Showing papers in "Ultrasound in Obstetrics & Gynecology in 2015"

Analysis of cell‐free DNA in maternal blood in screening for fetal aneuploidies: updated meta‐analysis

Abstract: Objective 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. Methods Searches of PubMed, EMBASE and The Cochrane Library were performed to identify all peer-reviewed articles on cfDNA testing in screening for aneuploidies between January 2011, when the first such study was published, and 4 January 2015. Results In total, 37 relevant studies were identified and these were used for the meta-analysis on the performance of cfDNA testing in screening for aneuploidies. These studies reported cfDNA results in relation to fetal karyotype from invasive testing or clinical outcome. Weighted pooled detection rates (DR) and false-positive rates (FPR) in singleton pregnancies were 99.2% (95% CI, 98.5–99.6%) and 0.09% (95% CI, 0.05–0.14%), respectively, for trisomy 21, 96.3% (95% CI, 94.3–97.9%) and 0.13% (95% CI, 0.07–0.20) for trisomy 18, 91.0% (95% CI, 85.0–95.6%) and 0.13% (95% CI, 0.05–0.26%) for trisomy 13, 90.3% (95% CI, 85.7–94.2%) and 0.23% (95% CI, 0.14–0.34%) for monosomy X and 93.0% (95% CI, 85.8–97.8%) and 0.14% (95% CI, 0.06–0.24%) for sex chromosome aneuploidies other than monosomy X. For twin pregnancies, the DR for trisomy 21 was 93.7% (95% CI, 83.6–99.2%) and the FPR was 0.23% (95% CI, 0.00–0.92%). Conclusion Screening for trisomy 21 by analysis of cfDNA in maternal blood is superior to that of all other traditional methods of screening, with higher DR and lower FPR. The performance of screening for trisomies 18 and 13 and sex chromosome aneuploidies is considerably worse than that for trisomy 21. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Procedure-related risk of miscarriage following amniocentesis and chorionic villus sampling: a systematic review and meta-analysis.

Abstract: Objectives To estimate procedure-related risks of miscarriage following amniocentesis and chorionic villus sampling (CVS) based on a systematic review of the literature and a meta-analysis. Methods A search of MEDLINE, EMBASE, CINHAL and The Cochrane Library (2000-2014) was performed to review relevant citations reporting procedure-related complications of amniocentesis and CVS. Only studies reporting data on more than 1000 procedures were included in this review to minimize the effect of bias from smaller studies. Heterogeneity between studies was estimated using Cochran's Q, the I(2) statistic and Egger bias. Meta-analysis of proportions was used to derive weighted pooled estimates for the risk of miscarriage before 24 weeks' gestation. Incidence-rate difference meta-analysis was used to estimate pooled procedure-related risks. Results The weighted pooled risks of miscarriage following invasive procedures were estimated from analysis of controlled studies including 324 losses in 42 716 women who underwent amniocentesis and 207 losses in 8899 women who underwent CVS. The risk of miscarriage prior to 24 weeks in women who underwent amniocentesis and CVS was 0.81% (95% CI, 0.58-1.08%) and 2.18% (95% CI, 1.61-2.82%), respectively. The background rates of miscarriage in women from the control group that did not undergo any procedures were 0.67% (95% CI, 0.46-0.91%) for amniocentesis and 1.79% (95% CI, 0.61-3.58%) for CVS. The weighted pooled procedure-related risks of miscarriage for amniocentesis and CVS were 0.11% (95% CI, -0.04 to 0.26%) and 0.22% (95% CI, -0.71 to 1.16%), respectively. Conclusion The procedure-related risks of miscarriage following amniocentesis and CVS are much lower than are currently quoted.

Terms, definitions and measurements to describe sonographic features of myometrium and uterine masses: a consensus opinion from the Morphological Uterus Sonographic Assessment (MUSA) group

Abstract: The MUSA (Morphological Uterus Sonographic Assessment) statement is a consensus statement on terms, definitions and measurements that may be used to describe and report the sonographic features of the myometrium using gray-scale sonography, color/power Doppler and three-dimensional ultrasound imaging. The terms and definitions described may form the basis for prospective studies to predict the risk of different myometrial pathologies, based on their ultrasound appearance, and thus should be relevant for the clinician in daily practice and for clinical research. The sonographic features and use of terminology for describing the two most common myometrial lesions (fibroids and adenomyosis) and uterine smooth muscle tumors are presented. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Non‐invasive prenatal testing for trisomies 21, 18 and 13: clinical experience from 146 958 pregnancies

Abstract: Objectives To report the clinical performance of massively parallel sequencing-based non-invasive prenatal testing (NIPT) in detecting trisomies 21, 18 and 13 in over 140 000 clinical samples and to compare its performance in low-risk and high-risk pregnancies. Methods Between 1 January 2012 and 31 August 2013, 147 314 NIPT requests to screen for fetal trisomies 21, 18 and 13 using low-coverage whole-genome sequencing of plasma cell-free DNA were received. The results were validated by karyotyping or follow-up of clinical outcomes. Results NIPT was performed and results obtained in 146 958 samples, for which outcome data were available in 112 669 (76.7%). Repeat blood sampling was required in 3213 cases and 145 had test failure. Aneuploidy was confirmed in 720/781 cases positive for trisomy 21, 167/218 cases positive for trisomy 18 and 22/67 cases positive for trisomy 13 on NIPT. Nine false negatives were identified, including six cases of trisomy 21 and three of trisomy 18. The overall sensitivity of NIPT was 99.17%, 98.24% and 100% for trisomies 21, 18 and 13, respectively, and specificity was 99.95%, 99.95% and 99.96% for trisomies 21, 18 and 13, respectively. There was no significant difference in test performance between the 72 382 high-risk and 40 287 low-risk subjects (sensitivity, 99.21% vs 98.97% (P = 0.82); specificity, 99.95% vs 99.95% (P = 0.98)). The major factors contributing to false-positive and false-negative NIPT results were maternal copy number variant and fetal/placental mosaicism, but fetal fraction had no effect. Conclusions Using a stringent protocol, the good performance of NIPT shown by early validation studies can be maintained in large clinical samples. This technique can provide equally high sensitivity and specificity in screening for trisomy 21 in a low-risk, as compared to high-risk, population. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Implementation of the sFlt-1/PlGF ratio for prediction and diagnosis of pre-eclampsia in singleton pregnancy: implications for clinical practice

Abstract: Pre-eclampsia (PE) is a leading cause of maternal and fetal/neonatal morbidity and mortality worldwide. Clinical diagnosis and definition of PE is commonly based on the measurement of non-specific signs and symptoms, principally hypertension and proteinuria1–3. However, due to the recognition that measurement of proteinuria is prone to inaccuracies and the fact that PE complications often occur before proteinuria becomes significant, most recent guidelines also support the diagnosis of PE on the basis of hypertension and signs of maternal organ dysfunction other than proteinuria3–5. Furthermore, the clinical presentation and course of PE is variable, ranging from severe and rapidly progressing early-onset PE, necessitating preterm delivery, to late-onset PE at term. There may be associated intrauterine growth restriction (IUGR), further increasing neonatal morbidity and mortality. These features suggest that the classical standards for the diagnosis of PE are not sufficient to encompass the complexity of the syndrome. Undoubtedly, proper management of pregnant women at high risk for PE necessitates early and reliable detection and intensified monitoring, with referral to specialized perinatal care centers, to reduce substantially maternal, fetal and neonatal morbidity6,7. In the decade since Maynard et al.8 reported that excessive placental production of soluble fms-like tyrosine kinase receptor-1 (sFlt-1), an antagonist of vascular endothelial growth factor and placental growth factor (PlGF), contributes to the pathogenesis of PE, extensive research has been published demonstrating the usefulness of angiogenic markers in both diagnosis and the subsequent prediction and management of PE and placenta-related disorders. Various reports have demonstrated that disturbances in angiogenic and antiangiogenic factors are implicated in the pathogenesis of PE and have possible relevance in the diagnosis and prognosis of the disease. Increased serum levels of sFlt-1 and decreased levels of PlGF, thereby resulting in an increased sFlt-1/PlGF ratio, can be detected in the second half of pregnancy in women diagnosed to have not only PE but also IUGR or stillbirth, i.e. placenta-related disorders. These alterations are more pronounced in early-onset rather than late-onset disease and are associated with severity of the clinical disorder. Moreover, the disturbances in angiogenic factors are reported to be detectable prior to the onset of clinical symptoms (disease), thereby allowing discrimination of women with normal pregnancies from those at high risk for developing pregnancy complications, primarily PE9–30. Plasma concentrations of angiogenic/antiangiogenic factors are of prognostic value in obstetric triage: similar to the progressively worsening clinical course observed in women with early-onset PE, changes in the angiogenic profile leading to a more antiangiogenic state can be found. Current definitions of PE are poor in predicting PE-related adverse outcomes. A diagnosis of PE based on blood pressure and proteinuria has a positive predictive value of approximately 30% for predicting PE-related adverse outcomes31. Estimation of the sFlt-1/PlGF ratio allows identification of women at high risk for imminent delivery and adverse maternal and neonatal outcome23,30,32–35. Moreover, it has also been shown that the time-dependent slope of the sFlt-1/PlGF ratio between repeated measurements is predictive for pregnancy outcome and the risk of developing PE, and repeated measurements have been suggested36. However, the ‘optimal’ time interval for a follow-up test remains unclear. Finally, high values are closely related to the need to deliver immediately22,23,37. Additionally, in normal and complicated pregnancies, angiogenic factors are correlated with Doppler ultrasound parameters, mainly uterine artery (UtA) indices38–42. Combining the sFlt-1/PlGF ratio with UtA Doppler ultrasound, at the time of diagnosis of early-onset PE, has prognostic value mainly for perinatal complications, being limited for the prediction of maternal complications37,43. The additional measurement of the sFlt-1/PlGF ratio has been shown to improve the sensitivity and specificity of Doppler measurement in predicting PE44–48, supporting its implementation in screening algorithms. Whereas studies on the predictive efficacy of the sFlt-1/PlGF ratio in the first trimester have yielded contradictory results49, reports on the use of this marker as an aid in prediction from the mid trimester onwards have led to its suggested use as a screening tool, especially for identifying all women developing PE and requiring delivery within the subsequent 4 weeks50–52. This short review of the literature highlights that measurement of the sFlt-1/PlGF ratio has the potential to become an additional tool in the management of PE, particularly as automated tests that allow rapid and easy measurement of these markers are now widely available. Nevertheless, although these markers were incorporated recently into the German guidelines53, no formal recommendation regarding how to use sFlt-1, PlGF or the sFlt-1/PlGF ratio has been established in any official protocol. The purpose of this paper is to answer questions that are frequently asked around the use of the sFlt-1/PlGF ratio in the diagnosis and prediction of PE and regarding the implications for clinical practice, in particular, ‘When?’ and ‘In which women?’ should the sFlt-1/PlGF ratio be measured and, ‘What should be done with the results?’, and to provide guidance to educate physicians on the use of the sFlt-1/PlGF ratio in clinical practice. To achieve this, international experts in the use of angiogenic markers have strived to develop a consensus statement on the clinical use of the sFlt-1/PlGF ratio and the consequential management in pregnant women with suspected PE or at a high risk of developing PE.

Prenatal diagnosis of critical congenital heart disease reduces risk of death from cardiovascular compromise prior to planned neonatal cardiac surgery: a meta-analysis.

Abstract: Objective To determine if prenatal diagnosis improves the chance that a newborn with critical congenital heart disease will survive to undergo planned cardiac surgery. Methods A systematic review of the medical literature identified eight studies which met the following criteria: compared outcomes between newborns with prenatal and those with postnatal diagnosis of critical congenital heart disease; compared groups of patients with the same anatomical diagnosis; provided detailed information on cardiac anatomy; included detailed information on preoperative cause of death. A meta-analysis was performed to assess differences in preoperative mortality rates between newborns with prenatal diagnosis and those with postnatal diagnosis. Patients with established risk factors for increased mortality (high risk) and those whose families chose comfort care rather than cardiac surgery were excluded. Results In patients with comparable anatomy, standard risk, a parental desire to treat and optimal care, newborns with a prenatal diagnosis of critical congenital heart disease were significantly less likely to die prior to planned cardiac surgery than were those with a comparable postnatal diagnosis (pooled odds ratio, 0.26; 95% CI, 0.08–0.84). Conclusions For newborns most likely to benefit from treatment for their critical congenital heart disease, because they did not have additional risk factors and their families pursued treatment, prenatal diagnosis reduced the risk of death prior to planned cardiac surgery relative to patients with a comparable postnatal diagnosis. Further study and efforts to improve prenatal diagnosis of congenital heart disease should therefore be considered. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of transvaginal ultrasound for diagnosis of deep endometriosis in uterosacral ligaments, rectovaginal septum, vagina and bladder: systematic review and meta-analysis.

Abstract: Objective To review the diagnostic accuracy of transvaginal ultrasound (TVS) in the preoperative detection of endometriosis in the uterosacral ligaments (USL), rectovaginal septum (RVS), vagina and bladder in patients with clinical suspicion of deep infiltrating endometriosis (DIE). Methods An extensive search was performed in MEDLINE (PubMed) and EMBASE for studies published between January 1989 and December 2014. Studies were considered eligible if they reported on the use of TVS for the preoperative detection of endometriosis in the USL, RVS, vagina and bladder in women with clinical suspicion of DIE using the surgical data as a reference standard. Study quality was assessed using the PRISMA guidelines and QUADAS-2 tool. Results Of the 801 citations identified, 11 studies (n = 1583) were considered eligible and were included in the meta-analysis. For detection of endometriosis in the USL, the overall pooled sensitivity and specificity of TVS were 53% (95%CI, 35–70%) and 93% (95%CI, 83–97%), respectively. The pretest probability of USL endometriosis was 54%, which increased to 90% when suspicion of endometriosis was present after TVS examination. For detection of endometriosis in the RVS, the overall pooled sensitivity and specificity were 49% (95%CI, 36–62%) and 98% (95%CI, 95–99%), respectively. The pretest probability of RVS endometriosis was 24%, which increased to 89% when suspicion of endometriosis was present after TVS examination. For detection of vaginal endometriosis, the overall pooled sensitivity and specificity were 58% (95%CI, 40–74%) and 96% (95%CI, 87–99%), respectively. The pretest probability of vaginal endometriosis was 17%, which increased to 76% when suspicion of endometriosis was present after TVS assessment. Substantial heterogeneity was found for sensitivity and specificity for all these locations. For detection of bladder endometriosis, the overall pooled sensitivity and specificity were 62% (95%CI, 40–80%) and 100% (95%CI, 97–100%), respectively. Moderate heterogeneity was found for sensitivity and specificity for bladder endometriosis. The pretest probability of bladder endometriosis was 5%, which increased to 92% when suspicion of endometriosis was present after TVS assessment. Conclusion Overall diagnostic performance of TVS for detecting DIE in uterosacral ligaments, rectovaginal septum, vagina and bladder is fair with high specificity. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Genomic microarray in fetuses with increased nuchal translucency and normal karyotype: a systematic review and meta-analysis

Abstract: Objective To estimate the incremental yield of detecting copy number variants (CNVs) by genomic microarray over karyotyping in fetuses with increased nuchal translucency (NT) diagnosed by first-trimester ultrasound. Methods This was a systematic review conducted in accordance with PRISMA criteria. We searched PubMed, Ovid MEDLINE and Web of Science for studies published between January 2009 and January 2015 that described CNVs in fetuses with increased NT, usually defined as ≥ 3.5 mm, and normal karyotype. Search terms included: fetal or prenatal, nuchal translucency or cystic hygroma or ultrasound anomaly, array comparative genomic hybridization or copy number variants, with related search terms. Risk differences were pooled to estimate the overall and stratified microarray incremental yield using RevMan. Quality assessment of included studies was performed using the Quality Assessment tool for Diagnostic Accuracy Studies (QUADAS-2) checklist. Results Seventeen studies met the inclusion criteria for analysis. Meta-analysis indicated an incremental yield of 5.0% (95% CI, 2.0–8.0%) for the detection of CNVs using microarray when pooling results. Stratified analysis of microarray results demonstrated a 4.0% (95% CI, 2.0–7.0%) incremental yield in cases of isolated NT and 7.0% (95% CI, 2.0–12.0%) when other malformations were present. The most common pathogenic CNVs reported were 22q11.2 deletion, 22q11.2 duplication, 10q26.12q26.3 deletion and 12q21q22 deletion. The pooled prevalence for variants of uncertain significance was 1%. Conclusion The use of genomic microarray provides a 5.0% incremental yield of detecting CNVs in fetuses with increased NT and normal karyotype. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Ovarian hyperstimulation syndrome: pathophysiology, staging, prediction and prevention.

Abstract: Objective To identify, appraise and summarize the current evidence regarding the pathophysiology, staging, prediction and prevention of ovarian hyperstimulation syndrome (OHSS). Methods Two comprehensive systematic reviews were carried out: one examined methods of predicting either high ovarian response or OHSS and the other examined interventions aimed at reducing the occurrence of OHSS. Additionally, we describe the related pathophysiology and staging criteria. Results Seven studies examining methods of predicting OHSS and eight more examining methods of predicting high ovarian response to controlled ovarian stimulation were included. Current evidence shows that the best methods of predicting high response are antral follicle count and anti-Mullerian hormone levels, and that a high ovarian response (examined by the number of large follicles, estradiol concentration or the number of retrieved oocytes) is the best method of predicting the occurrence of OHSS. Ninety-seven randomized controlled trials examining the effect of several interventions for reducing the occurrence of OHSS were included. There was high-quality evidence that replacing human chorionic gonadotropin by gonadotropin-releasing hormone agonists or recombinant luteinizing hormone, and moderate-quality evidence that antagonist protocols, dopamine agonists and mild stimulation, reduce the occurrence of OHSS. The evidence for the effect of the other interventions was of low/very low quality. Additionally, we identified and described 12 different staging criteria. Conclusions There are useful predictive tools and several preventive interventions aimed at reducing the occurrence of OHSS. Acknowledging and understanding them are of crucial importance for planning the treatment of, and, ultimately, eliminating, OHSS while maintaining high pregnancy rates. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Transvaginal sonographic features of diffuse adenomyosis in 18–30-year-old nulligravid women without endometriosis: association with symptoms

Abstract: OBJECTIVES To investigate whether there are sonographic features of diffuse adenomyosis in 18-30-year-old nulligravid women without endometriosis and to examine their association with symptoms of dysmenorrhea and abnormal uterine bleeding. METHODS This was a prospective observational study including women referred from a gynecology outpatient center to our university hospital for ultrasound examination. Inclusion criteria were age between 18 and 30 years, regular menstrual cycle and nulligravid status. Exclusion criteria were a past or current history of endometriosis, fibroids, ovarian cysts or lesions, endometrial pathology, current use of hormonal treatments or medications that would affect the menstrual cycle, previous uterine surgery and history of infertility. Women underwent a detailed clinical assessment and a two- (2D) and three-dimensional (3D) transvaginal ultrasound (TVS) examination. 2D-TVS features associated with diffuse adenomyosis were predefined as: (1) heterogeneous myometrium; (2) hypoechoic striation in the myometrium; (3) myometrial anechoic lacunae or cysts; (4) asymmetrical myometrial thickening of the uterine walls with the presence of straight vessels, extending into the hypertrophic myometrium, on power Doppler examination. On 3D-TVS, endomyometrial junctional zone (JZ) was measured as the distance from the basal endometrium to the internal layer of the outer myometrium on coronal section at any level of the uterus, and the smallest (JZmin) and largest (JZmax) JZ thicknesses and their difference (JZdiff) were recorded. 3D-TVS evaluation was considered suggestive for adenomyosis when JZmax ≥ 8 mm and/or JZdiff ≥ 4 mm. The presence of associated symptomatology represented our main outcome: the amount of menstrual loss was assessed by a pictorial blood loss analysis chart (PBAC) and painful symptoms were evaluated using a visual analog scale (VAS). RESULTS During the observation period, 205 women (median age, 24 (interquartile range, 23-27) years) were enrolled into the study and 156 met the inclusion criteria. According to the 2D-TVS criteria, diffuse adenomyosis was found in 53 (34.0%) women and asymmetrical myometrial thickening of the uterine walls was the most common sonographic feature observed. ANOVA showed a significant relationship between the number of 2D-TVS features of diffuse adenomyosis and VAS score for dysmenorrhea (P = 0.005) as well as PBAC score for menstrual loss (P = 0.03). 3D-TVS showed that women with 2D-TVS features of diffuse adenomyosis had a significantly higher value of JZmax (6.38 ± 2.30 mm, P < 0.001), JZmin (2.07 ± 0.43 mm, P = 0.002) and JZdiff (4.33 ± 1.99 mm, P < 0.001) than did women without these features. Women with sonographic features of diffuse adenomyosis were symptomatic in 83% of cases, reported dysmenorrhea in 79.2% and showed a higher incidence of heavy bleeding than did those without these features (18.9% vs 2.9%; P = 0.001). CONCLUSIONS Sonographic features suggestive of diffuse adenomyosis may develop earlier in reproductive life than previously thought, and may occur in association with dysmenorrhea and abnormal uterine bleeding in nulligravid women. Their observation in these women should therefore warrant further gynecological investigation.

Poor neonatal acid-base status in term fetuses with low cerebroplacental ratio.

Abstract: Objective To determine whether small- and appropriatefor-gestational-age (SGA and AGA) term fetuses with a low cerebroplacental ratio (CPR) have worse neonatal acid–base status than those with normal CPR. Methods This was a retrospective study of 2927 term fetuses divided into groups according to birth-weight centile and CPR multiple of the median. The acid–base status at birth as determined by arterial and venous umbilical cord blood pH was compared between weight-centile groups with and without low CPR. Results CPR was better correlated with umbilical cord blood pH (arterial pH, r 2 = 0.008, P < 0.0001 and venous pH, r 2 = 0.01, P < 0.0001) than was birth weight (arterial pH, r 2 = 0.001, P =0.180 and venous pH, r 2 = 0.005, P < 0.001). AGA fetuses with low CPR were more acidemic than were those with normal CPR (P = 0.0359 and 0.0006, respectively, for arterial and venous pH). Conclusions The findings of this study demonstrate that low CPR in AGA fetuses is an equally important marker of low neonatal pH secondary to placental underperfusion as is being SGA. Although the relative importance of low CPR and birth weight in identifying pregnancies at risk of placental hypoxemia and adverse fetal and neonatal outcome remains to be determined, this finding may be of particular value in the prediction and prevention of stillbirth and long-term neurodevelopmental disability.

An integrated model with classification criteria to predict small-for-gestational-age fetuses at risk of adverse perinatal outcome.

Abstract: Objective To develop an integrated model with the best performing criteria for predicting adverse outcome in small-for-gestational-age (SGA) pregnancies. Methods A cohort of 509 pregnancies with a suspected SGA fetus, eligible for trial of labor, was recruited prospectively and data on perinatal outcome were recorded. A predictive model for emergency Cesarean delivery because of non-reassuring fetal status or neonatal acidosis was constructed using a decision tree analysis algorithm, with predictors: maternal age, body mass index, smoking, nulliparity, gestational age at delivery, onset of labor (induced vs spontaneous), estimated fetal weight (EFW), umbilical artery pulsatility index (PI), mean uterine artery (UtA) PI, fetal middle cerebral artery PI and cerebroplacental ratio (CPR). Results An adverse outcome occurred in 134 (26.3%) cases. The best performing predictors for defining a high risk for adverse outcome in SGA fetuses was the presence of a CPR 95th centile or an EFW < 3rd centile. The algorithm showed a sensitivity, specificity and positive and negative predictive values for adverse outcome of 82.8% (95% CI, 75.1–88.6%), 47.7% (95% CI, 42.6–52.9%), 36.2% (95% CI, 30.8–41.8%) and 88.6% (95% CI, 83.2–92.5%), respectively. Positive and negative likelihood ratios were 1.58 and 0.36. Conclusions Our model could be used as a diagnostic tool for discriminating SGA pregnancies at risk of adverse perinatal outcome. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Serum placental growth factor in the three trimesters of pregnancy: effects of maternal characteristics and medical history.

Abstract: Objective To define the contribution of maternal variables which influence the measured level of maternal serum placental growth factor (PlGF) in screening for pregnancy complications. Methods Maternal characteristics and medical history were recorded and serum levels of PlGF were measured in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0t o 13+ 6, 19 + 0t o 24+ 6 and 30 + 0t o 34+ 6o r 35+ 0t o 37+ 6 weeks’ gestation. For women delivering phenotypically normal live births or stillbirths ≥ 24 weeks’ gestation, variables from maternal demographic characteristics and medical history important in the prediction of PlGF were determined from a linear mixed-effects multiple regression. Results Serum levels of PlGF were measured in 38 002 cases in the first trimester, 10 281 in the second trimester and 12 392 in the third trimester. Significant independent contributions to serum PlGF were provided by gestational age, maternal age, weight and racial origin, cigarette smoking, diabetes mellitus, and gestational age at delivery and birth-weight Z-score of the neonate in the previous pregnancy. The machine used to measure serum PlGF was also found to have a significant effect. Allowing for other factors, the effect of maternal age on PlGF changed over the three trimesters, whereas other variables had constant effects over the three trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured serum PlGF and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed pre-eclampsia and in those without this complication.

Fetal intervention for severe lower urinary tract obstruction: a multicenter case–control study comparing fetal cystoscopy with vesicoamniotic shunting

Abstract: Objective To evaluate the efficacy of fetal intervention using fetal cystoscopy or vesicoamniotic shunting in the treatment of severe lower urinary obstruction (LUTO) Methods A cohort of 111 fetuses with severe LUTO attending two centers between January 1990 and August 2013 were included retrospectively Fetuses were categorized into three groups based on the method of intervention: (1) fetal cystoscopy, (2) vesicoamniotic shunting or (3) no intervention Multivariate analyses were performed to determine the probability of survival and normal renal function until 6 months of age by comparing fetal cystoscopy and vesicoamniotic shunting to no fetal intervention Results Of the 111 fetuses with severe LUTO that were included in the analysis, fetal cystoscopy was performed in 34, vesicoamniotic shunting was performed in 16 and there was no fetal intervention in 61 Gestational age at diagnosis, method of fetal intervention and cause of bladder obstruction were associated with prognosis In multivariate analysis and after adjustment for potential confounders (considering all causes of LUTO) the overall probability of survival was significantly higher with fetal cystoscopy and vesicoamniotic shunting when compared to no intervention (adjusted relative risk (ARR), 186 (95% CI, 101–342; P = 0048) and ARR, 173 (95% CI, 101–308; P = 004) respectively) A clear trend for normal renal function was present in the fetal cystoscopy group (ARR, 173 (95% CI, 097–308; P = 006)) but was not observed in the vesicoamniotic shunt group (ARR, 116 (95% CI, 086–155; P = 033)) In cases in which there was a postnatal diagnosis of posterior urethral valves, fetal cystoscopy was effective in improving both the 6-month survival rate and renal function (ARR, 410 (95% CI, 175–962; P < 001) and 266 (95% CI, 125–570; P = 001) respectively) while vesicoamniotic shunting was associated only with an improvement in the 6-month survival rate (ARR, 376 (95% CI, 142–997; P < 001)) with no effect on renal function (ARR, 103 (95% CI, 049–217, P = 093)) Conclusion Fetal cystoscopy and vesicoamniotic shunting improve the 6-month survival rate in cases of severe LUTO However, only fetal cystoscopy may prevent impairment of renal function in fetuses with posterior urethral valves Our data support the idea of performing a subsequent randomized controlled trial to compare the effectiveness of fetal cystoscopy vs vesicoamniotic shunting for severe fetal LUTO Copyright © 2014 ISUOG Published by John Wiley & Sons Ltd

Natural history of early first-trimester pregnancies implanted in Cesarean scars.

Abstract: Objective To describe the ultrasound findings and natural history of pregnancies implanted within or on Cesarean section scars in the first trimester of pregnancy. Methods This was a prospective observational study of 10 women diagnosed with a pregnancy implanted in or on a Cesarean section scar in the first trimester, who declined medical intervention because of their desire to continue the pregnancy. The study population comprised women at < 12 weeks' gestation who were seen in our early pregnancy unit between January 2011 and September 2013. Nine women were followed up by serial ultrasound examinations and had detailed care plans for delivery at King's College Hospital (KCH). One woman was followed up and delivered at another teaching hospital. The first-trimester ultrasound findings were compared with the clinical outcome of the pregnancy. Results The nine patients who were followed up at KCH developed ultrasound findings of morbidly adherent placenta (MAP) in the second and third trimesters. All 10 patients were diagnosed with MAP at the time of delivery by Cesarean section. The gestational age at delivery ranged from 26 to 38 weeks. The uterus was conserved in five patients, and Cesarean hysterectomy was performed in the remaining five. All three women with complete implantation of the gestational sac within the scar and two of three cases with placental lakes in the first trimester had hysterectomies. The two cases with bulging of the gestational sac out of the uterine contour had a preterm emergency hysterectomy due to placenta percreta. Histology confirmed placenta accreta in the five hysterectomy specimens. There were no fetal or neonatal complications. Conclusions Implantation of a pregnancy on or in a Cesarean section scar is a precursor of MAP; however, the degree of morbidity associated with this implantation is variable and difficult to predict based on first-trimester ultrasound findings only. The assessment of ongoing pregnancies implanted in Cesarean scars is most beneficial when performed between 7 and 9 weeks' gestation. Complete implantation within the myometrial defect, bulging of the trophoblast from the uterine contour and large placental lakes in the first trimester are ultrasound findings that may predict severe placenta accreta or percreta and consequently a poor outcome. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

How to measure cervical length.

Abstract: Cervical-length measurement using transvaginal sonography (TVS) is an essential part of assessing the risk of preterm delivery. At mid-gestation, it provides a useful method with which to predict the likelihood of subsequent preterm birth in asymptomatic women. In women who present with threatened spontaneous preterm labor, TVS measurement of cervical length can help to distinguish between ‘true’ and ‘false’ spontaneous preterm labor. Additionally, there is some evidence that measurement of the cervix at the 11+0 to 13+6-week scan can help to establish the risk of preterm birth1,2. To et al.3 reported on cervical-length measurement between 22 and 24 weeks’ gestation in 39 000 women with a singleton pregnancy. The cervical length was found to be distributed normally, with a mean length of 36 mm. In about 1% of the women, the length was 15 mm or less. This cut-off is generally used to define the high-risk group in interventional studies4. In most studies focusing on asymptomatic twin pregnancies at 20 to 24 weeks, a cut-off of 25 mm is applied5. Celik et al.6 used cervical-length measurements obtained between 20 and 24 weeks’ gestation, along with maternal history, in more than 58 000 women to create computed risk models for preterm delivery. They compared patients who delivered before 28 weeks, between 28 and 30 weeks, between 31 and 33 weeks, and between 34 and 36 weeks’ gestation. For a 10% false-positive rate, the sensitivities were 81%, 59%, 53% and 29%, respectively. In a Health Technology Assessment report, Honest et al.7 summarized the results of five studies that used cervical-length measurements between 20 and 24 weeks, with cut-offs of 20–30 mm, to predict preterm birth before 34 weeks’ gestation. The resultant positive likelihood ratios ranged from 2.3 for 30 mm to 7.6 for 20 mm.

Screening for trisomies 21, 18 and 13 by cell-free DNA analysis of maternal blood at 10–11 weeks' gestation and the combined test at 11–13 weeks

Abstract: Objective To examine in a general population the performance of cell-free DNA (cfDNA) testing for trisomies 21, 18 and 13 at 10–11 weeks' gestation and compare it to that of the combined test at 11–13 weeks. Methods In 2905 singleton pregnancies, prospective screening for trisomies was performed by chromosome-selective sequencing of cfDNA in maternal blood at 10–11 weeks' gestation and by the combined test at 11–13 weeks' gestation. Results Median maternal age of the study population was 36.9 (range, 20.4–51.9) years. Results from cfDNA analysis were provided for 2851 (98.1%) cases and these were available within 14 days from sampling in 2848 (98.0%) cases. The trisomic status of the pregnancies was determined by prenatal or postnatal karyotyping or clinical examination of the neonates. Of the 2785 pregnancies with a cfDNA result and known trisomic status, cfDNA testing correctly identified all 32 cases with trisomy 21, nine of 10 with trisomy 18 and two of five with trisomy 13, with false-positive rates of 0.04%, 0.19% and 0.07%, respectively. In cases with discordant results between cfDNA testing and fetal karyotype, the median fetal fraction was lower than in those with concordant results (6% vs 11%). Using the combined test, the estimated risk for trisomy 21 was ≥ 1/100 in all trisomic cases and in 4.4% of the non-trisomic pregnancies. Conclusion The performance of first-trimester cfDNA testing for trisomies 21 and 18 in the general population is similar to that in high-risk pregnancies. Most false-positive and false-negative results from cfDNA testing could be avoided if the a priori risk from the combined test is taken into account in the interpretation of individual risk. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Human fetal growth is constrained below optimal for perinatal survival

Abstract: Objective The use of fetal growth charts assumes that the optimal size at birth is at the 50 th birth-weight centile, but interaction between maternal constraints on fetal growth and the risks associated with small and large fetal size at birth may indicate that this assumption is not valid for perinatal mortality rates. The objective of this study was to investigate the distribution and timing (antenatal, intrapartum or neonatal) of perinatal mortality and morbidity in relation to birth weight and gestational age at delivery. Methods Data from over 1 million births occurring at 28–43 weeks’ gestation from singleton pregnancies without congenital abnormalities in the period from 2002 to 2008 were collected from The Netherlands Perinatal Registry. The distribution of perinatal mortality according to birth-weight centile and gestational age at delivery was studied. Results In the 1 170 534 pregnancies studied, there were 5075 (0.43%) perinatal deaths. The highest perinatal mortality occurred in those with a birth weight below the 2.3 rd centile (25.4/1000 births) and the lowest mortality was in those with birth weights between the 80 th and 84 th centiles (2.4/1000 births), according to routinely used growth charts. Antepartum deaths were lowest in those with birth weight between the 90 th and 95 th centiles. Data were almost identical when the analysis was restricted to infants born at ≥ 37 weeks’ gestation. Conclusion From an immediate survival perspective, optimal fetal growth requires a birth weight between the 80 th and 84 th centiles for the population. Median birth weight in the population is, by definition, substantially lower than these centiles, implying that the majority of fetuses exhibit some form of maternal constraint on

Impact of cerebral redistribution on neurodevelopmental outcome in small‐for‐gestational‐age or growth‐restricted babies: a systematic review

Abstract: Objectives To review systematically the evidence on impact of cerebral redistribution, as assessed by fetal middle cerebral artery (MCA) Doppler, on neurological outcomes in small-for-gestational-age (SGA) or growth-restricted fetuses. Methods For this systematic review, MEDLINE was searched for all controlled studies reporting neurological outcomes in SGA or growth-restricted babies with cerebral redistribution based on MCA Doppler indices, from inception to September 2013. We used relative risk or odds ratios, with 95% CI, to identify the association of cerebral redistribution with neurological outcomes. Results The search yielded 1180 possible citations, of which nine studies were included in the review, with a total of 1198 fetuses. Definitions of SGA and cerebral redistribution were variable, as was study quality. Data could not be synthesized in meta-analyses because of heterogeneity in outcome reporting. Cerebral redistribution was not associated with increased risk of intraventricular hemorrhage in neonates (five studies; n = 806). When present in preterm fetuses, cerebral redistribution was associated with normal Neonatal Behavioral Assessment Scale (NBAS) scores at 40 weeks (one study; n = 62) but abnormal psychomotor development at 1 year of age on the Bayley scale (one study; n = 172). When present in term SGA fetuses, cerebral redistribution was associated with increased risk of motor and state organizational problems on NBAS (two studies; n = 158), and lower mean percentile scores in communication and problem solving at 2 years of age on the Ages and Stages Questionnaire (one study; n = 125). Conclusions SGA fetuses with cerebral redistribution may be at higher risk of neurodevelopmental problems. More data are needed from adequately controlled studies with long-term follow-up before conclusions can be drawn. If these findings are true, there is a need to re-evaluate timing of delivery in the management of SGA fetuses, particularly when cerebral redistribution is found at term gestation. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Performance of screening for aneuploidies by cell-free DNA analysis of maternal blood in twin pregnancies.

Abstract: Objectives To report clinical implementation of cell-free DNA (cfDNA) analysis of maternal blood in screening for trisomies 21, 18 and 13 in twin pregnancies and examine variables that could influence the failure rate of the test. Methods cfDNA testing was performed in 515 twin pregnancies at 10–28 weeks' gestation. The failure rate of the test to provide results was compared with that in 1847 singleton pregnancies, and logistic regression analysis was used to determine which factors among maternal and pregnancy characteristics were significant predictors of test failure. Results Failure rate of the cfDNA test at first sampling was 1.7% in singletons and 5.6% in twins. Of those with a test result, the median fetal fraction in twins was 8.7% (range, 4.1–30.0%), which was lower than that in singletons (11.7% (range, 4.0–38.9%)). Multivariable regression analysis demonstrated that twin pregnancy, higher maternal weight and conception by in-vitro fertilization provided significant independent prediction of test failure. Follow-up was available in 351 (68.2%) of the twin pregnancies and comprised 334 with euploid fetuses, 12 discordant for trisomy 21 and five discordant for trisomy 18. In all 323 euploid cases with a result, the risk score for each trisomy was < 1:10 000. In 11 of the 12 cases with trisomy 21 and in the five with trisomy 18, the cfDNA test gave a high-risk result, but in one case of trisomy 21, the score was < 1:10 000. Conclusion In twin pregnancies screening by cfDNA testing is feasible, but the failure rate is higher and detection rate may be lower than in singletons. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Array comparative genomic hybridization and fetal congenital heart defects: a systematic review and meta-analysis

Abstract: Objective Array comparative genomic hybridization (aCGH) is a molecular cytogenetic technique that is able to detect the presence of copy number variants (CNVs) within the genome. The detection rate of imbalances by aCGH compared to standard karyotyping and 22q11 microdeletion analysis by fluorescence in-situ hybridization (FISH), in the setting of prenatally-diagnosed cardiac malformations, has been reported in several studies. The objective of our study was to perform a systematic literature review and meta-analysis to document the additional diagnostic gain of using aCGH in cases of congenital heart disease (CHD) diagnosed by prenatal ultrasound examination, with the aim of assisting clinicians to determine whether aCGH analysis is warranted when an ultrasonographic diagnosis of CHD is made, and to guide counseling in this setting. Methods Articles in PubMed, EMBASE and Web of Science databases from January 2007 to September 2014 describing CNVs in prenatal cases of CHD were included. Search terms were: ‘array comparative genomic hybridization’, ‘copy number variants’ and ‘fetal congenital heart defects’. Articles regarding karyotyping or 22q11 deletion only were excluded. Results Thirteen publications (including 1131 cases of CHD) met the inclusion criteria for the analysis. Meta-analysis indicated an incremental yield of 7.0% (95% CI, 5.3–8.6%) for the detection of CNVs using aCGH, excluding aneuploidy and 22q11 microdeletion cases. Subgroup results showed a 3.4% (95% CI, 0.3–6.6%) incremental yield in isolated CHD cases, and 9.3% (95% CI, 6.6–12%) when extracardiac malformations were present. Overall, an incremental yield of 12% (95% CI, 7.6–16%) was found when 22q11 deletion cases were included. There was an additional yield of 3.4% (95% CI, 2.1–4.6%) for detecting variants of unknown significance (VOUS). Conclusions In this review we provide an overview of published data and discuss the benefits and limitations of using aCGH. If karyotyping and 22q11 microdeletion analysis by FISH are normal, using aCGH has additional value, detecting pathogenic CNVs in 7.0% of prenatally diagnosed CHD, with a 3.4% additional yield of detecting VOUS. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.

Umbilical and fetal middle cerebral artery Doppler at 35–37 weeks' gestation in the prediction of adverse perinatal outcome

Abstract: Objective To investigate the potential value of cerebroplacental ratio (CPR) at 36 weeks' gestation in the prediction of adverse perinatal outcome. Methods This was a screening study in 6178 singleton pregnancies at 35–37 weeks' gestation. Umbilical artery (UA) and fetal middle cerebral artery (MCA) pulsatility index (PI) were measured and the values were converted to multiples of the median (MoM) after adjustment from variables in maternal characteristics and medical history that affect the measurements. CPR was calculated by dividing MCA-PI MoM by UA-PI MoM. Multivariable logistic regression analysis was used to determine if measuring CPR improved the prediction of adverse perinatal outcome provided by maternal characteristics, medical history and obstetric factors. The detection rate (DR) and false-positive rate (FPR) of screening by CPR were estimated for stillbirth, Cesarean section for fetal distress, umbilical arterial cord blood pH ≤ 7.0, umbilical venous cord blood pH ≤ 7.1, 5-min Apgar score < 7 and admission to the neonatal unit (NNU) and neonatal intensive care unit (NICU). Results There was a linear association between CPR and both birth-weight Z-score and arterial or venous umbilical cord blood pH, but the steepness of the regression lines was inversely related to the interval from assessment to delivery. The performance of low CPR < 5th percentile in screening for each adverse outcome was poor, with DRs of 6–15% and a FPR of about 6%. In the small subgroup of the population delivering within 2 weeks of assessment, the DRs improved to 14–50%, but with a simultaneous increase in FPR, to about 10%. Conclusion The performance of CPR in routine screening for adverse perinatal outcome at 36 weeks' gestation is poor. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Fetal cardiac function in late-onset intrauterine growth restriction vs small-for-gestational age, as defined by estimated fetal weight, cerebroplacental ratio and uterine artery Doppler.

Abstract: Objective Among late-onset small fetuses, a combination of estimated fetal weight (EFW), cerebroplacental ratio (CPR) and mean uterine artery (UtA) pulsatility index (PI) can predict a subgroup of fetuses with poor perinatal outcome; however, the association of these criteria with fetal cardiac structure and function is unknown. Our aim was to determine the presence and severity of signs indicating cardiac dysfunction in small fetuses, classified as intrauterine growth-restricted (IUGR) or small-for-gestational age (SGA), according to EFW, CPR and UtA-PI. Methods A cohort of 209 late-onset small fetuses that were delivered > 34 weeks of gestation was divided in two categories: SGA (n = 59) if EFW was between the 3rd and 9th centiles with normal CPR and UtA-PI; and IUGR (n = 150) if EFW was 95th centile. The small population was compared with 150 appropriately grown fetuses (controls). Fetal cardiac morphometry and function were assessed by echocardiography using two-dimensional M-mode, conventional and tissue Doppler. Results Compared with controls, both IUGR and SGA fetuses showed larger and more globular hearts (mean left sphericity index ± SD: controls, 1.8 ± 0.3; SGA, 1.5 ± 0.2; and IUGR, 1.6 ± 0.3; P < 0.01) and showed signs of systolic and diastolic dysfunction, including decreased tricuspid annular plane systolic excursion (mean ± SD: controls, 8.2 ± 1.1; SGA, 7.4 ± 1.2; and IUGR, 6.9 ± 1.1; P < 0.001) and increased left myocardial performance index (mean ± SD: controls, 0.45 ± 0.14; SGA, 0.51 ± 0.08; and IUGR, 0.57 ± 0.1; P < 0.001). Conclusions Despite a perinatal outcome comparable to that of normal fetuses, the population of so-defined SGA fetuses showed signs of prenatal cardiac dysfunction. This supports the concept that at least a proportion of them are not ‘constitutionally small’ and that further research is needed. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Uterine artery pulsatility index in the three trimesters of pregnancy: effects of maternal characteristics and medical history

Abstract: Objective To define the contribution of maternal variables that influence the measured uterine artery pulsatility index (UtA-PI) in screening for pregnancy complications. Methods Maternal characteristics and medical history were recorded, and UtA-PI was measured, in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0 to 13 + 6 weeks, 19 + 0 to 24 + 6 weeks and 30 + 0 to 34 + 6 weeks or 35 + 0 to 37 + 6 weeks' gestation. For pregnancies delivering phenotypically normal live births or stillbirths at ≥ 24 weeks' gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of UtA-PI were determined from linear mixed-effects multiple regression. Results UtA-PI was measured in 90 484 cases in the first trimester, 66 862 cases in the second trimester and 33 470 cases in the third trimester of pregnancy. Significant independent contributions to UtA-PI were provided by gestational age, maternal age, weight, racial origin and a history of pre-eclampsia (PE) in the previous pregnancy. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured UtA-PI and express the values as multiples of the median (MoM). The model was shown to provide an adequate fit of MoM values for all covariates both in pregnancies that developed PE and in those that did not. Conclusions A model was fitted to express the measured UtA-PI as MoMs after adjustment for variables from maternal characteristics and medical history that affect this measurement. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Prediction and prevention of early-onset pre-eclampsia: impact of aspirin after first-trimester screening.

Abstract: Objective To examine the effect of a combination of screening and treatment with low-dose aspirin on the prevalence of early-onset pre-eclampsia (PE). Methods This was a retrospective analysis of two consecutive cohorts of women screened for early PE. The first cohort was observed to determine whether algorithms developed to screen for PE at 11 to 13 + 6 weeks' gestation could be applied to our population. High-risk women in the second cohort were advised on their risk and offered aspirin (150 mg at night), with treatment starting immediately after screening. The prevalence of early PE and the proportion of women with PE delivering at 34–37 weeks' gestation were compared between the cohorts. Results In the observational and interventional cohorts, 3066 and 2717 women, respectively, were screened. There were 12 (0.4%) cases of early PE in the observational cohort and one (0.04%) in the interventional cohort (P < 0.01). Among all women with PE delivering before 37 weeks, 25 (0.83%) were in the observational cohort and 10 (0.37%) in the interventional cohort (P = 0.03). Conclusions A strategy of first-trimester screening for early PE coupled with prescription of aspirin to the high-risk group appears to be effective in reducing the prevalence of early PE. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Accuracy of three-dimensional ultrasound compared with magnetic resonance imaging in diagnosis of Müllerian duct anomalies using ESHRE-ESGE consensus on the classification of congenital anomalies of the female genital tract.

Abstract: Objective To establish the accuracy of three-dimensional ultrasound (3D-US), compared with magnetic resonance imaging (MRI), for diagnosing uterine anomalies, using the European Society of Human Reproduction and Embryology–European Society for Gynaecological Endoscopy (ESHRE–ESGE) consensus on the classification of congenital anomalies of the female genital tract. Methods Sixty women with uterine anomalies suspected after examination by conventional two-dimensional ultrasound were evaluated with 3D-US and MRI. These data were analyzed retrospectively to confirm the presence and type of uterine malformation in accordance with the ESHRE–ESGE consensus. Sensitivity, specificity and positive (PPV) and negative (NPV) predictive values were calculated, using MRI as the gold standard, and agreement between the two methods was evaluated by kappa index. Results Compared with MRI, for the diagnosis of normal uteri, 3D-US had a sensitivity of 83.3%, specificity of 100%, PPV of 100%, NPV of 98.2% and kappa index of 0.900. For dysmorphic uteri and for hemi-uteri, the sensitivity, specificity, PPV and NPV were all 100%, and kappa was 1.00. For septate uteri, the sensitivity was 100%, specificity was 88.9%, PPV was 95.5%, NPV was 100% and kappa was 0.918. For bicorporeal uteri, the sensitivity was 83.3%, specificity was 100%, PPV was 100%, NPV was 98.2% and kappa was 0.900. Conclusions 3D-US is highly accurate for diagnosing uterine malformations, having a good level of agreement with MRI in the classification of different anomaly types based on the ESHRE–ESGE consensus. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Mean arterial pressure in the three trimesters of pregnancy: effects of maternal characteristics and medical history

Abstract: Objective To define the contribution of maternal variables that influence the measured mean arterial pressure (MAP) in screening for pregnancy complications. Methods Maternal characteristics and medical history were recorded, and MAP was measured, in women with a singleton pregnancy attending for three routine hospital visits at 11 + 0t o 13+ 6 weeks, 19 + 0t o 24+ 6 weeks and 30 + 0t o 34+ 6 weeks or 35+ 0t o 37+ 6 weeks’ gestation. For pregnancies delivering phenotypically normal live births or stillbirths at ≥ 24 weeks’ gestation, variables from maternal demographic characteristics and medical history that are important in the prediction of MAP were determined from linear mixed-effects multiple regression analysis. Results MAP was measured in 75 841 cases in the first trimester, 30 447 in the second trimester and 31 673 in the third trimester. Significant independent contributions to MAP were provided by gestational age, maternal age, weight, height, Afro-Caribbean racial origin, cigarette smoking, family history of pre-eclampsia (PE), history of PE in the previous pregnancy, interpregnancy interval, chronic hypertension and diabetes mellitus. The effects of some variables were similar, and for others differed, in the three different trimesters. Random-effects multiple regression analysis was used to define the contribution of maternal variables that influence the measured MAP and express the values as multiples of the median (MoMs). The model was shown to provide an adequate fit of MoM values for all covariates, both in pregnancies that developed PE and in those without this complication. Conclusions A model was fitted to express the measured MAP as MoMs after adjustment for variables from maternal characteristics and medical history that affect this measurement. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Ultrasound screening for fetal growth restriction at 36 vs 32 weeks' gestation: a randomized trial (ROUTE)

Abstract: Objective To compare the utility of routine third-trimester ultrasound examination at 36 weeks' gestation with that at 32 weeks in detecting fetal growth restriction (FGR). Methods This was an open-label parallel randomized trial (ROUTE study) conducted at a single general hospital serving a geographically well-defined catchment area in Barcelona, Spain, between May 2011 and April 2014. Women with no adverse medical or obstetric history and a singleton pregnancy without fetal abnormalities at routine second-trimester scan were assigned randomly to undergo a scan at 32 weeks' gestation (n = 1272) or at 36 weeks' gestation (n = 1314). Primary outcome measures were detection rates of FGR (customized birth weight < 10th centile) and severe FGR (customized birth weight < 3rd centile). Results There were no significant differences in perinatal outcome between those who underwent a scan at 32 weeks' gestation and those who underwent a scan at 36 weeks' gestation. Severe FGR at birth was associated significantly with emergency Cesarean delivery for fetal distress (odds ratio (OR), 3.4 (95% CI, 1.8–6.7)), neonatal admission (OR, 2.23 (95% CI, 1.23–4.05)), hypoglycemia (OR, 9.5 (95% CI, 1.8–49.8)) and hyperbilirubinemia (OR, 9.0 (95% CI, 4.6–17.6)). Despite similar false-positive rates (FPRs) (6.4% vs 8.2%), FGR detection rates were superior at 36 vs 32 weeks' gestation (sensitivity, 38.8% vs 22.5%; P = 0.006), with positive and negative likelihood ratios of 6.1 vs 2.7 and 0.65 vs 0.84, respectively. In cases of severe FGR, FPRs for both scans were also similar (8.5% vs 8.7%), but detection rates were superior at 36 vs 32 weeks' gestation (61.4% vs 32.5%; P = 0.008). Positive and negative likelihood ratios were 7.2 vs 3.7 and 0.4 vs 0.74, respectively. Conclusion In low-risk pregnancies, routine ultrasound examination at 36 weeks' gestation was more effective than that at 32 weeks' gestation in detecting FGR and related adverse perinatal and neonatal outcomes. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Sustained effect of simulation-based ultrasound training on clinical performance: a randomized trial.

Abstract: Objective To study the effect of initial simulation-based transvaginal sonography (TVS) training compared with clinical training only, on the clinical performance of residents in obstetrics and gynecology (Ob-Gyn), assessed 2 months into their residency. Methods In a randomized study, new Ob-Gyn residents (n = 33) with no prior ultrasound experience were recruited from three teaching hospitals. Participants were allocated to either simulation-based training followed by clinical training (intervention group; n = 18) or clinical training only (control group; n = 15). The simulation-based training was performed using a virtual-reality TVS simulator until an expert performance level was attained, and was followed by training on a pelvic mannequin. After 2 months of clinical training, one TVS examination was recorded for assessment of each resident's clinical performance (n = 26). Two ultrasound experts blinded to group allocation rated the scans using the Objective Structured Assessment of Ultrasound Skills (OSAUS) scale. Results During the 2 months of clinical training, participants in the intervention and control groups completed an average ± SD of 58 ± 41 and 63 ± 47 scans, respectively (P = 0.67). In the subsequent clinical performance test, the intervention group achieved higher OSAUS scores than did the control group (mean score, 59.1% vs 37.6%, respectively; P Conclusion Simulation-based ultrasound training leads to substantial improvement in clinical performance that is sustained after 2 months of clinical training. © 2015 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Fetal growth reference ranges in twin pregnancy: analysis of the Southwest Thames Obstetric Research Collaborative (STORK) multiple pregnancy cohort.

Abstract: Objective To generate reference charts for expected fetal growth in dichorionic diamniotic (DCDA) and monochorionic diamniotic (MCDA) twin pregnancies and to compare these with those from singleton pregnancies. Methods This was a retrospective study of biometric measurements from serial ultrasound examinations of twin pregnancies in the second and third trimesters, from 14 weeks' gestation to term, collected by nine hospitals over a 10-year period. The measurements obtained in each fetus at each examination included head circumference (HC), biparietal diameter (BPD), abdominal circumference (AC) and femur length (FL). Multilevel mixed effects statistical models were used to evaluate growth in each biometric variable in relation to gestational age, taking account of the serial examinations and the association between the two fetuses in each pregnancy, with separate models constructed for DCDA and MCDA pregnancies. Results The final dataset for analysis included a total of 9866 second- and third-trimester ultrasound examinations in 1802 DCDA and 323 MCDA twin pregnancies, with a median of five (range, 1–14) scans per pregnancy. For each variable, the mean value for DCDA twins was close to the reported value in singletons at 20–30 weeks and showed a decrease relative to singletons beyond 30 weeks. The differences were greater for AC and HC, for which the mean in twins was approximately equivalent to the 30th percentile in singletons at 18 weeks, the 35th percentile at 25 weeks and the 30th percentile at 35 weeks. Fetuses in MCDA twin pregnancies displayed lower mean measurements than did those in DCDA pregnancies throughout the gestational age range considered. Conclusions Ultrasound biometry shows a small but statistically significant reduction in fetal growth in twin pregnancies relative to that in singletons, particularly in the third trimester, with a more marked difference for MCDA than for DCDA pregnancies. Copyright © 2014 ISUOG. Published by John Wiley & Sons Ltd.