ArticleLiterature Review

Comparison between cerebroplacental ratio and umbilicocerebral ratio in predicting adverse perinatal outcome at term

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Abstract

Objective Cerebroplacental ratio (CPR) has been associated with adverse perinatal outcome irrespective of fetal weight. More recently, it has been proposed that the ratio between umbilical and middle cerebral artery pulsatility index, the umbilicocerebral ratio (UCR) had a higher diagnostic accuracy compared to CPR in predicting adverse outcome. The aim of the study was to compare the diagnostic accuracy of CPR and UCR in predicting adverse perinatal outcome in the third trimester of pregnancy. Study design Secondary analysis of prospective study carried out in a dedicated research ultrasound clinic in a single tertiary referral center over a one-year period. Inclusion criteria were consecutive singleton pregnancies between 36 + 0 and 37 + 6 weeks of gestation. Exclusion criteria were multiple gestations, pregnancies affected by structural or chromosomal anomalies, maternal medical complications or drugs intake and abnormal Doppler waveform in the UA, defined as PI>95th or absent/end diastolic flow. All women were pre-screened at 28-32 weeks of gestation in order to rule out signs of early fetal growth restriction. The primary outcome was to compare the diagnostic performance of CPR and UCR in detecting the presence of fetuses affected by a composite adverse outcome. Results Mean CPR (1.35 ± 0.39 vs 1.85 ± 0.58, p < 0.001) was significantly lower while mean UCR (0.78 ± 0.25 vs 0.58 ± 0.20, p = 0.001) was significantly higher in pregnancies experiencing compared to those not experiencing composite adverse outcome. There was no difference between CPR and UCR in predicting adverse perinatal outcome in the third trimester of pregnancy and both showed a very low diagnostic accuracy. CPR had an AUC of 0.51 (95% CI 0.43-0.58) while UCR had an AUC of 0.51 (95% CI 0.43-0.58) in predicting composite adverse outcome. Likewise, there was no difference in the diagnostic accuracy of CRP (AUC: 0.600, 95% CI 0.36-0.83) and UCR (AUC: 0.589, 95% CI 0.35-0.83) when considering only SGA fetuses. Conclusions A low CPR and a high UCR are significantly associated with adverse perinatal outcome in singleton pregnancies at term. There was no difference between CPR and UCR in predicting perinatal outcome. Despite this, the diagnostic accuracy of both these parameters is too poor to advocate for their use as a screening tool of perinatal impairment at term, unless specific indications, such as SGA or FGR, have been identified.

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Objectives In fetal growth restriction (FGR), Doppler ultrasound is the most important method for the detection and management. However, additional parameters are needed to improve the distinction between constitutionally small fetuses and fetuses affected by FGR. Methods A total of 445 singleton pregnancies between 23 and 40 weeks of gestation were included in our retrospective study, of which 67 with FGR and 378 normal fetuses. A 2D-plane of the fetal adrenal gland was obtained and the adrenal gland ratio was measured. Spearman’s correlation coefficient was calculated to assess the association of fetal Doppler and adrenal gland ratio with outcome parameters. Logistic regression analysis was performed to assess the statistical significance of “PI of the umbilical artery” and “adrenal gland ratio” as prognostic factors for intrauterine growth restriction (IUGR). Results PI of the umbilical artery was shown to correlate with outcome parameters (WG_Delivery: r=−0.125, p=0.008; birth weight: r=−0.268, p<0.001; birth weight centile: r=−0.248, p<0.001; APGAR at 5 min: r=−0.117, p=0.014). Adrenal gland ratio showed no correlation with any of the outcome parameters. In logistic regression however, both PI of the umbilical artery and the adrenal ratio were shown to be significantly associated with fetal IUGR. When combining the two parameters, predictive value was superior to the predictive value of each individual parameter (AUC 0.738 [95% CI 0.670; 0.806]). Conclusions The adrenal gland ratio can be a useful addition to Doppler ultrasound when it comes to the detection of fetal FGR. Prospective studies are needed to establish references ranges and cut-off values for clinical decision-making.
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Objective: We aim to evaluate the foetal aortic isthmus Doppler data after maternal COVID-19 disease. Material and Methods: Twenty six pregnant patient who recovered from COVID-19 and 43mhealthy patient were included in this prospective case–control study. The study group consisted of those who had COVID-19 disease and completed the quarantine period. Results: Doppler ultrasound evaluations were performed at the similar gestational week. We observed significantly high pulsatility indices (PI) of umbilical and aortic isthmus in study group than the control group (p=0,02, p=0,02). There was no significant change in cerebroplacental ratio (CPR) between the two groups (p>0.05). Conclusion: COVID-19 may affect placental function in pregnant women and could deterioration on foetal circulation and Doppler parameters. In particular, changes in aortic isthmus doppler flow indicating foetal circulation and cerebral oxygenation help to reflect the foetal effects of COVID-19.
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Purpose Aim of our study was to compare the prognostic value of the Umbilical-to-Cerebral ratio (UCR) directly to the Cerebroplacental ratio (CPR) in the prediction of poor perinatal outcomes in pregnancies complicated by Fetal Growth Restriction (FGR). Methods A retrospective study was carried out on pregnant women with either a small-for-gestational age (SGA) fetus or that were diagnosed with FGR. Doppler measurements of the two subgroups were assessed and the correlation between CPR, UCR and relevant outcome parameters was evaluated by performing linear regression analysis, binary logistic analysis and receiver operator characteristic (ROC) curves. Outcomes of interest were mode of delivery, acidosis, preterm delivery, gestational age at birth as well as birthweight and centiles. Results Boxplots and Scatterplots illustrated the different distribution of CPR and UCR leading to deviant correlational relationships with adverse outcome parameters. In almost all parameters examined, UCR showed a higher independent association with preterm delivery (OR: 5.85, CI 2.23–15.34), APGAR score < 7 (OR: 3.52; CI 1.58–7.85) as well as weight under 10th centile (OR: 2.04; CI 0.97–4.28) in binary logistic regression compared to CPR which was only associated with preterm delivery (OR: 0.38; CI 0.22–0.66) and APGAR score < 7 (OR: 0.27; CI 0.06–1.13). When combined with different ultrasound parameters in order to differentiate between SGA and FGR during pregnancy, odds ratios for UCR were highly significant compared to odds ratios for CPR (OR: 0.065, 0.168–0.901; p = 0.027; OR: 0.810, 0.369–1.781; p = 0.601). ROC curves plotted for CPR and UCR showed almost identical moderate prediction performance. Conclusion Since UCR is a better discriminator of Doppler values in abnormal range it presents a viable option to Doppler parameters and ratios that are used in clinical practice. UCR and CPR showed equal prognostic accuracy conserning sensitivity and specificity for adverse perinatal outcome, while adding UA PI and GA_scan increased prognostic accuracy regarding negative outcomes.
Article
Aim: Nearly half of the patients with stillbirths experience reduced fetal movements (RFM) in the preceding week. The standardized evaluation will help reduce stillbirths. Placental dysfunction is the underlying pathophysiology for RFM and low cerebroplacental ratio (CPR). We attempted to determine the application of CPR in evaluation of RFM. Methods: A prospective case-control study with 100 patients each of cases and controls were studied at a tertiary care hospital. Middle cerebral artery pulsatility index (MCA-PI), umbilical artery PI (UA-PI), and CPR were calculated as multiples of median (MoM) in patients presenting with RFM after 30 weeks and their matched controls and followed up. CPR values of various gestation ranges and single versus multiple episodes of RFM were analyzed. Results: Compared to controls, women with RFM showed a significantly low MCA PI MoM (0.94 vs 1.4; p = 0.00008) and low CPR MoM (1.48 vs 1.6; p = 0.015). Women with multiple RFM episodes had lower CPR MoM (1.2 vs 1.5; p < 0.00001) compared to single episode RFM. Multiple RFM episode patients had low MCA PI MoM (1.3 vs 1.4; p = 0.0038) and low CPR MoM (1.2 vs 1.6; p < 0.00001) compared to controls. There was a significantly low CPR in 32-34 weeks (1.35 vs 1.81; p = 0.004) and 36-38 weeks subgroups (1.39 vs 1.58; p = 0.002). No significant difference in birthweight centiles or AGA versus SGA categories between cases and controls was noted questioning current guidelines where ultrasound evaluation is done for RFM patients with FGR. Conclusion: Incorporation of routine CPR measurements can standardize evaluation of RFM patients, especially those with AGA to pick up patients at risk of poor outcome and bring down stillbirth rates.
Article
Objective: To explore the strength of association and the diagnostic accuracy of maternal hemodynamic parameters detected noninvasively in predicting an adverse perinatal outcome in labor. Methods: Prospective cohort study of singleton women undergoing antepartum care at 37-39 weeks of gestation. A noninvasive ultrasonic cardiac output monitor (USCOM®) was used for cardiovascular assessment. The study outcome was a composite score of adverse perinatal outcome, which included at least one of the following variables: Cesarean or instrumental delivery for abnormal fetal heart monitoring, umbilical artery pH <7.10 or admission to neonatal special care unit. Attending clinicians were blinded to maternal cardiovascular indices. Multivariate logistic regression and area under the curve (AUC) analyses were used to test the diagnostic accuracy of different maternal and ultrasound characteristics in predicting adverse perinatal outcome. Results: A total of 133 women were recruited. The rate of adverse perinatal outcome was 25.6% (34/133). Women who delivered without abnormal perinatal outcome (controls) were more likely to be parous, compared to those who had an adverse perinatal outcome (44.4 vs. 73.5%; p = .005). Control women had significantly lower systemic vascular resistance (SVR) (median, 1166 vs. 1352 dynes × s/cm5, p = .023) and SVR index (SVRI) (median, 2168 vs. 2627 dynes × s/cm5/m2, p = .039) compared to women who had an adverse perinatal outcome. In this latter group the prevalence of SV <50 ml was significantly higher than in the control group (38.2% (13/34) vs. 11.1%, (11/99) p = .0012). At multivariable logistic regression analysis, SVR (aOR 1.307; 95% CI 1.112-2.23), SV <50 ml (aOR 4.70; 95% CI 1.336-12.006) and parity (3.90: 95% CI 1.545-10.334) were the only variables independently associated with adverse perinatal outcome. A model considering only SVR showed an AUC of 0.631. Integration of SVR with SV <50 ml and parity significantly improves the diagnostic performance of SVR alone to predict adverse outcome (AUC 0.732; p = .016). Conclusion: Pre-labor modifications of maternal cardiovascular variables are associated with adverse perinatal outcome. However, their predictive accuracy for perinatal compromise is low, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.
Article
Introduction An abnormal third trimester cerebroplacental ratio has been previously associated with adverse perinatal outcome. The less studied inverse of the cerebroplacental ratio, the umbilicocerebral ratio, has been proposed as a better predictor of adverse perinatal outcome. However, little is known about the implication of either an abnormal cerebroplacental ratio or umbilicocerebral ratio in the second trimester. The objective of this study was to evaluate the relationship between an abnormal second trimester cerebroplacental ratio and adverse perinatal outcome and provide comparison to an abnormal second trimester umbilicocerebral ratio. Materials and methods This retrospective cohort study in a single tertiary referral center utilized data from all non-anomalous singleton pregnancies that underwent Doppler assessment of the cerebroplacental ratio between 20 and 28 weeks gestation. The study period was 1 January 2015 to 31 July 2018. Abnormal cerebroplacental ratio was defined as less than the 5th percentile for gestational age. If patients had more than one ultrasound during the study period (i.e. for serial assessment of fetal growth), the lowest value of the cerebroplacental ratio was recorded. The primary outcome was a composite of clinically relevant adverse perinatal outcomes including preterm delivery, small for gestational age, and neonatal intensive care unit admission. Secondary outcomes included urgent delivery for fetal distress (operative vaginal delivery or cesarean section) and hypertensive disorders of pregnancy. An abnormal umbilicocerebral ratio was defined as greater than 95th percentile for gestational age. Areas under the curve were calculated and compared for cerebroplacental ratio and umbilicocerebral ratio. Results 2326 pregnancies met inclusion criteria. Of these, 91 (3.9%) had an abnormal second trimester cerebroplacental ratio. Fetuses with an abnormal second trimester cerebroplacental ratio had a 2.3-fold (95% CI 1.5–3.6, p < .05) increased risk of adverse perinatal outcome after adjusting for potential confounders such as chronic hypertension, pregestational diabetes, and smoking during pregnancy. Significantly increased risks of preterm delivery (OR 2.0, 95% CI 1.1–38, p < .05) and neonatal intensive care unit admission (OR 2.1, 95% CI 1.2–3.6, p < .05) were also seen in a subgroup analysis of abnormal cerebroplacental ratio in appropriate for gestational age infants. 132 (5.7%) fetuses had an abnormal second trimester umbilicocerebral ratio, and these fetuses had a 2.0-fold (95% CI 1.4–3.0, p < .05) increased risk of adverse perinatal outcome. The area under the curve for CPR and UCR for prediction of the primary outcome was 0.6 for both (95% CI 0.57–0.61 and 0.57–0.62, respectively, both p < .05). Conclusion An abnormal second trimester cerebroplacental ratio or umbilicocerebral ratio is associated with adverse perinatal outcome. However, the predictive ability of either ratio remains suboptimal.
Article
Introduction: The role of cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) to predict adverse intrapartum and perinatal outcomes in pregnancies complicated by late fetal growth restriction (FGR) remains controversial. Methods: This was a multicenter, retrospective cohort study involving 5 referral centers in Italy and Spain, including singleton pregnancies complicated by late FGR, as defined by Delphi consensus criteria, with a scan 1 week prior to delivery. The primary objective was to compare the diagnostic accuracy of the CPR and UCR for the prediction of a composite adverse outcome, defined as the presence of either an adverse intrapartum outcome (need for operative delivery/cesarean section for suspected fetal distress) or an adverse perinatal outcome (intrauterine death, Apgar score <7 at 5 min, arterial pH <7.1, base excess of >-11 mEq/mL, or neonatal intensive care unit admission). Results: Median CPR absolute values (1.11 vs. 1.22, p = 0.018) and centiles (3 vs. 4, p = 0.028) were lower in pregnancies with a composite adverse outcome than in those without it. Median UCR absolute values (0.89 vs. 0.82, p = 0.018) and centiles (97 vs. 96, p = 0.028) were higher. However, the area under the curve, 95% confidence interval for predicting the composite adverse outcome showed a poor predictive value: 0.580 (0.512-0.646) for the raw absolute values of CPR and UCR, and 0.575 (0.507-0.642) for CPR and UCR centiles adjusted for gestational age. The use of dichotomized values (CPR <1, UCR >1 or CPR <5th centile, UCR >95th centile) did not improve the diagnostic accuracy. Conclusion: The CPR and UCR measured in the week prior delivery are of low predictive value to assess adverse intrapartum and perinatal outcomes in pregnancies with late FGR.
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The aim of this work is to study the state of the problem of the development of small-for-gestational-age fetus and fetal growth restriction over the past 5 years. A review of randomized trials of the PubMed database for the period of 2015 to 2020 was carried out. Experts reached an agreement on the definition of diagnostic criteria for small-for-gestational-age fetus and fetal growth restriction, a clinically valid classification was created, and the main monitoring strategies were developed. Due to the different pathogenesis, fetal growth restriction is divided into early and late. The observation algorithm includes tests that have shown higher sensitivity and specificity. There is no single standard for the median weight and abdominal circumference of a fetus, indicators of the reference range for fetal Doppler. Smoking cessation and taking acetylsalicylic acid at a dose of 150 mg at high risk of preeclampsia is recommended to prevent the small-for-gestational-age fetus and fetal growth restriction. The pregnancy management algorithm includes Doppler ultrasound examination of the umbilical artery, cardiotocography. If this pathology occurs before 32 weeks of pregnancy, the blood flow in ductus venosus is additionally examined, and after 32 weeks of pregnancy, the middle cerebral artery blood velocities and cerebroplacental ratio are assessed. Indicators of Doppler velocimetry and cardiotocography, which serve as criteria for early termination of pregnancy, are developed, measures are proposed to improve neonatal outcomes prevention of respiratory distress syndrome at 2434 weeks of gestation, as well as magnesium therapy for fetal neuroprotection. The problems of preventing fetal growth restriction and the algorithm for monitoring pregnant women who do not have risk factors for small-for-gestational-age fetus, management tactics and indications for delivery while slowing fetal weight gain remain unresolved.
Article
Background Cerebroplacental Doppler studies have been advocated to predict the risk of adverse perinatal outcome (APO) irrespective of fetal weight. Objective To report the diagnostic performance of cerebroplacental (CPR) and umbilicocerebral (UCR) ratios in predicting APO in appropriate for gestational age (AGA) fetuses and in those affected by late fetal growth restriction (FGR) attempting vaginal delivery. Study design Multicenter, retrospective, nested case-control study between 1 January 2017 and January 2020 involving five referral centers in Italy and Spain. Singleton gestations with a scan between 36 and 40 weeks and within two weeks of attempting vaginal delivery were included. Fetal arterial Doppler and biometry were collected. The AGA group was defined as fetuses with an estimated fetal weight and abdominal circumference >10th and <90th percentile, while the late FGR group was defined by Delphi consensus criteria. The primary outcome was the prediction of a composite of perinatal adverse outcomes including either intrauterine death, Apgar score at 5 min <7, abnormal acid-base status (umbilical artery pH < 7.1 or base excess of more than −11) and neonatal intensive care unit (NICU) admission. Area under the curve (AUC) analysis was performed. Results 646 pregnancies (317 in the AGA group and 329 in the late FGR group) were included. APO were present in 12.6% AGA and 24.3% late FGR pregnancies, with an odds ratio of 2.22 (95% CI 1.46–3.37). The performance of CPR and UCR for predicting APO was poor in both AGA [AUC: 0.44 (0.39–0.51)] and late FGR fetuses [AUC: 0.56 (0.49–0.61)]. Conclusions CPR and UCR on their own are poor prognostic predictors of APO irrespective of fetal weight.
Article
Late-onset FGR is a peculiar condition characterized by the inability for the fetus to reach its growth potential diagnosed from 32 weeks of gestation. Placental insufficiency is among the leading causes of late FGR and is commonly due to a primary maternal cardiovascular non-adaptation potentially leading to fetal decompensation during labor especially once exposed to uterine hyperstimulation. Abnormalities that usually characterize late FGR include reduced fetal growth, decreased amniotic fluid index, and loss of fetal heart rate variability at CTG. Fetal hemodynamics study by Doppler ultrasound significantly improved management of pregnancies affected by fetal growth restriction. A major issue when dealing with pregnancies complicated by late FGR is how to induce these women. Induction of labor (IOL) can be essentially accomplished by pharmacological and non-pharmacological agents. Recent studies suggested that the pregnancies complicated by late FGR should undergo a tailored approach for IOL in view of the higher risk of fetal decompensation following uterine hyperstimulation. The present review aims to provide an up to date on the different types of IOL which can guide clinical management.
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Introduction: The aim of this study was to compare vaginal dinoprostone and mechanical methods for induction of labor (IOL) in pregnancies complicated by late fetal growth restriction. Material and methods: Multicenter, retrospective, cohort study involving six referral centers in Italy and Spain. Inclusion criteria were pregnancies complicated by late fetal growth restriction as defined by Delphi consensus criteria. The primary outcome was the occurrence of uterine tachysystole; secondary outcomes were either cesarean delivery or operative vaginal delivery for non-reassuring fetal status, a composite score of adverse neonatal outcome and admission to neonatal intensive care unit (NICU). Univariate and multivariate logistic regression analysis was used to analyze the data. Results: A total of 571 pregnancies complicated by late fetal growth restriction undergoing IOL (391 with dinoprostone and 180 with mechanical methods) were included in the analysis. The incidence of uterine tachysystole (19.2% vs. 5.6%; p = 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. Similarly, the incidence of cesarean delivery or operative delivery for non-reassuring fetal status (25.6% vs. 17.2%; p = 0.027), composite adverse neonatal outcome (26.1% vs. 16.7%; p = 0.013) and NICU admission (16.9% vs. 5.6%; p < 0.001) was higher in women undergoing IOL with dinoprostone than in those undergoing IOL with mechanical methods. At logistic regression analysis, IOL with mechanical methods was associated with a significantly lower risk of uterine tachysystole (odds ratio 0.26, 95% confidence interval 0.13-0.54; p < 0.001). Conclusions: In pregnancies complicated by late fetal growth restriction, IOL with mechanical methods is associated with a lower risk of uterine tachysystole, cesarean delivery or operative delivery for non-reassuring fetal status, and adverse neonatal outcome compared with pharmacological methods.
Article
Objective: To evaluate the intra-observer variability of the middle cerebral artery (MCA) and umbilical artery (UA) Doppler measurement taken under optimal conditions in term, uncomplicated pregnancies. Methods: A prospective study on uncomplicated singleton term pregnancies was performed. Multiple Doppler measurements were taken in the MCA and the UA by one examiner. Intra-rater agreement was calculated. Doppler indices were correlated to fetal biometric parameters and to gestational age. Results: One hundred patients were recruited. MCA indices were found to have the highest strength of intra-rater/observer agreement (K = 0.888) versus only a "good" agreement for UA pulsatility index (PI) (K = 0.755).The MCA-PI was significantly correlated with BPD (r = -0.198, p = .047), EFW (r = -0.241, p = .01) and birthweight (r = -0.208, p = .03). A statistically significant decrease was found in the MCA PI (r = -.422, p < .001) and in the CPR (r = -0.444, p < .001) with advancing pregnancy, between 37 and 42 weeks gestation. The UA PI did not change significantly (p = .099) during this period. Conclusions: MCA PI measured at term is reproducible with a high ICC. MCA PI significantly decreases with advancing gestation at term. No correlation was found between Doppler measurements and time to delivery.
Article
Objective There is a lack of evidence on whether to favor cerebroplacental ratio (CPR) or umbilicocerebral ratio (UCR) when assessing pregnancies at risk of fetal growth restriction. The Recent evidences highlight a significant heterogeneity in the methodology of previously published studies reporting reference ranges for Doppler indices, which may affect the clinical applicability of these charts. The aim of this study was to develop charts of UCR based upon a recently proposed standardized methodology and using quantile regression. Methods This was a secondary analysis of a prospective cross-sectional study including low-risk singleton pregnancies between 24 and 40 weeks of gestation undergoing Doppler recordings. The UCR centile values were established by quantile regression at different gestational age intervals. Quantile regression analysis was used to build the UCR chart. Result 2516 low- risk singleton pregnancies were included in the analysis. UCR decreased with advancing gestational age. The 3rd, 5th 10th, 50th, 90th, 95th, and 97th centiles according to gestational age are provided, as well as equations to allow calculation of any other percentile. Conclusions We have established gestational age-specific normative centiles reference limits for UCR.
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Objectives: To explore the association between fetal umbilical and middle cerebral artery (MCA) Doppler abnormalities and outcome in late preterm pregnancies at risk of fetal growth restriction. Methods: This was a prospective cohort study of singleton pregnancies at risk of fetal growth restriction at 32 + 0 to 36 + 6 weeks of gestation, enrolled in 33 European centers between 2017 and 2018, in which umbilical and fetal MCA Doppler velocimetry was performed. Pregnancies were considered at risk of fetal growth restriction if they had estimated fetal weight and/or abdominal circumference (AC) < 10th centile, abnormal arterial Doppler and/or a fall in AC growth velocity of more than 40 centile points from the 20-week scan. Composite adverse outcome comprised both adverse immediate birth outcome and major neonatal morbidity. Using a range of cut-off values, the association of MCA pulsatility index and umbilicocerebral ratio (UCR) with composite adverse outcome was explored. Results: The study population comprised 856 women. There were two (0.2%) intrauterine deaths. Median gestational age at delivery was 38 (interquartile range (IQR), 37-39) weeks and birth weight was 2478 (IQR, 2140-2790) g. Compared with infants with normal outcome, those with composite adverse outcome (n = 93; 11%) were delivered at an earlier gestational age (36 vs 38 weeks) and had a lower birth weight (1900 vs 2540 g). The first Doppler observation of MCA pulsatility index < 5th centile and UCR Z-score above gestational-age-specific thresholds (1.5 at 32-33 weeks and 1.0 at 34-36 weeks) had the highest relative risks (RR) for composite adverse outcome (RR 2.2 (95% CI, 1.5-3.2) and RR 2.0 (95% CI, 1.4-3.0), respectively). After adjustment for confounders, the association between UCR Z-score and composite adverse outcome remained significant, although gestational age at delivery and birth-weight Z-score had a higher predictive importance. Conclusion: In this prospective multicenter study, fetal cerebral Doppler abnormalities were found to be associated with adverse outcome in late preterm singleton pregnancies at risk of fetal growth restriction. Whether cerebral redistribution is a marker describing the severity of fetal growth restriction or an independent risk factor for adverse outcome remains unclear, and whether it is useful for clinical management can be answered only in a randomized trial. This article is protected by copyright. All rights reserved.
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Objective: The cerebroplacental ratio (CPR) has been proposed for the routine surveillance of pregnancies with suspected fetal growth restriction (FGR), but the predictive performance of this test is unclear. The aim of this study was to determine the accuracy of the CPR for predicting adverse perinatal and neurodevelopmental outcomes in suspected FGR. Methods: PubMed, EMBASE, CINAHL, and Lilacs (all from inception to July 31, 2017) were searched for cohort or cross-sectional studies that reported on the accuracy of the CPR for predicting adverse perinatal and/or neurodevelopmental outcomes in singleton pregnancies with antenatally suspected FGR based on sonographic parameters. Summary receiver operating characteristic (ROC) curves, pooled sensitivities and specificities, and summary likelihood ratios (LRs) were generated. Results: Twenty-two studies (4301 women) met the inclusion criteria. Summary ROC curves showed that the best predictive accuracy of the CPR was for perinatal death and the worst was for neonatal acidosis, with areas under the summary ROC curves of 0.83 and 0.57, respectively. The predictive accuracy of the CPR was moderate-to-high for perinatal death (pooled sensitivity and specificity of 93% and 76%, respectively, and summary positive and negative LRs of 3.9 and 0.09, respectively), and low for composite of adverse perinatal outcomes, cesarean section for non-reassuring fetal status, Apgar <7 at 5 minutes, admission to the neonatal intensive care unit, neonatal acidosis, and neonatal morbidities with summary positive and negative LRs ranging from 1.1-2.5, and 0.3-0.9, respectively. An abnormal CPR result had moderate accuracy for predicting small for gestational age at birth (summary positive LR of 7.4). The CPR had a higher predictive accuracy in pregnancies with suspected early-onset FGR. No study provided data for assessing the predictive accuracy of the CPR for adverse neurodevelopmental outcomes. Conclusion: The CPR appears to be useful in predicting perinatal death in pregnancies with suspected FGR. Nevertheless, before incorporating the CPR into the routine clinical management of suspected FGR, randomized controlled trials should assess whether the use of the CPR reduces perinatal death or other adverse perinatal outcomes. This article is protected by copyright. All rights reserved.
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Background Reduced fetal middle cerebral artery Doppler impedance is associated with hypoxemia in fetal growth restriction. It remains unclear as to whether this finding could be useful in timing delivery, especially in the third trimester. In this regard there is a paucity of evidence from prospective studies. Objectives The aim of this study was to determine whether there is an association between middle cerebral artery Doppler impedance and its ratio with the umbilical artery in relation to neonatal and 2 year infant outcome in early fetal growth restriction (26+0–31+6 weeks of gestation). Additionally we sought to explore which ratio is more informative for clinical use. Study Design This is a secondary analysis from the Trial of Randomized Umbilical and Fetal Flow in Europe, a prospective, multicenter, randomized management study on different antenatal monitoring strategies (ductus venosus Doppler changes and computerized cardiotocography short-term variation) in fetal growth restriction diagnosed between 26+0 and 31+6 weeks. We analyzed women with middle cerebral artery Doppler measurement at study entry and within 1 week before delivery and with complete postnatal follow-up (374 of 503). The primary outcome was survival without neurodevelopmental impairment at 2 years corrected for prematurity. Neonatal outcome was defined as survival until first discharge home without severe neonatal morbidity. Z-scores were calculated for middle cerebral artery pulsatility index and both umbilicocerebral and cerebroplacental ratios. Odds ratios of Doppler parameter Z-scores for neonatal and 2 year infant outcome were calculated by multivariable logistic regression analysis adjusted for gestational age and birthweight p50 ratio. Results Higher middle cerebral artery pulsatility index at inclusion but not within 1 week before delivery was associated with neonatal survival without severe morbidity (odds ratio, 1.24; 95% confidence interval, 1.02–1.52). Middle cerebral artery pulsatility index Z-score and umbilicocerebral ratio Z-score at inclusion were associated with 2 year survival with normal neurodevelopmental outcome (odds ratio, 1.33; 95% confidence interval, 1.03–1.72, and odds ratio, 0.88; 95% confidence interval, 0.78–0.99, respectively) as were gestation at delivery and birthweight p50 ratio (odds ratio, 1.41; 95% confidence interval, 1.20–1.66, and odds ratio, 1.86; 95% confidence interval, 1.33–2.60, respectively). When comparing cerebroplacental ratio against umbilicocerebral ratio, the incremental range of the cerebroplacental ratio tended toward zero, whereas the umbilicocerebral ratio tended toward infinity as the values became more abnormal. Conclusion In a monitoring protocol based on ductus venosus and cardiotocography in early fetal growth restriction (26+0–31+6 weeks of gestation), the impact of middle cerebral artery Doppler and its ratios on outcome is modest and less marked than birthweight and delivery gestation. It is unlikely that middle cerebral artery Doppler and its ratios are informative in optimizing the timing of delivery in fetal growth restriction before 32 weeks of gestation. The umbilicocerebral ratio allows for a better differentiation in the abnormal range than the cerebroplacental ratio.
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Diagnostic accuracy studies are, like other clinical studies, at risk of bias due to shortcomings in design and conduct, and the results of a diagnostic accuracy study may not apply to other patient groups and settings. Readers of study reports need to be informed about study design and conduct, in sufficient detail to judge the trustworthiness and applicability of the study findings. The STARD statement (Standards for Reporting of Diagnostic Accuracy Studies) was developed to improve the completeness and transparency of reports of diagnostic accuracy studies. STARD contains a list of essential items that can be used as a checklist, by authors, reviewers and other readers, to ensure that a report of a diagnostic accuracy study contains the necessary information. STARD was recently updated. All updated STARD materials, including the checklist, are available at http://www.equator-network.org/reporting-guidelines/stard. Here, we present the STARD 2015 explanation and elaboration document. Through commented examples of appropriate reporting, we clarify the rationale for each of the 30 items on the STARD 2015 checklist, and describe what is expected from authors in developing sufficiently informative study reports.
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How the fetus withstands an environment of reduced oxygenation during life in the womb has been a vibrant area of research since this field was introduced by Joseph Barcroft, a century ago. Studies spanning five decades have since used the chronically instrumented fetal sheep preparation to investigate the fetal compensatory responses to hypoxia. This defence is contingent on the fetal cardiovascular system, which in late gestation adopts strategies to decrease oxygen consumption and redistribute the cardiac output away from peripheral vascular beds and towards essential circulations, such as those perfusing the brain. The introduction of simultaneous measurement of blood flow in the fetal carotid and femoral circulations by ultrasonic transducers has permitted investigation of the dynamics of the fetal brain sparing response for the first time. Now we know that major components of fetal brain sparing during acute hypoxia are triggered exclusively by a carotid chemoreflex and that they are modified by endocrine agents and the recently discovered vascular oxidant tone. The latter is determined by the interaction between nitric oxide and reactive oxygen species. The fetal brain sparing response matures as the fetus approaches term, in association with the prepartum increase in fetal plasma cortisol and treatment of the preterm fetus with clinically-relevant doses of synthetic steroids mimics this maturation. Despite intense interest into how the fetal brain sparing response may be affected by adverse intrauterine conditions, this area of research has been comparatively scant but it is likely to take centre stage in the near future. This article is protected by copyright. All rights reserved.
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Objectives. Few data exist for counseling and perinatal management of women after an antenatal diagnosis of early-onset fetal growth restriction. Yet, the consequences of preterm delivery and its attendant morbidity for both mother and baby are far reaching. The objective of this study was to describe perinatal morbidity and mortality following early-onset fetal growth restriction based on time of antenatal diagnosis and delivery. Methods. We report cohort outcomes for a prospective multicenter randomized management study of fetal growth restriction (Trial of Randomized Umbilical and Fetal Flow in Europe (TRUFFLE)) performed in 20 European perinatal centers between 2005 and 2010. Women with a singleton fetus at 26–32 weeks of gestation, with abdominal circumference < 10th percentile and umbilical artery Doppler pulsatility index >95th percentile, were recruited. The main outcome measure was a composite of fetal or neonatal death or severe morbidity: survival to discharge with severe brain injury, bronchopulmonary dysplasia, proven neonatal sepsis or necrotizing enterocolitis. Results Five-hundred and three of 542 eligible women formed the study group. Mean ± SD gestational age at diagnosis was 29 ± 1.6 weeks and mean ± SD estimated fetal weight was 881 ± 217 g; 12 (2.4%) babies died in utero. Gestational age at delivery was 30.7 ± 2.3 weeks, and birth weight was 1013 ± 321 g. Overall, 81% of deliveries were indicated by fetal condition and 97% were by Cesarean section. Of 491 liveborn babies, outcomes were available for 490 amongst whom there were 27 (5.5%) deaths and 118 (24%) babies suffered severe morbidity. These babies were smaller at birth (867 ± 251 g) and born earlier (29.6 ± 2.0 weeks). Death and severe morbidity were significantly related to estational age, both at study entry and delivery and also with the presence of maternal hypertensive morbidity. The median time to delivery was 13 days for women without hypertension, 8 days for those with gestational hypertension, 4 days for pre-eclampsia and 3 days for HELLP syndrome. Conclusions Fetal outcome in this study was better than expected from contemporary reports: perinatal death was uncommon (8%) and 70% survived without severe neonatal morbidity. The intervals to delivery, death and severe morbidity were related to the presence and severity of maternal hypertensive conditions.
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The Hosmer-Lemeshow test is a commonly used procedure for assessing goodness of fit in logistic regression. It has, for example, been widely used for evaluation of risk-scoring models. As with any statistical test, the power increases with sample size; this can be undesirable for goodness of fit tests because in very large data sets, small departures from the proposed model will be considered significant. By considering the dependence of power on the number of groups used in the Hosmer-Lemeshow test, we show how the power may be standardized across different sample sizes in a wide range of models. We provide and confirm mathematical derivations through simulation and analysis of data on 31,713 children from the Collaborative Perinatal Project. We make recommendations on how to choose the number of groups in the Hosmer-Lemeshow test based on sample size and provide example applications of the recommendations. Copyright © 2012 John Wiley & Sons, Ltd.
Article
Purpose: To elucidate the correlation between pre- and postnatal cerebral Doppler in pregnancies close to term and to explore whether they are associated with perinatal outcome. Materials and methods: Prospective study on singleton pregnancies at 36–37 weeks of gestation. The primary outcome was a composite score of perinatal morbidity, while secondary outcomes were adverse intra-partum outcome and abnormal acid–base status. All pregnancies underwent ultrasound assessment of umbilical artery (UA), middle cerebral artery (MCA), uterine arteries (UtAs) pulsatility index (PI), and cerebroplacental ratio (CPR). At birth, neonatal MCA PI was measured 72 h from delivery and correlated with prenatal Doppler, primary and secondary outcomes. Fisher’s test and multivariate logistic regression analysis were used to analyze the data. Results: One hundred and sixty-six fetuses with both pre- and postnatal Doppler assessment of the MCA were included in the study. The risk of composite perinatal morbidity was higher in fetuses (OR: 5.7, 95% CI 2.2–14.6) and newborns (OR: 4.1, 95% CI 1.8–9.6) with fetal MCA PI < 10th centile. Likewise, the incidence of abnormal acid–base status was higher both in fetuses (20 versus 4.2%, p = .026) and newborns (17.1 versus 3.2%, p = .001) with a low MCA PI before and at birth, respectively. At logistic regression analysis, fetal and neonatal MCAPI were independently associated with composite perinatal morbidity and abnormal acid–base status, but not with adverse intra-partum outcome. In small for gestational age (SGA) fetuses, the incidence of composite perinatal morbidity was higher in fetuses and new-borns presenting compared to those not presenting with an MCA PI < 10th centile (61.5 versus 20%, p = .003 and 52.6% versus 7.1%, p = .008, respectively), while such association was lost when considering non-SGA fetuses. Conclusion: A low MCA PI is associated with adverse perinatal outcome in pregnancies at term and tends to persist after birth.
Article
Objective To elucidate the role of Doppler ultrasound in predicting perinatal outcome in appropriate for gestational age (AGA) fetuses at term. Material and Methods Prospective study carried out in a dedicated research ultrasound clinic. The inclusion criterion was AGA fetuses, defined as those with an estimated fetal weight between the 10th and 90th percentile, at 36 + 0–37 + 6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome including either adverse intrapartum events or abnormal acid-base status at birth. Secondary outcomes were the individual components of the primary outcome. The Doppler parameters explored were umbilical artery (UA) PI, middle cerebral artery (MCA) PI, uterine arteries (UtA) PI and cerebroplacental ratio (CPR). Attending clinicians were blinded to Doppler findings. Logistic regression and ROC curve analyses were used to analyze the data. Results 553 AGA fetuses were included. There was no difference in mean UA PI (p = 0.486), MCA PI (p = 0.621), CPR (p = 0.832) and UtA PI (p = 0.611) between pregnancies complicated by composite perinatal morbidity compared to those not complicated by composite perinatal morbidity. In pregnancies complicated by adverse intrapartum outcome, the mean MCA PI (1.47 ± 0.4 vs 1.61 ± 0.4, p = 0.0039) was lower compared to the control group, while there was no difference in UA PI (p = 0.758), CPR (p = 0.108), and UtA PI (p = 0.177). Finally, there was no difference in any of the Doppler parameters explored between AGA fetuses with abnormal acid-base status at birth compared to those without abnormal acid-base status at birth. In the logistic regression analysis, UA PI, MCA PI, CPR, UtA PI, EFW and AC percentiles were not independently associated with composite adverse outcome, adverse intrapartum outcome or abnormal acid-base status at birth in non-SGA fetuses. The diagnostic performance of all of these Doppler parameters for predicting composite adverse outcome, adverse intrapartum outcome and abnormal acid-base status was poor. Conclusion Cerebroplacental and maternal Doppler is not associated with or predictive of adverse pregnancy outcome in AGA fetuses close to term.
Article
Introduction: To explore the strength of association and the diagnostic accuracy of umbilical (UA), middle cerebral (MCA), uterine arteries pulsatility index (PI) and the cerebroplacental ratio in predicting an adverse outcome when applied to singleton pregnancies at term. Material and methods: Prospective study carried out in a dedicated research ultrasound clinic. Attended clinicians were blinded to Doppler findings. Inclusion criteria were consecutive singleton pregnancies between 36+0 and 37+6 weeks of gestation. The primary outcome was a composite score of adverse perinatal outcome. Logistic regression and ROC curve analyses were used to analyze the data. Results: In all, 600 consecutive singleton pregnancies from 36 weeks of gestation were included in the study. Mean MCA PI (1.1 ± 0.2 vs 1.5 ± 0.4, P < 0.001) and cerebroplacental ratio (1.4 ± 0.4 vs 1.9 ± 0.6, P < 0.001) were lower, whereas uterine arteries PI (0.8 ±0.2 vs 0.7 ±0.3, P = 0.001) was higher in pregnancies experiencing than in those not experiencing composite adverse outcome. Conversely, there was no difference in either UA PI (P = 0.399) or estimated fetal weight centile (P = 0.712) between the two groups, but AC centile was lower in fetuses experiencing composite adverse outcome (45.4 vs 53.2, P = 0.040). At logistic regression analysis, MCA PI (odds ratio [OR] 0.1, 95% CI 0.01-.2, P = 0.001), uterine arteries PI (OR 1.4, 95% CI 1.2-1.6, P = 0.001), abdominal circumference centile (OR 1.12, 95% CI 1.1-1.4, P = 0.001) and gestational age at birth (OR 1.6, 95% CI 1.2-2.1, P = 0.004) were independently associated with composite adverse outcome. Despite this, the diagnostic accuracy of Doppler in predicting adverse pregnancy outcome at term was poor. Conclusions: MCA PI and cerebroplacental ratio are associated with adverse perinatal outcome at term. However, their predictive accuracy for perinatal compromise is poor, and thus their use as standalone screening test for adverse perinatal outcome in singleton pregnancies at term is not supported.
Article
Objective: To investigate the performance of screening for adverse perinatal outcome by the cerebroplacental ratio (CPR) measured within 24 hours of induction of labor. Methods: This was a prospective observational study in 1,902 singleton pregnancies undergoing induction of labor at ≥ 37 weeks' gestation. Doppler ultrasound was used to measure the pulsatility index (PI) in the umbilical artery (UA) and fetal middle cerebral artery (MCA) before induction of labor. The measured UA PI and MCA PI and their ratio were converted to multiples of the median (MoM) after adjustment for gestational age. Univariate and multivariate logistic regression analysis was used to determine whether CPR improved the prediction of adverse perinatal outcome that was 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 cesarean section for presumed fetal distress and neonatal adverse outcome, which included umbilical arterial or venous cord blood pH ≤7 and ≤7.1, respectively, 5-minute Apgar score <7, admission to the neonatal intensive care unit (NICU) for >24 hours, or hypoxic ischemic encephalopathy. Results: A combination of maternal and pregnancy characteristics, including age, weight, racial origin, previous obstetric history, preeclampsia, gestational age at delivery and amniotic fluid volume, identified 39% of pregnancies requiring cesarean section for fetal distress at FPR of 10%; addition of CPR did not improve the performance of screening. In screening for adverse neonatal outcome by a combination of parity and CPR the DR was 17% at FPR of 10%. Conclusion: Low CPR, measured within 24 hours of induction of labor, is associated with increased risk of cesarean section for fetal distress and adverse neonatal outcome, but the performance of CPR for such surrogates of adverse perinatal outcome is poor. This article is protected by copyright. All rights reserved.
Article
Introduction: Doppler ultrasound has recently been suggested to identify subclinical placental functional impairment among normal sized term fetuses. The objective of this study was to evaluate the relationship between cerebroplacental ratio (CPR) measured in early labor and perinatal and delivery outcomes in a cohort of uncomplicated singleton term pregnancies. Methods: This was a multicentre, prospective, observational study involving three Tertiary Centres. Low risk term pregnancies, as defined by the absence of any maternal morbidity and pregnancy complication and normal ultrasound and clinical screening of the fetal growth in the third trimester, with spontaneous onset of labor were included. Cases were submitted to Doppler measurement of the umbilical artery (UA) and middle cerebral artery (MCA) on admission for early labor. All measurements were performed in between uterine contractions and according to international standards. CPR was computed by dividing MCA and UA pulsatility index and converted into MoMs in order to adjust for gestation. Cases with reduced CPR MoM, as defined by CPR MoM within the lowest decile of the study population, were compared to those with normal CPR MoM. Data regarding mode of delivery and perinatal outcomes were collected and correlated to the Doppler evaluation. Doctors and midwifes involved in the clinical management of the patients were blinded to the results of the Doppler evaluation. Results: Overall, 562 patients were included. The rate of obstetric intervention for suspected fetal distress in labor was over three times higher among cases with reduced CPR MoM (9/54, 16.7%, vs 28/508, 5.5%, p 0.004). Furthermore, a significantly higher rate of composite adverse perinatal outcome was found in fetuses showing CPR MoM <10th percentile (6/54, 11.1%, vs 19/508, 3.7%, p 0.012). Conclusions: Data on a wide cohort of low risk term pregnancies in early labor have shown that a reduced CPR is associated with a higher risk of obstetric intervention due to fetal distress and adverse perinatal outcomes. This article is protected by copyright. All rights reserved.
Article
Objective: To study the accuracy of the cerebroplacental ratio (CPR) for the detection of intrapartum fetal compromise (IFC) in fetuses growing over the 10th centile. Methods: This was a prospective study of 569 nonsmall fetuses attending the day hospital unit of a tertiary hospital that underwent an ultrasound examination at 36–40 weeks, and were delivered within 4 weeks of examination. IFC was defined as a composite of: abnormal intrapartum fetal heart rate or intrapartum fetal scalp pH < 7.20 requiring cesarean section, neonatal umbilical cord pH < 7.20, 5’ Apgar score < 7 and postpartum admission to neonatal or pediatric intensive care units. The accuracy of CPR for the prediction of IFC was calculated alone and in combination with other perinatal parameters using univariate and multivariate logistic regression models, which alternatively included the onset of labor to evaluate the influence of induction of labor (IOL) on IFC and a brief composite adverse outcome of two parameters to prove the strength of the approach. Results: The incidence of IFC was 17.9%. CPR sensitivity was 30.4% for a false positive rate (FFR) of 10 and 14.7% for a FPP of 5% (AUC = 0.62, p < 0.001). The multivariate analysis showed that only fetal gender and parity increased the predictive accuracy of CPR alone, although the improvement was poor (AUC = 0.67, p < 0.001). No differences were observed using any of the alternative models. Finally, IOL had no influence of IFC. Conclusion: Despite their apparent normality, a proportion of fetuses growing over the 10th centile suffer IFC. Some of them are suitable for detection by means of CPR.
Article
Objectives: We sought to determine the screening performance of a low fetal cerebroplacental ratio (a marker of fetal adaptation to suboptimal growth) and maternal placental growth factor levels, respectively, both in isolation and in combination, for the detection of cesarean section for intrapartum fetal compromise and serious composite neonatal outcome. Methods: A prospective cohort study was performed on low risk women with uncomplicated singleton pregnancies from 36 weeks to delivery. Fortnightly assessment of the cerebroplacental ratio and placental growth factor was performed and intrapartum and neonatal outcomes were recorded. Values from the final assessment for each woman were corrected for gestation and assessed for screening performance, firstly as continuous variables and then as binary predictors. Results: Of the 264 women who consented to participate in the study, 207 were included in the final analysis. Babies born by cesarean section for intrapartum fetal compromise had lower cerebroplacental ratio and placental growth factor centiles than all other deliveries. Women with babies born with the serious composite neonatal outcome had lower placental growth factor centiles. The highest Area under the Receiver Operative Characteristic Curve for cesarean section for intrapartum fetal compromise (0.92, 95% CI 0.86-0.97) and serious composite neonatal outcome (0.64, 95% CI 0.54-0.74) was achieved by a combination of the cerebroplacental ratio 20th and placental growth factor 33rd centiles respectively. This produced sensitivities, specificities and positive likelihood ratios for cesarean section for intrapartum fetal compromise and serious composite neonatal outcome of 100%, 86%, and 7.14, and 34.2%, 87.0%, and 2.63, respectively. There was no statistical difference in the Area under the Receiver Operative Characteristic Curve between the combined model and the cerebroplacental ratio alone for cesarean section for intrapartum fetal compromise nor the combined model and the cerebroplacental ratio or placental growth factor in isolation for adverse neonatal outcome. Conclusion: This pilot, proof of principle study describes the screening performance for detection of cesarean section for intrapartum fetal compromise in low risk women from 36 weeks gestation using the fetal cerebroplacental ratio and maternal placental growth factor levels. We found that the cerebroplacental ratio and maternal placental growth factor improved the overall predictive utility for cesarean section for intrapartum fetal compromise and adverse neonatal outcome. However, given the lack of significant difference between the combined model and its individual components it is debatable that the combined model is a superior screening test.
Article
Background: Abnormal blood flow patterns in fetal circulation detected by Doppler ultrasound may indicate poor fetal prognosis. It is also possible that false positive Doppler ultrasound findings could lead to adverse outcomes from unnecessary interventions, including preterm delivery. Objectives: The objective of this review was to assess the effects of Doppler ultrasound used to assess fetal well-being in high-risk pregnancies on obstetric care and fetal outcomes. Search methods: We updated the search of Cochrane Pregnancy and Childbirth's Trials Register on 31 March 2017 and checked reference lists of retrieved studies. Selection criteria: Randomised and quasi-randomised controlled trials of Doppler ultrasound for the investigation of umbilical and fetal vessels waveforms in high-risk pregnancies compared with no Doppler ultrasound. Cluster-randomised trials were eligible for inclusion but none were identified. Data collection and analysis: Two review authors independently assessed the studies for inclusion, assessed risk of bias and carried out data extraction. Data entry was checked. We assessed the quality of evidence using the GRADE approach. Main results: Nineteen trials involving 10,667 women were included. Risk of bias in trials was difficult to assess accurately due to incomplete reporting. None of the evidence relating to our main outcomes was graded as high quality. The quality of evidence was downgraded due to missing information on trial methods, imprecision in risk estimates and heterogeneity. Eighteen of these studies compared the use of Doppler ultrasound of the umbilical artery of the unborn baby with no Doppler or with cardiotocography (CTG). One more recent trial compared Doppler examination of other fetal blood vessels (ductus venosus) with computerised CTG.The use of Doppler ultrasound of the umbilical artery in high-risk pregnancy was associated with fewer perinatal deaths (risk ratio (RR) 0.71, 95% confidence interval (CI) 0.52 to 0.98, 16 studies, 10,225 babies, 1.2% versus 1.7 %, number needed to treat (NNT) = 203; 95% CI 103 to 4352, evidence graded moderate). The results for stillbirths were consistent with the overall rate of perinatal deaths, although there was no clear difference between groups for this outcome (RR 0.65, 95% CI 0.41 to 1.04; 15 studies, 9560 babies, evidence graded low). Where Doppler ultrasound was used, there were fewer inductions of labour (average RR 0.89, 95% CI 0.80 to 0.99, 10 studies, 5633 women, random-effects, evidence graded moderate) and fewer caesarean sections (RR 0.90, 95% CI 0.84 to 0.97, 14 studies, 7918 women, evidence graded moderate). There was no comparative long-term follow-up of babies exposed to Doppler ultrasound in pregnancy in women at increased risk of complications.No difference was found in operative vaginal births (RR 0.95, 95% CI 0.80 to 1.14, four studies, 2813 women), nor in Apgar scores less than seven at five minutes (RR 0.92, 95% CI 0.69 to 1.24, seven studies, 6321 babies, evidence graded low). Data for serious neonatal morbidity were not pooled due to high heterogeneity between the three studies that reported it (1098 babies) (evidence graded very low).The use of Doppler to evaluate early and late changes in ductus venosus in early fetal growth restriction was not associated with significant differences in any perinatal death after randomisation. However, there was an improvement in long-term neurological outcome in the cohort of babies in whom the trigger for delivery was either late changes in ductus venosus or abnormalities seen on computerised CTG. Authors' conclusions: Current evidence suggests that the use of Doppler ultrasound on the umbilical artery in high-risk pregnancies reduces the risk of perinatal deaths and may result in fewer obstetric interventions. The results should be interpreted with caution, as the evidence is not of high quality. Serial monitoring of Doppler changes in ductus venosus may be beneficial, but more studies of high quality with follow-up including neurological development are needed for evidence to be conclusive.
Article
Background: The cerebroplacental ratio has been proposed as a marker of failure to reach growth potential near term. Low cerebroplacental ratio, regardless of the fetal size, is independently associated with the need for operative delivery for presumed fetal compromise and with neonatal unit admission at term. Objective: The main aim of this study was to evaluate whether the cerebroplacental ratio at term is a marker of reduced fetal growth rate. The secondary aim was to investigate the relationship between low cerebroplacental ratio at term, reduced fetal growth velocity and adverse pregnancy outcome. Design: retrospective cohort study of singleton pregnancies in a tertiary referral center. The abdominal circumference was measured at 20-24 weeks' gestation, and both abdominal circumference and fetal Dopplers recorded at or beyond 35 weeks, within two weeks of delivery. Abdominal circumference and birthweight values were converted into Z scores and centiles, respectively, and fetal Doppler parameters into multiples of median, adjusting for gestational age. Abdominal circumference growth velocity was quantified using the difference in abdominal circumference Z score, comparing the scan at or beyond 35 weeks with the scan at 20-24 weeks. Both univariable and multivariable logistic regression analyses were performed to investigate the association between low cerebroplacental ratio, low abdominal circumference growth velocity (in the lowest decile), and to identify and adjust for potential confounders. As a sensitivity analysis, we refitted the model excluding the data on pregnancies with small for gestational age neonates. Results: The study included 7944 pregnancies. Low cerebroplacental ratio multiples of median was significantly associated with both low abdominal circumference growth velocity (adjusted OR 2.10; 95%CI 1.71-2.57, p<0.001) and small for gestational age (adjusted OR 3.60; 95%CI 3.04-4.25, p<0.001). After the exclusion of pregnancies resulting in small for gestational age neonates, low cerebroplacental ratio multiples of median remained significantly associated with both low abdominal circumference growth velocity (adjusted OR 1.76; 95%CI 1.34-2.30, p<0.001) and birthweight centile (adjusted OR 0.99; 95%CI 0.998-0.995, p<0.001). The need for operative delivery for fetal compromise was significantly associated with low cerebroplacental ratio (adjusted OR 1.40; 95%CI 1.10-1.78, p=0.006), even after adjusting for both the umbilical artery pulsatility index multiples of median and middle cerebral artery pulsatility index multiples of median. The results were similar even after the exclusion of pregnancies resulting in small for gestational age neonates (adjusted OR 1.39; 95%CI 1.06-1.84, p=0.018). Low cerebroplacental ratio multiples of median remained significantly associated with the risk of operative delivery for presumed fetal compromise (p<0.001), even after adjusting for the known antenatal and intrapartum risk factors. These associations persisted even after exclusion of small for gestational age births. In appropriate for gestational age sized fetuses, abdominal circumference growth velocity was significantly lower in those with low cerebroplacental ratio multiples of median than in those with normal cerebroplacental ratio multiples of median (p<0.001). Conclusion: Cerebroplacental ratio is a marker of impaired fetal growth velocity and adverse pregnancy outcome, even in fetuses whose size is considered appropriate using conventional biometry.
Article
Objective: We sought to determine the cause of adverse perinatal outcome in fetal growth restriction (FGR) where umbilical artery (UA) Doppler was normal, as identified from the Prospective Observational Trial to Optimize Pediatric Health (PORTO). We compared cases of adverse outcome where UA Doppler was normal and abnormal. Study design: The PORTO study was a national multicenter study of >1100 ultrasound-dated singleton pregnancies with an estimated fetal weight <10th centile. Each pregnancy underwent intensive ultrasound, including multivessel Doppler. UA Doppler was considered abnormal when the pulsatility index was >95th centile or end-diastolic flow was absent/reversed. Adverse perinatal outcome was defined as a composite of intraventricular hemorrhage, periventricular leukomalacia, hypoxic ischemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, or death. Results: In all, 57 (5.0%) of the 1116 fetuses had an adverse perinatal outcome. Nine (1.3%) of 698 fetuses with normal UA Doppler had an adverse outcome, compared with 48 (11.5%) of 418 with abnormal UA Doppler (P < .0001). There were 2 perinatal deaths in the normal group and 6 in the abnormal group (P = .01). The perinatal deaths in the normal group were 1 case of pulmonary hypoplasia after prolonged preterm rupture of the membranes from 12 weeks' gestation and a case of placental abruption. Gestation at delivery was 33 ± 3 vs 31 ± 4 weeks (P = .05) and mean birthweight was 1830 ± 737 vs 1146 ± 508 g (P = .001) in the respective groups. Neonatal sepsis was the commonest adverse outcome in both groups: 0.1% and 0.4%, respectively (P = .01). Conclusion: Adverse perinatal outcome is uncommon in FGR with normal UA Doppler. The cases we identified were associated with heterogenous pathologies. FGR with normal UA blood flow is a largely benign condition.
Article
The aim of the Prospective Observational Trial to Optimize Pediatric Health in IUGR (PORTO) Study was to evaluate the optimal management of fetuses with estimated fetal weight (EFW) <10(th) centile. The objective of this secondary analysis was to describe the role of the cerebroplacental ratio (CPR) in the prediction of adverse perinatal outcome. Over 1,100 consecutive singleton pregnancies with IUGR were recruited over two years at seven centers, undergoing serial sonographic evaluation including multi-vessel Doppler measurement. CPR was calculated using the pulsatility (PI) and resistance (RI) indices of the middle cerebral (MCA) and umbilical artery (UA) Adverse perinatal outcome was defined as a composite of intraventricular haemorrhage, periventricular leukomalacia, hypoxic ischaemic encephalopathy, necrotizing enterocolitis, bronchopulmonary dysplasia, sepsis, and death. Data for CPR calculation was available in 881 cases which was performed at a mean gestational age of 33 weeks (IQR 28.7-35.9) Of the 146 cases with CPR <1, 18% (n=27) had an adverse perinatal outcome. This conferred an 11-fold increased risk (OR 11.7, p<0.0001) when compared to cases with normal CPR (2%; 14/735). An abnormal CPR was present in all 3 cases of mortality. Prediction of adverse outcomes was comparable when using all definitions of abnormal CPR. Irrespective of the CPR calculation employed, brainsparing is significantly associated with adverse perinatal outcome in IUGR. This adds further weight to integrating CPR evaluation into the clinical assessment of IUGR pregnancies. The impact of this finding on long term neurodevelopmental outcomes in this patient cohort is underway.
Article
Seventy-five high-risk pregnancies were studied in order to define the clinical value of the analysis of fetal blood flow velocity waveforms in early screening for growth retardation. Recordings were obtained at 26-28 weeks' gestation, in the absence of ultrasonographic signs of growth retardation, using a pulsed duplex Doppler system. The pulsatility index was evaluated at the level of the umbilical artery, descending aorta, and internal carotid artery. Fetuses (N = 23) who developed growth retardation showed higher values of pulsatility index in the umbilical artery (P less than .001) and descending aorta (P less than .05) than fetuses of normal growth. In the internal carotid artery, the pulsatility index was lower (P less than .001) in the fetuses who developed growth retardation than in those with normal growth. The ratio between the pulsatility indexes of the umbilical and internal carotid arteries proved an accurate predictor of growth retardation (specificity 92.3%; sensitivity 78.2%; positive predictive value 81.8%; negative predictive value 90.5%; accuracy 88%).
Article
An important quality of meta-analytic models for research synthesis is their ability to account for both within- and between-study variability. Currently available meta-analytic approaches for studies of diagnostic test accuracy work primarily within a fixed-effects framework. In this paper we describe a hierarchical regression model for meta-analysis of studies reporting estimates of test sensitivity and specificity. The model allows more between- and within-study variability than fixed-effect approaches, by allowing both test stringency and test accuracy to vary across studies. It is also possible to examine the effects of study specific covariates. Estimates are computed using Markov Chain Monte Carlo simulation with publicly available software (BUGS). This estimation method allows flexibility in the choice of summary statistics. We demonstrate the advantages of this modelling approach using a recently published meta-analysis comparing three tests used to detect nodal metastasis of cervical cancer.
Article
Diagnostic testing can be used to discriminate subjects with a target disorder from subjects without it. Several indicators of diagnostic performance have been proposed, such as sensitivity and specificity. Using paired indicators can be a disadvantage in comparing the performance of competing tests, especially if one test does not outperform the other on both indicators. Here we propose the use of the odds ratio as a single indicator of diagnostic performance. The diagnostic odds ratio is closely linked to existing indicators, it facilitates formal meta-analysis of studies on diagnostic test performance, and it is derived from logistic models, which allow for the inclusion of additional variables to correct for heterogeneity. A disadvantage is the impossibility of weighing the true positive and false positive rate separately. In this article the application of the diagnostic odds ratio in test evaluation is illustrated.
Chandraharan E; FIGO Intrapartum Fetal Monitoring Expert Consensus Panel
  • D Ayres-De-Campos
  • C Y Spong
Ayres-de-Campos D, Spong CY, Chandraharan E; FIGO Intrapartum Fetal Monitoring Expert Consensus Panel. Int J Gynaecol Obstet. 2015;131:13-24.
Biochemical monitoring of intra-partum asphyxia
  • L Nordstrom
  • S Arulkumaran
Nordstrom L, Arulkumaran S. Biochemical monitoring of intra-partum asphyxia. In Perinatal Asphyxia, Arulkumaran S, Jenkins HML (eds). Orient Longman: Hyderabad, 2000;156.