Showing papers in "Ultrasound in Obstetrics & Gynecology in 2017"

Analysis of cell-free DNA in maternal blood in screening for aneuploidies: updated meta-analysis: Cell-free DNA in screening for aneuploidies

Abstract: To review clinical validation or implementation studies of maternal blood cell‐free (cf) DNA analysis and define the performance of screening for fetal trisomies 21, 18 and 13 and sex chromosome aneuploidies (SCA).

ASPRE trial: performance of screening for preterm pre‐eclampsia

Abstract: Objective To examine the performance of screening for preterm and term pre-eclampsia (PE) in the study population participating in the ASPRE (Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention) trial. Methods This was a prospective first-trimester multicenter study on screening for preterm PE in 26 941 singleton pregnancies by means of an algorithm that combines maternal factors, mean arterial pressure, uterine artery pulsatility index and maternal serum pregnancy-associated plasma protein-A and placental growth factor at 11–13 weeks' gestation. Eligible women with an estimated risk for preterm PE of > 1 in 100 were invited to participate in a double-blind trial of aspirin (150 mg per day) vs placebo from 11–14 until 36 weeks' gestation, which showed that, in the aspirin group, the incidence of preterm PE was reduced by 62%. In the screened population, the detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 37 and ≥ 37 weeks were estimated after adjustment for the effect of aspirin in those receiving this treatment. We excluded 1144 (4.2%) pregnancies because of loss to follow-up or study withdrawal (n = 716), miscarriage (n = 243) or termination (n = 185). Results The study population of 25 797 pregnancies included 180 (0.7%) cases of preterm PE, 450 (1.7%) of term PE and 25 167 (97.6%) without PE. In combined first-trimester screening for preterm PE with a risk cut-off of 1 in 100, the DR was 76.7% (138/180) for preterm PE and 43.1% (194/450) for term PE, at screen-positive rate of 10.5% (2707/25 797) and FPR of 9.2% (2375/25 797). Conclusion The performance of screening in the ASPRE study was comparable with that of a study of approximately 60 000 singleton pregnancies used for development of the algorithm; in that study, combined screening detected 76.6% of cases of preterm PE and 38.3% of term PE at a FPR of 10%. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Multicenter screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation: comparison with NICE guidelines and ACOG recommendations.

Abstract: Objective To compare the performance of screening for pre-eclampsia (PE) based on risk factors from medical history, as recommended by NICE and ACOG, with the method proposed by The Fetal Medicine Foundation (FMF), which uses Bayes' theorem to combine the a-priori risk from maternal factors, derived by a multivariable logistic model, with the results of various combinations of biophysical and biochemical measurements. Methods This was a prospective multicenter study of screening for PE in 8775 singleton pregnancies at 11–13 weeks' gestation. A previously published FMF algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those derived from application of NICE guidelines and ACOG recommendations. According to NICE, all high-risk pregnancies should be offered low-dose aspirin. According to ACOG, use of aspirin should be reserved for women with a history of PE in at least two previous pregnancies or PE requiring delivery < 34 weeks' gestation. Results In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. Screening with use of the FMF algorithm based on a combination of maternal factors, mean arterial pressure (MAP), uterine artery pulsatility index (UtA-PI) and serum placental growth factor (PlGF) detected 100% (95% CI, 80–100%) of PE < 32 weeks, 75% (95% CI, 62–85%) of PE < 37 weeks and 43% (95% CI, 35–50%) of PE ≥ 37 weeks, at a 10.0% FPR. Screening with use of NICE guidelines detected 41% (95% CI, 18–67%) of PE < 32 weeks, 39% (95% CI, 27–53%) of PE < 37 weeks and 34% (95% CI, 27–41%) of PE ≥ 37 weeks, at 10.2% FPR. Screening with use of ACOG recommendations detected 94% (95% CI, 71–100%) of PE < 32 weeks, 90% (95% CI, 79–96%) of PE < 37 weeks and 89% (95% CI, 84–94%) of PE ≥ 37 weeks, at 64.2% FPR. Screening based on the ACOG recommendations for use of aspirin detected 6% (95% CI, 1–27%) of PE < 32 weeks, 5% (95% CI, 2–14%) of PE < 37 weeks and 2% (95% CI, 0.3–5%) of PE ≥ 37 weeks, at 0.2% FPR. Conclusion Performance of screening for PE at 11–13 weeks' gestation by the FMF algorithm using a combination of maternal factors, MAP, UtA-PI and PlGF, is by far superior to the methods recommended by NICE and ACOG. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

International estimated fetal weight standards of the INTERGROWTH-21st Project

Abstract: Objective Estimated fetal weight (EFW) and fetal biometry are complementary measures used to screen for fetal growth disturbances. Our aim was to provide international EFW standards to complement the INTERGROWTH-21st Fetal Growth Standards that are available for use worldwide. Methods Women with an accurate gestational-age assessment, who were enrolled in the prospective, international, multicenter, population-based Fetal Growth Longitudinal Study (FGLS) and INTERBIO-21st Fetal Study (FS), two components of the INTERGROWTH-21st Project, had ultrasound scans every 5 weeks from 9–14 weeks' until 40 weeks' gestation. At each visit, measurements of fetal head circumference (HC), biparietal diameter, occipitofrontal diameter, abdominal circumference (AC) and femur length (FL) were obtained blindly by dedicated research sonographers using standardized methods and identical ultrasound machines. Birth weight was measured within 12 h of delivery by dedicated research anthropometrists using standardized methods and identical electronic scales. Live babies without any congenital abnormality, who were born within 14 days of the last ultrasound scan, were selected for inclusion. As most births occurred at around 40 weeks' gestation, we constructed a bootstrap model selection and estimation procedure based on resampling of the complete dataset under an approximately uniform distribution of birth weight, thus enriching the sample size at extremes of fetal sizes, to achieve consistent estimates across the full range of fetal weight. We constructed reference centiles using second-degree fractional polynomial models. Results Of the overall population, 2404 babies were born within 14 days of the last ultrasound scan. Mean time between the last scan and birth was 7.7 (range, 0–14) days and was uniformly distributed. Birth weight was best estimated as a function of AC and HC (without FL) as log(EFW) = 5.084820 − 54.06633 × (AC/100)3 − 95.80076 × (AC/100)3 × log(AC/100) + 3.136370 × (HC/100), where EFW is in g and AC and HC are in cm. All other measures, gestational age, symphysis–fundus height, amniotic fluid indices and interactions between biometric measures and gestational age, were not retained in the selection process because they did not improve the prediction of EFW. Applying the formula to FGLS biometric data (n = 4231) enabled gestational age-specific EFW tables to be constructed. At term, the EFW centiles matched those of the INTERGROWTH-21st Newborn Size Standards but, at < 37 weeks' gestation, the EFW centiles were, as expected, higher than those of babies born preterm. Comparing EFW cross-sectional values with the INTERGROWTH-21st Preterm Postnatal Growth Standards confirmed that preterm postnatal growth is a different biological process from intrauterine growth. Conclusions We provide an assessment of EFW, as an adjunct to routine ultrasound biometry, from 22 to 40 weeks' gestation. However, we strongly encourage clinicians to evaluate fetal growth using separate biometric measures such as HC and AC, as well as EFW, to avoid the minimalist approach of focusing on a single value. © 2016 Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Accuracy of competing-risks model in screening for pre-eclampsia by maternal factors and biomarkers at 11-13 weeks' gestation.

Abstract: Objective To examine the diagnostic accuracy of a previously developed model for prediction of pre-eclampsia (PE) by a combination of maternal factors and biomarkers at 11–13 weeks' gestation. Methods This was a prospective first-trimester multicenter study of screening for PE in 8775 singleton pregnancies. A previously published algorithm was used for the calculation of patient-specific risk of PE in each individual. The detection rates (DRs) and false-positive rates (FPRs) for delivery with PE < 32, < 37 and ≥ 37 weeks were estimated and compared with those for the dataset used for development of the algorithm. Results In the study population, 239 (2.7%) cases developed PE, of which 17 (0.2%), 59 (0.7%) and 180 (2.1%) developed PE < 32, < 37 and ≥ 37 weeks, respectively. With combined screening by maternal factors, mean arterial pressure, uterine artery pulsatility index and serum placental growth factor, the DR was 100% (95% CI, 80–100%) for PE < 32 weeks, 75% (95% CI, 62–85%) for PE < 37 weeks and 43% (95% CI, 35–50%) for PE ≥ 37 weeks, at a 10% FPR. These DRs were similar to the estimated rates for the dataset used for development of the model: 89% (95% CI, 79–96%) for PE < 32 weeks, 75% (95% CI, 70–80%) for PE < 37 weeks and 47% (95% CI, 44–51%) for PE ≥ 37 weeks. Conclusion Assessment of a combination of maternal factors and biomarkers at 11–13 weeks provides effective first-trimester screening for preterm PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Physiological adaptation of maternal plasma volume during pregnancy: a systematic review and meta-analysis

Abstract: Objective To describe the physiological pattern of gestational plasma volume adjustments in normal singleton pregnancy and compare this with the pattern in pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction. Methods We performed a meta-analysis of the current literature on plasma volume adjustments during physiological and complicated pregnancies. Literature was retrieved from PubMed (NCBI) and EMBASE (Ovid) databases. Included studies reported both reference plasma volume measurements (non-pregnant, prepregnancy or postpartum) and measurements obtained during predetermined gestational ages. Mean differences bet ween the reference and pregnancy plasma volume measurements were calculated for predefined intervals of gestational age using a random-effects model described by DerSimonian and Laird. Results Thirty studies were included in the meta-analysis with publication dates ranging from 1934 to 2007. Plasma volume increased in the first weeks of pregnancy, with the steepest increase occurring during the second trimester. Plasma volume continued to increase in the third trimester with a pooled maximum increase of 1.13 L (95% CI, 1.07–1.19 L), an increase of 45.6% (95% CI, 43.0–48.1%) in physiological pregnancies compared with the reference value. The plasma volume expansion in gestational hypertensive and growth-restricted pregnancies was 0.80 L (95% CI, 0.59–1.02 L), an increase of 32.3% (95% CI, 23.6–41.1%) in the third trimester, a smaller increase than in physiological pregnancies (P < 0.0001). Conclusions During physiological pregnancy, plasma volume increases by, on average, more than 1 L as compared with non-pregnant conditions. In pregnancies complicated by pregnancy-induced hypertension, pre-eclampsia or fetal growth restriction, plasma volume increase in the third trimester is 13.3% lower than in normal pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Adaptacion fisiologica del volumen del plasma materno durante el embarazo: una revisi\xF3n sistematica y metaanalisis RESUMEN Objetivo Describir el patron fisiologico de los cambios en el volumen del plasma gestacional en embarazos normales con feto unico y compararlo con el patron en los embarazos complicados por hipertension gestacional, preeclampsia o restriccion del crecimiento fetal. Metodos Se realizo un metaanalisis de la literatura actual sobre los cambios en el volumen de plasma durante embarazos complicados y fisiologicos. La literatura se obtuvo de las bases de datos PubMed (NCBI) y EMBASE (Ovid). Los estudios incluidos mencionaban tanto mediciones de referencia del volumen plasmatico (no embarazada, antes del embarazo o despues del parto) como mediciones tomadas a edades gestacionales predeterminadas. Se calcularon las medias de las diferencias entre las mediciones de referencia y las del embarazo para el volumen plasmatico a intervalos predefinidos de la edad gestacional, utilizando un modelo de efectos aleatorios descrito por DerSimonian y Laird. Resultados En el metaanalisis se incluyeron treinta estudios con fechas de publicacion entre 1934 y 2007. El volumen plasmatico aumento en las primeras semanas de embarazo y el mayor incremento se produjo durante el segundo trimestre. El volumen de plasma continuo aumentando en el tercer trimestre con un aumento combinado maximo de 1,13L (IC 95%, 1,7–1,19 L), lo que supone un aumento del 45,6% (IC 95%, 43,0–48,1%) en embarazos fisiologicas en comparacion con el valor de referencia. El aumento del volumen plasmatico en los embarazos con hipertension y con crecimiento intrauterino restringido fue de 0,80L (IC 95%, 0,59–1,02 L), lo que supone un aumento del 32,3% (IC 95%, 23,6–41,1%) en el tercer trimestre, y un incremento menor que en los embarazos fisiologicos (P <0,0001). Conclusiones Durante el embarazo fisiologico el volumen de plasma aumenta, en promedio, mas de 1L, en comparacion con el de las no embarazadas. En los embarazos complicados por hipertension gestacional, preeclampsia o restriccion del crecimiento fetal, el aumento del volumen plasmatico en el tercer trimestre es un 13,3% menor que en el embarazo normal. 妊娠期母体血容量的生理适应性:系统综述和meta分析 目的 描述正常单胎妊娠中妊娠期血容量调整的生理模式,并与并发妊娠高血压、先兆子痫或胎儿生长受限的妊娠中的模式进行比较。 方法 我们对目前关于生理妊娠和妊娠并发症时血容量调整的文献进行meta分析。检索PubMed(NCBI)和EMBASE(Ovid)数据库中的文献。纳入的研究报道血容量测定参考值(非妊娠、妊娠前或产后)和预定孕周的测定结果。采用DerSimonian和Laird报道的随机效应模型,计算预定孕周的参考值和妊娠期血容量测定结果的均数差。 结果 Meta分析纳入30项研究,发表时间为1934年至2007年。妊娠早期血容量增加,妊娠中期增加最快。妊娠晚期血容量继续增加,汇总后最多增加1.13 L(95% CI,1.07~1.19 L),与参考值相比,生理妊娠时增加45.6%(95% CI,43.0%~48.1%)。妊娠高血压和胎儿生长受限时血容量扩增0.80 L(95%CI,0.59~1.02 L),妊娠晚期增加32.3%(95% CI,23.6%~41.1%),与生理妊娠相比增幅较小(P<0.0001)。 结论 与非妊娠时相比,生理妊娠时,血容量平均增加超过1 L。并发妊娠高血压、先兆子痫或胎儿生长受限的妊娠中,妊娠晚期血容量增加低于正常妊娠13.3%。

Vaginal progesterone decreases preterm birth and neonatal morbidity and mortality in women with a twin gestation and a short cervix: an updated meta-analysis of individual patient data.

Abstract: Objective To assess the efficacy of vaginal progesterone for the prevention of preterm birth and neonatal morbidity and mortality in asymptomatic women with a twin gestation and a sonographic short cervix (cervical length ≤ 25 mm) in the mid-trimester. Methods This was an updated systematic review and meta-analysis of individual patient data (IPD) from randomized controlled trials comparing vaginal progesterone with placebo/no treatment in women with a twin gestation and a mid-trimester sonographic cervical length ≤ 25 mm. MEDLINE, EMBASE, POPLINE, CINAHL and LILACS (all from inception to 31 December 2016), the Cochrane Central Register of Controlled Trials, Research Registers of ongoing trials, Google Scholar, conference proceedings and reference lists of identified studies were searched. The primary outcome measure was preterm birth < 33 weeks' gestation. Two reviewers independently selected studies, assessed the risk of bias and extracted the data. Pooled relative risks (RRs) with 95% confidence intervals (CI) were calculated. Results IPD were available for 303 women (159 assigned to vaginal progesterone and 144 assigned to placebo/no treatment) and their 606 fetuses/infants from six randomized controlled trials. One study, which included women with a cervical length between 20 and 25 mm, provided 74% of the total sample size of the IPD meta-analysis. Vaginal progesterone, compared with placebo/no treatment, was associated with a statistically significant reduction in the risk of preterm birth < 33 weeks' gestation (31.4% vs 43.1%; RR, 0.69 (95% CI, 0.51–0.93); moderate-quality evidence). Moreover, vaginal progesterone administration was associated with a significant decrease in the risk of preterm birth < 35, < 34, < 32 and < 30 weeks' gestation (RRs ranging from 0.47 to 0.83), neonatal death (RR, 0.53 (95% CI, 0.35–0.81)), respiratory distress syndrome (RR, 0.70 (95% CI, 0.56–0.89)), composite neonatal morbidity and mortality (RR, 0.61 (95% CI, 0.34–0.98)), use of mechanical ventilation (RR, 0.54 (95% CI, 0.36–0.81)) and birth weight < 1500 g (RR, 0.53 (95% CI, 0.35–0.80)) (all moderate-quality evidence). There were no significant differences in neurodevelopmental outcomes at 4–5 years of age between the vaginal progesterone and placebo groups. Conclusion Administration of vaginal progesterone to asymptomatic women with a twin gestation and a sonographic short cervix in the mid-trimester reduces the risk of preterm birth occurring at < 30 to < 35 gestational weeks, neonatal mortality and some measures of neonatal morbidity, without any demonstrable deleterious effects on childhood neurodevelopment. Published 2017. This article is a U.S. Government work and is in the public domain in the USA. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Systematic review of first-trimester ultrasound screening for detection of fetal structural anomalies and factors that affect screening performance.

Abstract: OBJECTIVES: To determine the sensitivity and specificity of first trimester ultrasound for the detection of fetal abnormalities; and to establish which factors might impact this screening. METHODS: Systematic review and meta-analysis of all relevant publications assessing the diagnostic accuracy of first trimester 2D (transabdominal and transvaginal) ultrasound in the detection of congenital fetal anomalies prior to 14 weeks gestation was performed. The reference standard used was the detection of abnormalities at birth or postmortem. Factors that may impact detection rates were evaluated including population characteristics, gestation, healthcare setting, ultrasound modality, use of an anatomical checklist for first trimester anomaly detection and what types of malformations were included in the study. In an effort to reduce the impact of study heterogeneity on results of the meta-analysis, data from the studies were analyzed within subgroups of major anomalies versus all types of anomalies; and low risk / unselected populations versus high risk populations. RESULTS: An initial electronic search identified 2,225 citations, from which a total of 30 relevant studies, published between 1991 and 2015, were selected for inclusion. For low risk or unselected populations (19 studies, 115,731 fetuses) the pooled estimate for detection of major abnormalities was 46.10% (95% C.I. 36.88-55.46). The detection rate for all abnormalities in low risk or unselected populations was 32.35% (95% C.I. 22.45-43.12), in 14 studies (97,976 fetuses); while the detection rate in high risk populations for the presence of all types of anomalies (six studies, 2,841 fetuses) was 61.18% (95% C.I. 37.71-82.19). Of the factors examined impacting detection rates there was a statistically significant relationship between the use of an anatomical protocol during first trimester anomaly screening and sensitivity for the detection of fetal anomalies in all subgroups (P < 0.0001). CONCLUSION: Detection rates for first trimester anomalies range from 32% in low risk, to over 60% in high risk groups. This demonstrates that first trimester ultrasound has the potential to identify a large proportion of fetuses affected with structural anomalies. The use of a standardized anatomical protocol improves the sensitivity of first trimester ultrasound screening for all anomalies and major anomalies in populations of varying risk. The development and introduction of international protocols with standard anatomical views should be undertaken, in order to optimize rates of first trimester anomaly detection.

ISUOG Practice Guidelines: performance of fetal magnetic resonance imaging

Abstract: The International Society of Ultrasound in Obstetrics and Gynecology (ISUOG) is a scientific organization that encourages sound clinical practice, and high-quality teaching and research related to diagnostic imaging in women’s healthcare. The ISUOG Clinical Standards Committee (CSC) has a remit to develop Practice Guidelines and Consensus Statements as educational recommendations that provide healthcare practitioners with a consensus-based approach, from experts, for diagnostic imaging. They are intended to reflect what is considered by ISUOG to be the best practice at the time at which they are issued. Although ISUOG has made every effort to ensure that Guidelines are accurate when issued, neither the Society nor any of its employees or members accepts any liability for the consequences of any inaccurate or misleading data, opinions or statements issued by the CSC. The ISUOG CSC documents are not intended to establish a legal standard of care because interpretation of the evidence that underpins the Guidelines may be influenced by individual circumstances, local protocol and available resources. Approved Guidelines can be distributed freely with the permission of ISUOG (info@isuog.org). These guidelines are based on consensus reached between participants following a survey of current practices, conducted by ISUOG in 2014 (Appendix S1).

Risk of Cesarean scar defect following single- vs double-layer uterine closure: systematic review and meta-analysis of randomized controlled trials.

Abstract: Objective There is a growing body of evidence that suggests that the surgical technique for uterine closure following Cesarean delivery influences the healing of the Cesarean scar, but there is still no consensus on the optimal technique. The aim of this systematic review and meta-analysis was to compare the effect of single- vs double-layer uterine closure on the risk of uterine scar defect. Methods MEDLINE, Scopus, ClinicalTrials.gov, PROSPERO, EMBASE and the Cochrane Central Register of Controlled Trials were searched from inception of each database until May 2016. All randomized controlled trials (RCTs) evaluating the effect of single- vs double-layer uterine closure following low transverse Cesarean section on the risk of uterine scar defect were included. The primary outcome was the incidence of uterine scar defects detected on ultrasound. Secondary outcomes were residual myometrial thickness evaluated by ultrasound and the incidence of uterine dehiscence and/or rupture in subsequent pregnancy. Summary measures were reported as relative risk (RR) or mean difference (MD), with 95% CIs. Quality of the evidence was assessed using the GRADE approach. Results Nine RCTs (3969 participants) were included in the meta-analysis. The overall risk of bias of the included trials was low. Statistical heterogeneity within the studies was low, with no inconsistency in the primary and secondary outcomes. Women who received single-layer uterine closure had a similar incidence of uterine scar defects as did women who received double-layer closure (25% vs 43%; RR, 0.77 (95% CI, 0.36–1.64); five trials; 350 participants; low quality of evidence). Compared with double-layer uterine closure, women who received single-layer closure had a significantly thinner residual myometrium on ultrasound (MD, –2.19 mm (95% CI, –2.80 to –1.57 mm); four trials; 374 participants; low quality of evidence). No difference was found in the incidence of uterine dehiscence (0.4% vs 0.2%; RR, 1.34 (95% CI, 0.24–4.82); three trials; 3421 participants; low quality of evidence) or uterine rupture (0.1% vs 0.1%; RR, 0.52 (95% CI, 0.05–5.53); one trial; 3234 participants; low quality of evidence) in a subsequent pregnancy. Conclusions Single- and double-layer closure of the uterine incision following Cesarean delivery are associated with a similar incidence of Cesarean scar defects, as well as uterine dehiscence and rupture in a subsequent pregnancy. However, the quality level of summary estimates, as assessed by GRADE, was low, indicating that the true effect may be, or is even likely to be, substantially different from the estimate of the effect. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Cerclage for sonographic short cervix in singleton gestations without prior spontaneous preterm birth: systematic review and meta-analysis of randomized controlled trials using individual patient-level data

Abstract: Objective The aim of this systematic review and meta-analysis was to quantify the efficacy of cervical cerclage in preventing preterm birth (PTB) in asymptomatic singleton pregnancies with a short mid-trimester cervical length (CL) on transvaginal sonography (TVS) and without prior spontaneous PTB. Methods Electronic databases were searched from inception of each database until February 2017. No language restrictions were applied. All randomized controlled trials (RCTs) of asymptomatic singleton pregnancies without prior spontaneous PTB, found to have short CL < 25 mm on mid-trimester TVS and then randomized to management with either cerclage or no cerclage, were included. Corresponding authors of all the included trials were contacted to obtain access to the data and perform a meta-analysis of individual patient-level data. Data provided by the investigators were merged into a master database constructed specifically for the review. Primary outcome was PTB < 35 weeks. Summary measures were reported as relative risk (RR) with 95% CI. The quality of the evidence was assessed using the GRADE approach. Results Five RCTs, including 419 asymptomatic singleton gestations with TVS-CL < 25 mm and without prior spontaneous PTB, were analyzed. In women who were randomized to the cerclage group compared with those in the control group, no statistically significant differences were found in PTB < 35 (21.9% vs 27.7%; RR, 0.88 (95% CI 0.63–1.23); I2 = 0%; five studies, 419 participants), < 34, < 32, < 28 and < 24 weeks, gestational age at delivery, preterm prelabor rupture of membranes (PPROM) and neonatal outcomes. In women who received cerclage compared with those who did not, planned subgroup analyses revealed a significantly lower rate of PTB < 35 weeks in women with TVS-CL < 10 mm (39.5% vs 58.0%; RR, 0.68 (95% CI, 0.47–0.98); I2 = 0%; five studies; 126 participants) and in women who received tocolytics (17.5% vs 32.7%; RR, 0.54 (95% CI, 0.31–0.93); I2 = 0%; four studies; 169 participants) or antibiotics (18.3% vs 31.5%; RR, 0.58 (95% CI, 0.33–0.98); I2 = 0%; three studies; 163 participants) as additional therapy to cerclage. The quality of evidence was downgraded two levels because of serious imprecision and indirectness, and therefore was judged as low. Conclusions In singleton gestations without prior spontaneous PTB but with TVS-CL < 25 mm in the second trimester, cerclage does not seem to prevent preterm delivery or improve neonatal outcome. However, in these pregnancies, cerclage seems to be efficacious at lower CLs, such as < 10 mm, and when tocolytics or antibiotics are used as additional therapy, requiring further studies in these subgroups. Given the low quality of evidence, further well-designed RCTs are needed to confirm the findings of this study. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Chronic hypertension and adverse pregnancy outcome: a cohort study

Abstract: Objective To examine the association between chronic hypertension (CH) and a wide range of adverse pregnancy outcomes after adjustment for confounding factors in obstetric history and maternal characteristics. Methods This was a prospective screening study for adverse pregnancy outcomes in women with singleton pregnancy attending their first routine hospital visit at 11 + 0 to 13 + 6 weeks' gestation. Data on maternal characteristics, medical and obstetric history and pregnancy outcome were collected. Regression analysis was performed to examine the association between CH and adverse pregnancy outcomes, including late miscarriage, stillbirth, pre-eclampsia (PE), gestational diabetes mellitus (GDM), spontaneous and iatrogenic preterm birth (PTB), small-for-gestational-age (SGA) neonate, large-for-gestational-age (LGA) neonate and elective and emergency Cesarean section (CS). Results The study population of 109 932 pregnancies included 1417 (1.3%) women with CH. After adjusting for potential confounding variables from maternal characteristics, medical and obstetric history, CH was associated with increased risk of stillbirth (odds ratio (OR), 2.38 (95% CI, 1.51–3.75)), PE (OR, 5.76 (95% CI, 4.93–6.73)), SGA (OR, 2.06 (95% CI, 1.79–2.39)), GDM (OR, 1.61 (95% CI, 1.27–2.05)), iatrogenic PTB < 37 weeks (OR, 3.73 (95% CI, 3.07–4.53)) and elective CS (OR, 1.79 (95% CI, 1.52–2.11)), decreased risk of LGA (OR, 0.65 (95% CI, 0.53–0.78)) and had no significant effect on late miscarriage, spontaneous PTB or emergency CS. Conclusion CH should be combined with other maternal characteristics and medical and obstetric history when calculating an individualized adjusted risk for adverse pregnancy complications. CH increases the risk of stillbirth, PE, SGA, GDM, iatrogenic PTB and elective CS and reduces the risk for LGA. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Blastocyst vs cleavage-stage embryo transfer: systematic review and meta-analysis of reproductive outcomes.

Abstract: Objectives Blastocyst transfer in assisted reproduction techniques could be advantageous because the timing of exposure of the embryo to the uterine environment is more analogous to a natural cycle and permits embryo self-selection after activation of the embryonic genome on day 3. Conversely, the in-vitro environment is likely to be inferior to that in vivo, and in-vitro culture beyond embryonic genomic activation could potentially harm the embryo. Our objective was to identify, appraise and summarize the available evidence comparing the effectiveness of blastocyst vs cleavage-stage embryo transfer. Methods This was a systematic review and meta-analysis of randomized controlled trials (RCTs) comparing the transfer of blastocysts (days 5–6) with the transfer of cleavage-stage embryos (days 2–3) in women undergoing in-vitro fertilization or intracytoplasmic sperm injection. The last electronic searches were run on 1 August 2016. Abstracts and studies with a mean difference between the two study groups of > 0.5 for the number of embryos transferred were excluded. Results We screened 1187 records and assessed 33 potentially eligible studies. Twelve studies were included, comprising a total of 1200 women undergoing blastocyst transfer and 1218 undergoing cleavage-stage embryo transfer. We observed low-quality evidence of no significant difference of blastocyst transfer on live birth/ongoing pregnancy (relative risk (RR), 1.11 (95% CI, 0.92–1.35), 10 RCTs, 1940 women, I2 = 54%), clinical pregnancy (RR, 1.10 (95% CI, 0.93–1.31), 12 RCTs, 2418 women, I2 = 64%), cumulative pregnancy (RR, 0.89 (95% CI, 0.67–1.16), four RCTs, 524 women, I2 = 63%) and miscarriage (RR, 1.08 (95% CI, 0.74–1.56), 10 RCTs, 763 pregnancies, I2 = 0%). There was moderate-quality evidence of a decrease in the number of women with surplus embryos after the blastocyst-stage embryo transfer (RR, 0.78 (95% CI, 0.66–0.91)). Overall, the quality of the evidence was limited by the quality of the included studies and by unexplained inconsistency across studies. Conclusions Current evidence shows no superiority of blastocyst compared with cleavage-stage embryo transfer in clinical practice. As the quality of the evidence for the primary outcomes is low, additional well-designed RCTs are still needed before robust conclusions can be drawn. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of first-trimester combined test in screening for trisomies 21, 18 and 13.

Abstract: Objective To examine the diagnostic accuracy of a previously developed model for the first-trimester combined test in screening for trisomies 21, 18 and 13. Methods This was a prospective validation study of screening for trisomies 21, 18 and 13 by assessment of a combination of maternal age, fetal nuchal translucency, fetal heart rate and serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) at 11 + 0 to 13 + 6 weeks' gestation in 108 982 singleton pregnancies undergoing routine care in three maternity hospitals. A previously published algorithm was used to calculate patient-specific risks for trisomy 21, 18 and 13 in each patient. The detection rate (DR) and false-positive rate (FPR) at estimated risk cut-offs from 1 in 2 to 1 in 1000 were determined. The proportions of trisomies detected were compared to their expected values in different risk groups. Results In the study population, there were 108 112 (99.2%) cases with normal fetal karyotype or birth of a phenotypically normal neonate and 870 (0.8%) cases with abnormal karyotype, including trisomy 21 (n = 432), trisomy 18 (n = 166), trisomy 13 (n = 56), monosomy X (n = 63), triploidy (n = 35) or other aneuploidy (n = 118). The screen-positive rates, standardized according to the maternal age distribution in England and Wales in 2011, of fetuses with abnormal or normal karyotype were compatible with those predicted from the previous model; at a risk cut-off of 1 in 100, the FPR was about 4% and the DRs for trisomies 21, 18 and 13 were 90%, 97% and 92%, respectively. There was evidence that the algorithm overestimated risk. This could, to some degree, reflect under-ascertainment in pregnancies ending in miscarriage or stillbirth. Conclusion In a prospective validation study, the first-trimester combined test detected 90%, 97% and 92% of trisomies 21, 18 and 13, respectively, as well as > 95% of cases of monosomy X and triploidies and > 50% of other chromosomal abnormalities, at a FPR of 4%. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cervical length screening for prevention of preterm birth in singleton pregnancy with threatened preterm labor: systematic review and meta-analysis of randomized controlled trials using individual patient-level data.

Abstract: Objective Cervical length screening by transvaginal sonography (TVS) has been shown to be a good predictive test for spontaneous preterm birth (PTB) in symptomatic singleton pregnancy with threatened preterm labor (PTL). The aim of this review and meta-analysis of individual participant data was to evaluate the effect of knowledge of the TVS cervical length (CL) in preventing PTB in singleton pregnancies presenting with threatened PTL. Methods We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (May 2016) and reference lists of retrieved studies. Selection criteria included randomized controlled trials of singleton gestations with threatened PTL randomized to management based mainly on CL screening (intervention group), or CL screening with no knowledge of results or no CL screening (control group). Participants included women with singleton gestations at 23 + 0 to 36 + 6 weeks with threatened PTL. We contacted corresponding authors of included trials to request access to the data and perform a meta-analysis of individual participant data. Data provided by the investigators were merged into a master database constructed specifically for the review. The primary outcome was PTB < 37 weeks. Summary measures were reported as relative risk (RR) or as mean difference (MD) with 95% CI. Results Three trials including a total of 287 singleton gestations with threatened PTL between 24 + 0 and 35 + 6 weeks were included in the meta-analysis, of which 145 were randomized to CL screening with knowledge of results and 142 to no knowledge of CL. Compared with the control group, women who were randomized to the known CL group had a significantly lower rate of PTB < 37 weeks (22.1% vs 34.5%; RR, 0.64 (95% CI, 0.44–0.94); three trials; 287 participants) and a later gestational age at delivery (MD, 0.64 (95% CI, 0.03–1.25) weeks; MD, 4.48 (95% CI, 1.18–8.98) days; three trials; 287 participants). All other outcomes for which there were available data were similar in the two groups. Conclusions There is a significant association between knowledge of TVS CL and lower incidence of PTB and later gestational age at delivery in symptomatic singleton gestations with threatened PTL. Given that in the meta-analysis we found a significant 36% reduction in the primary outcome, but other outcomes were mostly statistically similar, further study needs to be undertaken to understand better whether the predictive characteristics of CL screening by TVS can be translated into better clinical management and therefore better outcomes and under what circumstances. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Cribado mediante la longitud cervical para la prevencion del parto pretermino en embarazos con feto unico y riesgo de parto prematuro: revision sistematica y metaanalisis de ensayos controlados aleatorizados haciendo uso de los datos individuales de las pacientes RESUMEN Objetivo El cribado mediante la longitud cervical obtenida con ecografia transvaginal (ETV) ha demostrado ser una buena prueba para la prediccion del parto pretermino espontaneo (PPTE) en embarazos con feto unico sintomaticos debido a la amenaza de parto pretermino (PPT). El objetivo de esta revision y metaanalisis de los datos de participantes individuales fue evaluar el efecto de medir la longitud cervical (LC) mediante ETV con el fin de prevenir el parto prematuro en embarazos unicos con amenaza de PPT. Metodos Se realizaron busquedas en los ficheros de ensayos de Cochrane Pregnancy and Childbirth Group y Complementary Medicine Field (mayo de 2016), y en las listas de referencias de los estudios encontrados. Los criterios de seleccion incluyeron ensayos controlados aleatorizados de embarazos con feto unico y riesgo de PPT con aleatorizacion de la paciente basada principalmente en el cribado mediante la LC (grupo de intervencion), el cribado mediante la LC sin conocimiento de los resultados, o sin cribado de LC (grupo de control). Las participantes fueron mujeres embarazadas con feto unico desde las 23 + 0 hasta las 36 + 6 semanas y con riesgo de PPT. Se establecio contacto con los autores de los ensayos incluidos para solicitar el acceso a los datos y llevar a cabo un metaanalisis de los datos de las participantes individualmente. Los datos proporcionados por los investigadores se agregaron a una base de datos maestra creada especificamente para esta revision. El resultado primario fue el PPTE < 37 semanas. Las medidas resumen se reportaron como riesgo relativo (RR) o como diferencia de medias (DM) con IC del 95%. Resultados En el metaanalisis se incluyeron tres ensayos con un total de 287 embarazos con feto unico y riesgo de PPT entre 24 + 0 y 35 + 6 semanas, de los cuales 145 fueron asignados al azar a un cribado mediante la LC con conocimiento de los resultados y 142 a aquellos para los que se desconocia la LC. En comparacion con el grupo control, las mujeres que fueron asignadas aleatoriamente al grupo en el que se conocia la LC tuvieron una tasa de parto prematuro a < 37 semanas significativamente menor (22,1% vs. 34,5%; RR 0,64 (IC 95%, 0,44–0,94); 3 ensayos; 287 participantes ) y una edad gestacional al momento del parto mas tardia (DM 0,64 (IC 95%, 0.03–1.25) semanas; DM 4,48 (IC 95%, 1,18–8,98) dias; 3 ensayos; 287 participantes). El resto de los resultados para los cuales habia datos disponibles fueron similares en ambos grupos. Conclusiones Existe una asociacion significativa entre el conocimiento de la LC obtenida mediante ETV y una menor incidencia de PPTE y edad gestacional mas tardia en el momento del parto en embarazos con feto unico sintomaticos debido al riesgo de parto pretermino (PPT). Teniendo en cuenta que en el metaanalisis se encontro una reduccion significativa del 36% en el resultado primario, pero que los otros resultados fueron estadisticamente similares en su mayoria, seran necesarios mas estudios para entender mejor si las propiedades predictivas del cribado mediante la LC obtenida con ETV se pueden traducir en una mejor atencion clinica y por lo tanto mejores resultados dependiendo de las circunstancias. 出现先兆早产的单胎妊娠中筛查宫颈长度预防早产的发生:采用单个病例数据进行随机对照试验的系统综述和meta分析 目的 已有研究显示,在出现先兆早产(preterm labor,PTL)的有症状的单胎妊娠中,采用经阴道超声检查(transvaginal sonography,TVS)进行宫颈长度筛查是一种很好的预测自发性早产(spontaneous preterm birth,PTB)发生的方法。本篇对单个病例数据的综述和meta分析的目的是评估在出现先兆PTL的单胎妊娠中,知晓TVS宫颈长度(cervical length,CL)对预防PTB的作用。 方法 检索Cochrane妊娠和分娩组试验注册资料库和Cochrane辅助医学试验注册资料库(2016年5月)以及检索到的研究的参考文献列表。纳入标准为出现先兆PTL的单胎妊娠的随机对照试验,随机分为主要根据CL筛查结果进行处理(干预组)或者进行CL筛查但不知晓结果或未进行CL筛查(对照组)。研究对象为孕23 + 0周至孕36+6周出现先兆PTL的单胎妊娠孕妇。我们与纳入试验的通信作者取得联系,获准使用数据,并进行单个病例数据的meta分析。将研究人员提供的数据合并到特别建立的主数据库中以进行评价。主要结局为孕37周前发生PTB。综合检测结果以相对危险度(relative risk,RR)或平均差和95%CI(mean difference,MD)表示。 结果 meta分析纳入3项试验,共包括287例在孕24 + 0周至孕35+6周间出现先兆PTL的单胎妊娠,其中145例随机分至知晓结果的CL筛查组,142例分至不知晓CL组。与对照组相比,随机分至知晓CL组的孕妇孕37周前PTB发生率明显较低[22.1%和34.5%;RR,0.64(95% CI,0.44 ~ 0.94);3项试验;287名研究对象],分娩孕周延长[MD,0.64(95% CI,0.03 ~ 1.25)周;MD,4.48(95% CI,1.18 ~ 8.98)天;3项试验;287研究对象]。2组相比,现有数据的所有其他结局相似。 结论 出现先兆PTL的有症状的单胎妊娠中,知晓TVS CL与PTB发病率较低和分娩孕周延长呈显著相关。鉴于在meta分析中我们发现主要结局发生率显著降低36%,而其他结局大多统计学相似,因此需要进行进一步研究,以更深入了解采用TVS进行CL筛查的预测特点能否以及在何种情况下可以用于进行更好的临床管理,从而得到更好的结局。

Placental histopathology associated with pre‐eclampsia: systematic review and meta‐analysis

Abstract: Objective Pre-eclampsia (PE) is associated with impaired trophoblastic invasion and typical villous and vascular placental lesions. The primary aim of this study was to quantify the prevalence of placental histopathological lesions in pregnancies complicated by PE. Methods MEDLINE, EMBASE and CINAHL were searched electronically, and relevant articles reporting on placental histopathological lesions were assessed according to the following criteria: study design, number of pregnancies included, severity of PE and whether the pathologist was blinded to the clinical information. Prospective and retrospective case–control studies including ≥ 100 pregnancies were included in the systematic review. The incidence of each type of histological lesion according to the Perinatal Section of the Society for Pediatric Pathology classification in pre-eclamptic and normal pregnancies was identified, and lesions were categorized into two main groups: villous lesions and vascular lesions. Random-effects meta-analysis of proportions was used for analysis. Between-study heterogeneity was assessed using the I2 statistic. Results The search yielded 717 citations, and a total of eight studies (four blinded and four non-blinded) were included in the review. In unblinded studies, the pooled prevalence of villous lesions was 11.6% and 48.2% in normal and pre-eclamptic pregnancies, respectively, giving a pooled odds ratio (OR) of 7.59. In blinded studies, the pooled prevalence of villous lesions was 18.5% and 42.0% in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 4.28. In unblinded studies, the pooled prevalence of vascular lesions was 8.1% and 37.3% in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 20.34. In blinded studies, the pooled prevalence of vascular lesions was 9.8% and 38.9%, in normal and pre-eclamptic pregnancies, respectively, giving a pooled OR of 7.08. Conclusions In blinded studies, the incidence of both placental villous and vascular histopathological lesions is four- to seven-fold higher in pre-eclamptic than in normal pregnancies. Greater differences are reported in unblinded studies. Despite the higher probability (point prevalence) of finding abnormal placental pathology in pregnancies with PE, placental lesions are not specific to the diagnosis of PE. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Complications of intrauterine intravascular blood transfusion: lessons learned after 1678 procedures.

Abstract: Background maternal alloimmunization to fetal red blood cell antigens is a major cause of fetal anemia, which in untreated cases can lead to hydrops and perinatal death. The cornerstone of the management during pregnancy is intrauterine intravascular blood transfusion. Although this procedure is considered to be relatively safe, (procedure-related) complications continue to occur. Objectives to evaluate procedure-related complications and perinatal loss rates of intrauterine transfusion and changes over time, aiming to identify factors leading to improved outcome. Methods retrospective analysis of a large single center cohort of all intrauterine transfusions for red cell alloimmunization performed in the national referral center for Fetal Therapy in the Netherlands, from 1988 until 2014. Differences in complications and associations with alterations in technique before and after 2001 were assessed. Results in 27 years, 1678 intrauterine transfusions were performed in 589 fetuses. In the second half of this cohort, a significant improvement in survival, 88.6 vs 97.0% (P<0.001) and a decline in procedure-related complication rates per fetus (9.8 to 3.3%, P=0.001) and per procedure (3.4 to 1.2%, P=0.003) were observed. Procedure-related perinatal loss declined from 4.7% to 1.8% per fetus (P=0.053). Relevant changes in transfusion technique were routine use of fetal paralysis, avoidance of arterial puncture and increased use of intrahepatic transfusion. Conclusions intrauterine transfusion became an even safer procedure in recent years, in experienced hands. The chosen technique should be fine-tuned on the patient's situation. The declining complication rates are most likely related to center volume: this rare procedure is best performed in experienced fetal therapy centers.

Association between Zika virus and fetopathy: a prospective cohort study in French Guiana

Abstract: Objective To establish the incidence of fetal central nervous system (CNS) anomalies (including microcephaly), signs of congenital infection and fetal loss in pregnant women infected with Zika virus (ZIKV) and non-infected pregnant women in western French Guiana. Methods This prospective cohort study was conducted between 1 January and 15 July 2016. We evaluated and compared clinical and fetal ultrasound examinations of 301 pregnant women with biological confirmation of ZIKV infection and 399 pregnant women who were negative for ZIKV infection. Results Overall, the total number of fetuses with CNS involvement was higher in the infected than in the control group (9.0% vs 4.3%; relative risk, 2.11 (95% CI, 1.18–4.13)). Anomalies of the corpus callosum and presence of cerebral hyperechogenicities were significantly more common in the infected group. There was an increased risk of microcephaly in the infected compared with the control group (1.7% vs 0.3%; relative risk, 6.63 (95% CI, 0.78–57.83)), although this was not statistically significant. When the mother was infected during the first or second trimester, there was a greater risk of severe CNS involvement, more signs of infection and intrauterine fetal death than with infection in the third trimester. The rate of vertical transmission in the exposed group was 10.9%. Conclusion ZIKV infection during pregnancy is associated with a significant risk of fetal CNS involvement and intrauterine fetal death, particularly when infection occurs during the first or second trimesters. Microcephaly was not present in every case of congenital ZIKV syndrome that we observed. Until more is known about this disease, it is paramount to evaluate suspected cases by detailed neurosonography on a monthly basis, paying particular attention to the corpus callosum and the presence of hyperechogenic foci. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.

Pre-eclampsia: an important risk factor for asymptomatic heart failure.

Abstract: Objectives Pre-eclampsia (PE) is associated with both postpartum structural asymptomatic heart disease (i.e. heart failure Stage B (HF-B)) and conventional cardiovascular (CV) risk factors. We aimed to evaluate the extent to which PE, adjusted for conventional CV risk factors, is associated independently with asymptomatic cardiac abnormalities postpartum. Methods In this cross-sectional cohort study, 107 formerly pre-eclamptic women and 41 women with uneventful previous pregnancy (controls) were invited for CV risk assessment 4–10 years postpartum. This included cardiac ultrasound, blood pressure (BP) measurement and evaluation of metabolic syndrome determinants. Asymptomatic structural and functional cardiac abnormalities were classified as HF-B, according to the American Heart Association guidelines. Prehypertension was defined as systolic BP of 120–139 mmHg and/or diastolic BP of 80–89 mmHg. Univariate and multivariate regression analyses were performed to calculate associations of PE and conventional risk factors with HF-B. Results The prevalence of asymptomatic HF-B was approximately 3.5-fold higher in the PE group compared with controls (25% vs 7%, P < 0.01); 67% of this group had concentric remodeling and 22% had mildly impaired ejection fraction. After adjustment for postpartum interval, hypertension and high-density lipoprotein, PE was significantly associated with HF-B (adjusted odds ratio, 4.4 (95% CI, 1.0–19.1)). Moreover, in the formerly pre-eclamptic group, prehypertension was associated significantly with HF-B (odds ratio, 4.3 (95% CI, 1.4–12.7)), while metabolic syndrome determinants were not. Conclusion PE is associated with a four-fold increased female-specific risk of asymptomatic cardiac abnormalities. Prehypertension apparently increases this risk significantly, while metabolic syndrome determinants do not. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Effectiveness of vesicoamniotic shunt in fetuses with congenital lower urinary tract obstruction: an updated systematic review and meta-analysis

Abstract: Objectives to evaluate the effect of vesico-amniotic shunt for treatment of lower obstructive uropathy on perinatal and postnatal survival. Data sources search was conducted from inception to June 2015 including Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Study eligibility criteria Search for studies that compare outcomes of vesico-amniotic shunt to conservative management was performed using relevant search terms. Cohort studies and clinical trials were eligible. Single arm studies and studies that did not report survival were excluded. Sample size and language were not criteria for selection. Study appraisal and synthesis Two reviewers independently abstracted data in a standardized form including study characteristics and results. Primary outcomes were perinatal and postnatal survival. Secondary outcome was postnatal renal function. Data on fetal survival were expressed as odds ratios (OR) and 95% confidence interval (CI). Statistical analysis was performed using Review Manager (RevMan) Version 5.3. Main Results Out of 423 selected abstracts, 9 studies were eligible. These studies included 112 fetuses treated with shunting versus 134 that were conservatively managed. There was heterogeneity in study designs. Although available data demonstrated that there was difference in effect estimates between the arms in terms of perinatal survival (OR = 2.54, 95% CI 1.14 - 5.67), there was no difference in 6–12 month survival (OR = 1.77, 95% CI 0.25 – 12.71) or 2-year survival (OR 1.81, 95% CI 0.09 – 38.03). In addition, there was no difference in effect of renal function between fetuses that underwent fetal intervention and those that did not (OR 2.09, 95% CI 0.74 – 5.94) Conclusions Available data seem to support perinatal survival advantage in fetuses treated with vesico-amniotic shunt over conservative management. However, 1–2 year survival and renal function outcome after vesico-amniotic shunt are still uncertain. Further studies are still necessary to evaluate the effectiveness of fetal intervention for LUTO based on different severity of the disease, due to the very low quality of the studies based on the GRADE guidelines.

Hidden high rate of pre-eclampsia in twin compared with singleton pregnancy.

Abstract: Objectives To examine the gestational age at delivery in dichorionic (DC) and monochorionic (MC) twin pregnancies, with and without pre-eclampsia (PE), and to determine the relative risk of total and preterm PE compared with that in singleton pregnancies. Methods This was a screening study for PE in twin pregnancies undergoing first-trimester combined screening for aneuploidy and subsequently delivering two phenotypically normal live or stillborn babies at ≥ 24 weeks' gestation. The distribution of gestational age at delivery in DC and MC twins was determined and compared with that in singleton pregnancies from the same population. The relative risk for total and preterm PE in twins compared with singleton pregnancies was determined. Kaplan–Meier estimates of the cumulative incidence of PE in twin and singleton pregnancies, assuming no other cause for delivery, were determined and hazard ratios for twins relative to singletons were obtained from a Cox proportional hazards regression model. Results The incidence of PE in singletons was 2.3% (2162/93 297), in DC twin pregnancies was 8.1% (145/1789) and in MC twin pregnancies was 6.0% (26/430). Compared with singletons, the relative risk of total PE was 3.5 for DC twins and 2.6 for MC twins. Delivery < 37 weeks' gestation occurred in 5.5% of singletons, 46.5% of DC twins and 91.4% of MC twins. The incidence of preterm PE was 0.6%, 5.5% and 5.8% for singletons, DC twins and MC twins, respectively. Compared with singletons, the relative risk of preterm PE was 8.7 for DC twins and 9.1 for MC twins. In the Cox proportional hazards regression model, the hazard ratios for DC and MC twin pregnancies relative to singleton pregnancies were 14 and 23, respectively. Conclusions The relative risk of preterm PE in DC and MC twins is similar and substantially higher than in singleton pregnancies. In ongoing twin pregnancies, the high relative risk of PE may merit a higher intensity of monitoring than is routine for singleton pregnancies. © 2017 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

ISUOG updated consensus statement on the impact of cfDNA aneuploidy testing on screening policies and prenatal ultrasound practice

Abstract: The widespread use of fetal cell-free DNA (cfDNA)-based techniques to screen for trisomy 21 and other aneuploidies has expanded greatly the range of prenatal tests available over the last few years. cfDNA tests are being incorporated rapidly into prenatal care, thus changing the traditional approach to prenatal screening and diagnosis. However, although cfDNA techniques are highly efficient, their role and performance must be considered alongside and combined with other screening modalities. The role of prenatal ultrasound, in particular, needs to be reaffirmed as cfDNA testing becomes more widely available. It is important to emphasize that the main goal of prenatal screening is to provide accurate information that will facilitate the delivery of optimized antenatal care, with the best possible outcome for both mother and fetus. Women should be informed about the prevalence and the clinical manifestation of the disease of interest and about prenatal screening performance (detection rate, false-positive rate, positive predictive value in the general population, failure rate) by appropriately trained health professionals, allowing them to make an informed decision. It is the parent’s choice to undergo such procedures, and their wishes should be determined and respected. This consensus statement constitutes a revised and updated version of the previously published ISUOG consensus statement on the impact of non-invasive prenatal testing (NIPT) on prenatal ultrasound practice1; updates will be produced on a regular basis.

Natural history of Cesarean scar pregnancy on prenatal ultrasound: the crossover sign.

Abstract: Objective Advances in prenatal imaging techniques have led to an increase in the diagnosis of Cesarean scar pregnancy (CSP). However, antenatal counseling when CSP is diagnosed is challenging, and current evidence is derived mainly from small series reporting high rates of adverse maternal outcomes. The aim of this study was to ascertain the performance of prenatal ultrasound in predicting the natural history of CSP using a new sonographic sign, the crossover sign (COS). Methods This was a retrospective analysis of early first-trimester (6–8 weeks' gestation) ultrasound images in women with morbidly adherent placenta (MAP) managed in the third trimester of pregnancy. The relationship between the gestational sac of the CSP, anterior uterine wall and Cesarean scar, defined as the COS, was analyzed to determine whether it could predict evolution in these cases. Odds ratios (ORs) were calculated and logistic regression analysis was performed to investigate the association between different types of COS (COS-1, COS-2+ or COS-2–) and the occurrence of MAP. Results Sixty-eight pregnancies with MAP were included. The risk of placenta percreta was significantly higher in pregnancies with COS-1 than in those with COS-2 (OR, 6.67 (95% CI, 1.3–33.3)). When evaluating the two variants of COS-2 separately, the risk of placenta percreta was significantly higher in pregnancies with COS-1 vs COS-2+ (OR, 5.83 (95% CI, 1.1–30.2)) and this risk was even higher when comparing cases with COS-1 vs COS-2– (OR, 12.0 (95% CI, 1.9–75.7)). Logistic regression analysis showed that COS-1 was associated independently with severe forms of MAP, such as placenta percreta and increta (OR, 12.85 (95% CI, 2.0–84.0)), while COS-2+ was associated independently with placenta accreta (OR, 4.37 (95% CI, 1.1–17.0)). Conclusions Ultrasound assessment of the relationship between the gestational sac of a CSP and the endometrial line (the COS) may help to determine whether a CSP will progress towards a less severe form of MAP, amenable to postnatal treatment, and successful pregnancy outcome. Large prospective studies are needed to confirm our findings and elucidate the natural history of this condition. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Estimating risk of malignancy in adnexal masses: external validation of the ADNEX model and comparison with other frequently used ultrasound methods.

Abstract: Objectives To validate externally the performance of the Assessment of Different NEoplasias in the adneXa (ADNEX) model and compare this model with other frequently used models in the differentiation between benign and malignant adnexal masses. Methods In this retrospective diagnostic accuracy study, we assessed data collected prospectively from patients with adnexal pathology who underwent real-time transvaginal or transrectal ultrasound by a single expert ultrasonographer in a tertiary care hospital between July 2011 and July 2015. The presence of a malignancy was determined by subjective assessment and use of four prediction models: the ADNEX model, simple ultrasound-based rules (simple rules), Logistic Regression model 2 (LR2) and the Risk of Malignancy Index (RMI), of which three different variants were assessed. Pathology was the clinical reference standard. Results In total, 851 consecutive patients underwent ultrasound examination for an adnexal mass. For 326 patients (128 premenopausal and 198 postmenopausal), pathology results were available (211 (64.7%) benign; 115 (35.3%) malignant) and these were included in the analysis. The area under the receiver–operating characteristics curve (AUC) of the ADNEX model for the discrimination between benign and malignant tumors was 0.93 (95% CI, 0.89–0.95). AUCs for the subtypes of malignancy (i.e. borderline, Stage I–IV and metastatic adnexal tumors) ranged between 0.60 and 0.90. Only subjective assessment (AUC, 0.96 (95% CI, 0.93–0.98)) was superior to the ADNEX model (P = 0.01) in differentiating malignant from benign tumors. AUCs for the other models were 0.92 (95% CI, 0.89–0.95) for LR2, 0.85 (95% CI, 0.81–0.89) for RMI-I, 0.82 (95% CI, 0.77–0.86) for RMI-II and 0.84 (95% CI, 0.80–0.88) for RMI-III. At the proposed cut-off of ≥ 10%, the ADNEX model had the highest sensitivity (0.98 (95% CI, 0.93–1.00)) but the lowest specificity (0.62 (95% CI, 0.55–0.68)) compared with the other models. Both subjective assessment (sensitivity, 0.90 (95% CI, 0.83–0.95); specificity 0.91 (95% CI, 0.86–0.94)) and the simple rules model with inconclusive cases classified by subjective assessment (sensitivity, 0.89 (95% CI, 0.81–0.94); specificity, 0.90 (95% CI, 0.85–0.94)) had lower sensitivity, but their sensitivity and specificity were better balanced. Conclusions Although the test performance of subjective assessment by an expert remains superior, the ADNEX model can help in the differentiation between benign and malignant ovarian tumors. The advantage of the ADNEX model as a polytomous model remains to be shown. © 2016 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Descriptive analysis of different phenotypes of cardiac remodeling in fetal growth restriction.

Abstract: Objective To identify the presence of different cardiac phenotypes among FGR. Study Design Fetal echocardiography was performed in 126 FGR (defined as birth weight <10th centile) and 64 adequate for gestational age (AGA). Principal component and cluster analyses were performed to identify different cardiac phenotypes among FGR cases. Results Three different cardiac phenotypes were identified within FGR: globular, elongated and hypertrophic. Most FGR cases (54%) were characterized by a ‘globular’ heart with the lowest left ventricular sphericity index (controls: median 1.78 (interquartile range 1.62-1.97), FGR-elongated: 1.92 (1.78-2.09), FGR-globular 1.44 (1.36-1.52) and FGR-hypertrophic 1.65 (1.42-1.77), P = 0.001), while 29% of the cases showed an ‘elongated’ left ventricle with nearly normal cardiac dimensions. Finally, 17% of the FGR showed a ‘hypertrophic’ phenotype with the highest values in left ventricular wall thickness (controls: 1.22 mm/kg (1.1-1.67), FGR-elongated: 1.52 (1.28-1.86), FGR-globular 1.65 (1.39-1.99) and FGR-hypertrophic 3.68 (3.45-4.71), P = 0.001) and cardiac dimensions. The globular and elongated phenotype showed fetoplacental profile of late-onset FGR while the hypertrophic phenotype showed signs of early-onset FGR The hypertrophic cluster also showed the worst perinatal results presenting the lowest birthweight centile, gestational age at birth, Apgar score, and the highest postnatal blood pressure and carotid intima media thickness. Conclusions FGR induces at least 3 different cardiac phenotypes, with early-onset FGR cases associated with a hypertrophic response and worse perinatal outcomes. This cardiac phenotypic classification may improve identification of those FGR cases with the highest perinatal and long-term cardiovascular risk.

Outcome of monochorionic twin pregnancy with selective intrauterine growth restriction according to umbilical artery Doppler flow pattern of smaller twin: systematic review and meta-analysis.

Abstract: Objective To explore the outcome of monochorionic twin pregnancies affected by selective intrauterine growth restriction (sIUGR) according to the umbilical artery Doppler pattern of the smaller twin. Methods An electronic search of MEDLINE, EMBASE, CINAHL and ClinicalTrials.gov databases (2000–2016) was performed. sIUGR was defined as the presence of one twin with an estimated fetal weight and/or abdominal circumference < 10th or < 5th percentile and classified according to the umbilical artery Doppler flow pattern of the smaller twin (Type I: persistently positive; Type II: persistently absent/reversed; Type III: intermittently absent/reversed). Primary outcomes were perinatal mortality, intrauterine death, neonatal death and double fetal loss. Secondary outcomes were neonatal morbidity, including abnormal postnatal brain imaging, intraventricular hemorrhage, periventricular leukomalacia, admission to neonatal intensive care unit and respiratory distress syndrome, deterioration of fetal status, gestational age at delivery and degree of birth-weight discordance. A composite adverse outcome, defined as the presence of any mortality or abnormal brain findings, was also assessed. Quality assessment of the included studies was performed using the Newcastle–Ottawa Scale. A random-effects meta-analysis was used to compute the summary odds ratios (ORs), mean differences (MD) and proportions for the different outcomes. Results Thirteen studies (610 pregnancies) were included. The risk of perinatal mortality was higher in twins affected by Type II compared with Type I sIUGR (OR, 4.1 (95% CI, 1.6–10.3)), whereas there was no difference among the other variants of growth restriction. Risk of abnormal postnatal brain imaging was significantly higher in twins affected by either Type II (OR, 4.9 (95% CI, 1.9–12.9)) or Type III (OR, 8.2 (95% CI, 2.0–33.1)) sIUGR compared with Type I sIUGR. The risk for neonatal intensive care unit admission was higher in Type II compared with Type I sIUGR (OR, 18.3 (95% CI, 1.0–339.7)). Twin pregnancies affected by Type I sIUGR were delivered at a significantly later gestational age compared with Type II (MD, 2.8 (95% CI, 1.83–3.86) weeks) and Type III (MD, 2.1 (95% CI, 0.97–3.19) weeks). The degree of birth-weight discordance was higher in Type II compared with Type I (MD, 21.6% (95% CI, 9.9–33.2%)) and Type III (MD, 9.3% (95% CI, 3.8–14.9%)) sIUGR. Conclusion Monochorionic twin pregnancies affected by Type II sIUGR are at a higher risk of perinatal mortality and morbidity compared with Type I. The likelihood of an abnormal outcome is usually not significantly different between sIUGR Types II and III, although the latter has an unpredictable clinical course. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Oligohydramnios in complicated and uncomplicated pregnancy: a systematic review and meta-analysis.

Abstract: Objective To evaluate adverse pregnancy outcomes in singleton pregnancies diagnosed with oligohydramnios through a systematic review and meta-analysis of controlled trials. Methods We searched electronic databases via OVID, EBSCO, Web of Science, Google Scholar and others from 1980 to 2015. Prospective and retrospective studies with a control group were included. Two authors independently reviewed the abstracts from the literature search. Inclusion criteria were: studies in English, singleton pregnancy, normal fetal anatomy, intact membranes and oligohydramnios determined by the amniotic fluid index (AFI) technique. We stratified the meta-analysis into two groups according to risk: high risk including studies of oligohydramnios with comorbid conditions (e.g. hypertension) and low risk including studies of isolated oligohydramnios. Results Fifteen trials met the inclusion criteria. Nine were high-risk and six were low-risk studies, including 8067 and 27 526 women, respectively. Compared with women with normal AFI, those with isolated oligohydramnios had significantly higher rates of an infant with meconium aspiration syndrome (relative risk (RR), 2.83; 95% CI, 1.38–5.77), Cesarean delivery for fetal distress (RR, 2.16; 95% CI, 1.64–2.85) and admission to the neonatal intensive care unit (NICU) (RR, 1.71; 95% CI, 1.20–2.42). Patients with oligohydramnios and comorbidities were more likely to have an infant with low birth weight (RR, 2.35; 95% CI, 1.27–4.34). However, rates of 5-min Apgar score < 7 (RR, 1.85; 95% CI, 0.69–4.96), NICU admission (RR, 2.09; 95% CI, 0.80–5.45), meconium-stained amniotic fluid (RR, 1.32; 95% CI, 0.62–2.81) and Cesarean delivery for fetal distress (RR, 1.65; 95% CI, 0.81–3.36) were similar to those for women with normal AFI. Stillbirth rates were too low to analyze in the meta-analysis. Conclusions This review helps to delineate which adverse outcomes are increased with oligohydramnios in low-risk pregnancy (NICU admission, Cesarean delivery for fetal distress and meconium aspiration syndrome), but does not provide enough data to determine the optimal timing of delivery in such cases. Oligohydramnios in complicated pregnancy is associated with an increased risk of delivery of an infant with low birth weight, but this may be confounded by the comorbid condition. Therefore, in high-risk pregnancy, management should be dictated by the comorbid condition and not the presence of oligohydramnios. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Cardiac output assessment in pregnancy: comparison of two automated monitors with echocardiography.

Abstract: Objective To compare non-invasive hemodynamic measurements obtained in pregnant and postpartum women using two automated cardiac output monitors against those obtained by two-dimensional (2D) transthoracic echocardiography (TTE). Methods This was a cross-comparison study into which we recruited 114 healthy women, either with normal singleton pregnancy (across all three trimesters) or within 72 hours following delivery. Cardiac output estimations were obtained non-invasively using two different monitors, Ultrasound Cardiac Output Monitor (USCOM®, which uses continuous-wave Doppler analysis of transaortic blood flow) and Non-Invasive Cardiac Output Monitor (NICOM®, which uses thoracic bioreactance), and 2D-TTE. The performance of each monitor was assessed relative to that of TTE by calculating bias, precision, 95% limits of agreement and mean percentage difference (MPD). Intraobserver repeatability was assessed for both monitors and interobserver reproducibility was assessed for USCOM, NICOM being operator-independent. Results Following exclusions due to poor-quality results of a monitor or TTE, or for medical reasons, our analysis included 98 women (29 in the first trimester, 25 in the second and 21 in the third, and 23 postpartum). For cardiac output estimation, when compared with TTE, USCOM had a bias ranging from 0.4 to 0.9 L/min. The MPD of USCOM was 29% in the third-trimester cohort. NICOM had a bias ranging from −1.0 to 0.6 L/min, with a MPD of 32% in the third-trimester group. There was limited agreement between the cardiac output monitors and TTE in the first and second trimesters, with a MPD of 38% for USCOM in both first and second trimesters, and 71% and 61% for NICOM in first and second trimesters, respectively. For cardiac output estimation using USCOM, we found excellent intraobserver repeatability (intraclass correlation coefficient (ICC), 0.97; 95% CI, 0.95–0.98) and interobserver reproducibility (ICC, 0.90; 95% CI, 0.81–0.94), and the repeatability for NICOM was comparable (ICC, 0.95; 95% CI, 0.93–0.97). Conclusions We found good agreement of both USCOM and NICOM when compared with 2D-TTE, specifically in the third trimester of pregnancy. Both devices had good intraobserver repeatability and either had good interobserver reproducibility or were operator-independent. Future studies should take into account the significant differences in the precise maternal hemodynamic values obtained by these devices, and consider developing device-specific reference ranges in pregnancy and the postpartum period. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Vaginal progesterone vs intramuscular 17α-hydroxyprogesterone caproate for prevention of recurrent spontaneous preterm birth in singleton gestations: systematic review and meta-analysis of randomized controlled trials

Abstract: Objective Randomized controlled trials (RCTs) have recently compared intramuscular 17α-hydroxyprogesterone caproate (17-OHPC) with vaginal progesterone for reducing the risk of spontaneous preterm birth (SPTB) in singleton gestations with prior SPTB. The aim of this systematic review and meta-analysis was to evaluate the efficacy of vaginal progesterone compared with 17-OHPC in prevention of SPTB in singleton gestations with prior SPTB. Methods Searches of electronic databases were performed to identify all RCTs of asymptomatic singleton gestations with prior SPTB that were randomized to prophylactic treatment with either vaginal progesterone (intervention group) or intramuscular 17-OHPC (comparison group). No restrictions for language or geographic location were applied. The primary outcome was SPTB < 34 weeks. Secondary outcomes were SPTB < 37 weeks, < 32 weeks, < 28 weeks and < 24 weeks, maternal adverse drug reaction and neonatal outcomes. The summary measures were reported as relative risk (RR) with 95% CI. Risk of bias for each included study was assessed. Results Three RCTs (680 women) were included. The mean gestational age at randomization was about 16 weeks. Women were given progesterone until 36 weeks or delivery. Regarding vaginal progesterone, one study used 90 mg gel daily, one used 100 mg suppository daily and one used 200 mg suppository daily. All included RCTs used 250 mg intramuscular 17-OHPC weekly in the comparison group. Women who received vaginal progesterone had significantly lower rates of SPTB < 34 weeks (17.5% vs 25.0%; RR, 0.71 (95% CI, 0.53–0.95); low quality of evidence) and < 32 weeks (8.9% vs 14.5%; RR, 0.62 (95% CI, 0.40–0.94); low quality of evidence) compared with women who received 17-OHPC. There were no significant differences in the rates of SPTB < 37 weeks, < 28 weeks and < 24 weeks. The rate of women who reported adverse drug reactions was significantly lower in the vaginal progesterone group compared with the 17-OHPC group (7.1% vs 13.2%; RR, 0.53 (95% CI, 0.31–0.91); very low quality of evidence). Regarding neonatal outcomes, vaginal progesterone was associated with a lower rate of neonatal intensive care unit admission compared with 17-OHPC (18.7% vs 23.5%; RR, 0.63 (95% CI, 0.47–0.83); low quality of evidence). For the comparison of 17-OHPC vs vaginal progesterone, the quality of evidence was downgraded for all outcomes by at least one degree due to imprecision (the optimal information size was not reached) and by at least one degree due to indirectness (different interventions). Conclusions Daily vaginal progesterone (either suppository or gel) started at about 16 weeks' gestation is a reasonable, if not better, alternative to weekly 17-OHPC injection for prevention of SPTB in women with singleton gestations and prior SPTB. However, the quality level of the summary estimates was low or very low as assessed by GRADE, indicating that the true effect may be, or is likely to be, substantially different from the estimate of the effect. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Comparacion entre la progesterona vaginal y el 17α-hidroxiprogesterona caproato intramuscular para la prevencion del parto pretermino espontaneo recurrente en embarazos con feto unico: revision sistematica y metaanalisis de ensayos controlados aleatorios RESUMEN Objetivo Recientemente se han realizado varios ensayos controlados aleatorios (ECA) que comparaban el caproato de 17α-hidroxiprogesterona (17-OHPC, por sus siglas en ingles) por via intramuscular con la progesterona por via vaginal para la reduccion del riesgo de parto pretermino espontaneo (PPTE) en embarazos con feto unico de gestantes con historial de PPTE. El objetivo de esta revision sistematica y metaanalisis fue evaluar la eficacia de la progesterona vaginal en comparacion con la 17-OHPC en la prevencion de embarazos con feto unico de gestantes con historial de PPTE. Metodos Se realizaron busquedas en bases de datos electronicas para identificar todos los ECA con embarazos de feto unico asintomaticos con historial de PPTE antes de ser asignados al azar a un tratamiento profilactico, ya fuera con progesterona vaginal (grupo de intervencion) o con 17-OHPC intramuscular (grupo de control). No se aplicaron restricciones respecto al idioma o la ubicacion geografica. El resultado primario fue PPTE < 34 semanas. Los resultados secundarios fueron PPTE <37 semanas, < 32 semanas, < 28 semanas y < 24 semanas, la reaccion materna adversa al farmaco y los resultados neonatales. Las medidas del resumen se reportaron como riesgo relativo (RR) con IC del 95%. Para cada estudio incluido se evaluo el riesgo de sesgo. Resultados Se incluyeron tres ECA (680 mujeres). La media de la edad gestacional en el momento de la aleatorizacion fue de 16 semanas. A las mujeres se les administro progesterona hasta la semana 36 o hasta el parto. Con respecto a la progesterona vaginal, un estudio utilizo gel de 90 mg diariamente, otro utilizo un supositorio diario de 100 mg y el otro utilizo un supositorio diario de 200 mg. Todos los ECA incluidos en el grupo de comparacion utilizaron 250 mg semanales de 17-OHPC por via intramuscular. Las mujeres que recibieron progesterona vaginal tuvieron tasas significativamente mas bajas de PPTE < 34 semanas (17,5% vs. 25,0%; RR 0,71 (IC 95%, 0,53–0,95); calidad de la evidencia baja) y < 32 semanas (8,9% vs. 14,5%; RR 0,62 (IC 95%, 0,40–0,94); calidad de evidencia baja), en comparacion con las mujeres que recibieron 17-OHPC. No hubo diferencias significativas en las tasas de PPTE < 37 semanas, < 28 semanas y < 24 semanas. La tasa de mujeres que reportaron reacciones adversas a los medicamentos fue significativamente menor en el grupo de progesterona vaginal en comparacion con el grupo de 17-OHPC (7,1% vs. 13,2%; RR 0,53 (IC 95%, 0,31–0,91); calidad de la evidencia muy baja). En cuanto a los resultados neonatales, la progesterona vaginal se asocio a una menor tasa de admisiones en la unidad neonatal de cuidados intensivos en comparacion con la 17-OHPC (18,7% vs. 23,5%; RR 0,63 (IC 95%, 0,47–0,83); calidad de evidencia baja). Para la comparacion del 17-OHPC con la progesterona vaginal se rebajo la calidad de las pruebas para todos los resultados en al menos un grado debido a imprecisiones (no se alcanzo el tamano optimo de la informacion) y en al menos un grado debido al caracter indirecto de los estudios (diferentes intervenciones). Conclusiones La progesterona vaginal administrada diariamente (ya fuera como supositorio o como gel) desde la semana 16 de gestacion es una alternativa razonable, si no mejor, a una inyeccion semanal de 17-OHPC para la prevencion de PPTE en mujeres con embarazos de feto unico e historial de PPTE. Sin embargo, el nivel de calidad de las estimaciones del resumen fue bajo o muy bajo segun lo evaluado por GRADE, lo que indica que el verdadero efecto puede ser, o es probable que sea, sustancialmente diferente de la estimacion del efecto. 单胎妊娠时黄体酮阴道给药与肌肉注射17α-已酸羟孕酮预防复发性自发性早产:系统回顾和随机对照试验的meta分析 目的 最近有随机对照试验(randomized controlled trials,RCTs)对比了有自发性早产(spontaneous preterm birth,SPTB)既往史的单胎妊娠中肌肉注射17α-已酸羟孕酮(intramuscular 17α-hydroxyprogesterone caproate,17-OHPC)与黄体酮阴道给药降低SPTB的风险。本篇系统回顾和meta分析的目的是评估在有SPTB既往史的单胎妊娠中黄体酮阴道给药对比17-OHPC预防SPTB的疗效。 方法 检索电子数据库,查找关于有SPTB既往史的无症状单胎妊娠的所有RCTs,RCTs中将患者随机分为接受黄体酮阴道给药(干预组)或肌肉注射17-OHPC(对照组)。对语言或地理位置无限制。主要结局为孕34周前发生SPTB。次要结局为孕37周前、孕32周前、孕28周前和孕24周前发生SPTB,母亲不良药物反应以及新生儿结局。综合检测结果以相对危险度(relative risk,RR)和95%CI表示。对每项纳入研究的偏倚风险进行评估。 结果 纳入3项RCTs(680例孕妇)。随机分组时平均孕周约为16周。给予孕妇黄体酮,直至孕36周或分娩。在黄体酮阴道给药组中,一项研究采用每日90 mg凝胶,一项采用每日100 mg栓剂,另外一项研究采用每日200 mg栓剂。对照组中,所有纳入的RCTs均采用每周250 mg 17-OHPC肌肉注射。与17-OHPC组孕妇相比,黄体酮阴道给药组孕妇孕34周前 [17.5%和25.0%;RR,0.71(95% CI,0.53 ~ 0.95);低质量证据]和孕32周前[8.9%和14.5%;RR,0.62(95% CI,0.40 ~ 0.94);低质量证据]SPTB的发生率明显较低。孕37周前、孕28周前和孕24周前SPTB的发生率无明显差异。黄体酮阴道给药组与17-OHPC组比较,孕妇不良药物反应的发生率明显较低[7.1%和13.2%;RR,0.53(95% CI,0.31 ~ 0.91);极低质量证据]。在新生儿结局方面,与17-OHPC组比较,黄体酮阴道给药组新生儿重症监护病房住院率较低[18.7%和23.5%;RR,0.63(95% CI,0.47 ~ 0.83);低质量证据]。对17-OHPC和黄体酮阴道给药进行比较,所有结局的证据质量由于不精确降低至少一级(未达到最佳信息量),由于间接性至少降低一级(不同干预措施)。 结论 为了预防有SPTB既往史的单胎妊娠孕妇发生SPTB,在约孕16周时开始每日黄体酮阴道给药(栓剂或凝胶)是每周注射17-OHPC的一项合理的,即使不是更好的替代方案。然而,根据GRADE,综合评估的质量水平较低或极低,表明真实的效果可能或很可能与估计的效果大不相同。

Ultrasound characteristics of endometrial cancer as defined by International Endometrial Tumor Analysis (IETA) consensus nomenclature: prospective multicenter study.

Abstract: Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd. Objective: To describe the sonographic features of endometrial cancer in relation to tumor stage, grade and histological type, using the International Endometrial Tumor Analysis (IETA) terminology. Methods: This was a prospective multicenter study of 1714 women with biopsy-confirmed endometrial cancer undergoing standardized transvaginal grayscale and Doppler ultrasound examination according to the IETA study protocol, by experienced ultrasound examiners using high-end ultrasound equipment. Clinical and sonographic data were entered into a web-based database. We assessed how strongly sonographic characteristics, according to IETA, were associated with outcome at hysterectomy, i.e. tumor stage, grade and histological type, using univariable logistic regression and the c-statistic. Results: In total, 1538 women were included in the final analysis. Median age was 65 (range, 27–98) years, median body mass index was 28.4 (range 16–67) kg/m2, 1377 (89.5%) women were postmenopausal and 1296 (84.3%) reported abnormal vaginal bleeding. Grayscale and color Doppler features varied according to grade and stage of tumor. High-risk tumors, compared with low-risk tumors, were less likely to have regular endometrial–myometrial junction (difference of −23%; 95% CI, −27 to −18%), were larger (mean endometrial thickness; difference of +9%; 95% CI, +8 to +11%), and were more likely to have non-uniform echogenicity (difference of +7%; 95% CI, +1 to +13%), a multiple, multifocal vessel pattern (difference of +21%; 95% CI, +16 to +26%) and a moderate or high color score (difference of +22%; 95% CI, +18 to +27%). Conclusion: Grayscale and color Doppler sonographic features are associated with grade and stage of tumor, and differ between high- and low-risk endometrial cancer. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.