The effectiveness of screening for macrosomia is not well established. One of the critical elements of an effective screening program is the diagnostic accuracy of a test at predicting the condition. ...The objective of this study is to investigate the diagnostic effectiveness of universal ultrasonic fetal biometry in predicting the delivery of a macrosomic infant, shoulder dystocia, and associated neonatal morbidity in low- and mixed-risk populations.
We conducted a predefined literature search in Medline, Excerpta Medica database (EMBASE), the Cochrane library and ClinicalTrials.gov from inception to May 2020. No language restrictions were applied. We included studies where the ultrasound was performed as part of universal screening and those that included low- and mixed-risk pregnancies and excluded studies confined to high risk pregnancies. We used the estimated fetal weight (EFW) (multiple formulas and thresholds) and the abdominal circumference (AC) to define suspected large for gestational age (LGA). Adverse perinatal outcomes included macrosomia (multiple thresholds), shoulder dystocia, and other markers of neonatal morbidity. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2) tool. Meta-analysis was carried out using the hierarchical summary receiver operating characteristic (ROC) and the bivariate logit-normal (Reitsma) models. We identified 41 studies that met our inclusion criteria involving 112,034 patients in total. These included 11 prospective cohort studies (N = 9986), one randomized controlled trial (RCT) (N = 367), and 29 retrospective cohort studies (N = 101,681). The quality of the studies was variable, and only three studies blinded the ultrasound findings to the clinicians. Both EFW >4,000 g (or 90th centile for the gestational age) and AC >36 cm (or 90th centile) had >50% sensitivity for predicting macrosomia (birthweight above 4,000 g or 90th centile) at birth with positive likelihood ratios (LRs) of 8.74 (95% confidence interval CI 6.84-11.17) and 7.56 (95% CI 5.85-9.77), respectively. There was significant heterogeneity at predicting macrosomia, which could reflect the different study designs, the characteristics of the included populations, and differences in the formulas used. An EFW >4,000 g (or 90th centile) had 22% sensitivity at predicting shoulder dystocia with a positive likelihood ratio of 2.12 (95% CI 1.34-3.35). There was insufficient data to analyze other markers of neonatal morbidity.
In this study, we found that suspected LGA is strongly predictive of the risk of delivering a large infant in low- and mixed-risk populations. However, it is only weakly (albeit statistically significantly) predictive of the risk of shoulder dystocia. There was insufficient data to analyze other markers of neonatal morbidity.
Despite the relative ease with which breech presentation can be identified through ultrasound screening, the assessment of foetal presentation at term is often based on clinical examination only. Due ...to limitations in this approach, many women present in labour with an undiagnosed breech presentation, with increased risk of foetal morbidity and mortality. This study sought to determine the cost effectiveness of universal ultrasound scanning for breech presentation near term (36 weeks of gestational age wkGA) in nulliparous women.
The Pregnancy Outcome Prediction (POP) study was a prospective cohort study between January 14, 2008 and July 31, 2012, including 3,879 nulliparous women who attended for a research screening ultrasound examination at 36 wkGA. Foetal presentation was assessed and compared for the groups with and without a clinically indicated ultrasound. Where breech presentation was detected, an external cephalic version (ECV) was routinely offered. If the ECV was unsuccessful or not performed, the women were offered either planned cesarean section at 39 weeks or attempted vaginal breech delivery. To compare the likelihood of different mode of deliveries and associated long-term health outcomes for universal ultrasound to current practice, a probabilistic economic simulation model was constructed. Parameter values were obtained from the POP study, and costs were mainly obtained from the English National Health Service (NHS). One hundred seventy-nine out of 3,879 women (4.6%) were diagnosed with breech presentation at 36 weeks. For most women (96), there had been no prior suspicion of noncephalic presentation. ECV was attempted for 84 (46.9%) women and was successful in 12 (success rate: 14.3%). Overall, 19 of the 179 women delivered vaginally (10.6%), 110 delivered by elective cesarean section (ELCS) (61.5%) and 50 delivered by emergency cesarean section (EMCS) (27.9%). There were no women with undiagnosed breech presentation in labour in the entire cohort. On average, 40 scans were needed per detection of a previously undiagnosed breech presentation. The economic analysis indicated that, compared to current practice, universal late-pregnancy ultrasound would identify around 14,826 otherwise undiagnosed breech presentations across England annually. It would also reduce EMCS and vaginal breech deliveries by 0.7 and 1.0 percentage points, respectively: around 4,196 and 6,061 deliveries across England annually. Universal ultrasound would also prevent 7.89 neonatal mortalities annually. The strategy would be cost effective if foetal presentation could be assessed for £19.80 or less per woman. Limitations to this study included that foetal presentation was revealed to all women and that the health economic analysis may be altered by parity.
According to our estimates, universal late pregnancy ultrasound in nulliparous women (1) would virtually eliminate undiagnosed breech presentation, (2) would be expected to reduce foetal mortality in breech presentation, and (3) would be cost effective if foetal presentation could be assessed for less than £19.80 per woman.
To estimate the association between birth weight percentile and the risk of perinatal death at term in relation to the cause of death.
We performed a retrospective cohort study of all term singleton ...births in delivery units in Scotland between 1992 and 2008 (n=784,576), excluding perinatal deaths ascribed to congenital anomaly.
There were 1,700 perinatal deaths in the cohort, which were not the result of congenital anomaly (21.7/10,000 women at term). We observed a reversed J-shaped association between birth weight percentile and the risk of antepartum stillbirth in all women, but the associations significantly differed (P<.001) according to smoking status. The highest risk (adjusted odds ratio referent to 21st-80th percentile, 95% confidence interval) among nonsmokers was for birth weight third or less percentile (10.5, 8.2-13.3), but there were also positive associations for birth weight percentiles 4th-10th (3.8, 3.0-4.8), 11th-20th (1.9, 1.5-2.4), and 98th-100th (1.8, 1.3-2.4). Among smokers, the associations with being small were weaker and the associations with being large were stronger. We also observed a reversed J-shaped association between birth weight percentile and the risk of delivery-related perinatal death (ie, intrapartum stillbirth or neonatal death), but there was no interaction with smoking. The highest risk was for birth weight greater than the 97th percentile (2.3, 1.6-3.3), but there were also associations with third or less percentile (2.1, 1.4-3.1), 4th-10th (1.8, 1.4-2.4), and 11th-20th (1.5, 1.2-2.0). Analysis of the attributable fraction indicated that approximately one in three antepartum stillbirths and one in six delivery-related deaths at term could be related to birth weight percentile outside the range 21st-97th percentile.
Effective detection of variation in fetal size at term has potential as a screening test for the risk of perinatal death.
II.
Currently, pregnant women are screened using ultrasound to perform gestational aging, typically at around 12 weeks' gestation, and around the middle of pregnancy. Ultrasound scans thereafter are ...performed for clinical indications only.
We sought to assess the case for offering universal late pregnancy ultrasound to all nulliparous women in the UK. The main questions addressed were the diagnostic effectiveness of universal late pregnancy ultrasound to predict adverse outcomes and the cost-effectiveness of either implementing universal ultrasound or conducting further research in this area.
We performed diagnostic test accuracy reviews of five ultrasonic measurements in late pregnancy. We conducted cost-effectiveness and value-of-information analyses of screening for fetal presentation, screening for small for gestational age fetuses and screening for large for gestational age fetuses. Finally, we conducted a survey and a focus group to determine the willingness of women to participate in a future randomised controlled trial.
We searched MEDLINE, EMBASE and the Cochrane Library from inception to June 2019.
The protocol for the review was designed a priori and registered. Eligible studies were identified using keywords, with no restrictions for language or location. The risk of bias in studies was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Health economic modelling employed a decision tree analysed via Monte Carlo simulation. Health outcomes were from the fetal perspective and presented as quality-adjusted life-years. Costs were from the perspective of the public sector, defined as NHS England, and the costs of special educational needs. All costs and quality-adjusted life-years were discounted by 3.5% per annum and the reference case time horizon was 20 years.
Umbilical artery Doppler flow velocimetry, cerebroplacental ratio, severe oligohydramnios and borderline oligohydramnios were all either non-predictive or weakly predictive of the risk of neonatal morbidity (summary positive likelihood ratios between 1 and 2) and were all weakly predictive of the risk of delivering a small for gestational age infant (summary positive likelihood ratios between 2 and 4). Suspicion of fetal macrosomia is strongly predictive of the risk of delivering a large infant, but it is only weakly, albeit statistically significantly, predictive of the risk of shoulder dystocia. Very few studies blinded the result of the ultrasound scan and most studies were rated as being at a high risk of bias as a result of treatment paradox, ascertainment bias or iatrogenic harm. Health economic analysis indicated that universal ultrasound for fetal presentation only may be both clinically and economically justified on the basis of existing evidence. Universal ultrasound including fetal biometry was of borderline cost-effectiveness and was sensitive to assumptions. Value-of-information analysis indicated that the parameter that had the largest impact on decision uncertainty was the net difference in cost between an induced delivery and expectant management.
The primary literature on the diagnostic effectiveness of ultrasound in late pregnancy is weak. Value-of-information analysis may have underestimated the uncertainty in the literature as it was focused on the internal validity of parameters, which is quantified, whereas the greatest uncertainty may be in the external validity to the research question, which is unquantified.
Universal screening for presentation at term may be justified on the basis of current knowledge. The current literature does not support universal ultrasonic screening for fetal growth disorders.
We describe proof-of-principle randomised controlled trials that could better inform the case for screening using ultrasound in late pregnancy.
This study is registered as PROSPERO CRD42017064093.
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in
; Vol. 25, No. 15. See the NIHR Journals Library website for further project information.
Fetal growth restriction is a major risk factor for stillbirth. A routine late-pregnancy ultrasound scan could help detect this, allowing intervention to reduce the risk of stillbirth. Such a scan ...could also detect fetal presentation and predict macrosomia. A trial powered to detect stillbirth differences would be extremely large and expensive.
It is therefore critical to know whether this would be a good investment of public research funds. The aim of this study is to estimate the cost-effectiveness of various late-pregnancy screening and management strategies based on current information and predict the return on investment from further research.
Synthesis of current evidence structured into a decision model reporting expected costs, quality-adjusted life-years, and net benefit over 20 years and value-of-information analysis reporting predicted return on investment from future clinical trials.
Given a willingness to pay of £20 000 per quality-adjusted life-year gained, the most cost-effective strategy is a routine presentation-only scan for all women. Universal ultrasound screening for fetal size is unlikely to be cost-effective. Research exploring the cost implications of induction of labor has the greatest predicted return on investment. A randomized, controlled trial with an endpoint of stillbirth is extremely unlikely to be a value for money investment.
Given current value-for-money thresholds in the United Kingdom, the most cost-effective strategy is to offer all pregnant women a presentation-only scan in late pregnancy. A randomized, controlled trial of screening and intervention to reduce the risk of stillbirth following universal ultrasound to detect macrosomia or fetal growth restriction is unlikely to represent a value for money investment.
The objective of this study was to investigate the accuracy of universal third trimester umbilical artery (UA) Doppler to predict adverse pregnancy outcome at term. We searched Medline, EMBASE, the ...Cochrane library and ClinicalTrials.gov from inception to October 2020 and we also analyzed previously unpublished data from a prospective cohort study of nulliparous women, the Pregnancy Outcome Prediction (POP) study. We included studies that performed a third-trimester ultrasound scan in unselected, low or mixed risk populations, excluding studies which only included high risk pregnancies. Meta-analysis was performed using the hierarchal summary receiver operating characteristic curve (HSROC) analysis and bivariate logit-normal models. We identified 13 studies (including the POP study) involving 67,764 pregnancies which met our inclusion criteria. The overall quality was variable and only six studies (N = 5777 patients) blinded clinicians to the UA Doppler result. The summary sensitivity and positive likelihood ratio (LR) for small for gestational age (SGA; birthweight <10th centile) were 21.7% (95% CI 13.2–33.6%) and 2.65 (95% CI 1.89–3.72) respectively. The summary positive LR for NICU admission and metabolic acidosis were 1.35 (95% CI 0.93–1.97) and 1.34 (95% CI 0.86–2.08) respectively. The results were similar in the POP study: associations with SGA (positive LR 2.66 95% CI 2.11–3.36) and severe SGA (birthweight <3rd centile; positive LR 3.27 95% CI 2.29–4.68) but no statistically significant association with neonatal morbidity. We conclude that third trimester UA Doppler has moderate predictive accuracy for small for gestational age but not for indicators of neonatal morbidity in unselected and low risk pregnancies.
•This meta-analysis included 13 studies, involving 67,764 low or mixed risk pregnancies.•The umbilical artery (UA) Doppler is moderately predictive of the delivery of SGA infants.•The UA Doppler is not predictive of other markers of neonatal morbidity.•Universal screening using the UA Doppler alone is unlikely to reduce neonatal morbidity.•However, pregnancies with elevated UA Doppler require further monitoring.
Stretch of the myometrium promotes its contractility and is believed to contribute to the control of parturition at term and to the increased risk of preterm birth in multiple pregnancies.
To ...determine the effects of the putative oxytocin receptor (OTR) inverse agonist retosiban on (1) the contractility of human myometrial explants and (2) labor in nonhuman primates.
Human myometrial biopsies were obtained at planned term cesarean, and explants were exposed to stretch in the presence and absence of a range of drugs, including retosiban. The in vivo effects of retosiban were determined in cynomolgus monkeys.
Prolonged mechanical stretch promoted myometrial extracellular signal-regulated kinase (ERK)1/2 phosphorylation. Moreover, stretch-induced stimulation of myometrial contractility was prevented by ERK1/2 inhibitors. Retosiban (10 nM) prevented stretch-induced stimulation of myometrial contractility and phosphorylation of ERK1/2. Moreover, the inhibitory effect of retosiban on stretch-induced ERK1/2 phosphorylation was prevented by coincubation with a 100-fold excess of a peptide OTR antagonist, atosiban. Compared with vehicle-treated cynomolgus monkeys, treatment with oral retosiban (100 to 150 days of gestational age) reduced the risk of spontaneous delivery (hazard ratio = 0.07, 95% confidence interval 0.01 to 0.60, P = 0.015).
The OTR acts as a uterine mechanosensor, whereby stretch increases myometrial contractility through agonist-free activation of the OTR. Retosiban prevents this through inverse agonism of the OTR and, in vivo, reduced the likelihood of spontaneous labor in nonhuman primates. We hypothesize that retosiban may be an effective preventative treatment of preterm birth in high-risk multiple pregnancies, an area of unmet clinical need.
Multiple pregnancy is a major cause of spontaneous preterm birth, which is related to uterine overdistention. The objective of this study was to determine whether an oxytocin receptor antagonist, ...retosiban (GSK221149A), inhibited the procontractile effect of stretch on human myometrium. Myometrial biopsies were obtained at term planned cesarean delivery (n = 12). Each biopsy specimen was dissected into 8 strips that were exposed in pairs to low or high stretch (0.6 or 2.4 g) in the presence of retosiban (1 μM) or vehicle (dimethylsulfoxide) for 24 hours. Subsequently, we analyzed the contractile responses to KCl and oxytocin in the absence of retosiban. We found that incubation under high stretch in vehicle alone increased the response of myometrial explants to both KCl (P = .007) and oxytocin (P = .01). However, there was no statistically significant effect of stretch when explants were incubated with retosiban (P = .3 and .2, respectively). Incubation with retosiban in low stretch had no statistically significant effect on the response to either KCl or oxytocin (P = .8 and >.9, respectively). Incubation with retosiban in high stretch resulted in a statistically significant reduction (median fold change, interquartile range, P) in the response to both KCl (0.74, 0.60–1.03, P = .046) and oxytocin (0.71, 0.53–0.91, P = .008). The greater the effect of stretch on explants from a given patient, the greater was the inhibitory effect of retosiban (r = −0.65, P = .02 for KCl and r= −0.73, P = .007 for oxytocin). These results suggest that retosiban prevented stretch-induced stimulation of human myometrial contractility. Retosiban treatment is a potential approach for preventing preterm birth in multiple pregnancy.
To examine the performance of different fetal growth charts in the prediction of large-for-gestational-age (LGA) and neonatal morbidity at term in a multi-ethnic, obese population.
Our retrospective ...cohort study included 253 non-anomalous, singleton, term pregnancies who underwent serial third trimester ultrasound scans because of maternal BMI 35 and above. We compared the Hadlock, GROW, INTERGROWTH-21
(IG-21), World Health Organisation (WHO), and Fetal Medicine Foundation (FMF) fetal growth reference charts. LGA was defined as a birthweight above the 90
percentile and neonatal morbidity as a composite of NICU admission or 5-minute Apgar score below 7.
53 (20.9%) infants were born LGA, 27 (10.7%) experienced neonatal morbidity, and 9 (3.6%) were LGA with neonatal morbidity (which we defined as associated morbidity). The Hadlock and GROW charts showed similar performance in predicting LGA with sensitivities of 66.0% for both charts and specificities of 82.5% and 83.5% respectively. The positive likelihood ratios (LR) were 3.77 (2.64-5.40) and 4.00 (2.77-5.78) respectively. IG-21, WHO, and FMF performed similarly and had higher sensitivities of about 85% with specificities between 66 and 72%. The positive LRs were 2.74 (2.16-3.47), 2.50 (2.00-3.12) and 3.03 (2.36-3.89) respectively. All charts had a high sensitivity for predicting morbidity associated with LGA with the positive LRs ranging between 2.35 and 3.61.
In our obese population all charts performed well at predicting LGA and associated morbidity. However, the choice of fetal reference chart is likely to affect intervention rates. This article is protected by copyright. All rights reserved.
Commingled remains describes the situation of intermixed skeletal elements, an extremely common occurrence in contemporary forensic cases, archaeological mass graves, as well as fossil hominin ...assemblages. Given that reliable identification is typically impossible for commingled contexts, a plethora of previous studies has focused on the development of refined methods for reassociating the bones of each individual skeleton. Here, a novel virtual approach for quantifying the degree of three-dimensional shape compatibility between two adjoining bone articular surfaces is put forth. Additionally, the integrability of this method with traditional osteometric techniques is evaluated. We focus on the paradigm of the hip joint, whose articulating bone elements (the femur and the innominate bone) are crucial for reconstructing the biological profile of unidentified human remains. The results demonstrate that this new semi-automated methodology is highly accurate both for large commingled assemblages (such as those resulting from mass disasters or burials) as well as smaller-scale contexts (such as those resulting from secondary burials).
PDF
