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Pediatric Neurology May 2023Prenatal diagnosis of fetal brain abnormalities is rapidly evolving with the advancement of neuroimaging techniques, thus adding value to prognostic counseling and... (Review)
Review
Prenatal diagnosis of fetal brain abnormalities is rapidly evolving with the advancement of neuroimaging techniques, thus adding value to prognostic counseling and perinatal management. However, challenges and uncertainties persist in prenatal counseling due to limitations of prenatal imaging, continued development and maturation of the brain structure, and the heterogeneity and paucity of outcome studies. This topical review of fetal neurological consultations highlights prenatally diagnosed brain abnormalities that challenged prognostic counseling and perinatal management. Representative cases across multiple centers that highlighted diagnostic challenges were selected. Charts were reviewed for neuroimaging, genetic evaluation, prenatal prognostic discussion, postnatal imaging and testing, and infant outcome. We present case studies with prenatal and postnatal information discussing prenatal testing, fetal MRI interpretation, and complexities in the prognostic counseling process. Advocating for large-scale multicenter studies and a national collaborative fetal neurological registry to help guide the ever-expanding world of prenatal diagnostics and prognostic counseling is critical to this field. Study of large-scale outcomes data from such a registry can better guide fetal neurological consultations and facilitate comprehensive multidisciplinary planning and program development for educational curriculum for fetal-neonatal neurology.
Topics: Pregnancy; Infant; Infant, Newborn; Female; Humans; Prognosis; Prenatal Diagnosis; Counseling; Neuroimaging; Magnetic Resonance Imaging; Nervous System Malformations; Brain Diseases; Ultrasonography, Prenatal; Retrospective Studies
PubMed: 36934462
DOI: 10.1016/j.pediatrneurol.2023.02.013 -
Ultrasound in Obstetrics & Gynecology :... Dec 2023Congenital knee dislocation (CKD) is a rare condition, affecting 1 in 100 000 newborns. Its prenatal diagnosis is challenging and not well described in the literature,... (Review)
Review
OBJECTIVES
Congenital knee dislocation (CKD) is a rare condition, affecting 1 in 100 000 newborns. Its prenatal diagnosis is challenging and not well described in the literature, especially when it appears isolated and not as part of a complex malformation or syndromic pattern. The purpose of this study was to provide a comprehensive review of the available literature on the prenatal diagnosis and postnatal outcome of CKD and to summarize the current evidence on this topic.
METHODS
A systematic review of the literature on the prenatal diagnosis of CKD was performed in PubMed, Scopus and EMBASE. A predefined combination of specific keywords was used, focusing on intrauterine manifestations, diagnostic methods, prenatal behavior, postnatal treatment and neonatal outcome as well as long-term outcome in terms of ambulation, motion and joint stability. The quality of studies was assessed using the National Institutes of Health tool for quality assessment of case series. A summary of results was carried out providing proportions and rates of diagnostic and prognostic features associated with this rare condition.
RESULTS
In total, 20 cases were retrieved for analysis, of which 19 were obtained from the identified eligible studies (n = 16) and one was an unpublished case from our center. The median gestational age at prenatal diagnosis, which was made using ultrasound in most cases, was 20 weeks (range, 14-38 weeks). Bilaterality was observed in 11/20 (55%) cases. The condition was isolated in 7/20 (35%) cases and associated with other anomalies in 13/20 (65%) cases. An association was observed with oligohydramnios (4/20 (20%)), and an invasive procedure was performed in 13/20 (65%) cases, including 11 cases with an invasive procedure performed for diagnostic purposes. Genetic testing was normal in all isolated cases for which information was available (4/7), while a genetic syndrome was present in 10/13 (77%) non-isolated cases (Larsen, Noonan, Grebe, Desbuquois or Escobar syndrome). There were seven terminations of pregnancy, of which six were performed in cases with associated anomalies and one in an isolated case, 11 cases of postnatal survival, one case of intrauterine death and one of neonatal death. The fetal and neonatal deaths occurred in cases with associated anomalies or abnormal genetic findings. Postnatal treatment was mostly conservative, with only two reports (18% of the 11 surviving neonates) of surgical intervention, both in cases with associated anomalies. Postnatal follow-up was up to 1 year in most cases, and motor outlook appeared normal in all isolated cases.
CONCLUSIONS
CKD is a rare fetal anomaly with a prenatal diagnosis achievable from the early second trimester, for which a favorable outcome can be expected when no associated anomalies are present. Prenatal diagnosis should include detailed ultrasound assessment and amniocentesis for extensive genetic studies, particularly in non-isolated cases. Early postnatal treatment achieves success in most cases without surgical intervention and leads to a normal motor outlook. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Fetus; Genetic Testing; Prenatal Diagnosis; Renal Insufficiency, Chronic; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 37289939
DOI: 10.1002/uog.26283 -
European Journal of Medical Genetics Feb 2022The use of exome sequencing (ES) in the prenatal setting improves the diagnostic yield of genetic testing for fetuses with ultrasound anomalies. However, while the... (Review)
Review
The use of exome sequencing (ES) in the prenatal setting improves the diagnostic yield of genetic testing for fetuses with ultrasound anomalies. However, while the purpose of ES is to explain the fetal phenotype, secondary or incidental findings unrelated to the observed abnormalities might be detected. Recently, requests for ES in fetuses with no sonographic abnormalities have been increasing, raising serious ethical and medico-legal concerns. Variant interpretation is complex even in the postnatal setting and performing broad genomic data analyses in the prenatal setting presents additional dilemmas. This article discusses challenges and questions related to prenatal ES, including variant interpretation of incidental findings in cases of indicated prenatal ES, as well as in situations where ES is performed in asymptomatic fetuses.
Topics: Female; Humans; Mutation; Phenotype; Pregnancy; Prenatal Diagnosis; Exome Sequencing
PubMed: 34952236
DOI: 10.1016/j.ejmg.2021.104410 -
Journal of Magnetic Resonance Imaging :... Jun 2021
Topics: Female; Fetus; Humans; Hypospadias; Magnetic Resonance Imaging; Male; Pregnancy; Prenatal Diagnosis; Ultrasonography, Prenatal
PubMed: 33554381
DOI: 10.1002/jmri.27520 -
Disease Markers 2022Copy number variations (CNVs) at the chromosomal 1q21.1 region represent a group of hot-spot recurrent rearrangements in human genome, which have been detected in...
Copy number variations (CNVs) at the chromosomal 1q21.1 region represent a group of hot-spot recurrent rearrangements in human genome, which have been detected in hundreds of patients with variable clinical manifestations. Yet, report of such CNVs in prenatal scenario was relatively scattered. In this study, 17 prenatal cases involving the 1q21.1 microdeletion or duplication were recruited. The clinical survey and imaging examination were performed; and genetic detection with karyotyping and CNV analysis using chromosomal microarray (CMA) or CNVseq were subsequently carried out. These cases were all positive with 1q21.1 CNV, yet presented with exceedingly various clinical and utrasonographic indications. Among them, 12 pregnancies carried 1q21.1 deletions, while the other 5 carried 1q21.1 duplications, all of which were within the previously defined breaking point (BP) regions. According to the verification results, 9 CNVs were , 7 were familial, and the other 1 was not certain. We summarized the clinical information of these cases, and the size and distribution of CNVs, and attempted to analyze the association between these two aspects. The findings in our study may provide important basis for the prenatal diagnosis and genetic counseling on such conditions in the future.
Topics: Pregnancy; Female; Humans; DNA Copy Number Variations; Chromosome Deletion; Prenatal Diagnosis; Abnormalities, Multiple
PubMed: 37284664
DOI: 10.1155/2022/5487452 -
Seminars in Pediatric Neurology Jul 2022Given the advancements in prenatal testing, child neurologists are becoming involved in earlier stages of patient care, often being consulted during the gestational... (Review)
Review
Given the advancements in prenatal testing, child neurologists are becoming involved in earlier stages of patient care, often being consulted during the gestational stage rather than during the postnatal period. Thus, it is essential that pediatric neurologists understand the strengths and limitations of prenatal testing when counseling families. In this review we separate prenatal testing into screening and diagnostic testing. On the one hand, screening testing is noninvasive and does not have an increased risk for miscarriage. Diagnostic tests, on the other hand, are invasive and include chorionic villus sampling and amniocentesis. Understanding that screening tests are not diagnostic is imperative, therefore, attention should be placed on the positive and negative predictive values when interpreting results within the clinical context. Given their invasive nature, prenatal diagnostic tests increase the risk for complications such as miscarriage. Diagnostic tests include biochemical marker testing, enzyme testing, karyotype, microarray, whole exome sequencing, and whole genome sequencing. With each test, pretest and post-test counseling is crucial for informed decision making, and the strengths and limitations should be discussed when obtaining consent. Prior to obtaining testing, clinicians must consider unexpected and unrelated findings of testing and must acknowledge that the patient always has the option to decline the test.
Topics: Abortion, Spontaneous; Amniocentesis; Child; Chorionic Villi Sampling; Female; Genetic Testing; Humans; Pregnancy; Prenatal Diagnosis
PubMed: 35868736
DOI: 10.1016/j.spen.2022.100976 -
Fetal Diagnosis and Therapy 2023Skeletal dysplasias (SDs) are a heterogeneous group of heritable disorders that affect development of bone and cartilage. Because each SD is individually rare and... (Review)
Review
Skeletal dysplasias (SDs) are a heterogeneous group of heritable disorders that affect development of bone and cartilage. Because each SD is individually rare and because of the heterogeneity within and among disorders, prenatal diagnosis of a specific SD remains challenging. Molecular genetic diagnosis involves invasive testing, which some patients are not amenable to. Further, genetic analysis is time consuming, and results may not become available in time to make pregnancy management decisions. Low-dose fetal CT can aid in the prenatal evaluation of SDs. The main downside is the low but true risk of fetal radiation exposure. As such, fetal CT should only be performed when there is concern for a severe skeletal dysplasia and the diagnosis is in question after a detailed ultrasound or if molecular genetic testing is unavailable and when prenatal diagnosis may affect management or counseling. Fetal CT should be obtained after consultation with geneticists, maternal-fetal medicine specialists, and fetal radiologists, and sometimes orthopedic surgeons or neonatologists. The purpose of this study was to review the technique of and indications for fetal CT, as well as discuss fetal radiation risk. Illustrative cases will demonstrate when and how CT may be helpful in the diagnosis of SDs.
Topics: Female; Pregnancy; Humans; Bone Diseases, Developmental; Prenatal Diagnosis; Ultrasonography; Fetus; Tomography, X-Ray Computed; Ultrasonography, Prenatal
PubMed: 36948169
DOI: 10.1159/000528692 -
Archives of Gynecology and Obstetrics Apr 2023A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal... (Review)
Review
A systematic evaluation of the fetal anatomy as part of the second trimester ultrasound examination in pregnancy is useful in detecting pregnancy complications, fetal abnormalities, and genetic diseases. We aim to illustrate the basic and detailed second trimester scan, according to current international and national guidelines, as well as to our own every-day practice in the Department for Prenatal Diagnosis at the University of Tübingen, Germany.
Topics: Pregnancy; Female; Humans; Pregnancy Trimester, Second; Ultrasonography, Prenatal; Fetus; Prenatal Diagnosis; Prenatal Care; Pregnancy Trimester, First
PubMed: 35543741
DOI: 10.1007/s00404-022-06569-2 -
The Journal of Maternal-fetal &... Dec 2023Prenatal ultrasound has been regularly used as the screening tool for agenesis of corpus callosum (ACC) of the fetuses, which were mainly suspected on the basis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prenatal ultrasound has been regularly used as the screening tool for agenesis of corpus callosum (ACC) of the fetuses, which were mainly suspected on the basis of indirect signs rather than the visualization of the CC. However, the diagnostic accuracy of prenatal ultrasound for ACC, compared to the gold standard of postmortem diagnosis or postnatal images, is still unknown. This meta-analysis was performed to comprehensively evaluate the efficacy of prenatal ultrasound for the diagnosis of ACC.
METHODS
Studies evaluating the diagnostic accuracy of prenatal ultrasound for ACC compared to postmortem diagnosis or postnatal images were retrieved by searching PubMed, Embase, and Web of Science databases. Pooled sensitivity and specificity were calculated with a random-effects model. The diagnostic accuracy was measured by summarized area under the receiver operating characteristic (AUC) curve.
RESULTS
Twelve studies involving 544 fetuses with suspected anomalies of central nervous system were included, and 143 of them were with validated diagnosis of ACC. Pooled results showed that prenatal ultrasound has satisfying diagnostic efficacy for ACC, with the pooled sensitivity, specificity, positive and negative likelihood ratios of 0.72 (95% confidence interval [CI]: 0.39-0.91), 0.98 (95% CI: 0.79-1.00), 43.73 (95% CI: 3.42-558.74, and 0.29 (95% CI: 0.11-0.74), respectively. The pooled AUC was 0.94 (95% CI: 0.92-0.96), suggesting good diagnostic performance of prenatal ultrasound. Subgroup analysis according to the prenatal ultrasound procedures showed a better diagnostic efficacy of neurosonography than that of regular ultrasound screening (sensitivity: 0.84 versus 0.57, specificity: 0.98 versus 0.89, and AUC: 0.97 versus 0.78).
CONCLUSIONS
Prenatal ultrasound, particularly for the neurosonography, confers satisfying efficacy for the diagnosis of ACC.
Topics: Pregnancy; Female; Humans; Agenesis of Corpus Callosum; Prenatal Diagnosis; Ultrasonography, Prenatal; Magnetic Resonance Imaging; Ultrasonography
PubMed: 37365011
DOI: 10.1080/14767058.2023.2228454 -
Prenatal Diagnosis Jun 2021The objective of this study was to describe molecular findings and phenotypic features among individuals referred for prenatal Beckwith-Wiedemann syndrome (BWS) testing.
OBJECTIVE
The objective of this study was to describe molecular findings and phenotypic features among individuals referred for prenatal Beckwith-Wiedemann syndrome (BWS) testing.
METHODS
Molecular diagnostic testing was performed using a sensitive quantitative real-time PCR-based assay capable of detecting mosaic methylation to the level of 3% at IC1 and IC2. Sanger sequencing of CDKN1C was performed in cases with normal methylation.
RESULTS
Of the 94 patients tested, a molecular diagnosis was identified for 25.5% of cases; 70.9% of diagnosed cases had loss of methylation at IC2, 4.2% had gain of methylation at IC1, 12.5% had paternal uniparental isodisomy, and 12.5% had CDKN1C loss-of-function variants. Methylation level changes in prenatal cases were significantly greater than changes identified in cases tested after birth. Cases with a prenatal molecular diagnosis had a significantly greater number of BWS-associated phenotypic features. The presence of either macroglossia or placentomegaly was most predictive of a BWS diagnosis.
CONCLUSION
Our results support the consensus statement advocating BWS molecular testing for all patients with one or more BWS-associated prenatal features and suggest that low-level mosaic methylation changes may be uncommon among prenatal BWS diagnoses.
Topics: Adult; Beckwith-Wiedemann Syndrome; Cyclin-Dependent Kinase Inhibitor p57; Female; Humans; Molecular Diagnostic Techniques; Pregnancy; Prenatal Diagnosis
PubMed: 33974722
DOI: 10.1002/pd.5953