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The Cochrane Database of Systematic... Nov 2015Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Down's syndrome occurs when a person has three, rather than two copies of chromosome 21; or the specific area of chromosome 21 implicated in causing Down's syndrome. It is the commonest congenital cause of mental disability and also leads to numerous metabolic and structural problems. It can be life-threatening, or lead to considerable ill health, although some individuals have only mild problems and can lead relatively normal lives. Having a baby with Down's syndrome is likely to have a significant impact on family life.Noninvasive screening based on biochemical analysis of maternal serum or urine, or fetal ultrasound measurements, allows estimates of the risk of a pregnancy being affected and provides information to guide decisions about definitive testing. However, no test can predict the severity of problems a person with Down's syndrome will have.
OBJECTIVES
The aim of this review was to estimate and compare the accuracy of first trimester serum markers for the detection of Down's syndrome in the antenatal period, both as individual markers and as combinations of markers. Accuracy is described by the proportion of fetuses with Down's syndrome detected by screening before birth (sensitivity or detection rate) and the proportion of women with a low risk (normal) screening test result who subsequently had a baby unaffected by Down's syndrome (specificity).
SEARCH METHODS
We conducted a sensitive and comprehensive literature search of MEDLINE (1980 to 25 August 2011), Embase (1980 to 25 August 2011), BIOSIS via EDINA (1985 to 25 August 2011), CINAHL via OVID (1982 to 25 August 2011), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 25 August 2011), MEDION (25 August 2011), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (25 August 2011), The National Research Register (Archived 2007), Health Services Research Projects in Progress database (25 August 2011). We did forward citation searching ISI citation indices, Google Scholar and PubMed 'related articles'. We did not apply a diagnostic test search filter. We also searched reference lists and published review articles.
SELECTION CRITERIA
We included studies in which all women from a given population had one or more index test(s) compared to a reference standard (either chromosomal verification or macroscopic postnatal inspection). Both consecutive series and diagnostic case-control study designs were included. Randomised trials where individuals were randomised to different screening strategies and all verified using a reference standard were also eligible for inclusion. Studies in which test strategies were compared head-to-head either in the same women, or between randomised groups were identified for inclusion in separate comparisons of test strategies. We excluded studies if they included less than five Down's syndrome cases, or more than 20% of participants were not followed up.
DATA COLLECTION AND ANALYSIS
We extracted data as test positive or test negative results for Down's and non-Down's pregnancies allowing estimation of detection rates (sensitivity) and false positive rates (1-specificity). We performed quality assessment according to QUADAS (Quality Assessment of Diagnostic Accuracy Studies) criteria. We used hierarchical summary ROC meta-analytical methods or random-effects logistic regression methods to analyse test performance and compare test accuracy as appropriate. Analyses of studies allowing direct and indirect comparisons between tests were undertaken.
MAIN RESULTS
We included 56 studies (reported in 68 publications) involving 204,759 pregnancies (including 2113 with Down's syndrome). Studies were generally of good quality, although differential verification was common with invasive testing of only high-risk pregnancies. We evaluated 78 test combinations formed from combinations of 18 different tests, with or without maternal age; ADAM12 (a disintegrin and metalloprotease), AFP (alpha-fetoprotein), inhibin, PAPP-A (pregnancy-associated plasma protein A, ITA (invasive trophoblast antigen), free βhCG (beta human chorionic gonadotrophin), PlGF (placental growth factor), SP1 (Schwangerschafts protein 1), total hCG, progesterone, uE3 (unconjugated oestriol), GHBP (growth hormone binding protein), PGH (placental growth hormone), hyperglycosylated hCG, ProMBP (proform of eosinophil major basic protein), hPL (human placental lactogen), (free αhCG, and free ßhCG to AFP ratio. Direct comparisons between two or more tests were made in 27 studies.Meta-analysis of the nine best performing or frequently evaluated test combinations showed that a test strategy involving maternal age and a double marker combination of PAPP-A and free ßhCG significantly outperformed the individual markers (with or without maternal age) detecting about seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate (FPR). Limited evidence suggested that marker combinations involving PAPP-A may be more sensitive than those without PAPP-A.
AUTHORS' CONCLUSIONS
Tests involving two markers in combination with maternal age, specifically PAPP-A, free βhCG and maternal age are significantly better than those involving single markers with and without age. They detect seven out of 10 Down's affected pregnancies for a fixed 5% FPR. The addition of further markers (triple tests) has not been shown to be statistically superior; the studies included are small with limited power to detect a difference.The screening blood tests themselves have no adverse effects for the woman, over and above the risks of a routine blood test. However some women who have a 'high risk' screening test result, and are given amniocentesis or chorionic villus sampling (CVS) have a risk of miscarrying a baby unaffected by Down's. Parents will need to weigh up this risk when deciding whether or not to have an amniocentesis or CVS following a 'high risk' screening test result.
Topics: ADAM Proteins; ADAM12 Protein; Biomarkers; Chorionic Gonadotropin, beta Subunit, Human; Down Syndrome; Female; Humans; Maternal Age; Membrane Proteins; Predictive Value of Tests; Pregnancy; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Prenatal Diagnosis; alpha-Fetoproteins
PubMed: 26617074
DOI: 10.1002/14651858.CD011975 -
The Cochrane Database of Systematic... Apr 2018Identification of the causes of stillbirth is critical to the primary prevention of stillbirth and to the provision of optimal care in subsequent pregnancies. A wide... (Review)
Review
BACKGROUND
Identification of the causes of stillbirth is critical to the primary prevention of stillbirth and to the provision of optimal care in subsequent pregnancies. A wide variety of investigations are available, but there is currently no consensus on the optimal approach. Given their cost and potential to add further emotional burden to parents, there is a need to systematically assess the effect of these interventions on outcomes for parents, including psychosocial outcomes, economic costs, and on rates of diagnosis of the causes of stillbirth.
OBJECTIVES
To assess the effect of different tests, protocols or guidelines for investigating and identifying the causes of stillbirth on outcomes for parents, including psychosocial outcomes, economic costs, and rates of diagnosis of the causes of stillbirth.
SEARCH METHODS
We searched Cochrane Pregnancy and Childbirth's Trials Register (31 August 2017), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP) (15 May 2017).
SELECTION CRITERIA
We planned to include randomised controlled trials (RCTs), quasi-RCTs, and cluster-RCTs. We planned to include studies published as abstract only, provided there was sufficient information to allow us to assess study eligibility. We planned to exclude cross-over trials.Participants included parents (including mothers, fathers, and partners) who had experienced a stillbirth of 20 weeks' gestation or greater.This review focused on interventions for investigating and identifying the causes of stillbirth. Such interventions are likely to be diverse, but could include:* review of maternal and family history, and current pregnancy and birth history;* clinical history of present illness;* maternal investigations (such as ultrasound, amniocentesis, antibody screening, etc.);* examination of the stillborn baby (including full autopsy, partial autopsy or noninvasive components, such as magnetic resonance imaging (MRI), computerised tomography (CT) scanning, and radiography);* umbilical cord examination;* placental examination including histopathology (microscopic examination of placental tissue); and* verbal autopsy (interviews with care providers and support people to ascertain causes, without examination of the baby).We planned to include trials assessing any test, protocol or guideline (or combinations of tests/protocols/guidelines) for investigating the causes of stillbirth, compared with the absence of a test, protocol or guideline, or usual care (further details are presented in the Background, see Description of the intervention).We also planned to include trials comparing any test, protocol or guideline (or combinations of tests/protocols/guidelines) for investigating the causes of stillbirth with another, for example, the use of a limited investigation protocol compared with a comprehensive investigation protocol.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trial eligibility independently.
MAIN RESULTS
We excluded five studies that were not RCTs. There were no eligible trials for inclusion in this review.
AUTHORS' CONCLUSIONS
There is currently a lack of RCT evidence regarding the effectiveness of interventions for investigating and identifying the causes of stillbirth. Seeking to determine the causes of stillbirth is an essential component of quality maternity care, but it remains unclear what impact these interventions have on the psychosocial outcomes of parents and families, the rates of diagnosis of the causes of stillbirth, and the care and management of subsequent pregnancies following stillbirth. Due to the absence of trials, this review is unable to inform clinical practice regarding the investigation of stillbirths, and the specific investigations that would determine the causes.Future RCTs addressing this research question would be beneficial, but the settings in which the trials take place, and their design, need to be given careful consideration. Trials need to be conducted with the utmost care and consideration for the needs, concerns, and values of parents and families. Assessment of longer-term psychosocial variables, economic costs to health services, and effects on subsequent pregnancy care and outcomes should also be considered in any future trials.
Topics: Cause of Death; Female; Humans; Pregnancy; Stillbirth
PubMed: 29709055
DOI: 10.1002/14651858.CD012504.pub2 -
Ultrasound in Obstetrics & Gynecology :... Nov 2020To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To assess the rate of fetal loss following amniocentesis or chorionic villus sampling (CVS) in twin pregnancy.
METHODS
MEDLINE, EMBASE and Cochrane databases were searched for studies reporting procedure-related complications following amniocentesis or CVS in twin pregnancy. The primary outcome was the rate of procedure-related fetal loss. The secondary outcomes were fetal loss occurring before 24 weeks of gestation and fetal loss occurring within 4 weeks after the procedure. Head-to-head meta-analyses were used to compare directly each outcome, between women undergoing amniocentesis and those not undergoing amniocentesis and between women undergoing CVS and those not undergoing CVS, and to compute pooled risk differences (RD) between women exposed and those not exposed to each invasive procedure. Additionally, meta-analyses of proportions were used to estimate the pooled rates of each of the three outcomes in women undergoing amniocentesis or CVS and in controls.
RESULTS
Sixteen studies (3419 twin pregnancies undergoing and 2517 not undergoing an invasive procedure) were included. Head-to-head meta-analyses comparing directly twin pregnancies undergoing and those not undergoing amniocentesis showed a higher risk for overall fetal loss in those undergoing amniocentesis (odds ratio (OR), 1.46 (P = 0.04); RD, 0.013 (P = 0.04)), while there was no difference in the risk of either fetal loss before 24 weeks of gestation (OR, 1.59 (P = 0.06); RD, 0.010 (P = 0.11)) or fetal loss within 4 weeks after the procedure (OR, 1.38 (P = 0.3); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.4% (95% CI, 1.4-3.6%) in twin pregnancies undergoing amniocentesis compared with 2.4% (95% CI, 0.9-4.6%) in those not undergoing amniocentesis. Head-to-head meta-analyses directly comparing twin pregnancies undergoing and those not undergoing CVS showed no significant difference in either overall fetal loss (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)) or fetal loss before 24 weeks of gestation (OR, 1.61 (P = 0.5); RD, 0.003 (P = 0.8)). Overall, the pooled rate of fetal loss was 2.0% (95% CI, 0.0-6.5%) in twin pregnancies undergoing CVS compared with 1.8% (95% CI, 0.3-4.2%) in those not undergoing CVS.
CONCLUSION
The risk of fetal loss following amniocentesis and CVS in twins is lower than reported previously and the rate of fetal loss before 24 weeks of gestation, or within 4 weeks after the procedure, did not differ from the background risk in twin pregnancy not undergoing invasive prenatal testing. These data can guide prenatal counseling for twin pregnancies undergoing invasive procedures. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Topics: Abortion, Spontaneous; Adult; Amniocentesis; Chorionic Villi Sampling; Female; Fetal Death; Humans; Odds Ratio; Pregnancy; Pregnancy, Twin; Risk Factors
PubMed: 32632979
DOI: 10.1002/uog.22143 -
Acta Obstetricia Et Gynecologica... Nov 2020Emergency cerclage is the most common active intervention in pregnant women with cervical insufficiency. This meta-analysis aimed to compare the effectiveness of... (Comparative Study)
Comparative Study Meta-Analysis
INTRODUCTION
Emergency cerclage is the most common active intervention in pregnant women with cervical insufficiency. This meta-analysis aimed to compare the effectiveness of emergency cerclage vs expectant management on maternal and perinatal outcomes, and to assess the current status of evidence.
MATERIAL AND METHODS
A search was conducted from 1 June 2019 until 1 September 2019 and eligible studies were identified in the MEDLINE, Scopus, Cochrane and US clinical trials registry without limitations concerning the publication dates and languages. Randomized controlled trials (RCTs), non-RCTs and observational studies comparing emergency cerclage with no cerclage/expectant management, in women presenting with painless cervical dilatation were included.
RESULTS
The electronic search yielded 3607 potential studies, of which 38 were fully reviewed and 12 observational studies (1021 participants) were included. Cerclage was superior to expectant management for the primary outcomes of preterm birth before 28 and 32 gestational weeks, OR 0.25 (95% CI 0.16-0.39, five studies, N = 392, I = 41%, low quality) and 0.08 (95% CI 0.02-0.29, four studies, N = 176, I = 51%, low quality), respectively. Cerclage was also superior to expectant management for the secondary outcomes of fetal loss OR 0.26 (95% CI 0.12-0.56, 8 studies, N = 455, I = 46%, very low-quality), pregnancy prolongation in days mean difference 47.45 (95% CI 39.89-55.0, 12 studies, N = 1027 I = 86%, very low quality), gestational age at birth in weeks mean difference 5.68 (95% CI 4.69-6.67, 9 studies, N = 892, I = 73%, very low quality), admission to neonatal intensive care OR 0.21 (95% CI 0.07-0.70, two studies, N = 79, I = 36%, very low quality) and neonatal death OR 0.12 (95% CI 0.04-0.34, five studies, N = 130, I = 0%, very low quality). There were no differences between cerclage and expectant management concerning premature rupture of membranes during or after the procedure OR 0.68 (95% CI 0.31-1.48, two studies, N = 155, I = 85%, very low quality) and chorioamnionitis OR 1.14 (95% CI 0.31-4.25, three studies, N = 88, I = 33%, very low quality).
CONCLUSIONS
Emergency cerclage in pregnant women with painless cervical dilatation seems to decrease preterm births, prolong the pregnancy, and decrease the neonatal deaths and fetal losses, but does not increase the risk of chorioamnionitis and premature rupture of membranes. Despite the extremely favorable estimates for cerclage, the results should be viewed with caution because, as a result of the lack of randomized control trials, the quality of evidence is low to very low.
Topics: Cerclage, Cervical; Emergencies; Female; Humans; Infant; Infant Mortality; Infant, Newborn; Intensive Care, Neonatal; Pregnancy; Premature Birth; Treatment Outcome; Uterine Cervical Incompetence; Watchful Waiting
PubMed: 32757297
DOI: 10.1111/aogs.13968 -
PloS One 2021Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in...
Current practices of management of maternal and congenital Cytomegalovirus infection during pregnancy after a maternal primary infection occurring in first trimester of pregnancy: Systematic review.
INTRODUCTION
Congenital CMV infection is the first worldwide cause of congenital viral infection but systematic screening of pregnant women and newborns for CMV is still debated in many countries.
OBJECTIVES
This systematic review aims to provide the state of the art on current practices concerning management of maternal and congenital CMV infection during pregnancy, after maternal primary infection (PI) in first trimester of pregnancy.
DATA SOURCES
Electronically searches on databases and hand searches in grey literature.
STUDY ELIGIBILITY CRITERIA AND PARTICIPANTS
Primary outcome was listing biological, imaging, and therapeutic management interventions in two distinct populations: population 1 are pregnant women with PI, before or without amniocentesis; population 2 are pregnant women with congenitally infected fetuses (after positive amniocentesis). Secondary outcome was pregnancy outcome in population 2.
RESULTS
Out of 4,134 studies identified, a total of 31 studies were analyzed, with 3,325 pregnant women in population 1 and 1,021 pregnant women in population 2, from 7 countries (Belgium, France, Germany, Israel, Italy, Spain and USA). In population 1, ultrasound (US) examination frequency was 0.75/month, amniocentesis in 82% cases, maternal viremia in 14% and preventive treatment with hyperimmune globulins (HIG) or valaciclovir in respectively 14% and 4% women. In population 2, US examination frequency was 1.5/month, magnetic resonance imaging (MRI) in 44% cases at 32 weeks gestation (WG), fetal blood sampling (FBS) in 24% at 28 WG, and curative treatment with HIG or valaciclovir in respectively 9% and 8% patients.
CONCLUSIONS
This systematic review illustrates management of maternal and congenital CMV during pregnancy in published and non-published literature, in absence of international consensus.
SYSTEMATIC REVIEW REGISTRATION
PROSPERO CRD42019124342.
Topics: Amniocentesis; Cytomegalovirus; Cytomegalovirus Infections; Disease Management; Female; Fetal Diseases; Humans; Infant, Newborn; Infectious Disease Transmission, Vertical; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Prenatal Diagnosis
PubMed: 34860861
DOI: 10.1371/journal.pone.0261011 -
Journal of the Turkish German... 2016To perform a meta-analysis for an assessment of the risk of preeclampsia or gestational hypertension following chorionic villus sampling (CVS).
OBJECTIVE
To perform a meta-analysis for an assessment of the risk of preeclampsia or gestational hypertension following chorionic villus sampling (CVS).
DATA SOURCE
PubMed was systematically searched from its inception through January 2016.
MATERIAL AND METHODS
Nine reports were identified. A pre-specified scale was used to assess their quality.
TABULATION INTEGRATION AND RESULTS
We performed pooling into three subgroups with respect to the control group: A) Patients with no invasive prenatal diagnostic procedure served as a control group for comparison. The odds ratios for gestational hypertension (0.76, 95% CI 0.46-1.26), preeclampsia (0.83, 95% CI 0.42-1.67), and severe preeclampsia (0.49, 95% CI 0.04-5.78) or when hypertension categories were pooled (0.80, 95% CI 0.46-1.41) were not significantly different. B) Patients with midtrimester diagnostic amniocentesis and patients with no invasive prenatal diagnostic procedure were combined as a control group for comparison. The odds ratios for preeclampsia (1, 95% CI 0.46-2.18), severe preeclampsia (0.83, 95% CI 0.14-4.85), and pooled hypertension categories (1.07, 95% CI 0.63-1.84) were not significantly different. C) Patients with midtrimester diagnostic amniocentesis served as a control group. There was a significant difference in the odds ratio for preeclampsia between the CVS and amniocentesis groups (2.47, 95% CI 1.14-5.33). There was a marginal difference in the odds ratio for combined pregnancy-induced hypertension categories between the CVS and amniocentesis groups (1.61, 95% CI 1.02-2.53).
CONCLUSION
The available data do not indicate an increased risk of preeclampsia or gestational hypertension following first trimester CVS. The heterogeneity and retrospective design of existing studies are limiting factors for our analysis and findings.
PubMed: 27403071
DOI: 10.5152/jtgga.2016.16026 -
Ultrasound in Obstetrics & Gynecology :... Nov 2019To investigate the ultrasound characteristics and outcome of fetuses with non-visualization of the fetal gallbladder (NVFGB) followed in our tertiary university... (Meta-Analysis)
Meta-Analysis
OBJECTIVES
To investigate the ultrasound characteristics and outcome of fetuses with non-visualization of the fetal gallbladder (NVFGB) followed in our tertiary university hospital, and to provide a comprehensive review of the literature on prenatal findings and outcome of NVFGB.
METHODS
NVFGB was defined as non-visualization of the gallbladder on two targeted ultrasound examinations performed within a 1-week period. First, we reviewed the medical records of NVFGB cases managed in our center over a 9-year period. Then, we performed a systematic review of the literature to identify studies on NVFGB. The incidence of chromosomal anomalies, later visualization of the gallbladder, gallbladder agenesis, cystic fibrosis and biliary atresia was assessed in fetuses with isolated and non-isolated NVFGB. The role of hepatic enzyme measurements in the diagnosis of cystic fibrosis and biliary atresia in fetuses with NVFGB was also reviewed.
RESULTS
Sixteen cases of NVFGB were followed in our center, in 10 (62.5%) of which it was an isolated finding. The incidence of biliary atresia was 12.5% and that of gallbladder agenesis was 12.5%, while no case of cystic fibrosis was reported. The gallbladder was visualized later in pregnancy or postnatally in 43.8% and 25.0% of cases, respectively. A total of seven studies, including our cohort, involving a total of 280 NVFGB cases, met the inclusion criteria for the systematic review. Overall, 20.5% of fetuses had an associated ultrasound anomaly, and the incidence of chromosomal anomaly in this group was 20.4%. In cases with isolated NVFGB, the incidence of chromosomal anomaly was 1.9%. In fetuses with normal karyotype and isolated NVFGB, the gallbladder was later visualized in 70.4% of cases, while the incidence of gallbladder agenesis, cystic fibrosis and biliary atresia was 25.2%, 3.1% and 4.8%, respectively. In fetuses with non-isolated NVFGB, the incidence of cystic fibrosis and biliary atresia was 23.1% and 18.2%, respectively. The negative predictive value of amniotic fluid enzyme levels for the prediction of severe disease (including biliary atresia or cystic fibrosis) ranged between 94% and 100% when evaluated before 22 weeks' gestation, and dropped to 88% after 22 weeks.
CONCLUSIONS
In cases with persistent NVFGB, the risk of a severe postnatal condition should be considered. A detailed ultrasound scan should be offered and parents tested for cystic fibrosis gene mutation. An invasive procedure for karyotyping and measurement of liver enzyme concentrations before 22 weeks constitutes a reasonable work-up. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.
Topics: Amniocentesis; Biliary Atresia; Chromosome Aberrations; Cystic Fibrosis; Female; Gallbladder; Humans; Pregnancy; Pregnancy Trimester, Second; Prospective Studies; Retrospective Studies; Ultrasonography, Prenatal
PubMed: 30809885
DOI: 10.1002/uog.20252 -
Experimental and Therapeutic Medicine Sep 2020Fetal goitrous hypothyroidism is a rare condition associated with important obstetrical, neonatal complications, and neurodevelopmental impairments. Prenatal treatment...
Fetal goitrous hypothyroidism is a rare condition associated with important obstetrical, neonatal complications, and neurodevelopmental impairments. Prenatal treatment remains controversial, and the risk to benefit ratio must be accurately assessed and considered for individualized management. The objective of this review was to evaluate the feasibility, safety, and effectiveness of the conservative treatment of fetal goitrous hypothyroidism. In total, 25 reports that met our inclusion criteria were selected and the management of 38 cases was analyzed. Prenatal diagnosis consisted mainly of ultrasonographic findings. Fetal thyroid status was assessed by cordocentesis. Prenatal treatment varied widely in terms of levothyroxine (LT4) route of administration, dosage, number of injections, and frequency. Although different regimens and routes of administration were proposed, they seem to have similar results regarding fetal goiter reduction and thyroid status at birth. At birth, most babies had hypothyroidism, but the long-term follow-up indicated a normal psycho-neuromotor development. Our data confirm the feasibility of conservative treatment with LT4 for fetal goitrous hypothyroidism. Further studies are needed to determine the optimal management of this disorder.
PubMed: 32765729
DOI: 10.3892/etm.2020.8794