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Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.

ABSTRACT: Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters.We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and consulting with experts. Four of us independently selected studies, extracted data and assessed study validity. We performed a bivariable meta-analysis of sensitivity and specificity and calculated likelihood ratios.We identified 74 studies of pre-eclampsia (total 79,547 patients) and 61 studies of intrauterine growth restriction (total 41 131 patients). Uterine artery Doppler ultrasonography provided a more accurate prediction when performed in the second trimester than in the first-trimester. Most Doppler indices had poor predictive characteristics, but this varied with patient risk and outcome severity. An increased pulsatility index with notching was the best predictor of pre-eclampsia (positive likelihood ratio 21.0 among high-risk patients and 7.5 among low-risk patients). It was also the best predictor of overall (positive likelihood ratio 9.1) and severe (positive likelihood ratio 14.6) intrauterine growth restriction among low-risk patients.Abnormal uterine artery waveforms are a better predictor of pre-eclampsia than of intrauterine growth restriction. A pulsatility index, alone or combined with notching, is the most predictive Doppler index. These indices should be used in clinical practice. Future research should also concentrate on combining uterine artery Doppler ultrasonography with other tests.

SUBMITTER: Cnossen JS

PROVIDER: S-EPMC2263112 | biostudies-literature | 2008 Mar

REPOSITORIES: biostudies-literature

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Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.

Cnossen Jeltsje S JS Morris Rachel K RK ter Riet Gerben G Mol Ben W J BW van der Post Joris A M JA Coomarasamy Arri A Zwinderman Aeilko H AH Robson Stephen C SC Bindels Patrick J E PJ Kleijnen Jos J Khan Khalid S KS

CMAJ : Canadian Medical Association journal = journal de l'Association medicale canadienne 20080301 6

<h4>Background</h4>Alterations in waveforms in the uterine artery are associated with the development of pre-eclampsia and intrauterine growth restriction. We investigated the predictive accuracy of all uterine artery Doppler indices for both conditions in the first and second trimesters.<h4>Methods</h4>We identified relevant studies through searches of MEDLINE, EMBASE, the Cochrane Library and Medion databases (all records to April 2006) and by checking bibliographies of identified studies and ...[more]

PMID: 18332385

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Project description:Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE.In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n?=?8; PE, n?=?5; PE+IUGR, n?=?10) and controls (term, n?=?13; preterm, n?=?7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE.Combining bioinformatic analysis, molecular biological experiments and mathematical diagramming, this study has demonstrated systematic alterations of nutrient transporter expressions in IUGR/PE. Among 46 initially targeted transporters, three significantly regulated genes were further investigated based on the severity and the disease specificity for IUGR and PE. Confirmed by mRNA and protein expression, the amino acid transporters SLC7A7 and SLC38A5 showed marked differences between controls and IUGR/PE and were regulated by both diseases. In contrast, ABCA1 may play an exclusive role in the development of PE.

Project description:IntroductionPre-eclampsia (PE) and intrauterine growth restriction (IUGR) are two major pregnancy complications, related to chronic uteroplacental hypoperfusion. Nowadays, there is no screening or diagnostic test for uteroplacental vascularisation deficiency in pregnant women. Since 2004, 3 three-imensional power Doppler (3DPD) angiography has been used for the evaluation of uteroplacental vascularisation and three vascular indices are usually calculated: Vascularisation Index (VI), Flow Index (FI) and vascularisation-FI (VFI). A high intraobserver and interobserver reproducibility and a potential interest for placental function study were reported by our team and others.The main objective of our study is to determine differences in 3DPD indices at first trimester between pregnancies defined at their outcome as uncomplicated pregnancy, PE (mild and severe) and IUGR in nulliparous women.Methods and analysisThis is a national multicentre prospective cohort study conducted in four French maternity units. We expect to include 2200 women in a period of 36 months. The nulliparous pregnant women will be recruited during their first trimester consultation (11-13+6 gestation week (GW)).The 3DPD and uterine artery Doppler acquisition will be included in the current routine 11-13+6 GW ultrasound. Also, additional blood samples will be taken for biomarker analysis (PAPP-A and P1GF) and biological collection. Uteroplacental VIs (FI and VFI) will be measured. For each subgroup (uncomplicated pregnancy, PE and IUGR), mean values in 3DPD indices will be computed and compared using a pairwise t test with a Bonferroni correction p value adjustment.Ethics and disseminationThe study was approved by the French Ethics Committee, the Comité de Protection des Personnes SUD MEDITERRANEE IV on 13 February 2018 with reference number 17 12 03. The results of this study will be published in a peer-reviewed journal and will be presented at relevant conferences.Trial registration numberNCT03342014; Pre-results. PHRCN-16-0567.

Project description:IntroductionPregnancy in sickle cell disease is fraught with many complications including pre-eclampsia (PE) and intrauterine growth restriction (IUGR). Previously, we found an abnormality in prostacyclin-thromboxane ratio in sickle cell pregnant women, a situation that is also found in non-sickle pregnancies with PE and unexplained IUGR. Low-dose aspirin (LDA) has been shown to reduce the incidence of PE and IUGR in high-risk women by reducing the vasoconstrictor thromboxane while sparing prostacyclin, in effect 'correcting' the ratio. It has been found to be safe for use in pregnancy but has not been tested in sickle cell pregnancy. We hypothesise that LDA will reduce the incidence of IUGR and PE in pregnant haemoglobin SS (HbSS) and haemoglobin SC (HbSC) women.Methods and analysisThis is a multisite, double blind, randomised controlled trial, comparing a daily dose of 100 mg aspirin to placebo, from 12 to 16 weeks' gestation until 36 weeks, in Lagos state, Nigeria. Four hundred and seventy-six eligible pregnant HbSS and HbSC women will be recruited consecutively, randomly assigned to either group and followed from recruitment until delivery. The primary outcome will be the incidence of birth weight below 10th centile for gestational age on INTERGROWTH 21 birth weight charts, or incidence of miscarriage or perinatal death. Secondary outcomes will include PE, maternal death, preterm delivery, perinatal death, number of crises, need for blood transfusion and complications such as infections and placental abruption. Analysis will be by intention to treat and the main treatment effects will be quantified by relative risk with 95% CI, at a 5% significance level.Ethical approvalEthical approval has been granted by the Health Research and Ethics committees of the recruiting hospitals and the National Health Research and Ethics Committee. Study findings will be presented at conferences and published appropriately.Trail registration numberPACTR202001787519553; Pre-results.

Project description:BACKGROUND:Trophoblastic invasion of the uterine spiral arteries substantially increases compliance to accommodate increased blood flow to the placenta. Failure of this process impedes uterine artery blood flow, and this may be detected by uterine artery Doppler flow studies. However, the clinical utility of uterine artery Doppler flow studies in the prediction of adverse pregnancy outcomes in a general population remains largely unknown. OBJECTIVE:We sought to determine the utility of early second-trimester uterine artery Doppler studies as a predictor of small-for-gestational-age neonates. STUDY DESIGN:Nulliparous women with a viable singleton pregnancy were recruited during their first trimester into an observational prospective cohort study at 8 institutions across the United States. Participants were seen at 3 study visits during pregnancy and again at delivery. Three indices of uterine artery Doppler flow (resistance index, pulsatility index, and diastolic notching) were measured in the right and left uterine arteries between 16 weeks 0 days' and 22 weeks 6 days' gestation. Test characteristics for varying thresholds in the prediction of small for gestational age (defined as birthweight <5th percentile for gestational age [Alexander growth curve]) were evaluated. RESULTS:Uterine artery Doppler indices, birthweight, and gestational age at birth were available for 8024 women. Birthweight <5th percentile for gestational age occurred in 358 (4.5%) births. Typical thresholds for the uterine artery Doppler indices were all associated with birthweight <5th percentile for gestational age (P < .0001 for each), but the positive predictive values for these cutoffs were all <15% and areas under receiver operating characteristic curves ranged from 0.50-0.60. Across the continuous scales for these measures, the areas under receiver operating characteristic curves ranged from 0.56-0.62. Incorporating maternal age, early pregnancy body mass index, race/ethnicity, smoking status prior to pregnancy, chronic hypertension, and pregestational diabetes in the prediction model resulted in only modest improvements in the areas under receiver operating characteristic curves ranging from 0.63-0.66. CONCLUSION:In this large prospective cohort, early second-trimester uterine artery Doppler studies were not a clinically useful test for predicting small-for-gestational-age babies.

Project description:INTRODUCTION:Mid-trimester uterine artery resistance measured with Doppler sonography is predictive for iatrogenic preterm birth. In view of the emerging association between hypertensive disease in pregnancy and spontaneous preterm birth, we hypothesized that uterine artery resistance could also predict spontaneous preterm birth. MATERIAL AND METHODS:We performed a cohort study of women with singleton pregnancies. Uterine artery resistance was routinely measured at the 18-22 weeks anomaly scan. Pregnancies complicated by congenital anomalies or intrauterine fetal death were excluded. We analyzed if the waveform of the uterine artery (no notch, unilateral notch or bilateral notch) was predictive for spontaneous and iatrogenic preterm birth, defined as delivery before 37 weeks of gestation. Furthermore, we assessed whether the uterine artery pulsatility index was associated with the risk of preterm birth. RESULTS:Between January 2009 and December 2016 we collected uterine Doppler indices and relevant outcome data in 4521 women. Mean gestational age at measurement was 19+6 weeks. There were 137 (3.0%) women with a bilateral and 213 (4.7%) with a unilateral notch. Mean gestational age at birth was 38+6 weeks. Spontaneous and iatrogenic preterm birth rates were 5.7% and 4.9%, respectively. Mean uterine artery resistance was 1.12 in the spontaneous preterm birth group compared with 1.04 in the term group (P = 0.004) The risk of preterm birth was increased with high uterine artery resistance (OR 2.9 per unit; 95% CI 2.4-3.9). Prevalence of spontaneous preterm birth increased from 5.5% in women without a notch in the uterine arteries to 8.0% in women with a unilateral notch and 8.0% in women with a bilateral notch. For iatrogenic preterm birth, these rates were 3.9%, 13.6% and 23.4%, respectively. Likelihood ratios for the prediction of spontaneous preterm birth were 1.6 (95% CI 1.0-2.6) and 1.9 (95% CI 1.0-3.5) for unilateral and bilateral notches, respectively, and for iatrogenic preterm birth they were 3.6 (95% CI 2.5-5.2) and 6.8 (95% CI 4.7-9.9) for unilateral and bilateral notches, respectively. Of all women with bilateral notching, 31.4% delivered preterm. CONCLUSIONS:Mid-trimester uterine artery resistance measured at 18-22 weeks of gestation is a weak predictor of spontaneous preterm birth.

Dataset Information

Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.

Publications

Use of uterine artery Doppler ultrasonography to predict pre-eclampsia and intrauterine growth restriction: a systematic review and bivariable meta-analysis.

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