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Ultrasound in Obstetrics & Gynecology :... Apr 2017The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
The majority of studies on fetal ventriculomegaly have focused on the perinatal and long-term outcomes in fetuses with an antenatal diagnosis of bilateral ventriculomegaly. The aim of this study was to undertake a systematic review and meta-analysis to quantify the perinatal and long-term outcomes in fetuses diagnosed in the second or third trimester of pregnancy with isolated unilateral ventriculomegaly.
METHODS
MEDLINE, EMBASE and The Cochrane Library were searched electronically. Outcomes investigated included incidence of aneuploidy, congenital infection, progression of ventriculomegaly, associated brain and extracerebral abnormalities in the apparently isolated cases and neurodevelopmental delay in both apparently and truly isolated cases. Sensitivity analysis was performed according to whether the ventriculomegaly was mild/moderate (atrial width < 15 mm) or severe (atrial width ≥ 15 mm). Reference lists within relevant articles and reviews were hand-searched for additional reports. Cohort and case-control studies were included. Meta-analysis of proportions was used, and between-study heterogeneity was assessed using the I test.
RESULTS
The search yielded 2053 citations. The full text was retrieved for 202, and 11 studies were included in the systematic review. In fetuses with apparently isolated unilateral ventriculomegaly, no chromosomal abnormalities were identified and the pooled prevalence of congenital infection was 8.2% (95% CI, 3.6-14.5%). The pooled prevalence of additional brain abnormalities detected prenatally and postnatally by magnetic resonance imaging was 5.1% (95% CI, 0.2-16.1%) and 6.4% (95% CI, 0.3-19.4%), respectively. The pooled prevalence of abnormal neurodevelopment was 5.9% (95% CI, 2.2-11.2%) in apparently isolated cases with an atrial width of < 15 mm, and it was 7.0% (95% CI, 3.2-12.2%) in fetuses with truly isolated unilateral ventriculomegaly. Most cases with apparently isolated ventriculomegaly were classified as mild/moderate (93.5%) and therefore the outcomes in this group were similar to those in the whole cohort of apparently isolated ventriculomegaly.
CONCLUSIONS
The prevalence of aneuploidy, congenital infection and neurodevelopmental delay in fetuses with a prenatal diagnosis of isolated unilateral ventriculomegaly is likely to be low. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Aneuploidy; Congenital Abnormalities; Female; Fetal Diseases; Humans; Hydrocephalus; Infections; Neurodevelopmental Disorders; Perinatal Care; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, Second; Pregnancy Trimester, Third; Ultrasonography, Prenatal
PubMed: 27091707
DOI: 10.1002/uog.15943 -
BMJ Open Jan 2016To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To measure test accuracy of non-invasive prenatal testing (NIPT) for Down, Edwards and Patau syndromes using cell-free fetal DNA and identify factors affecting accuracy.
DESIGN
Systematic review and meta-analysis of published studies.
DATA SOURCES
PubMed, Ovid Medline, Ovid Embase and the Cochrane Library published from 1997 to 9 February 2015, followed by weekly autoalerts until 1 April 2015.
ELIGIBILITY CRITERIA FOR SELECTING STUDIES
English language journal articles describing case-control studies with ≥ 15 trisomy cases or cohort studies with ≥ 50 pregnant women who had been given NIPT and a reference standard.
RESULTS
41, 37 and 30 studies of 2012 publications retrieved were included in the review for Down, Edwards and Patau syndromes. Quality appraisal identified high risk of bias in included studies, funnel plots showed evidence of publication bias. Pooled sensitivity was 99.3% (95% CI 98.9% to 99.6%) for Down, 97.4% (95.8% to 98.4%) for Edwards, and 97.4% (86.1% to 99.6%) for Patau syndrome. The pooled specificity was 99.9% (99.9% to 100%) for all three trisomies. In 100,000 pregnancies in the general obstetric population we would expect 417, 89 and 40 cases of Downs, Edwards and Patau syndromes to be detected by NIPT, with 94, 154 and 42 false positive results. Sensitivity was lower in twin than singleton pregnancies, reduced by 9% for Down, 28% for Edwards and 22% for Patau syndrome. Pooled sensitivity was also lower in the first trimester of pregnancy, in studies in the general obstetric population, and in cohort studies with consecutive enrolment.
CONCLUSIONS
NIPT using cell-free fetal DNA has very high sensitivity and specificity for Down syndrome, with slightly lower sensitivity for Edwards and Patau syndrome. However, it is not 100% accurate and should not be used as a final diagnosis for positive cases.
TRIAL REGISTRATION NUMBER
CRD42014014947.
Topics: Biomarkers; Chromosome Disorders; Chromosomes, Human, Pair 13; Chromosomes, Human, Pair 18; DNA; Down Syndrome; Female; Humans; Pregnancy; Prenatal Diagnosis; Sensitivity and Specificity; Trisomy; Trisomy 13 Syndrome; Trisomy 18 Syndrome
PubMed: 26781507
DOI: 10.1136/bmjopen-2015-010002 -
Genetics and Molecular Research : GMR Sep 2015We evaluated the system accuracy of noninvasive prenatal diagnosis for abnormal chromosome genetic diseases using cell-free fetal DNA in maternal plasma. Previous... (Review)
Review
We evaluated the system accuracy of noninvasive prenatal diagnosis for abnormal chromosome genetic diseases using cell-free fetal DNA in maternal plasma. Previous studies were searched in the MEDLINE database using the following keywords: "prenatal" and "aneuploidy" and "noninvasive or non-invasive" and "maternal". Identified studies were filtered using a QUADAS instrument. Four studies were identified and analyzed using QUADAS. The studies included 4167 cases of Down syndrome patients determined by noninvasive prenatal diagnosis with a sensitivity of 100% and specificity of 99.3%; There were 3455 cases of Edwards syndrome patients determined by noninvasive prenatal diagnosis with a sensitivity of 97.4% and specificity of 99.95%. Therefore, noninvasive prenatal diagnosis can be used to identify abnormal chromosomes with high accuracy using free fetal DNA in the maternal plasma.
Topics: Adult; Aneuploidy; Chromosomes, Human, Pair 18; DNA; Down Syndrome; Female; Fetus; Humans; Male; Pregnancy; Prenatal Diagnosis; Trisomy; Trisomy 18 Syndrome
PubMed: 26400291
DOI: 10.4238/2015.September.9.1 -
Annals of Oncology : Official Journal... Apr 2015There is an urgent need for biomarkers to help predict prognosis and guide management of esophageal cancer. This review identifies, evaluates and meta-analyses the... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
There is an urgent need for biomarkers to help predict prognosis and guide management of esophageal cancer. This review identifies, evaluates and meta-analyses the evidence for reported somatic and germline DNA sequence biomarkers of outcome and stage.
METHODS
A systematic review was carried out of the PubMed, EMBASE and Cochrane databases (20 August 2014), in conjunction with the ASCO Level of Evidence scale for biomarker research. Meta-analyses were carried out for all reported markers associated with outcome measures by more than one study.
RESULTS
Four thousand and four articles were identified, 762 retrieved and 182 studies included. There were 65 reported markers of survival or recurrence 12 (18.5%) were excluded due to multiple comparisons. Following meta-analysis, significant associations were seen for six tumor variants (mutant TP53 and PIK3CA, copy number gain of ERBB2/HER2, CCND1 and FGF3, and chromosomal instability/ploidy) and seven germline polymorphisms: ERCC1 rs3212986, ERCC2 rs1799793, TP53 rs1042522, MDM2 rs2279744, TYMS rs34743033, ABCB1 rs1045642 and MTHFR rs1801133. Twelve germline markers of treatment complications were reported; 10 were excluded. Two tumor and 15 germline markers (11 excluded) of chemo (radio)therapy response were reported. Following meta-analysis, associations were demonstrated for mutant TP53, ERCC1 rs11615 and XRCC1 rs25487. There were 41 tumor/germline reported markers of stage; 27 (65.9%) were excluded.
CONCLUSIONS
Numerous DNA markers of outcome and stage have been reported, yet few are backed by high-quality evidence. Despite this, a small number of variants appear reliable. These merit evaluation in prospective trials, within the context of high-throughput sequencing and gene expression.
Topics: Biomarkers, Tumor; DNA, Neoplasm; Esophageal Neoplasms; Germ-Line Mutation; Humans; Neoplasm Staging; Polymorphism, Single Nucleotide; Prognosis
PubMed: 25214541
DOI: 10.1093/annonc/mdu449 -
Ultrasound in Obstetrics & Gynecology :... Jan 2015To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVES
To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta-analysis.
METHODS
A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000-2014) was performed to review relevant citations reporting procedure-related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I(2) statistic and Egger bias. Meta-analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence-rate difference meta-analysis was used to estimate pooled procedure-related risks.
RESULTS
The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58-1.08%) and 2.18% (95% CI, 1.61-2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46-0.91%) for amniocentesis and 1.79% (95% CI, 0.61-3.58%) for CVS. The weighted pooled procedure-related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, -0.04 to 0.26%) and 0.22% (95% CI, -0.71 to 1.16%), respectively.
CONCLUSION
The procedure-related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted.
Topics: Abortion, Spontaneous; Amniocentesis; Aneuploidy; Chorionic Villi Sampling; Decision Making; Female; Gestational Age; Humans; Odds Ratio; Patient Education as Topic; Pregnancy; Prenatal Diagnosis; Risk Factors
PubMed: 25042845
DOI: 10.1002/uog.14636 -
Ultrasound in Obstetrics & Gynecology :... Dec 2013To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid-trimester anomaly scan. (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To review the available literature on outcome of pregnancy when an isolated single umbilical artery (iSUA) is diagnosed at the time of the mid-trimester anomaly scan.
METHODS
We searched MEDLINE (1948-2012), EMBASE (1980-2012) and the Cochrane Library (until 2012) for relevant citations reporting on outcome of pregnancy with iSUA seen on ultrasound. Data were extracted by two reviewers. Where appropriate, we pooled odds ratios (ORs) for the dichotomous outcome measures: small for gestational age (SGA), perinatal mortality and aneuploidy. For birth weight we determined the mean difference with 95% CI.
RESULTS
We identified three cohort studies and four case-control studies reporting on 928 pregnancies with iSUA. There was significant heterogeneity between cohort and case-control studies. Compared to fetuses with a three-vessel cord, fetuses with an iSUA were more likely to be SGA (OR 1.6 (95% CI, 0.97-2.6); n = 489) or suffer perinatal mortality (OR 2.0 (95% CI, 0.9-4.2); n = 686), although for neither of the outcomes was statistical significance reached. The difference in mean birth weight was 51 g (95% CI, -154.7 to 52.6 g): n = 407), but again this difference was not statistically significant. We found no evidence that fetuses with iSUA have an increased risk for aneuploidy.
CONCLUSION
In view of the non-significant association between iSUA and fetal growth and perinatal mortality, and in view of the heterogeneity in studies on aneuploidy, we feel that large-scale, prospective cohort studies are needed to reach definitive conclusions on the appropriate work-up in iSUA pregnancies. At present, targeted growth assessment after diagnosis of iSUA should not be routine practice.
Topics: Aneuploidy; Birth Weight; Female; Fetal Development; Fetal Growth Retardation; Humans; Infant, Low Birth Weight; Infant, Newborn; Infant, Small for Gestational Age; Odds Ratio; Perinatal Mortality; Pregnancy; Risk; Single Umbilical Artery; Ultrasonography, Prenatal
PubMed: 23775879
DOI: 10.1002/uog.12541 -
Molecular Vision 2012To investigate the genetic associations of polypoidal choroidal vasculopathy (PCV), the genetic difference between PCV and age-related macular degeneration (AMD), and... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To investigate the genetic associations of polypoidal choroidal vasculopathy (PCV), the genetic difference between PCV and age-related macular degeneration (AMD), and the genotype-phenotype correlation of PCV.
METHODS
A systematic review and meta-analysis were performed. Published articles about genetic associations of PCV identified from a literature search were reviewed. The following data from individual studies were extracted and analyzed: 1) comparison of genetic polymorphisms between PCV and controls; 2) comparison of genetic polymorphisms between PCV and AMD; and 3) comparison of phenotypes between different genotype groups.
RESULTS
A total of 33 articles fulfilled the inclusion criteria. With meta-analyses, variants in four genes were found to be significantly associated with PCV: LOC387715 rs10490924 (n=9, allelic odds ratio [OR]=2.27, p<0.00001), HTRA1 rs11200638 (n=4, OR=2.72, p<0.00001), CFH rs1061170 (n=4, OR=1.72, p<0.00001), CFH rs800292 (n=5, OR=2.10, p<0.00001), and C2 rs547154 (n=3, OR=0.56, p=0.01). LOC387715 rs10490924 was the only variant showing a significant difference between PCV and wet AMD (n=5, OR=0.66, p<0.00001). The risk genotypes of rs10490924 were associated with larger lesion size, greater chance of vitreous hemorrhage, and worse therapeutic response in PCV.
CONCLUSIONS
LOC387715 rs10490924 was associated with PCV and its clinical manifestations, and showed a discrepant distribution between PCV and AMD. Variants in HTRA1, CFH, and C2 were also associated with PCV.
Topics: Alleles; Asian People; Choroid; Choroidal Neovascularization; Female; Gene Frequency; Genetic Association Studies; Genotype; Humans; Macular Degeneration; Male; Phenotype; Polymorphism, Single Nucleotide; Polyploidy; Proteins
PubMed: 22509112
DOI: No ID Found -
Genetics in Medicine : Official Journal... May 2011Autism is one of the most heritable complex disorders, but the genetic etiology of autism spectrum disorders is unexplained in ∼ 90% of cases. Highly penetrant... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Autism is one of the most heritable complex disorders, but the genetic etiology of autism spectrum disorders is unexplained in ∼ 90% of cases. Highly penetrant microdeletions and microduplications of 16p11.2 contribute to the pathogenesis of autism spectrum disorder, but the extent to which these variants account for the total burden of idiopathic autism spectrum disorders has not been systematically investigated.
METHODS
A systematic literature review and meta-analysis were performed to determine the prevalence of these variants among individuals diagnosed with autism spectrum disorders. A planned subgroup analysis was conducted to assess prevalence differences between sporadic and familial autism spectrum disorder cases.
RESULTS
In the combined analysis of 3613 idiopathic autism spectrum disorder cases from seven studies, the meta-analytic prevalence of these microdeletions and microduplications was 0.76% (95% CI, 0.51-1.12%). When stratified by copy number variant-type, the prevalence of microdeletions was 0.50% (95% CI, 0.31-0.82%) and the prevalence of microduplications was 0.28% (95% CI, 0.14-0.56%). Sporadic autism spectrum disorder cases showed only a slightly higher prevalence than familial cases.
CONCLUSION
The number needed to test to identify one such variant is 132 patients (95% CI, 89-198). Such information, especially as it pertains to diagnostic yield in genetic testing, should prove useful to clinicians considering chromosomal microarray analysis in subjects with autism spectrum disorders.
Topics: Child; Child Development Disorders, Pervasive; Chromosome Deletion; Chromosome Duplication; Chromosomes, Human, Pair 16; DNA Copy Number Variations; Gene Dosage; Humans; Incidence; Publication Bias
PubMed: 21289514
DOI: 10.1097/GIM.0b013e3182076c0c -
Developmental Medicine and Child... Feb 2010To review systematically the neurodevelopmental characteristics of individuals with sex chromosome trisomies (SCTs). (Review)
Review
AIM
To review systematically the neurodevelopmental characteristics of individuals with sex chromosome trisomies (SCTs).
METHOD
A bibliographic search identified English-language articles on SCTs. The focus was on studies unbiased by clinical referral, with power of at least 0.69 to detect an effect size of 1.0.
RESULTS
We identified 35 articles on five neonatally identified samples that had adequate power for our review. An additional 11 studies were included where cases had been identified for reasons other than neurodevelopmental concerns. Individuals with an additional X chromosome had mean IQs that were within broadly normal limits but lower than the respective comparison groups, with verbal IQ most affected. Cognitive outcomes were poorest for females with XXX. Males with XYY had normal-range IQs, but all three SCT groups (XXX, XXY, and XYY) had marked difficulties in speech and language, motor skills, and educational achievement. Nevertheless, most adults with SCTs lived independently. Less evidence was available for brain structure and for attention, social, and psychiatric outcomes. Within each group there was much variation.
INTERPRETATION
Individuals with SCTs are at risk of cognitive and behavioural difficulties. However, the evidence base is slender, and further research is needed to ascertain the nature, severity, and causes of these difficulties in unselected samples.
Topics: Child; Chromosome Disorders; Databases, Factual; Developmental Disabilities; Female; Humans; Intellectual Disability; Karyotyping; Male; Neuropsychological Tests; Sex Chromosomes; Trisomy
PubMed: 20059514
DOI: 10.1111/j.1469-8749.2009.03545.x -
Fetal Diagnosis and Therapy 2009Pentasomy 49,XXXXY is a rare sex chromosome polysomy usually diagnosed postnatally by the combina- tion of mental retardation, facial dysmorphism, and genital, cardiac... (Review)
Review
OBJECTIVES
Pentasomy 49,XXXXY is a rare sex chromosome polysomy usually diagnosed postnatally by the combina- tion of mental retardation, facial dysmorphism, and genital, cardiac and skeletal malformations. Prenatal detection of 49,XXXXY is unusual and may be incidental due to non-specific ultrasound (US) findings. We report a case of 49,XXXXY diagnosed prenatally and present a literature review of the few prenatally diagnosed cases.
METHODS
We searched the PubMed electronic database without year and language restriction, using the keywords 'Prenatal', 'Diagnosis', and '49,XXXY', performing a systematic review.
RESULTS
We report a 35-year-old patient with normal first-trimester US but increased combined risk for trisomies 18 and 13. Amniocentesis at 16 weeks of gestation revealed a 49,XXXXY karyotype. Pregnancy was terminated at 19 weeks' gestation, and a male fetus with facial dysmorphism and hypospadia was delivered. A total of 12 articles were identified in the systematic review. All were case reports and dated from 1980 until 2008. The mean maternal age was 34.8 years (range 30-41). The most common prenatal US feature was cystic hygroma, present in 5 cases. Hypogenitalism was the most common macroscopic clinical feature identified after pathology examination in 7 cases. In 2 cases, there was an increase in first-trimester combined risk for trisomy 21.
CONCLUSIONS
Pentasomy 49,XXXXY is associated with a variety of non-specific US findings, of which cystic hygroma was the commonest. No specific sequence of findings could be identified in this review.
Topics: Adult; Amniocentesis; Aneuploidy; Female; Humans; Male; Pregnancy; Sex Chromosome Disorders
PubMed: 19816022
DOI: 10.1159/000236351