Cervical cerclage is a well-known surgical procedure carried out during pregnancy. It involves positioning of a suture (stitch) around the neck of the womb (cervix), aiming to give mechanical support ...to the cervix and thereby reduce risk of preterm birth. The effectiveness and safety of this procedure remains controversial. This is an update of a review last published in 2012.
To assess whether the use of cervical stitch in singleton pregnancy at high risk of pregnancy loss based on woman's history and/or ultrasound finding of 'short cervix' and/or physical exam improves subsequent obstetric care and fetal outcome.
We searched Cochrane Pregnancy and Childbirth's Trials Register (30 June 2016) and reference lists of identified studies.
We included all randomised trials of cervical suturing in singleton pregnancies. Cervical stitch was carried out when the pregnancy was considered to be of sufficiently high risk due to a woman's history, a finding of short cervix on ultrasound or other indication determined by physical exam. We included any study that compared cerclage with either no treatment or any alternative intervention. We planned to include cluster-randomised studies but not cross-over trials. We excluded quasi-randomised studies. We included studies reported in abstract form only.
Three review authors independently assessed trials for inclusion. Two review authors independently assessed risk of bias and extracted data. We resolved discrepancies by discussion. Data were checked for accuracy. The quality of the evidence was assessed using the GRADE approach.
This updated review includes a total of 15 trials (3490 women); three trials were added for this update (152 women). Cerclage versus no cerclageOverall, cerclage probably leads to a reduced risk of perinatal death when compared with no cerclage, although the confidence interval (CI) crosses the line of no effect (RR 0.82, 95% CI 0.65 to 1.04; 10 studies, 2927 women; moderate quality evidence). Considering stillbirths and neonatal deaths separately reduced the numbers of events and sample size. Although the relative effect of cerclage is similar, estimates were less reliable with fewer data and assessed as of low quality (stillbirths RR 0.89, 95% CI 0.45 to 1.75; 5 studies, 1803 women; low quality evidence; neonatal deaths before discharge RR 0.85, 95% CI 0.53 to 1.39; 6 studies, 1714 women; low quality evidence). Serious neonatal morbidity was similar with and without cerclage (RR 0.80, 95% CI 0.55 to 1.18; 6 studies, 883 women; low-quality evidence). Pregnant women with and without cerclage were equally likely to have a baby discharged home healthy (RR 1.02, 95% CI 0.97 to 1.06; 4 studies, 657 women; moderate quality evidence).Pregnant women with cerclage were less likely to have preterm births compared to controls before 37, 34 (average RR 0.77, 95% CI 0.66 to 0.89; 9 studies, 2415 women; high quality evidence) and 28 completed weeks of gestation.Five subgroups based on clinical indication provided data for analysis (history-indicated; short cervix based on one-off ultrasound in high risk women; short cervix found by serial scans in high risk women; physical exam-indicated; and short cervix found on scan in low risk or mixed populations). There were too few trials in these clinical subgroups to make meaningful conclusions and no evidence of differential effects. Cerclage versus progesteroneTwo trials (129 women) compared cerclage to prevention with vaginal progesterone in high risk women with short cervix on ultrasound; these trials were too small to detect reliable, clinically important differences for any review outcome. One included trial compared cerclage with intramuscular progesterone (75 women) which lacked power to detect group differences. History indicated cerclage versus ultrasound indicated cerclageEvidence from two trials (344 women) was too limited to establish differences for clinically important outcomes.
Cervical cerclage reduces the risk of preterm birth in women at high-risk of preterm birth and probably reduces risk of perinatal deaths. There was no evidence of any differential effect of cerclage based on previous obstetric history or short cervix indications, but data were limited for all clinical groups. The question of whether cerclage is more or less effective than other preventative treatments, particularly vaginal progesterone, remains unanswered.
As a consequence of the introduction of effective screening methods, the number of invasive prenatal diagnostic procedures is steadily declining. The aim of this review is to summarize the risks ...related to these procedures.
Review of the literature.
Data from randomised controlled trials as well as from systematic reviews and a large national registry study are consistent with a procedure-related miscarriage rate of 0.5-1.0% for amniocentesis as well as for chorionic villus sampling (CVS). In single-center studies performance may be remarkably good due to very skilled operators, but these figures cannot be used for general counselling. Amniocentesis performed prior to 15 weeks had a significantly higher miscarriage rate than CVS and mid-trimester amniocentesis, and also increased the risk of talipes equinovarus. Amniocentesis should therefore not be performed before 15 + 0 weeks' gestation. CVS on the other hand should not be performed before 10 weeks' gestation due to a possible increase in risk of limb reduction defects.
Experienced operators have a higher success rate and a lower complication rate. The decreasing number of prenatal invasive procedures calls for quality assurance and monitoring of operators' performance.
Cervical cerclage is a surgical intervention involving placing a stitch around the uterine cervix. The suture material aims to prevent cervical shortening and opening, thereby reducing the risk of ...preterm birth. The effectiveness and safety of this procedure in multiple gestations remains controversial.
To assess whether the use of a cervical cerclage in multiple gestations, either at high risk of pregnancy loss based on just the multiple gestation (history-indicated cerclage), the ultrasound findings of 'short cervix' (ultrasound-indicated cerclage), or the physical exam changes in the cervix (physical exam-indicated cerclage), improves obstetrical and perinatal outcomes. The primary outcomes assessed were perinatal deaths, serious neonatal morbidity, and perinatal deaths and serious neonatal morbidity.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 June 2014) and reference lists of retrieved studies.
All randomised controlled trials (RCTs) of cervical cerclage in multiple pregnancies. Quasi-RCTs and RCTs using a cluster-randomised design were eligible for inclusion (but none were identified). Studies using a cross-over design and those presented only as abstracts were not eligible for inclusion.We included studies comparing cervical cerclage with no cervical cerclage in multiple pregnancies.Studies comparing cervical stitch versus any other preventative therapy (e.g. progesterone) in multiple pregnancies, and studies involving comparisons between different cerclage protocols (history-indicated versus ultrasound-indicated versus physical exam-indicated cerclage) were also eligible for inclusion but none were identified.
Two review authors independently assessed trials for inclusion and risk of bias. Two review authors extracted data. Data were checked for accuracy.
We included five trials, which in total randomised 1577 women, encompassing both singleton and multiple gestations. After excluding singletons, the final analysis included 128 women, of which 122 women had twin gestations, and six women had triplet gestations. Two trials (n = 73 women) assessed history-indicated cerclage, while three trials (n = 55 women) assessed ultrasound-indicated cerclage. The five trials were judged to be of average to above average quality, with three of the trials at unclear risk regarding selection and detection biases.Concerning the primary outcomes, when outcomes for cerclage were pooled together for all indications and compared with no cerclage, there was no statistically significant differences in perinatal deaths (19.2% versus 9.5%; risk ratio (RR) 1.74, 95% confidence intervals (CI) 0.92 to 3.28, five trials, n = 262), serious neonatal morbidity (15.8% versus 13.6%; average RR 0.96, 95% CI 0.13 to 7.10, three trials, n = 116), or composite perinatal death and neonatal morbidity (40.4% versus 20.3%; average RR 1.54, 95% CI 0.58 to 4.11, three trials, n = 116).Among the secondary outcomes, there were no significant differences between the cerclage and the no cerclage groups. To name a few, there were no significant differences among the following: preterm birth less than 34 weeks (average RR 1.16, 95% CI 0.44 to 3.06, four trials, n = 83), preterm birth less than 35 weeks (average RR 1.11, 95% CI 0.58 to 2.14, four trials, n = 83), low birthweight less than 2500 g (average RR 1.10, 95% CI 0.82 to 1.48, four trials, n = 172), very low birthweight less than 1500 g (average RR 1.42, 95% CI 0.52 to 3.85, four trials, n = 172), and respiratory distress syndrome (average RR 1.70, 95% CI 0.15 to 18.77, three trials, n = 116). There were also no significant differences between the cerclage and no cerclage groups when examining caesarean section (elective and emergency) (RR 1.24, 95% CI 0.65 to 2.35, three trials, n = 77) and maternal side-effects (RR 3.92, 95% CI 0.17 to 88.67, one trial, n = 28).Examining the differences between prespecified subgroups, ultrasound-indicated cerclage was associated with an increased risk of low birthweight (average RR 1.39, 95% CI 1.06 to 1.83, Tau² = 0.01, I² = 15%, three trials, n = 98), very low birthweight (average RR 3.31, 95% CI 1.58 to 6.91, Tau² = 0, I² = 0%, three trials, n = 98), and respiratory distress syndrome (average RR 5.07, 95% CI 1.75 to 14.70, Tau² = 0, I² = 0%, three trials, n = 98). However, given the low number of trials, as well as substantial heterogeneity and subgroup differences, these data must be interpreted cautiously.No trials reported on long-term infant neurodevelopmental outcomes. There were no physical exam-indicated cerclages available for comparison among the studies included.
This review is based on limited data from five small studies of average to above average quality. For multiple gestations, there is no evidence that cerclage is an effective intervention for preventing preterm births and reducing perinatal deaths or neonatal morbidity.
Pre-term birth (PTB) remains the leading cause of infant mortality and morbidity. Its etiology is multifactorial, with a strong genetic component. Genetic predisposition for the two subtypes, ...spontaneous PTB with intact membranes (sPTB) and preterm prelabor rapture of membranes (PPROM), and differences between them, have not yet been systematically summarised.
Our literature search identified 15 association studies conducted in 3,600 women on 2175 SNPs in 274 genes. We used Ingenuity software to impute gene pathways and networks related to sPTB and PPROM. Detailed insight in the defined functional ontologies clearly separated integrated datasets for sPTB and PPROM. Our analysis of upstream regulators of genes suggests that glucocorticoid receptor (NR3C1), peroxisome proliferator activated receptor γ (PPARG) and interferon regulating factor 3 (IRF3) may be sPTB specific. PPROM-specific genes may be regulated by estrogen receptor2 (ESR2) and signal transducer and activator of transcription (STAT1). The inflammatory transcription factor NFκB is linked to both sPTB and PPROM, however, their inflammatory response is distinctly different.
Based on our analyses, we propose an autoimmune/hormonal regulation axis for sPTB, whilst pathways implicated in the etiology of PPROM include hematologic/coagulation function disorder, collagen metabolism, matrix degradation and local inflammation. Our hypothesis generating study has identified new candidate genes in the pathogenesis of PPROM and sPTB, which should be validated in large cohorts.
Preterm birth prevention is multifaceted and produces many nuanced questions. This review addresses six important clinical questions about preterm birth prevention as voted for by members of the UK ...Preterm Clinical Network. The questions cover the following areas: preterm birth prevention in ‘low‐risk’ populations; screening for asymptomatic genital tract infection in women at high risk of preterm birth; cervical length screening with cerclage or vaginal pessary in situ; cervical shortening whilst using progesterone; use of vaginal progesterone in combination with cervical cerclage; and optimal advice about intercourse for women at high risk of preterm birth.
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What stumps preterm birth experts? Evidence summary and expert opinion on the top six clinical controversies as voted by members of the UK Preterm Clinical Network.
This article includes Author Insights, a video available at https://vimeo.com/rcog/authorinsights16544.
Preterm birth (PTB) occurs before 37 weeks of gestation. Risk factors include genetics and infection/inflammation. Different mechanisms have been reported for spontaneous preterm birth (SPTB) and ...preterm birth following preterm premature rupture of membranes (PPROM). This study aimed to identify early pregnancy biomarkers of SPTB and PPROM from the maternal genome and transcriptome. Pregnant women were recruited at the Liverpool Women's Hospital. Pregnancy outcomes were categorised as SPTB, PPROM (≤ 34 weeks gestation, n = 53), high-risk term (HTERM, ≥ 37 weeks, n = 126) or low-risk (no history of SPTB/PPROM) term (LTERM, ≥ 39 weeks, n = 188). Blood samples were collected at 16 and 20 weeks gestation from which, genome (UK Biobank Axiom array) and transcriptome (Clariom D Human assay) data were acquired. PLINK and R were used to perform genetic association and differential expression analyses and expression quantitative trait loci (eQTL) mapping. Several significant molecular signatures were identified across the analyses in preterm cases. Genome-wide significant SNP rs14675645 (ASTN1) was associated with SPTB whereas microRNA-142 transcript and PPARG1-FOXP3 gene set were associated with PPROM at week 20 of gestation and is related to inflammation and immune response. This study has determined genomic and transcriptomic candidate biomarkers of SPTB and PPROM that require validation in diverse populations.
Down's syndrome occurs when a person has three copies of chromosome 21 - or the specific area of chromosome 21 implicated in causing Down's syndrome - rather than two. It is the commonest congenital ...cause of mental retardation. 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.
To estimate and compare the accuracy of second trimester serum markers for the detection of Down's syndrome.
We carried out a sensitive and comprehensive literature search of MEDLINE (1980 to May 2007), EMBASE (1980 to 18 May 2007), BIOSIS via EDINA (1985 to 18 May 2007), CINAHL via OVID (1982 to 18 May 2007), The Database of Abstracts of Reviews of Effectiveness (The Cochrane Library 2007, Issue 1), MEDION (May 2007), The Database of Systematic Reviews and Meta-Analyses in Laboratory Medicine (May 2007), The National Research Register (May 2007), Health Services Research Projects in Progress database (May 2007). We studied reference lists and published review articles.
Studies evaluating tests of maternal serum in women at 14-24 weeks of gestation for Down's syndrome, compared with a reference standard, either chromosomal verification or macroscopic postnatal inspection.
Data were extracted as test positive/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 criteria. We used hierarchical summary ROC meta-analytical methods to analyse test performance and compare test accuracy. Analysis of studies allowing direct comparison between tests was undertaken. We investigated the impact of maternal age on test performance in subgroup analyses.
Fifty-nine studies involving 341,261 pregnancies (including 1,994 with Down's syndrome) were included. Studies were generally high quality, although differential verification was common with invasive testing of only high-risk pregnancies. Seventeen studies made direct comparisons between tests. Fifty-four test combinations were evaluated formed from combinations of 12 different tests and maternal age; alpha-fetoprotein (AFP), unconjugated oestriol (uE3), total human chorionic gonadotrophin (hCG), free beta human chorionic gonadotrophin (βhCG), free alpha human chorionic gonadotrophin (αhCG), Inhibin A, SP2, CA125, troponin, pregnancy-associated plasma protein A (PAPP-A), placental growth factor (PGF) and proform of eosinophil major basic protein (ProMBP).Meta-analysis of 12 best performing or frequently evaluated test combinations showed double and triple tests (involving AFP, uE3, total hCG, free βhCG) significantly outperform individual markers, detecting six to seven out of every 10 Down's syndrome pregnancies at a 5% false positive rate. Tests additionally involving inhibin performed best (eight out of every 10 Down's syndrome pregnancies) but were not shown to be significantly better than standard triple tests in direct comparisons. Significantly lower sensitivity occurred in women over the age of 35 years. Women who miscarried in the over 35 group were more likely to have been offered an invasive test to verify a negative screening results, whereas those under 35 were usually not offered invasive testing for a negative screening result. Pregnancy loss in women under 35 therefore leads to under ascertainment of screening results, potentially missing a proportion of affected pregnancies and affecting the accuracy of the sensitivity.
Tests involving two or more markers in combination with maternal age are significantly more sensitive than those involving one marker. The value of combining four or more tests or including inhibin have not been proven to show statistically significant improvement. Further study is required to investigate reduced test performance in women aged over 35 and the impact of differential pregnancy loss on study findings.
Physiological changes of pregnancy and monitoring Carlin, Andrew, MSc, MRCOG; Alfirevic, Zarko, MD, MRCOG
Best practice & research. Clinical obstetrics & gynaecology,
10/2008, Letnik:
22, Številka:
5
Journal Article
Recenzirano
Advances in medical care have led to increasing numbers of complex, high-risk obstetric patients. Specialist training and a sound knowledge of normal maternal physiology are essential to optimize ...outcomes. One of the earliest observed changes is peripheral vasodilatation; this causes a fall in systemic vascular resistance and triggers physiological changes in the cardiovascular and renal systems, with 40–50% increases in cardiac output and glomerular filtration rates. Safety concerns over Swan Ganz catheters have driven the increasing interest in alternative techniques, such as echocardiography, thoracic bioimpedance and pulse contour analysis, although their exact roles in future obstetric high-dependency care have yet to be established. Analysis of arterial blood gases is fundamental to the management of sick patients, and correct interpretation can be aided by a systematic approach. Observation charts are almost ubiquitous in all aspects of medicine, but little evidence exists to support their use in the high-dependency setting.
Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible false positive Doppler ultrasound findings could encourage ...inappropriate early delivery.
The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes.
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (September 2009) and the reference lists of identified studies.
Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared to no Doppler ultrasound.
Two authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked.
Eighteen completed studies involving just over 10,000 women were included. The trials were generally of unclear quality with some evidence of possible publication bias. The use of Doppler ultrasound in high-risk pregnancy was associated a reduction in perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, numbers needed to treat = 203; 95%CI 103 to 4352). There were also fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random effects) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women). No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women) nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies).
Current evidence suggests that the use of Doppler ultrasound in high-risk pregnancies reduced the risk of perinatal deaths and resulted in less obstetric interventions. The quality of the current evidence was not of high quality, therefore, the results should be interpreted with some caution. Studies of high quality with follow-up studies on neurological development are needed.
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