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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 -
Prenatal Diagnosis Mar 2021An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance... (Review)
Review
An omphalocele is a congenital defect in the abdominal wall characterized by absent abdominal muscles, fascia, and skin. The characteristic ultrasound appearance includes a midline defect with herniation of abdominal contents into the base of the umbilical cord. Other anatomic abnormalities are seen in approximately 50% of cases, most notably cardiac defects (19%-32%). Approximately, 50% of cases are associated with genetic and multiple malformation syndromes including trisomy 13/18, pentalogy of Cantrell and Beckwith-Wiedemann syndrome. Therefore, a thorough evaluation is recommended, including detailed anatomic survey, fetal echocardiogram, genetic counseling, and prenatal diagnostic testing. Overall prognosis depends on the size of the omphalocele, genetic studies, and associated anomalies. Early prenatal diagnosis remains important in order to provide parental counseling and assist in pregnancy management. Delivery should occur at a tertiary care center. Timing and mode of delivery should be based on standard obstetric indications with cesarean delivery reserved for large omphalocele (>5 cm) or those that involve the fetal liver. Neonatal management involves either primary or staged reduction, both of which can be associated with a prolonged neonatal hospitalization.
Topics: Female; Hernia, Umbilical; Humans; Infant, Newborn; Magnetic Resonance Imaging; Parents; Pregnancy; Prenatal Diagnosis; Professional-Patient Relations; Truth Disclosure
PubMed: 33540475
DOI: 10.1002/pd.5886 -
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 -
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 -
Taiwanese Journal of Obstetrics &... Mar 2022To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic...
OBJECTIVES
To investigate the phenotypes, biochemical features and genotypes for 244 pedigrees with methylmalonic aciduria (MMA) in China, and to perform the prenatal genetic diagnosis by chorionic villus for these pedigrees.
MATERIALS AND METHODS
Gene analyses were performed for 244 pedigrees. There are 130 pedigrees, chorionic villus sampling was performed on the pregnant women to conduct the prenatal diagnosis.
RESULTS
Among 244 patients, 168 (68.9%) cases were combined methylmalonic aciduria and homocystinuria, 76 (31.1%) cases were isolated methylmalonic aciduria. All the patients were diagnosed with MMA by their clinical manifestation, elevated blood propionylcarnitine, propionylcarnitine to acetylcarnitine ratio, and/or urine/blood methylmalonic acid with or without homocysteine. MMACHC, MMUT, SUCLG1 and LMBRD1 gene variants were found in 236 (96.7%) pedigrees included 6 probands with only one heterozygous variant out of 244 cases. For the 130 pedigrees who received a prenatal diagnosis, 22 fetuses were normal, 69 foetuses were carriers of heterozygous variants, and the remaining 39 foetuses harboured compound heterozygous variants or homozygous variants. The follow-up results were consistent with the prenatal diagnosis.
CONCLUSION
The present study indicates genetic heterogeneity in MMA patients. Genetic analysis is a convenient method for prenatal diagnosis that will aid in avoiding the delivery of MMA patients.
Topics: Amino Acid Metabolism, Inborn Errors; China; Female; Genotype; Humans; Nucleocytoplasmic Transport Proteins; Oxidoreductases; Pedigree; Pregnancy; Prenatal Diagnosis
PubMed: 35361390
DOI: 10.1016/j.tjog.2022.02.017 -
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 -
The British Journal of Radiology Jul 2023Bone dysplasias are individually rare but collectively common. The prenatal diagnosis of bone dysplasias, especially perinatally lethal dysplasias, is of major interest... (Review)
Review
Bone dysplasias are individually rare but collectively common. The prenatal diagnosis of bone dysplasias, especially perinatally lethal dysplasias, is of major interest to obstetric services. The current nosology of genetic skeletal disorders addresses over 400 disorders. However, in clinical practice, we encounter only a limited number of disorders, such as . The recent development of non-invasive prenatal genetic testing using cell-free fetal DNA in maternal blood samples has had a major impact on the prenatal diagnosis of genetic diseases. However, imaging examinations remain critical for the final diagnosis of bone dysplasias because molecular testing only shows genetic variants, and not their pathogenicity - most variants are clinically insignificant. Bone dysplasias are typically suspected when limb shortening is identified by screening ultrasound. Further assessment can be followed by more detailed ultrasound, magnetic resonance imaging (MRI), and CT. Based on these data, rational decision-making is feasible, even when the definitive prenatal diagnosis is not feasible. Here, we highlight key images of common bone dysplasias obtained by currently available modalities.
Topics: Pregnancy; Female; Humans; Prenatal Diagnosis; Bone Diseases, Developmental; Ultrasonography; Fetus; Receptor, Fibroblast Growth Factor, Type 3; Ultrasonography, Prenatal
PubMed: 37351952
DOI: 10.1259/bjr.20221025 -
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 -
Prenatal Diagnosis Sep 2021The positive predictive values of cell free DNA (cfDNA) and rates of confined placental mosaicism (CPM), imprinting and other factors vary by chromosome. (Review)
Review
OBJECTIVE
The positive predictive values of cell free DNA (cfDNA) and rates of confined placental mosaicism (CPM), imprinting and other factors vary by chromosome.
METHODS
We sought to review the literature for each of these features for each chromosome and provide recommendations on chorionic villus sampling (CVS) versus amniocentesis after an abnormal cfDNA result.
RESULTS
For chromosomes with high rates of CPM (trisomy 13, monosomy X and rare autosomal trisomies [RATs]), an amniocentesis should be considered if the first trimester ultrasound is normal. For monosomy X on cfDNA with an unaffected fetus, maternal karyotyping should be considered after normal fetal diagnostic testing. In cfDNA cases with a trisomy involving a chromosome with imprinted genes (6, 7, 11, 14, 15 and 20), CVS should be considered, followed by amniocentesis if abnormal. If the fetus is unaffected, methylation studies should be considered given the risk of uniparental disomy. A third trimester growth ultrasound should be considered for patients with a positive cfDNA screen for a RAT and an unaffected fetus, especially in the case of trisomy 16. For patients with multiple aneuploidy results on cfDNA, a work-up for maternal malignancy should be considered.
CONCLUSIONS
Clinicians should consider rates of CPM, imprinting, ultrasound findings and maternal factors when considering whether to recommend amniocentesis or CVS after an abnormal cfDNA result.
Topics: Adult; Cell-Free Nucleic Acids; Female; Humans; Pregnancy; Prenatal Diagnosis; Trisomy
PubMed: 34386984
DOI: 10.1002/pd.6021 -
The Urologic Clinics of North America Aug 2023Fetal upper tract urinary system dilation is one of the most common findings on prenatal ultrasonography. Rarely, this may represent fetal lower urinary tract... (Review)
Review
Fetal upper tract urinary system dilation is one of the most common findings on prenatal ultrasonography. Rarely, this may represent fetal lower urinary tract obstruction (LUTO), of which posterior urethral valves are the predominant etiology. LUTO is the most dire fetal urologic diagnosis, as it affects not only the baby's management after birth but sometimes the course of the pregnancy itself. A variety of treatment options are available prenatally; these include observation, vesicoamniotic shunt placement, amnioinfusion, and attempts at direct treatment of the valves themselves. All fetal interventions carry substantial risks; caution should attend every discussion of treatment.
Topics: Infant; Female; Pregnancy; Humans; Prenatal Diagnosis; Ultrasonography, Prenatal; Urethral Diseases; Urology
PubMed: 37385699
DOI: 10.1016/j.ucl.2023.04.006