Abnormal Uterine Artery Doppler Research Articles

Effects of High-Dose Vitamin D Supplementation on Metabolic Status and Pregnancy Outcomes in Pregnant Women at Risk for Pre-Eclampsia

This study was designed to assess the beneficial effects of high-dose (cholecalciferol) vitamin D supplementation on metabolic profiles and pregnancy outcomes among pregnant women at risk for pre-eclampsia. This randomized double-blind placebo-controlled clinical trial was performed among 60 pregnant women at risk for pre-eclampsia according to abnormal uterine artery Doppler waveform. Subjects were randomly divided into 2 groups to receive 50 000 IU vitamin D supplements (n=30) or receive placebo (n=30) every 2 weeks from 20 to 32 weeks of gestation. Fasting blood samples were taken at baseline study and 12 weeks after the intervention to quantify relevant variables. Newborn's anthropometric measurements were determined. Pregnant women who received cholecalciferol supplements had significantly increased serum 25-hydroxyvitamin D concentrations (+17.92±2.28 vs. +0.27±3.19 ng/ml, p<0.001) compared with the placebo. The administration of cholecalciferol supplements, compared with the placebo, resulted in significant differences in serum insulin concentrations (+1.08±6.80 vs. +9.57±10.32 μIU/ml, p<0.001), homeostasis model of assessment-insulin resistance (HOMA-IR) (+0.19±1.47 vs. +2.10±2.67, p<0.001), homeostatic model assessment-beta cell function (HOMA-B) (+5.82±29.58 vs. +39.81±38.00, p<0.001) and quantitative insulin sensitivity check index (QUICKI) score (-0.009±0.03 vs. -0.04±0.03, p=0.004). Furthermore, cholecalciferol-supplemented pregnant women had increased HDL-cholesterol concentrations (+2.67 ± 8.83 vs. -3.23±7.76 mg/dl, p=0.008) compared with the placebo. Finally, cholecalciferol supplementation led to a significant rise in plasma total antioxidant capacity (TAC) concentrations (+79.00±136.69 vs. -66.91±176.02 mmol/l, p=0.001) compared with the placebo. Totally, the administration of cholecalciferol supplements among pregnant women at risk for pre-eclampsia for 12 weeks had favorable effects on insulin metabolism parameters, serum HDL-cholesterol, and plasma TAC concentrations.

Neurosonographic Assessment of the Corpus Callosum as Imaging Biomarker of Abnormal Neurodevelopment in Late-Onset Fetal Growth Restriction

Objective: To explore corpus callosum (CC) developmental differences by ultrasound in late-onset small fetuses compared with adequate for gestational age (AGA) controls. Study Design: Ninety four small (estimated fetal weight <10th centile) and 71 AGA fetuses were included. Small fetuses were further subdivided into fetal growth restriction (IUGR, n = 64) and small for gestational age (SGA, n = 30) based on poor perinatal outcome factors, that is, birth weight <3rd centile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler. The entire cohort was scanned to assess CC by transvaginal neurosonography obtaining axial, coronal and midsagittal images. CC length, thickness, total area and the areas after a subdivision in 7 portions were evaluated by semiautomatic software. Furthermore, the weekly average growth of the CC in each study group was calculated and compared. Results: Small fetuses showed significantly shorter (small fetuses: 0.49 vs. AGA: 0.52; p < 0.01) and smaller CC (1.83 vs. 2.03; p < 0.01) with smaller splenium (0.47 vs. 0.55; p < 0.01) compared to controls. The CC growth rate was also reduced when compared to controls. Changes were more prominent in small fetuses with abnormal cerebroplacental Doppler suggesting fetal growth restriction. Conclusions: Neurosonographic assessment of CC showed significantly altered callosal development, suggesting in-utero brain reorganization in small fetuses. This data support the potential value of CC assessment by US to monitor brain development in fetuses at risk.

Clinical utility of third-trimester uterine artery Doppler in the prediction of brain hemodynamic deterioration and adverse perinatal outcome in small-for-gestational-age fetuses.

To assess the clinical value of third-trimester uterine artery (UtA) Doppler ultrasound in the prediction of hemodynamic deterioration and adverse perinatal outcome in term small-for-gestational-age (SGA) fetuses. UtA Doppler parameters, cerebroplacental ratio (CPR) and fetal middle cerebral artery (MCA) pulsatility index (PI) were evaluated weekly, starting from the time of SGA diagnosis until 24 h before induction of labor, in a cohort of 327 SGA fetuses with normal umbilical artery PI (< 95th centile), delivered at > 37 weeks' gestation. Differences in the sequence of CPR and MCA-PI changes < 5th centile, between the group with normal UtA Doppler indices at diagnosis and those with abnormal UtA indices, were analyzed by survival analysis. In addition, the use of UtA Doppler value, alone or in combination with a brain Doppler scan before delivery, to predict the risk of Cesarean section, Cesarean section for non-reassuring fetal status (NRFS), neonatal acidosis and neonatal hospitalization was evaluated by logistic regression analysis, adjusted for gestational age at birth and birth-weight percentile. Abnormal UtA Doppler at diagnosis of SGA was associated with a higher risk of developing abnormal brain Doppler indices before induction of labor than in those with a normal UtA at diagnosis (62.7% vs 34.6%, respectively; P < 0.01). Compared to those with normal UtA Doppler indices, those with abnormal UtA Doppler findings were associated with a higher risk of intrapartum Cesarean section (52.2% vs 37.3%, respectively; P = 0.03), Cesarean section for NRFS (35.8% vs 23.1%, respectively; P = 0.03), neonatal acidosis (10.4% vs 7.7%, respectively; P = 0.47) and neonatal hospitalization (23.9% vs 16.5%, respectively; P = 0.16). Logistic regression analysis indicated that UtA Doppler findings were not significantly associated with adverse perinatal outcome independent of brain Doppler findings. UtA Doppler indices predict adverse perinatal outcome, but do not help to improve the predictive value of brain Doppler indices. However, at the time of SGA diagnosis they identify the subgroup of fetuses at highest risk of progression to abnormal brain Doppler findings.

Uterine and umbilical artery Doppler at 28 weeks for predicting adverse pregnancy outcomes in women with abnormal uterine artery Doppler findings in the early second trimester.

The objective of this study was to determine the contribution of uterine (UtA) and umbilical arteries (UA) Doppler examination at 28 weeks to predict adverse pregnancy outcomes in women who had increased resistance in UtA in the early second trimester. Women with UtA mean pulsatility index (PI) above the 95th centile at 19-22 weeks of gestation were offered a growth scan including Doppler examination of UtA and UA at 28 weeks. Adverse pregnancy outcomes included small for gestational age (SGA), defined as birth weight below the tenth centile, preeclampsia (PE) and early-onset PE (PE before 34 weeks). We studied 266 pregnant women with elevated PI in the UtAs in the second trimester and ultrasound reassessment at 28 weeks. UtA PI >95th centile at 28 weeks was associated with subsequent PE [odds ratio (OR): 10.0, 95% CI: 2.3-43.5], early-onset PE (OR: 57.7, 95% CI: 3.8-87.6) and SGA less than the tenth centile (OR: 5.5, 2.2-13.9). UA PI >95th centile at 28 weeks was not significantly associated with any adverse outcome. In women with abnormal UtA Doppler in the early second trimester scan, persistence of elevated UtA PI, but not abnormal UA PI, is associated with adverse pregnancy outcomes including PE, early-onset PE and SGA. © 2014 John Wiley & Sons, Ltd.

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Objectives We examined how mid-pregnancy placental growth factor (PlGF) levels and uterine artery Dopplers predict adverse outcomes in a cohort of high-risk pregnancies. Methods Forty-six patients with high risk pregnancies were recruited between June 2011 and August 2012 from the UCSD Placenta Clinic. Serum PlGF measurements (Alere Inc. Triage platform) were collected and uterine artery (UtA) pulsatility index (PI) and notching were assessed by velocimetry at approximately 24 weeks. Adverse outcomes included pre-eclampsia (PET), pre-term birth 34 weeks (PTB), and/or SGA newborn (birth weight 10%). Results The median gestational age at recruitment was 24.6 weeks. Delivery outcomes were collected from 43 (93.5%) patients. The median gestational age at delivery was 38.9 weeks (range 26.4–41.3 weeks) and 37.2% of patients had Cesarean sections. 32.6% had an adverse outcome (11.6% PET, 4.7% PTB, 25.6% SGA). 16.3% had abnormal UtA Dopplers (mean UtA PI > 1.6 and/or bilateral UtA notching), with no significantly increased risk for an adverse outcome (RR 2.625, 95% CI 0.80–8.6). PlGF measurements were collected from 38 (82.6%) patients. The median PlGF was 287 pg/mL, and 4 patients (10.5%) had a low PlGF ( 55 pg/mL). All patients with a low PlGF had an adverse outcome. The 10 patients (27.0%) with an abnormal PlGF and/or UtA Doppler had a significantly increased risk of an adverse outcome (RR 4.04, 95% CI 1.2–14.2). Adding PlGF measurements to UtA Doppler screening at mid-pregnancy increased the positive likelihood ratio of predicting an adverse outcome from 1.4 to 2.4, and yields a negative likelihood ratio of 0.14. Conclusions There is a significant association between low PlGF at mid-pregnancy and subsequent adverse outcomes. Adding PLGF measurements to UtA Doppler screening improves prediction of adverse outcomes by 71%, as these combined modalities test placental and maternal maladaptation respectively at mid-pregnancy. Disclosures K. Kjos: None. R. Ghashghaei: None. K. Klisser: None. D. Woelkers: None.

Umbilical Cord Blood CD33 and Erythropoietin Levels of Pregnants with Abnormal Doppler Waveforms and to Compare with Normal Pregnancies

Objective: In this study, we aimed to investigate umbilical cord blood CD33 and erythropoietin (EPO) levels of pregnants with abnormal umbilical and uterine artery doppler waveforms and to compare with normal pregnancies. Materials and Methods: Total 40 pregnant women were included in this study. Of these 40 women, while 20 patients had abnormal umbilical and uterine artery doppler waveforms, the other 20 patients had normal umbilical and uterine artery doppler waveforms. After the delivery, blood samples were taken from umbilical artery of double clemped umbilical cord for blood gas parameters, EPO and CD33 levels. Sociodemographic findings, antepartum, intrapartum test results, labor and delivery characteristics and newborn examination results were recorded. Blood gas parameters, EPO and CD33 levels between groups were analyzed. Mann-Whitney U test and t-test were used as statistical methods. Results: There were no differences between parity, gestational ages and newborn weights of the groups. Cord blood CD33 and EPO levels of group with abnormal umbilical and uterine artery doppler waveforms were significantly higher than group with normal umbilical and uterine artery doppler waveforms (p < 0.01). Conclusion: Pathology on doppler screen shows to us a connection between chronic hypoxemia and abnormal on doppler screen. Preference of high blood CD33 levels for cord blood transplantation especially during last years can also be used with preference of cord blood with abnormal doppler findings.

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Objectives The risk factors for both preeclampsia (PE) and gestational hypertension (GH) are limited. Recent data suggested that decreased circulating galectin-1 ( Gal-1), which binds to neuropirin-1, may have a pathologic role. Our aim was to evaluate whether serum level of Gal-1 in the second trimester could predict not only PE but also GH. Methods We prospectively recruited 1413 women at 19–25 weeks, and serum levels of soluble endoglin (sEng) and Gal-1 were measured in consecutive 72 normal pregnant women, and all women with PE ( n = 36) and GH ( n = 21). Results Gal-1 in women with subsequent onset of PE and GH was significantly lower than in controls, respectively (median [interquartile range]: 8.21 [6.05–10.11], 7.73 [6.41–10.56] vs. 9.84 [8.39–10.56]). High blood pressure (BP) (⩾120/80 mmHg), abnormal uterine artery Doppler, sEng ⩾2.5th percentile, and Gal-1 Conclusions Decreased levels of Gal-1 in the second trimester predict the subsequent onset of not only PE but also GH. Disclosures A. Ohkuchi: None. C. Hirashima: None. S. Nagayama: None. H. Suzuki: None. K. Takahashi: None. S. Matsubara: None. M. Suzuki: None.

The Role of Uterine and Umbilical Arterial Doppler in High-risk Pregnancy: A Prospective Observational Study from India.

AIMTo study the role of Doppler imaging in prediction of high-risk pregnancies and their outcomes.METHODS AND MATERIALThis prospective study in a setup of tertiary-level care center includes 500 high-risk pregnant women from rural and urban sectors and evaluates the predictive values of various Doppler indices.RESULTSOut of 500 patients, 110 patients had abnormal Doppler among them, 70 patients had abnormal uterine artery Doppler, and 50 patients had abnormal umbilical artery Doppler flow indices. In all, 10 patients had both umbilical artery and uterine artery abnormal Doppler indices. When uterine artery was abnormal (70 patients), 20 patients had preeclampsia, 10 patients had pregnancy-induced hypertension (PIH), and 25 patients had intrauterine growth restriction (IUGR). Systolic/diastolic (S/D) ratio and notch had sensitivity of 60% and positive predictive value of 33.3% and 37.5%, respectively. When umbilical artery was abnormal (50 patients), 10 had preeclampsia, 15 had PIH, and 15 had IUGR. S/D ratio had the highest positive predictive value of 40%; sensitivity is same for all. In uterine artery, combination of parameters had the best sensitivity of 80%, followed by notch and S/D ratio. In umbilical artery, combination of parameters, S/D ratio, and RI (resistance index) had sensitivity of 40%; specificity of all the indices was 91–96%. In all, 20 patients had bilateral notch, and among them 15 developed preeclampsia and 15 developed IUGR. When both uterine and umbilical artery Doppler were abnormal (10 patients), all patients had preeclampsia and IUGR.CONCLUSIONTherefore, Doppler study may be used for the prediction of preeclampsia and IUGR to reduce the maternal and perinatal morbidity and mortality.

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Objectives The objectives of the study were to analyze the influence of maternal demographic characteristics and uterine artery (UA) Doppler parameters on the occurrence of hypertension. Methods This prospective cohort study included 162 low-risk women with singleton pregnancies and no fetal diseases. Maternal demographic data and UA Doppler parameters were collected prospectively twice, first at 11–14 weeks of gestation and second at 20–24 weeks. The presence of an early diastolic notch in the waveform was noted, and the mean pulsatility and resistance indices were calculated during both intervals. Abnormal UA Doppler study was defined as the presence of bilateral uterine artery diastolic notches and/or a mean pulsatility index or resistance index above the 95th percentile for the gestational age. The primary outcome was the development of hypertension. Chi-square test, receiver operating characteristic curve, and multiple logistic regressions were used for statistical analyses. Results Fifteen (9.25%) women developed a hypertensive disorder. Significant independent prediction of hypertension was provided by mean PI, mean RI, and parity. Parity of two was associated with an increase in risk for the condition (OR 5.9, 95% CI 1.01–34.44, p p p Conclusions First-trimester screening combining maternal factors and UA Doppler indices is useful to predict hypertension in a routine care setting and could be investigated for application of targeted prophylactic strategies. Disclosures A.C. Marcolin: None. R.M. Scandiuzzi: None. S.M. Quintana: None. E.D. Moises: None. R.C. Cavalli: None. G. Duarte: None.

Abnormal uterine artery Doppler velocimetry predicts adverse outcomes in patients with abnormal analytes.

Our aim was to determine if uterine artery (UtA) Doppler studies would risk-stratify women with abnormal serum analytes on prenatal genetic screening into those at baseline and increased risk for preeclampsia and small-for-gestational age (SGA). This retrospective cohort study examined outcomes of patients with ⩾one abnormal analyte (PAPP-A<0.3, hCG>3.0, AFP>2.5, inhibin>2.0, or unconjugated estriol<0.3MoM). At approximately 24weeks, we assessed UtA pulsatility index (PI). Preeclampsia, preterm preeclampsia, SGA (birthweight (BW) <10%) and intrauterine growth restriction (IUGR) (BW<3%). We identified 132 patients with ⩾one abnormal analyte, UtA Doppler screening, and delivery outcomes. Twenty-four (18%) had an elevated UtA PI (PI>1.6); preeclampsia occurred in 16 (12%) and 26 (20%) delivered a SGA neonate. Abnormal UtA Doppler PI increased the likelihood of a composite outcome of preeclampsia or SGA from 27% to 71% (LR 6.48 (2.93, 14.30)); a negative UtA Doppler PI reduced the likelihood to 18% (LR 0.57 (0.42, 0.78)). Abnormal UtA Doppler PI increased the likelihood of a more severe composite outcome of preterm preeclampsia or IUGR from 11% to 39% (LR 5.49 (3.03, 9.97)); a negative UtA Doppler study reduced the likelihood to 4% (LR 0.35 (0.16, 0.80)). In patients with abnormal serum analytes, abnormal UtA Doppler PI is significantly associated with preeclampsia or SGA and improves the prediction of these adverse outcomes by 9-15-fold. Providers can incorporate UtA Doppler PI into an abbreviated surveillance regimen; they can be reassured that a normal study markedly decreases the risk of a severe early adverse outcome.

Uterine artery Doppler in high-risk pregnancies at 23-24 gestational weeks is of value in predicting adverse outcome of pregnancy and selecting cases for more intense surveillance.

To assess the role of the placental arterial Doppler examination at 23-24 gestational weeks for predicting adverse perinatal outcome in high-risk pregnancies. Retrospective register study. Skåne University Hospital in Malmö. Six hundred and forty-five women with high-risk pregnancies, without fetal malformations or chromosomal abnormalities. Placental (uterine and umbilical artery) Doppler ultrasound examination at 23-24 gestational weeks. Adverse perinatal outcomes including preeclampsia, small-for-gestational age newborns (smaller than 3rd percentile or smaller than the 10th percentile), preterm delivery (<34 weeks or <37 weeks of gestation at delivery), cesarean section, admission to the neonatal intensive care unit and intra-uterine fetal death. Abnormal uterine artery Doppler values were detected in 45% of this high-risk group but abnormal umbilical artery Doppler indices were only seen in 3.7%. Adverse perinatal outcome increased significantly with increasing placental vascular impedance (p < 0.0001). There were seven cases of intrauterine fetal death and in five the uterine artery Doppler values at 23-24 weeks were abnormal. A strong correlation between abnormal uterine artery Doppler and preeclampsia was present, but not with other forms of hypertensive disorder. Placental Doppler screening at 23-24 weeks can be used in detecting pregnancies at risk of adverse outcome and in selecting cases for more intense surveillance. A surveillance plan is proposed based on Doppler screening at 23-24 weeks of gestation.

OP08.07: Cerebroaortic ratio: a new index for the prediction of adverse perinatal outcome in term small‐for‐gestational age fetuses with normal umbilical artery Doppler

To evaluate the clinical value of cerebroaortic ratio in predicting the risk of Caesarean section (CS) non-reassuring fetal status (NRFS) in term small-for-gestational-age (SGA) fetuses with normal umbilical artery Doppler. Combination of middle cerebral artery (MCA) and Aortic Isthmus (AoI) pulsatility indices (PI) in the cerebroaortic ratio (CAR = MCA/AoI) was evaluated within 1 week before labour induction in a cohort of 106 singleton consecutive SGA fetuses with normal umbilical artery PI (<95th centile) delivered above 37 weeks. The contribution of CAR to predict CS for NRFS alone or in combination with MCA PI, cerebroplacental ratio (CPR), AoI PI and uterine artery Doppler was assessed by logistic regression and decision tree analysis. Individual Doppler abnormalities were significantly associated with the risk of CS for NRFS, with an odds ratio (OR) of 4.9 (95% confidence intervals (CI) 4.9-11.9, p < 0.001) for abnormal CAR (<0.48), OR of 4.2 (95% CI 1.6-10.7, p = 0.003) for abnormal MCA (<5th centile), OR of 3.9 (95% CI 1.6-9.8, p = 0.003) for abnormal CPR (<5th centile) and OR of 2.8 (95% CI 1.1-7.3, p = 0.03) for abnormal uterine artery Doppler (mean PI >95th centile). Decision tree analysis combining abnormalities in CAR, MCA, CPR, and uterine artery Doppler identified the CAR as the best individual predictor discriminating two groups with high (51.0%) and low risk (17.5%). Combination of brain Doppler and Aortic Isthmus in the cerebroaortic ratio better discriminates term SGA fetuses at risk of adverse perinatal outcome.

Prediction of preeclampsia and induced delivery at

BackgroundWomen with bilateral abnormal uterine artery Doppler velocimetry (UtADV) are at increased risk for an adverse pregnancy outcome. This study aimed to determine if additional assessment of midtrimester angiogenic factors improves the predictive accuracy of Doppler results for various outcome parameters.MethodsWomen with a bilateral abnormal UtADV, which was defined as a postsystolic incision and/or an increased pulsatility index greater than the 95th centile, and a singleton pregnancy were prospectively recruited between 19 + 0 and 26 + 6 weeks of gestation. Maternal serum levels of placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFLT-1) were measured with a fully automated immunoassay and their ratio was calculated.ResultsAngiogenic factors could predict the development of preeclampsia (PE), as well as induced delivery at <34 weeks of gestation, but failed to predict the development of normotensive intrauterine growth restriction. Twelve (24.0%) of the 50 recruited women developed PE. Nine of these patients had early-onset disease (<34 + 0 weeks). Six (12.0%) patients were delivered at <34 + 0 weeks. The most useful test results in the prediction of PE and induced delivery at <34 + 0 weeks were observed using the sFLT-1/PlGF >95th centile ratio with a sensitivity, specificity, positive predictive value, and negative predictive value (NPV) of 66.7%, 89.5%, 66.7%, and 89.5% for PE, and 85.7%, 86.1%, 50.1%, and 97.4% for induced delivery, respectively. Positive and negative likelihood ratios were 6.33 (95% CI 2.31–17.38) and 0.37 (95% CI 0.17–0.84) for PE, and 6.14 (95% CI 2.76–13.69) and 0.17 (0.03–1.02) for induced delivery, respectively. Corresponding odds ratios were 17.0 (95% CI 3.5–83.0) and 37.0 (95% CI 3.8–363.9), respectively.ConclusionsMeasurement of angiogenic factors improves the specificity of an abnormal UtADV for prediction of PE. Compared with prediction of PE an abnormal sFLT-1/PlGF ratio revealed higher sensitivity for prediction of induced delivery at <34 + 0 weeks. The NPV of 97% will help to reassure most patients with an abnormal UtADV and a normal sFLT-1/PlGF ratio.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2393-14-292) contains supplementary material, which is available to authorized users.

Proton Magnetic Resonance Spectroscopy Assessment of Fetal Brain Metabolism in Late-Onset ‘Small for Gestational Age' versus ‘Intrauterine Growth Restriction' Fetuses

Objectives: We used magnetic resonance spectroscopy (MRS) to evaluate brain metabolic differences in small fetuses near term as compared to appropriate for gestational age (AGA) fetuses. Study Design: 71 term small fetuses (estimated fetal weight <10th centile for gestational age with normal umbilical artery Doppler sonography) were subclassified as late intrauterine growth restriction (IUGR) (n = 50) or small for gestational age (SGA) (n = 21), and compared with 65 AGA fetuses. IUGR was defined by either abnormal middle cerebral artery, abnormal uterine artery Doppler sonography or estimated fetal weight <3rd centile. All participants underwent brain magnetic resonance imaging at 37 weeks of gestation, and single-voxel magnetic resonance spectra were obtained from the frontal lobe on a 3-tesla scanner. N-acetylaspartate (NAA)/choline (Cho), NAA/creatine (Cr) and Cho/Cr ratios were calculated and compared between cases and controls. The association of the metabolic ratios with the study groups was tested. Results: After MRS processing and applying quality control criteria, 31 spectra from late-onset IUGR, 11 from SGA and 30 from AGA fetuses were selected for further analysis. Both SGA and late-onset IUGR fetuses showed significantly reduced NAA/Cho levels when compared to AGA fetuses. This decrease followed a linear trend across the three clinical groups that were considered. Conclusions: Both SGA and late-onset IUGR fetuses showed differences in MRS brain metabolic ratios. The findings suggest that despite near-normal perinatal outcomes, SGA fetuses are not constitutionally small and may represent a form of growth disorder that needs to be clarified.

A trio of risk factors for the onset of preeclampsia in the second and early third trimesters.

We evaluated the biological interaction among mean blood pressure (MBP), uterine artery Doppler (UAD), and the soluble fms-like tyrosine kinase 1 (sFlt-1)/placental growth factor (PlGF) ratio for preeclampsia (PE) risk. A prospective cohort study. In 1239 pregnant women, MBP and UAD were measured at 16-23weeks of gestation, and plasma levels of the sFlt-1/PlGF ratio at 19-25weeks and 26-31weeks. A Cox proportional hazard model was used. Women with a low sFlt-1/PlGF ratio and either low BP or normal UAD were set as controls. The relative excess risk due to biological interaction (RERI) was calculated using the following equation: RERI=hazard ratio (HR) in women with high sFlt-1/PlGF and both high BP and abnormal UAD (group 3) - HR in women with both high BP and abnormal UAD alone (group 1) - HR in women with high sFlt-1/PlGF alone (group 2)+1. RERI⩾10 was considered to be strong. At 19-25weeks, the HR and 95% confidence intervals (CI) in group 1, group 2, and group 3 were 7.4 (3.1-17.4), 15.3 (4.5-52.2), and 107.0 (41.0-279), respectively, and the RERI for PE was 85.3. At 26-31weeks, the HR and 95% CI in each group were 8.3 (2.9-23.2), 7.5 (0.97-57.8), and 69.0 (18.5-256), respectively; the RERI for PE was 54.2. We found a trio of risk factors for the onset of PE in the second and early third trimesters: high BP, abnormal UAD, and high sFlt-1/PlGF ratio.

Aortic and carotid intima–media thickness in term small‐for‐gestational‐age newborns and relationship with prenatal signs of severity

To assess carotid and aortic intima-media thickness (IMT) in term small-for-gestational-age (SGA) newborns with and without prenatal signs of severity. This prospective study comprised 67 cases diagnosed prenatally and 134 normally grown newborns. Cases were subclassified into SGA with no signs of severity and those with signs of severity, defined as a birth weight below the 3(rd) percentile or abnormal uterine artery Doppler or cerebroplacental ratio. Blood pressure and vascular IMT were evaluated. SGA newborns showed a non-significant trend for higher values of blood pressure. IMT values were significantly increased in SGA newborns, with and without signs of severity, compared with controls. The magnitude of the increase was higher in SGA newborns with signs of severity. Vascular IMT was increased in SGA newborns, irrespective of the presence or absence of prenatal signs of severity. This finding challenges the notion of 'constitutionally small' SGA, and supports the premise that the majority of SGA newborns have true growth restriction and suffer fetal cardiovascular programming.

Association between reduced fetal movements at term and abnormal uterine artery Doppler indices

To evaluate the association between second-trimester uterine artery (UtA) Doppler pulsatility index (PI) with reduced fetal movements (RFM) and adverse pregnancy outcome at term. This was a retrospective cohort study of all singleton pregnancies referred for routine antenatal care at a fetal medicine unit over a 5-year period. UtA Doppler indices were obtained at the time of the routine anomaly scan between 19 and 23 weeks' gestation to assess the risk for pre-eclampsia. All episodes of RFM within 1 month of the expected date of delivery were recorded. Regression and sensitivity analyses were used to assess the relationship between UtA-PI with RFM, small-for-gestational-age (SGA) fetuses and stillbirth after 36 weeks' gestation. Overall, 17, 649 pregnancies were included in the analysis, of which 742 presented with RFM, 1494 gave birth to an SGA newborn and 53 were complicated by stillbirth after 36 weeks' gestation. Logistic regression analysis showed a significant and independent association between UtA-PI and RFM (odds ratio (OR), 5.03 (95% CI, 4.21-6.01); P < 0.001), SGA (OR 2.41 (95% CI, 2.09-2.79); P < 0.001) and stillbirth (OR 1.55 (95% CI, 1.21-1.98); P< 0.001). The association between UtA-PI and SGA was significantly stronger in women presenting with RFM than in the rest of the cohort (P < 0.001). Similarly the association between UtA-PI and RFM was significantly stronger in those pregnancies complicated by stillbirth (P < 0.001). Compared with normal pregnancies, those complicated by RFM, SGA and stillbirth at term had higher UtA-PI at 19-23 weeks' gestation. These findings support the assertion that RFM at term is independently related to placental dysfunction and subsequent risk for SGA and stillbirth.

Aspirin plus calcium supplementation to prevent superimposed preeclampsia: a randomized trial.

Preeclampsia is an important cause of maternal and perinatal morbidity and mortality. Previous studies have tested calcium supplementation and aspirin separately to reduce the incidence of preeclampsia but not the effects of combined supplementation. The objective of this study was to investigate the effectiveness of aspirin combined with calcium supplementation to prevent preeclampsia in women with chronic hypertension. A double-blind, placebo-controlled randomized clinical trial was carried out at the antenatal clinic of a large university hospital in São Paulo, SP, Brazil. A total of 49 women with chronic hypertension and abnormal uterine artery Doppler at 20-27 weeks gestation were randomly assigned to receive placebo (N = 26) or 100 mg aspirin plus 2 g calcium (N = 23) daily until delivery. The main outcome of this pilot study was development of superimposed preeclampsia. Secondary outcomes were fetal growth restriction and preterm birth. The rate of superimposed preeclampsia was 28.6% lower among women receiving aspirin plus calcium than in the placebo group (52.2 vs 73.1%, respectively, P=0.112). The rate of fetal growth restriction was reduced by 80.8% in the supplemented group (25 vs 4.8% in the placebo vs supplemented groups, respectively; P=0.073). The rate of preterm birth was 33.3% in both groups. The combined supplementation of aspirin and calcium starting at 20-27 weeks of gestation produced a nonsignificant decrease in the incidence of superimposed preeclampsia and fetal growth restriction in hypertensive women with abnormal uterine artery Doppler.

First‐trimester uterine artery Doppler and adverse pregnancy outcome: a meta‐analysis involving 55 974 women

To determine the accuracy with which uterine artery Doppler in the first trimester of pregnancy predicts pre-eclampsia and fetal growth restriction, particularly early-onset disease. We searched MEDLINE (1951-2012), EMBASE (1980-2012) and the Cochrane Library (2012) for relevant citations without language restrictions. Two reviewers independently selected studies that evaluated the accuracy of first-trimester uterine artery Doppler to predict adverse pregnancy outcome and performed data extraction to construct 2 × 2 tables. We synthesized sensitivity and specificity for various Doppler indices using a bivariate random-effects model. From 1866 citations, we identified 18 studies (55,974 women). The sensitivity and specificity of abnormal uterine artery flow velocity waveform (FVW) in the prediction of early-onset pre-eclampsia were 47.8% (95% CI: 39.0-56.8) and 92.1% (95% CI: 88.6-94.6), and in the prediction of early-onset fetal growth restriction were 39.2% (95% CI: 26.3-53.8) and 93.1% (95% CI: 90.6-95.0), respectively. The sensitivities for predicting any pre-eclampsia and fetal growth restriction were 26.4% (95% CI: 22.5-30.8) and 15.4% (95% CI: 12.4-18.9), respectively, and the specificities were 93.4% (95% CI: 90.4-95.5%) and 93.3% (95% CI: 90.9-95.1), respectively. The number needed to treat (NNT) with aspirin to prevent one case of early-onset pre-eclampsia fell from 1000 to 173 and from 2500 to 421 for background risks varying between 1% and 0.4%, respectively. First-trimester uterine artery Doppler is a useful tool for predicting early-onset pre-eclampsia, as well as other adverse pregnancy outcomes. Based on the NNT, abnormal uterine artery Doppler in low-risk women achieves a sufficiently high performance to justify aspirin prophylaxis in those who test positive.

Combination of plasma-soluble fms-like tyrosine kinase 1 and uterine artery Doppler for the prediction of preeclampsia in cases of elderly gravida

The aim of this study was to determine the predictive value of the combination of plasma-soluble fms-like tyrosine kinase 1 (sFlt-1) and uterine artery Doppler for the detection of preeclampsia in women of advanced age at 16-18 weeks of gestation and to identify associations between other pregnancy complications and abnormalities of these combined tests. The maternal plasma sFlt-1 level was measured, and uterine artery Doppler was performed at 16-18 weeks of gestation in 314 cases of elderly gravida. The main outcome was preeclampsia. Fourteen women (4.46%) developed preeclampsia. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of uterine artery Doppler combined with plasma sFlt-1 for preeclampsia prediction were 28.6, 95.7, 23.5 and 96.6%, respectively. For the prediction of early-onset preeclampsia, the sensitivity, specificity, PPV and NPV were 80, 95.8, 23.5 and 99.7%, respectively. Patients with abnormal uterine artery Doppler findings and an abnormal plasma s Flt-1 level (greater than 1724.5 pg ml(-1)) had a higher risk of preterm delivery (relative risk (RR)=3.38, 95% confidence interval (CI) 1.47-7.59), neonatal respiratory distress syndrome (RR=52.06, 95% CI 5.71-474.45) and perinatal death (RR=17.35, 95% CI 1.13-265.64). Our findings indicate that the combination of uterine artery Doppler and sFlt-1 level at 16-18 weeks of gestation in cases of elderly gravida has a high predictive value for early-onset preeclampsia, but not for overall preeclampsia. This combination test may be a useful early second trimester screening test for the prediction of early-onset preeclampsia in cases of elderly gravida.