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American Journal of Obstetrics &... Sep 2023This study aimed to determine the incremental diagnostic yield of prenatal exome sequencing after negative chromosomal microarray analysis results in prenatally... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
This study aimed to determine the incremental diagnostic yield of prenatal exome sequencing after negative chromosomal microarray analysis results in prenatally diagnosed bilateral severe ventriculomegaly or hydrocephalus; another objective was to categorize the associated genes and variants.
DATA SOURCES
A systematic search was performed to identify relevant studies published until June 2022 using 4 databases (Cochrane Library, Web of Science, Scopus, and MEDLINE).
STUDY ELIGIBILITY CRITERIA
Studies in English reporting on the diagnostic yield of exome sequencing following negative chromosomal microarray analysis results in cases of prenatally diagnosed bilateral severe ventriculomegaly were included.
METHODS
Authors of cohort studies were contacted for individual participant data, and 2 studies provided their extended cohort data. The incremental diagnostic yield of exome sequencing was assessed for pathogenic/likely pathogenic findings in cases of: (1) all severe ventriculomegaly; (2) isolated severe ventriculomegaly (as the only cranial anomaly); (3) severe ventriculomegaly with other cranial anomalies; and (4) nonisolated severe ventriculomegaly (with extracranial anomalies). To be able to identify all reported genetic associations, the systematic review portion was not limited to any minimal severe ventriculomegaly case numbers; however, for the synthetic meta-analysis, we included studies with ≥3 severe ventriculomegaly cases. Meta-analysis of proportions was done using a random-effects model. Quality assessment of the included studies was performed using the modified STARD (Standards for Reporting of Diagnostic Accuracy Studies) criteria.
RESULTS
A total of 28 studies had 1988 prenatal exome sequencing analyses performed following negative chromosomal microarray analysis results for various prenatal phenotypes; this included 138 cases with prenatal bilateral severe ventriculomegaly. We categorized 59 genetic variants in 47 genes associated with prenatal severe ventriculomegaly along with their full phenotypic description. There were 13 studies reporting on ≥3 severe ventriculomegaly cases, encompassing 117 severe ventriculomegaly cases that were included in the synthetic analysis. Of all the included cases, 45% (95% confidence interval, 30-60) had positive pathogenic/likely pathogenic exome sequencing results. The highest yield was for nonisolated cases (presence of extracranial anomalies; 54%; 95% confidence interval, 38-69), followed by severe ventriculomegaly with other cranial anomalies (38%; 95% confidence interval, 22-57) and isolated severe ventriculomegaly (35%; 95% confidence interval, 18-58).
CONCLUSION
There is an apparent incremental diagnostic yield of prenatal exome sequencing following negative chromosomal microarray analysis results in bilateral severe ventriculomegaly. Although the greatest yield was found in cases of nonisolated severe ventriculomegaly, consideration should also be given to performing exome sequencing in cases of isolated severe ventriculomegaly as the only brain anomaly identified on prenatal imaging.
Topics: Pregnancy; Female; Humans; Exome Sequencing; Hydrocephalus; Cohort Studies
PubMed: 37311485
DOI: 10.1016/j.ajogmf.2023.101048 -
Autism : the International Journal of... Jan 2022Autism spectrum disorders comprise a complex group with many subtypes of behaviorally defined neurodevelopmental abnormalities in two core areas: deficits in social... (Review)
Review
Autism spectrum disorders comprise a complex group with many subtypes of behaviorally defined neurodevelopmental abnormalities in two core areas: deficits in social communication and fixated, restricted, repetitive, or stereotyped behaviors and interests each with potential unique risk factors and characteristics. The underlying mechanisms and the possible causes of autism spectrum disorder remain elusive and while increased prevalence is undoubtable, it is unclear if it is a reflection of diagnostic improvement or emerging risk factors such as endocrine disrupting chemicals. Epidemiological studies, which are used to study the relation between endocrine disrupting chemicals and autism spectrum disorder, can have inherent methodological challenges that limit the quality and strength of their findings. The objective of this work is to systematically review the treatment of these challenges and assess the quality and strength of the findings in the currently available literature. The overall quality and strength were "moderate" and "limited," respectively. Risk of bias due to the exclusion of potential confounding factors and the lack of accuracy of exposure assessment methods were the most prevalent. The omnipresence of endocrine disrupting chemicals and the biological plausibility of the association between prenatal exposure and later development of autism spectrum disorder highlight the need to carry out well-designed epidemiological studies that overcome the methodological challenges observed in the currently available literature in order to be able to inform public policy to prevent exposure to these potentially harmful chemicals and aid in the establishment of predictor variables to facilitate early diagnosis of autism spectrum disorder and improve long-term outcomes.
Topics: Autism Spectrum Disorder; Endocrine Disruptors; Female; Humans; Pregnancy; Prenatal Exposure Delayed Effects; Risk Factors; Stereotyped Behavior
PubMed: 34412519
DOI: 10.1177/13623613211039950 -
Journal of Clinical Medicine Apr 2023Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the... (Review)
Review
Neonatal hemochromatosis (NH) is an uncommon, severe disorder that results in fetal loss or neonatal death due to liver failure. NH is currently regarded as the phenotypic expression of gestational alloimmune liver disease (GALD). The diagnosis of NH-GALD is rarely prenatally established. In addition to providing a systematic review of the prenatal features that are identifiable using ultrasound (US) and MRI, we suggest a prenatal diagnosis algorithm for use in suspected NH during the first affected pregnancy. From a total of 586 database entries identified in PubMed, Google Scholar, and ResearchGate, we selected 18 studies published from 1993 to 2021 that reported maternal medical and obstetric history, prenatal ultrasound findings, and postpartum outcomes. We investigated the ultrasound and MRI features of these studies, along with the outcome due to this condition. A total of 74 cases were identified. The main reported prenatal US finding was fetal growth restriction (FGR) (33%), followed by oligohydramnios (13%) and hydrops fetalis (13%), with 13% cases described as uneventful. Other rare prenatal findings were fetal anemia, ascites, and abnormal fetal liver and spleen. Most pregnancies ended with fetal/perinatal death or therapeutic interruption of pregnancy. Favorable evolution with treatment (ensanguine transfusion and intravenous immunoglobulin (IVIG)) was reported for only 7% of fetuses. Using T2-weighted MRI, fetal extrahepatic siderosis confirmed prenatally in two cases and postnatally in 11 cases. IVIG treatment throughout subsequent pregnancies was found to significantly improve fetal prognosis. MRI should be indicated in selected cases of oligohydramnios, fetal hydrops, fetal hepatomegaly, ascites, or unexplained FGR or anemia after ruling out all other more frequently encountered conditions. MRI can be used to detect iron overload in the liver and extrahepatic siderosis.
PubMed: 37048762
DOI: 10.3390/jcm12072679 -
Children (Basel, Switzerland) Feb 2022Tetralogy of Fallot (TOF) represents between 7 and 10% of the total cases of congenital heart defects (CHD) and is estimated to be the most common cyanotic CHD,... (Review)
Review
BACKGROUND
Tetralogy of Fallot (TOF) represents between 7 and 10% of the total cases of congenital heart defects (CHD) and is estimated to be the most common cyanotic CHD, requiring medical or surgical intervention within the first year of life. Current advances in prenatal screening and fetal echocardiography led to increased rates of prenatal diagnosis of TOF. Furthermore, improvements in initial medical care, surgical repair, and long-term care are associated with excellent long-term survival until adulthood. Consequently, issues of morbidity have come under the spotlight, specifically neurodevelopmental and psychiatric adverse outcomes, which affect the quality of life of TOF survivors.
METHOD
This study is a systematic review of English articles, using PUBMED and applying the following search terms, Tetralogy of Fallot, neurodevelopment, autism, cerebral palsy, attention-deficit hyperactivity disorder. Data were extracted by two authors.
RESULTS
Most researchers suggest that TOF survivors score lower in neurodevelopmental tests than healthy populations of the same age and are in danger of neurodevelopmental impairments. Furthermore, it is suggested that TOF adolescents show higher rates of psychiatric disorders.
CONCLUSIONS
The neurodevelopment of TOF survivors is not intensively studied. Existing studies in TOF survivors focus on different developmental aspects, using different evaluation methods and thus making conclusions for either one of the four aspects of neurodevelopment (executive function, cognition, and adaptive function, speech-language and motor function, or neuropsychiatric domain). The poor outcomes of these isolated studies indicate the need for future research as well as for continuous neuropsychological assessment and close monitoring of children and adolescents with TOF.
PubMed: 35204984
DOI: 10.3390/children9020264 -
Developmental Medicine and Child... Feb 2021To determine how the severity of antenatally diagnosed germinal matrix-intraventricular hemorrhage (GMH-IVH) relates to morbidity and mortality, and to explore potential... (Meta-Analysis)
Meta-Analysis
AIM
To determine how the severity of antenatally diagnosed germinal matrix-intraventricular hemorrhage (GMH-IVH) relates to morbidity and mortality, and to explore potential risk factors.
METHOD
We conducted a systematic review and individual patient data meta-analysis of antenatally diagnosed fetal GMH-IVH. The primary outcomes were mortality and morbidity. Potential associations with clinical factors during pregnancy were explored. Analysis employed Fisher's exact test and logistic regression.
RESULTS
We included 240 cases from 80 studies. Presence of venous infarction was associated with mortality (odds ratio [OR] 4.3, 95% confidence interval [CI] 1.4-13.25), motor impairment (OR 103.2, 95% CI 8.6-1238), epilepsy (OR 6.46, 95% CI 2.64-16.06), and developmental delay (OR 8.55, 95% CI 2.12-48.79). Shunt placement was associated with gestational age at GMH-IVH diagnosis and in utero progression. Many cases had uncomplicated pregnancies but possible co-occurring conditions included twin gestation, small for gestational age, and congenital anomalies.
INTERPRETATION
Severity of fetal GMH-IVH, specifically venous infarction, is associated with overall mortality and morbidity. Risk factors for fetal GMH-IVH are poorly understood and controlled studies are required.
WHAT THIS PAPER ADDS
Preterm germinal matrix-intraventricular hemorrhage (GMH-IVH) grading can be applied to fetuses. Many fetal germinal matrix hemorrhages occur in otherwise typical pregnancies. Half of fetuses with post-hemorrhagic ventricular dilatation receive a shunt after delivery. Fetuses with grade I or II GMH-IVH have few sequelae. Fetuses with periventricular hemorrhagic infarction have a high burden of motor impairment.
Topics: Cerebral Infarction; Cerebral Intraventricular Hemorrhage; Female; Fetal Diseases; Humans; Infant, Newborn; Male; Pregnancy; Prenatal Diagnosis
PubMed: 33094492
DOI: 10.1111/dmcn.14713 -
Viruses Oct 2023Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
Cytomegalovirus (CMV) infection is a significant health concern affecting numerous expectant mothers across the globe. CMV is the leading cause of health problems and developmental delays among infected infants. Notably, this study examines CMV infection in pregnancy, its management, prevention mechanisms, and treatment options.
METHODS
Specifically, information from the Cochrane Library, PUBMED, Wiley Online, Science Direct, and Taylor Francis databases were reviewed along with additional records identified through the register, the Google Scholar search engine. Based on the search, 21 articles were identified for systematic review.
RESULTS
A total of six randomized controlled trials (RCTs) were utilized for a meta-analytic review. As heterogeneity was substantial, the random effects model was used for meta-analysis. Utilizing the random-effects model, the restricted maximum likelihood (REML) approach, the estimate of effect size (d = -0.479, 95% CI = -0.977 to 0.019, = 0.060) suggests the results are not statistically significant, so it cannot be inferred that the prevention methods used were effective, despite an inverse relationship between treatment and number of infected cases. The findings indicated that several techniques are used to prevent, diagnose, and manage CMV infection during pregnancy, including proper hygiene, ultrasound examination (US), magnetic resonance imaging (MRI), amniocentesis, viremia, hyperimmunoglobulin (HIG), and valacyclovir (VACV).
CONCLUSIONS
The current review has significant implications for addressing CMV infection in pregnancy. Specifically, it provides valuable findings on contemporary management interventions to prevent and treat CMV infection among expectant mothers. Therefore, it allows relevant stakeholders to address these critical health concerns and understand the effectiveness of the proposed prevention and treatment options.
Topics: Pregnancy; Infant; Female; Humans; Pregnancy Complications, Infectious; Cytomegalovirus Infections; Amniocentesis; Infectious Disease Transmission, Vertical
PubMed: 38005820
DOI: 10.3390/v15112142 -
Ultrasound in Obstetrics & Gynecology :... Aug 2022To evaluate the incidence of antenatally diagnosed brain injury in twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and to quantify the perinatal... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To evaluate the incidence of antenatally diagnosed brain injury in twin pregnancy complicated by twin-to-twin transfusion syndrome (TTTS) and to quantify the perinatal mortality, morbidity and long-term neurodevelopmental outcome of these fetuses.
METHODS
MEDLINE, EMBASE, ClinicalTrials.gov and The Cochrane Library databases were searched. Inclusion criteria were studies reporting on brain abnormality diagnosed antenatally in twin pregnancies complicated by TTTS. The primary outcome was the incidence of prenatal brain abnormality. The secondary outcomes were intrauterine demise (IUD), neonatal death, termination of pregnancy (TOP) and long-term morbidity. Outcomes were explored in the population of fetuses with antenatal diagnosis of brain abnormality. Subgroup analysis according to the type of treatment, gestational age, Quintero stage at diagnosis and/or treatment, and cotwin death was planned. Meta-analysis of proportions was used to combine data and pooled proportions and their 95% CI were reported.
RESULTS
Thirteen studies including 1573 cases of TTTS and 88 fetuses with an antenatal diagnosis of brain abnormality were included in the systematic review. The meta-analysis included only studies reporting on brain abnormality in twin pregnancy complicated by TTTS cases and treated with laser surgery. Overall, brain injury occurred in 2.2% (52/2410) of fetuses (eight studies). Brain abnormality was reported in 1.03% and 0.82% of recipients and donors, respectively. The most common type of abnormality was ischemic lesions (30.4% (95% CI, 19.1-43.0%)), followed by destructive lesions (23.9% (95% CI, 13.7-35.9%)), ventriculomegaly (19.9% (95% CI, 10.6-31.3%)) and hemorrhagic lesions (15.3% (95% CI, 7.1-25.8%)). Spontaneous IUD occurred in 13.4% (95% CI, 5.1-24.8%) of fetuses, while TOP was chosen by parents in 53.5% (95% CI, 38.9-67.8%) cases. Neonatal death was reported by only three studies, with an incidence of 15.4% (95% CI, 2.8-35.4%). Finally, only two studies reported on composite morbidity, with an overall rate of the outcome of 20.4% (95% CI, 2.5-49.4%) and rates of 29.7% and 20.4% in the recipient and donor fetuses, respectively. Due to the small numbers, only composite morbidity was analyzed and no information on neonatal intensive care unit admission, respiratory distress syndrome or other long-term outcomes, such as neurodevelopmental delay and cerebral palsy, could be retrieved reliably.
CONCLUSIONS
The overall incidence of antenatally diagnosed fetal brain abnormality in twin pregnancy complicated by TTTS treated with laser surgery is around 2% and is mainly ischemic in nature (30.4%). TOP was chosen by parents in more than half of cases (53.5%). No information could be retrieved on morbidity outcomes, highlighting the urgent need for long-term follow-up studies of these children. © 2022 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Brain; Brain Injuries; Child; Female; Fetofetal Transfusion; Gestational Age; Humans; Incidence; Infant, Newborn; Nervous System Malformations; Perinatal Death; Pregnancy; Pregnancy Outcome; Pregnancy, Twin
PubMed: 35233861
DOI: 10.1002/uog.24895 -
Ultrasound in Obstetrics & Gynecology :... May 2021To derive accurate estimates of perinatal survival in pregnancies with and without a prenatal diagnosis of vasa previa based on a systematic review of the literature and... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To derive accurate estimates of perinatal survival in pregnancies with and without a prenatal diagnosis of vasa previa based on a systematic review of the literature and meta-analysis.
METHODS
A search of MEDLINE, EMBASE and The Cochrane Library was performed to review relevant citations reporting on the perinatal outcomes of pregnancies with vasa previa. We included prospective and retrospective cohort and population studies that provided data on pregnancies with a prenatal diagnosis of vasa previa or cases diagnosed at birth or following postnatal placental examination. Meta-analysis using a random-effects model was performed to derive weighted pooled estimates of perinatal survival (excluding stillbirths and neonatal deaths) and intact perinatal survival (additionally excluding hypoxic morbidity). Incidence rate difference (IRD) meta-analysis was used to estimate the significance of differences in pooled proportions between cases of vasa previa with and those without a prenatal diagnosis. Heterogeneity between studies was estimated using Cochran's Q and the I statistic.
RESULTS
We included 21 studies reporting on the perinatal outcomes of 683 pregnancies with a prenatal diagnosis of vasa previa. There were three stillbirths (1.01% (95% CI, 0.40-1.87%)), five neonatal deaths (1.19% (95% CI, 0.52-2.12%)) and 675 surviving neonates, resulting in a pooled estimate for perinatal survival of 98.6% (95% CI, 97.6-99.3%). Based on seven studies that included cases of vasa previa with and without a prenatal diagnosis, the pooled perinatal survival in pregnancies without a prenatal diagnosis (61/118) was 72.1% (95% CI, 50.6-89.4%) vs 98.6% (95% CI, 96.7-99.7%) in cases with a prenatal diagnosis (224/226). Therefore, the risk of perinatal death was 25-fold higher when a diagnosis of vasa previa was not made antenatally, compared with when it was (odds ratio (OR), 25.39 (95% CI, 7.93-81.31); P < 0.0001). Similarly, the risk of hypoxic morbidity was increased 50-fold in cases with vasa previa without a prenatal diagnosis compared with those with a prenatal diagnosis (36/61 vs 5/224; OR, 50.09 (95% CI, 17.33-144.79)). The intact perinatal survival rate in cases of vasa previa without a prenatal diagnosis was significantly lower than in those with a prenatal diagnosis (28.1% (95% CI, 14.1-44.7%) vs 96.7% (95% CI, 93.6-98.8%)) (IRD, 73.4% (95% CI, 53.9-92.7%); Z = -7.4066, P < 0.001).
CONCLUSIONS
Prenatal diagnosis of vasa previa is associated with a high rate of perinatal survival, whereas lack of an antenatal diagnosis significantly increases the risk of perinatal death and hypoxic morbidity. Further research should be undertaken to investigate strategies for incorporating prenatal screening for vasa previa into routine clinical practice. © 2020 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; Perinatal Mortality; Pregnancy; Pregnancy Outcome; Prenatal Diagnosis; Prospective Studies; Retrospective Studies; Vasa Previa
PubMed: 32735754
DOI: 10.1002/uog.22166 -
The Journal of Obstetrics and... Jul 2023To identify the additional diagnostic value of CNV-seq over conventional karyotyping on the part of chromosomal abnormalities in prenatal diagnosis. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To identify the additional diagnostic value of CNV-seq over conventional karyotyping on the part of chromosomal abnormalities in prenatal diagnosis.
METHOD
This was a systematic review conducted in accordance with PRISMA criteria. In order to clarify related research, PubMed, Web of Science databases (including Core Collection, BIOSIS Previews, MEDLINE, and so on), The Cochrane Library and Wiley Online Library were searched with the terms: "prenatal diagnosis," "CNV-seq," "karyotyping," published from January 2010 to May 2022. No language restrictions. RenMan 5.4 was used for the meta-analysis.
RESULTS
Eight studies were included in this systemic review and meta-analysis, including 11 091 pregnant women with high-risk pregnancy factors or with structurally abnormal fetus under ultrasound. CNV-seq detected a 2% (95% CI, -0% to 4%) additional chromosomal anomalies over conventional karyotyping in the six series. A 4% (95% CI, 3%-6%) pooled mean incremental yield of pathogenic CNVs by CNV-seq over karyotyping was observed, with a 1%-16% range.
CONCLUSION
CNV-seq, applied in prenatal diagnosis, may detect more chromosomal abnormalities when compared with karyotyping. With the advantages of wide coverage, high throughput, high resolution, no culture, good compatibility, and adjustable sequencing depth, CNV-seq has high application value in prenatal diagnosis.
Topics: Pregnancy; Female; Humans; Karyotyping; Chromosome Aberrations; Prenatal Diagnosis; Chromosome Disorders; Pregnancy, High-Risk; DNA Copy Number Variations
PubMed: 37037422
DOI: 10.1111/jog.15652 -
American Journal of Obstetrics &... Aug 2020To systematically review published literature and calculate the prevalence of vasa previa and its known risk factors. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To systematically review published literature and calculate the prevalence of vasa previa and its known risk factors.
MATERIALS AND METHODS
MEDLINE, Embase, the Cochrane Library, PubMed (non-MEDLINE and in process), and www.clinicaltrials.gov were searched from inception to March 2018 using indexing terms "vasa previa," "placenta previa," "low lying placenta," "succenturiate lobe," "bilobate placenta," "bilobed placenta," and "velamentous insertion." All original research studies reporting on 5 or more pregnancies with vasa previa were included. The search was limited to studies on human data and those published in the English language. Two reviewers independently screened titles and abstracts, completed data extraction, and assessed reporting quality using the Study Quality Assessment Tool for Case Series Studies of the National Heart, Lung, and Blood Institute. Disagreements were discussed and resolved at each step of the process.
RESULTS
We included 21 studies that reported 428 pregnancies with vasa previa of 1,027,918 deliveries (0.46 cases of vasa previa per 1000 deliveries). These studies fared well on risk of bias assessment using the Study Quality Assessment Tool for Case Series Studies of the National Heart, Lung, and Blood Institute. The prevalence and 95% confidence intervals of known risk factors for vasa previa included a low-lying placenta (61.5%, 53.0%-70.0%), velamentous cord insertion (52.2%, 39.6%-64.7%), bilobed or succenturiate lobed placenta (33.3%, 20.9%-45.7%), use of in vitro fertilization (26.4%, 16.0%-36.8%), and multiple gestation (8.92%, 5.33%-12.5%).
CONCLUSION
Vasa previa affects 0.46 cases per 1000 pregnancies. Given the high prevalence of prenatally detectable risk factors in affected pregnancies, the cost-effectiveness of screening strategies for vasa previa either in isolation, using a risk factor-based approach, or universally, in tandem with cervical-length screening using transvaginal ultrasound, should be revisited.
Topics: Female; Humans; Placenta; Placenta Previa; Pregnancy; Risk Factors; Ultrasonography, Prenatal; Vasa Previa
PubMed: 33345868
DOI: 10.1016/j.ajogmf.2020.100117