newborn pulse oximetry, are likely to modify the epidemiology and clinical outcomes of CCHD in the near future.
Topics: Asia; Europe; Female; Heart Defects, Congenital; Humans; Infant, Newborn; Male; North America; Pregnancy; Prenatal Diagnosis; Prevalence; Retrospective Studies; South America
PubMed: 31270117
DOI: 10.1136/bmjopen-2018-028139 -
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 -
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 -
Taiwanese Journal of Obstetrics &... Aug 2015Prenatal examination plays an important role in present medical diagnosis. It provides information on fetal health status as well as the diagnosis of fetal treatment... (Review)
Review
Prenatal examination plays an important role in present medical diagnosis. It provides information on fetal health status as well as the diagnosis of fetal treatment feasibility. The diagnosis can provide peace of mind for the perspective mother. Timely pregnancy termination diagnosis can also be determined if required. Amniocentesis and chorionic villus sampling are two widely used invasive prenatal diagnostic procedures. To obtain complete fetal genetic information and avoid endangering the fetus, noninvasive prenatal diagnosis has become the vital goal of prenatal diagnosis. However, the development of a high-efficiency separation technology is required to obtain the scarce fetal cells from maternal circulation. In recent years, the rapid development of microfluidic systems has provided an effective method for fetal cell separation. Advantages such as rapid analysis of small samples, low cost, and various designs, greatly enhance the efficiency and convenience of using microfluidic systems for cell separation. In addition, microfluidic disks can be fully automated for high throughput of rare cell selection from blood samples. Therefore, the development of microfluidic applications in noninvasive prenatal diagnosis is unlimited.
Topics: Adult; Amniocentesis; Chorionic Villi Sampling; DNA; Female; Humans; Maternal Health; Maternal Serum Screening Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy Trimester, Third; Prenatal Diagnosis; RNA, Messenger; Sensitivity and Specificity; Ultrasonography, Prenatal
PubMed: 26384048
DOI: 10.1016/j.tjog.2015.05.002 -
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