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First trimester screening for pre-eclampsia and intrauterine growth restriction using three-dimensional Doppler angiography (SPIRIT): protocol for a multicentre prospective study in nulliparous pregnant women.

ABSTRACT: INTRODUCTION:Pre-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 ANALYSIS:This 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 DISSEMINATION:The 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 NUMBER:NCT03342014; Pre-results. PHRCN-16-0567.

SUBMITTER: Bertholdt C

PROVIDER: S-EPMC7574950 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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First trimester screening for pre-eclampsia and intrauterine growth restriction using three-dimensional Doppler angiography (SPIRIT): protocol for a multicentre prospective study in nulliparous pregnant women.

Bertholdt Charline C Hossu Gabriela G Banasiak Claire C Beaumont Marine M Morel Olivier O

BMJ open 20201019 10

<h4>Introduction</h4>Pre-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), Flo ...[more]

PMID: 33077562

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Project description:BackgroundGestational 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.ResultsIn 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.ConclusionsCombining 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: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:OBJECTIVE:To estimate the effect of inadequate maternal weight gain in the third trimester on the risk of intrauterine growth restriction (IUGR) in rural Bangladesh. METHODS:This study analyzed data from 1,463 mother-infant pairs in Matlab, Bangladesh which were available through the electronic databases of Matlab Health and Demographic Surveillance System and Matlab hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh (icddr,b). All the mothers were admitted to Matlab hospital for childbirth from January 2012 to December 2014, and they had singleton live births at term. Third-trimester weight gain (kg) was calculated by subtracting the estimated weight at the end of the second trimester from the weight taken before childbirth. Inadequate third-trimester weight gain was defined as 4 kg or less irrespective of pre-gravid nutritional status. IUGR was defined as a birth weight below 2500 g in full-term newborns (LBW-Term), and a birth weight for gestational age and infant sex less than the 10th percentile (SGA-10th) and 2 standard deviations below the mean birth weight (SGA-2SD) based on the international newborn standards from the INTERGROWTH-21st project. Multivariable logistic regression models were fitted to determine the independent effect of inadequate weight gain in the third trimester on the risk of IUGR. RESULTS:A total of 824 (56.3%) women experienced inadequate weight gain in the third trimester of pregnancy. In this study, 215 (14.7%), 573 (39.2%) and 220 (15.0%) infants were born as LBW-Term, SGA-10th and SGA-2SD, respectively. In the multivariable logistic regression models, compared to adequate weight gain in the third-trimester, the odds ratios (OR) for LBW-Term, SGA-10th and SGA-2SD for inadequate weight gain were 1.8 (95% CI: 1.3, 2.5; p < 0.001), 1.4 (95% CI: 1.1, 1.8; p = 0.002) and 1.8 (95% CI: 1.3, 2.4; p = 0.001), respectively. CONCLUSIONS:Both inadequate third-trimester weight gain and IUGR are prevailing public health concerns in rural Bangladesh. Inadequate weight gain in the third trimester substantially increased the risk of IUGR. Public health programs focusing on the promotion of adequate weight gain in the third trimester of pregnancy with an ultimate aim to decrease IUGR should be implemented.

Project description:INTRODUCTION:Knowledge about the mechanisms leading to the establishment of uteroplacental vascularisation is inadequate, and some of what has been thought to be known for decades has recently been challenged by showing that the intervillous space, the major area of maternal-fetal exchange, appears to be perfused by maternal blood at as early as 6 weeks of gestation. The vascular flow then seems relatively constant until 13 weeks when it appears to increase suddenly. OBJECTIVES:The principal objective is to quantify the perfusion of the intervillous space by contrast-enhanced ultrasonography (CEUS) during the first-trimester at three different gestational ages (8, 11 and 13 weeks). The secondary objectives are to: (1) describe the indicators of vascularisation of the placenta (intervillous space) and the myometrium at the three gestational ages, measured by CEUS and three-dimensional power Doppler (3DPD) angiography; (2) compare the diagnostic performance of CEUS and 3DPD for the demonstration and quantification of uteroplacental vascularisation and (3) establish a biological collection of placentas to increase knowledge about placental development and functions during pregnancy. METHODS AND ANALYSIS:This is a prospective, cross-sectional, multicentre and non-randomised open study. We will include 42 women with ongoing pregnancy and divided into three groups of gestational ages (ie, 14 women by per group): 8, 11 and 13 weeks of gestation. 3DPD and then CEUS will be performed and the data about the perfusion kinetics and the 3DPD indices will be calculated and then compared with each other and for each gestational age. ETHICS AND DISSEMINATION:The appropriate French Ethics Committee Est III approved this study and the related consent forms on 5 April 2016, and the competent authority (Agence Nationale de Sécurité du Médicament et des Produits de Santé) authorised the study on 21 June 2016. The results of this study will be published in a peer-reviewed journal and will be presented at relevant conferences. TRIAL REGISTRATION NUMBERS:ClinicalTrials.gov registry (NCT02884297); EudraCT registry (2015-005655-27).

Project description:BackgroundSelective fetal restriction growth (sFGR) is one of the common diseases of monochorionic diamniotic (MCDA) twin pregnancies, resulting in many adverse outcomes. At present, second trimester ultrasonography is widely used in the prenatal diagnosis of sFGR, but the diagnostic effectiveness is still uncertain. The aim of this study is to assess the diagnostic accuracy of second trimester Doppler ultrasound measurements for sFGR.MethodsA retrospective study included 280 pregnant women (118 with and 162 without sFGR) with MCDA pregnancies was conducted in the fetal medicine center from Leiden University Medical Center from January 2008 to December 2013. The women participating had already undergone an ultrasound examination in the second trimester. The postnatal criteria of sFGR was a single birth weight (BW) < 3 rd percentile in a twin, or birth weight discordance (BWD)≥25% between two twins, while the BW of the smaller twin < 10th percentile. Early prenatal diagnosis of sFGR was defined as a single EFW < 3 rd percentile in a twin, or at least 2 of the following 4 parameters must be met (fetal weight of one fetus < 10th percentile, AC of one fetus <10th percentile, EFW discordance≥25%, UA pulsatility index (PI) of the smaller fetus > 95th percentile). According to the diagnosis of sFGR after birth, we evaluate diagnostic effectiveness of Doppler ultrasound in the second trimester for sFGR.ResultsOf these 280 participants, the mean age was 32.06 ± 4.76 years. About 43.9% of pregnant women were primiparas. The ability of second trimester Doppler ultrasound to accurately diagnosed sFGR is 75.4%, missed diagnosis rate and the misdiagnosis rate were 24.6% and 10.5% respectively. The ROC curve indicated that the combination of AC discordance, EFW discordance, and small fetal UA blood flow was the best diagnostic indicator of sFGR in MCDA pregnancy with the AUC was 0.882 (95%CI, 0.839-0.926).ConclusionsSecond trimester Doppler and ultrasound measurements is an effective method for early prenatal diagnosis of sFGR. The combined indicator of AC discordance, EFW discordance, and the small fetal UA blood flow reaches highest diagnostic value.

Dataset Information

First trimester screening for pre-eclampsia and intrauterine growth restriction using three-dimensional Doppler angiography (SPIRIT): protocol for a multicentre prospective study in nulliparous pregnant women.

Publications

First trimester screening for pre-eclampsia and intrauterine growth restriction using three-dimensional Doppler angiography (SPIRIT): protocol for a multicentre prospective study in nulliparous pregnant women.

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