Background: As by definition, mean arterial pressure equals the product of cardiac output (CO) and total vascular resistance (TPR), we hypothesized that, irrespective of thresholds to define hypertension, a CO-TPR imbalance might exist in first-trimester normotensive pregnancies with altered risks for adverse gestational outcomes. Methods: A standard protocol was used for automated blood pressure measurement combined with impedance cardiography assessment of CO and TPR (NICCOMO). First-trimester normotensive pregnant women were categorized into 3 groups relative to the reference 75th percentile (P75) of CO and TPR: (1) normal CO and TPR, (2) high CO, and (3) high TPR. These subgroups were compared at blood pressure thresholds 140/90, 130/85, and 130/80 mmHg. The gestational outcome was categorized after birth according to International Society for Studies of Hypertension in Pregnancy criteria. Results: Compared with pregnancies with normal CO and TPR (≤P75), women with high TPR at blood pressure <140/90 mmHg are at risk for developing gestational hypertension (odds ratio, 3.795 [1.321–10.904]; P <0.010), late-onset preeclampsia (odds ratio, 3.137 [1.060–9.287]; P <0.050), and neonates small for gestational age (odds ratio, 1.780 [1.056–2.998]; P <0.050). Conclusions: Cardiovascular imbalance can present in normotensive women in the first trimester and is associated with increased risks for adverse gestational outcomes. This study illustrates the relevance of CO and TPR assessments as an adjunct to blood pressure measurement and invites for further exploring their value in screening algorithms for gestational hypertensive disorders and/or small for gestational age.

Background: Pregnancies complicated with small for gestational age (SGA) neonates are reported with maternal circulatory maladaptations. Objectives: We aimed to understand the pathophysiology of the maternal circulation in normotensive SGA pregnancies and to point out the trimestral differences from those with appropriate-to-large (non-SGA [NGA]) neonates. Methods: An observational study was conducted in 3 trimestral cohorts of normotensive pregnancies, categorized after birth according to neonatal birth weight percentile (BW%) as SGA (BW% ≤10, n = 158) or NGA (BW% > 10, n = 1,038). Standardized electrocardiogram-Doppler ultrasound, impedance cardiography, and bio-impedance were used to assess the maternal heart, arteries, veins, and fluid. Results: Diastolic blood pressure and mean arterial pressure were not significantly different, unless in the third trimester. In SGA compared to NGA pregnancies, total peripheral resistance (TPR) was higher and total arterial compliance, cardiac output (CO), and total body water (TBW) were lower throughout pregnancy. Venous return-enhancing functions were activated. In NGA but not SGA pregnancies, a positive correlation was found between BW% and CO + TBW and a negative correlation between BW% and TPR. Conclusions: SGA pregnancies are characterized by lower maternal body fluid volume and CO, while normal blood pressures are maintained via increased TPR already from the first trimester onwards. Pregnancy-induced hemodynamic changes are superimposed on these characteristics.

BACKGROUND:To investigate the possibility of using maternal biophysical parameters only in screening for the different types of gestational hypertensive diseases.METHODS:A total of 969 pregnant women were randomly screened in first and second trimester, of which 8 developed Early-onset Preeclampsia, 29 Late-onset Preeclampsia, 35 Gestational Hypertension and 897 women had a normal outcome. An observational maternal hemodynamics assessment was done via standardized electrocardiogram-Doppler ultrasonography, Impedance Cardiography and bio-impedance, acquiring functional information on heart, arteries, veins and body fluid. Preliminary prediction models were developed to test the screening potential for early preeclampsia, late preeclampsia and gestational hypertension using a Partial Least Square Discriminant Analysis.RESULTS:A combined model using maternal characteristics with cardiovascular parameters in first and second trimester offers high screening performance with Area Under the Curve of 99,9% for Early-onset Preeclampsia, 95,3% for Late-onset Preeclampsia and 94% for Gestational Hypertension.CONCLUSIONS:Using biophysical parameters as fundament for a new prediction model, without the need of biochemical parameters, seems feasible. However, validation in a large prospective study will reveal its true potential.

A combined assessment of heart, arteries, veins, and body fluid content throughout pregnancy has not yet been reported. We hypothesized that a gradual aggravation of circulatory dysfunction exists from the latent to the clinical phase of gestational hypertensive disease (GHD), and that pathways are unique for preeclampsia with early onset < 34 wk (EPE) and late onset ≥ 34 wk (LPE), and gestational hypertension (GH). Women with singleton pregnancy and no known diseases were invited for a prospective, observational study and had standardized sphygmomanometric blood pressure measurement, bioimpedance body water spectrum analysis, impedance cardiography for cardiac and arterial assessment, and combined Doppler-ECG of hepatic and renal interlobar veins and uterine arteries. Outcome was categorized as uncomplicated (UP, n = 1,700), EPE ( n = 87), LPE ( n = 218), or GH ( n = 188). A linear mixed model for repeated measurements, corrected for age, parity, and body mass index, was employed in SAS 9.4 to analyze trimestral changes within and between groups. From the first to the third trimester, body water increased in all groups, and an increasing number of abnormal parameters relative to UP occurred in all GHD. First-trimester blood pressure and peripheral resistance were higher in GHD than UP, together with increased uterine flow resistance and extracellular water in EPE, and with lower heart rate and aorta flow velocity in LPE. An overall gestational rise of body water volumes coexists with a gradual worsening of cardiovascular dysfunction in GHD, of which pathophysiological pathways are unique for EPE, LPE, and GH, respectively.

Background Obesity is a major risk factor for cardiovascular diseases. In this study, we aimed to investigate the maternal circulatory differences during pregnancy between obese and normal weight women. Materials and methods The functioning of the maternal circulation (arteries, veins, heart and body fluid) was assessed by ECG-Doppler ultrasound, impedance cardiography (ICG) and bio-impedance during pregnancy in obese women (BMI >= 30 kg/m(2)) and normal weight, nonobese women (BMI 20-25 kg/m(2)). In this observational study, 232 assessments were performed in the obese group, whereas 919 assessments were performed in the nonobese group. Results Relative to nonobese women, the overall cardiovascular function in obese women during first and second trimester is consistent with a high volume/low-resistance circulation. In third trimester, cardiac output of obese women decreases from 9.2 (8.2-10.7) L/min to 8.5 (7.6-9.6) L/min (P = .037) whereas this is not true in the nonobese women (from 7.8 (7-8.5) L/min to 7.8 (6.8-8.9) L/min, P = .536). Simultaneously, the persistently lower peripheral vascular resistance in obese vs nonobese women disappears (880 (761-1060) dyn.sec/cm(5) vs 928 (780-1067). Conclusions The circulatory gestational adaptations between nonobese and obese women were generally similar. The findings in the third trimester suggest that a pregnancy in obese women start as a state of high volume/low resistance, gradually shifting to a volume overload with decrease of cardiac output and disappearance of low vascular resistance. This evolution makes obese women vulnerable for gestational hypertensive diseases.

Normal reference ranges of maternal impedance cardiography, bioimpedance spectrum analysis and venous combined ECG-Doppler sonography, as applied in the protocol for Maternal Cardiovascular Profiling published as10.17504/protocols.io.tffejjn

A maternal cardiovascular profile was assessed in every pregnant woman combining three non-invasive techniques to obtain information about arteries, veins, heart and body fluid content (Table 1). A standardized protocol was used as reported in previous studies, as enlisted below.

Objectives To evaluate body water volumes and cardiac output in each trimester of pregnancies complicated with hypertension and/or poor fetal growth, relative to uncomplicated pregnancy. Methods In this semi-longitudinal cohort study, a standardised non-invasive maternal hemodynamics assessment in first, second or third trimester was performed in 1068 women with uncomplicated pregnancy (UP), 75 with early onset (EPE) and 117 with late onset preeclampsia (LPE), 139 with gestational hypertension (GH), 129 with small for gestational age (SGA) neonates and 43 with essential hypertension (EH). Women with hypertension or SGA were included prior to onset of symptoms or at diagnosis of disease; 46% of women (758/1631) were assessed in ≥ 2 trimesters. Impedance cardiography and spectrum analysis were used to measure cardiac output, total body water (TBW), extracellular (ECW) and intracellular water (ICW). A linear mixed model was used for inter-trimestrial comparison of parity-, age- and BMI-corrected values within and between groups. Results For all pregnancies, TBW is higher in each consecutive trimester, mainly due to increasing fraction of ECW (ECW%). Compared to first trimester UP, ECW and ECW% are higher in EPE whereas TBW, ECW and ICW are lower in SGA. Compared to inter-trimestrial differences in UP, abnormal changes for body water volumes are observed in GH, EPE and LPE and for CO in EPE and LPE. Changes in EH are not different from UP. Conclusions This study is the first to show that concomitant gestational changes of ECW and CO are different from UP already in preclinical stages of pregnancies complicated with hypertension and/or poor fetal growth, except EH. This finding highlights the relevance of early gestational assessment of maternal body fluid status in pregnancies at risk for hypertension or poor fetal growth.

Abstract Venous compliance is known to differ between uncomplicated and preeclamptic pregnancies and can be assessed using Doppler ultrasonography. The purpose of this report is to address some of the interfering conditions in order to illustrate some of the limitations of venous Doppler sonography. Five case reports of pregnant women with important morbidity were selected: (1) auto-immune vasculitis, (2) polycystic renal dysplasia, (3) hydronephrosis, (4) HELLP syndrome and (5) morbid obesity. All cases had a Doppler flow examination of renal interlobar veins according to a standardized protocol and venous impedance index of left and right kidney was calculated. Results were plotted on a normal reference curve. Renal venous Doppler sonography may be hampered by maternal comorbidities or disease-specific conditions due to which it is difficult or even impossible to perform or interpret the Doppler signal.

Abstract Venous compliance is known to differ between uncomplicated and preeclamptic pregnancies and can be assessed using Doppler ultrasonography. The purpose of this report is to address some of the interfering conditions in order to illustrate some of the limitations of venous Doppler sonography. Five case reports of pregnant women with important morbidity were selected: (1) auto-immune vasculitis, (2) polycystic renal dysplasia, (3) hydronephrosis, (4) HELLP syndrome and (5) morbid obesity. All cases had a Doppler flow examination of renal interlobar veins according to a standardized protocol and venous impedance index of left and right kidney was calculated. Results were plotted on a normal reference curve. Renal venous Doppler sonography may be hampered by maternal comorbidities or disease-specific conditions due to which it is difficult or even impossible to perform or interpret the Doppler signal.

A standardized combined Doppler-electrocardiography technique was developed for measurement of the triphasic waveform characteristics in the internal jugular vein. Flow velocities at the A, X, V and Y peaks, the RR interval and the PA and RX times were measured. From these the venous impedance index ([X-A]/X) and the ratios PA/RR and RX/RR were calculated. Six measurements were performed at three different locations by two ultrasonographers in 21 randomly selected pregnant and non-pregnant women. Statistical models proved the feasibility and reproducibility of this technique, with the highest concordance correlation coefficients in the right distal internal vein. Bootstrapping revealed that repeating the measurements more than four times would not significantly enhance the precision of the estimated mean. Concordance correlation coefficients for the venous impedance index, PA time and PA/RR ratio were >0.63 for all three locations, proving their possible use in ongoing and future studies, analogous to previous studies in kidney and liver.

Introduction: Subclinical hypertension has been reported in the first trimester of future hypertensive patients compared to normotensive patients. However, in clinical practice today, a cut off of 140/90 mmHg is still used to discriminate normotension from hypertension during pregnancy. We aim to investigate the most appropriate threshold for early gestational blood pressure values, which allow discriminating pregnant women between those at low or at high risk for gestational hypertensive diseases.Methods: Singleton pregnancies were included. A standard protocol was used to measure systolic (SBP), diastolic (DBP) and mean arterial pressure (MAP) in supine and standing position, by mode of an oscillometric sphygmomanometer around 12 weeks and 20 weeks of gestation. After delivery, gestational outcome was categorized in normotensive pregnancies (NP) or gestational hypertensive disease (GHD). ROC analysis was used to define the early gestational blood pressure cut off value with best possible performance in predicting GHD. Mann–Whitney U tests at nominal level a <0.05 were performed using SPSS for intergroup comparison.Results: A total of 780 women were measured at 12 weeks. Of these, 433 pregnant women were reevaluated around 20 weeks. At 12 and 20 weeks, blood pressures in GHD were higher than in NP (Table 1).B4. Normal and abnormal blood pressures in early pregnancy: are we using the right cut off values?All authorsS. Vonck, J. Oben, A. S. Staelens, D. Lanssens, K. Tomsin & W. Gyselaershttps://doi.org/10.1080/14767058.2016.1234769Published online:29 September 2016Figure 1. (A) Boxplot NP versus GHD of DBP at 12 weeks, where redline indicates the threshold. (B) Boxplot UP versus GHD of DBP at 20 weeks with red line as threshold.Figure 1. (A) Boxplot NP versus GHD of DBP at 12 weeks, where redline indicates the threshold. (B) Boxplot UP versus GHD of DBP at 20 weeks with red line as threshold.Conclusions: Simple sphygmomanometric blood pressure measurements in standing position under standardized conditions at 12 weeks and 20 weeks has ≥96% negative predictive value for gestational hypertensive disease when DBP cut off is set at 81 and 78 mm Hg, respectively.

Introduction: Maternal cardiovascular adaptations are mandatory for a normal course of pregnancy. Disturbed adaptations predispose to gestational complications further in pregnancy such as hypertension disorders and/or fetal growth restriction. We aim to explore the early gestational cardiovascular profile in uncomplicated pregnancy, in gestational hypertensive disorders and isolated intra-uterine growth retardation.Methods: Cardiovascular assessments were done using a standard protocol with impedance cardiography (Niccomo, SonoSite, MedisMedinizinischeMesstechnik GmbH, Ilmenau, Germany) and bio-impedance (Maltron BIOSCAN 920-II; Maltron International LTD, Essex, UK) around 12 weeks of gestation. Only singleton pregnancies were included. After delivery, gestational outcome was categorized in essential hypertension (EH), gestational hypertension (GH), early preeclampsia (EPE), late preeclampsia (LPE), HELLP, intra-uterine growth retardation (IUGR; <10th percentile) or uncomplicated pregnancy (UP). Independent sampled t-tests at nominal level a < 0.05 were performed using SPSS for comparison between UP and other groups. Pathologies with <5 inclusions were not considered.Results: A total of 777 women were measured: 17 EH, 21 GH, 19 LPE, 74 IUGR and 643 UP. Three patients were excluded from the diagnosis HELLP (n = 1) and early preeclampsia (n = 2). Results are shown in Table 1. Parameters are marked " or # when measurements in pathology groups were higher (") or lower (#) then in UP. The combination of abnormal parameters is different between groups.Conclusions: Cardiovascular profiling around 12 weeks could be useful to specify the type of cardiovascular dysfunction before the onset of gestational hypertensive disorder and/or a growth restriction.

Objective: To address the question whether maternal venous abnormalities exist at the onset of, or develop during the course of pregnancy.Methods: We present five case reports of patients with early onset preeclampsia (EPE), late onset preeclampsia (LPE), gestational hypertension (GH), essential hypertension (EH) and an uncomplicated pregnancy (UP). Maternal renal and hepatic vein Doppler waves and maternal venous pulse transit times (VPTT) were assessed in early pregnancy and again shortly before delivery.Results: In all cases, maternal VPTT were normal in early pregnancy and changed to abnormal values in EPE and LPE, which was not true for UP and GH or EH.Conclusion: These observations support the view that venous hemodynamic dysfunction of preeclampsia (PE) develops during the course of pregnancy. Therefore, assessment of an individual's venous function for prediction of PE should be serial and longitudinal.

SummaryPosture changes may differ between types of hypertensive disease. The aim is to evaluate the orthostatic response of impedance cardiography (ICG) measurements in uncomplicated and hypertensive pregnancies. Measurements were performed in supine and standing position in 202 women: 41 uncomplicated pregnancies (UP), 59 gestational hypertension (GH), 35 early‐onset (EPE, < 34 weeks) and 67 late‐onset (LPE, ≥ 34 weeks) preeclampsia were assessed. Measurements were recorded of heart rate, blood pressure, aortic flow parameters, cardiac output, pre‐ejection period and left ventricular ejection time. Overall, orthostatic shifts were different between all groups (P < 0.001). UP was different from the hypertensive complicated gestations in the orthostatic change of the aortic acceleration. In contrast to patients with preeclampsia, those with GH had an increased blood pressure and Heather index, and stable pre‐ejection period after posture change. EPE differed from LPE by change in blood pressure and aortic flow parameters. In addition to static ICG‐measurements, orthostatic shifts improved group characterization from 57.4% to 65.8%. The orthostatic response is altered in hypertensive pregnancies. ICG measurements in the upright as well as during an orthostatic test might have the potential to improve the discriminative yield between hypertensive diseases in pregnancy.

This review summarizes current knowledge from experimental and clinical studies on renal function and venous hemodynamics in normal pregnancy, in gestational hypertension (GH) and in two types of preeclampsia: placental or early-onset preeclampsia (EPE) and maternal or late-onset (LPE) preeclampsia, presenting at <34 weeks and ≥34 weeks respectively. In addition, data from maternal venous Doppler studies are summarized, showing evidence for (1) the maternal circulation functioning closer to the upper limits of capacitance than in non-pregnant conditions, with intrinsic risks for volume overload, (2) abnormal venous Doppler measurements obtainable in preeclampsia, more pronounced in EPE than LPE, however not observed in GH, and (3) abnormal venous hemodynamic function installing gradually from first to third trimester within unique pathways of general circulatory deterioration in GH, EPE and LPE. These associations have important clinical implications in terms of screening, diagnosis, prevention and management of gestational hypertensive diseases. They invite for further hypothesis-driven research on the role of retrograde venous congestion in the etiology of preeclampsia-related organ dysfunctions and their absence in GH, and also challenge the generally accepted view of abnormal placentation as the primary cause of preeclampsia. The striking similarity between abnormal maternal venous Doppler flow patterns and those observed at the ductus venosus and other abdominal veins of the intra-uterine growth restricted fetus, also invites to explore the role of venous congestion in the intra-uterine programming of some adult diseases.

Background: It is well known that hepatic hemodynamics is an important physiologic mechanism in the regulation of cardiac output (CO). It has been reported that maternal cardiac output relates to neonatal weight at birth. Aims: In this study, we assessed the correlation between maternal hepatic vein Doppler flow parameters, cardiac output and neonatal birth weight.Methods: Healthy women with uncomplicated second or third trimester pregnancy attending the outpatient antenatal clinic of Ziekenhuis Oost-Limburg in Genk (Belgium), had a standardized combined electrocardiogram-Doppler ultrasound with Impedance Cardiography, for measurement of Hepatic Vein Impedance Index (HVI = [maximum velocity - minimum velocity]/maximum velocity), venous pulse transit time (VPTT = time interval between corresponding ECG and Doppler wave characteristics) and cardiac output (heart rate x stroke volume). After delivery, a population-specific birth weight chart, established from a cohort of 27000 neonates born in the index hospital, was used to define customized birth weight percentiles (BW%). Correlations between HVI, VPTT, CO and BW% were calculated using Spearman's rho, linear regression analysis and R-2 goodness of fit in SPSS 22.0.Results: A total of 73 women were included. There was a negative correlation between HVI and VPTT (rho = -0.719, p<0.001). Both HVI and VPTT correlated with CO (rho = -0.403, p<0.001 and rho=0.332, p<0.004 resp.) and with BW% (rho=-0.341, p<0.003 and rho=0.296, p<0.011 resp.)Conclusion: Our data illustrate that the known contribution of hepatic hemodynamics in the regulation of cardiac output is also true for women with uncomplicated pregnancies. Our study is the first to illustrate a potential link between maternal hepatic hemodynamics and neonatal birth weight. Whether this link is purely associative or whether hepatic vascular physiology has a direct impact on fetal growth is to be evaluated in more extensive clinical and experimental research.

OBJECTIVE:To determine intra-abdominal pressure (IAP) and to evaluate the reproducibility of IAP-measurements using the Foley Manometer Low Volume (FMLV) in term uncomplicated pregnancies before and after caesarean section (CS), relative to two different reference points and to non-pregnant values.DESIGN:Observational cohort study.SETTING:Secondary level referral center for feto-maternal medicine.POPULATION:Term uncomplicated pregnant women as the case-group and non-pregnant patients undergoing a laparoscopic assisted vaginal hysterectomy (LAVH) as control group.METHODS:IAP was measured in 23 term pregnant patients, before and after CS and in 27 women immediately after and 1 day after LAVH. The midaxillary line was used as zero-reference (IAPMAL) in all patients and in 13 CS and 13 LAVH patients, the symphysis pubis (IAPSP) was evaluated as additional zero-reference. Intraobserver correlation (ICC) was calculated for each zero-reference. Paired student's t-tests were performed to compare IAP values and Pearson's correlation was used to assess correlations between IAP and gestational variables.MAIN OUTCOME MEASURES:ICC before and after surgery, IAP before and after CS, IAP after CS and LAVH.RESULTS:The ICC for IAPMAL before CS was lower than after (0.71 versus 0.87). Both mean IAPMAL and IAPSP were significantly higher before CS than after: 14.0±2.6 mmHg versus 9.8±3.0 mmHg (p<0.0001) and 8.2±2.5 mmHg versus 3.5±1.9 mmHg (p = 0.010), respectively. After CS, IAP was not different from values measured in the LAVH-group.CONCLUSION:IAP-measurements using FMLV is reproducible in pregnant women. Before CS, IAP is increased in the range of intra-abdominal hypertension for non-pregnant individuals. IAP significantly decreases to normal values after delivery.

The nature of venous Doppler waves is highly variable. An additional electrocardiogram (ECG) improves the interpretation of venous Doppler wave characteristics and allows measurement of venous pulse transit time. The purpose of this study was to assess the reproducibility of ECG-guided repeated measurements of venous Doppler flow characteristics before and after sonographer training and the inter- and intra-observer variability. In four groups of 25 healthy women, venous Doppler flow measurements were performed at the level of the kidneys and liver according to a standardized protocol. Intra-observer Pearson correlation coefficients of the renal interlobar vein Doppler indices were ≥ 0.80 with the addition of the ECG, which are higher than the results of a former study. The inter-observer correlation between an experienced ultrasonographer and an inexperienced ultrasonographer improved from ≥ 0.71 to ≥ 0.91 after training. The correlation range of all parameters between two independent observers improved when values were based on repeated measures. The addition of an ECG to the Doppler image, training and repeated measurements are helpful in improving venous Doppler wave interpretation.

Objectives: To evaluate in early and late preeclampsia a correlation of maternal venous Doppler flow characteristics with biochemical parameters in maternal serum and urine, or with gestational outcome.Study design: In this observational cross-sectional study, renal interlobar vein impedance index (RIVI) was measured according to a standardised protocol for combined electrocardiogram-Doppler ultrasonography in 86 women with uncomplicated pregnancy, 78 women with late onset preeclampsia (>= 34 w) and 67 with early onset preeclampsia (<34 w). For each group, maternal age, pre-gestational BMI and parity were recorded together with birth weight and percentile. For both early onset and late onset preeclampsia, maternal serum was analysed for thrombocyte count and concentrations of creatinine, ASAT, ALAT and uric acid and 24 h urine collections were analysed for creatinine clearance and proteinuria (mg/24 h). A non-parametric Mann Whitney U-tests was performed for continuous data and a Fisher's exact tests for categorical data. Significant linear dependence between variables was identified using Pearson's correlation coefficient at nominal level a = 0.05.Results: Proteinuria was higher in early onset than in late onset preeclampsia (1756 mg [838-6116 mg] versus 877 mg [416-1696 mg], p < 0.001), and this was also true for RIVI in both left (0.45 [0.40-0.55] versus 0.41 [0.35-0.45], p = 0.001) and right kidney (0.45 [0.39-0.55] versus 0.38 [0.30-0.43],p < 0.001). In our data set, there was a significant correlation between proteinuria and RIVI of left (correlation coefficient = 0.172, p = 0.036) and right kidney (correlation coefficient = 0.218, p = 0.009) in late onset but not early onset preeclampsia.Conclusion: Maternal RIVI may correlate with proteinuria of late onset preeclampsia. (C) 2014 Elsevier Ireland Ltd. All rights reserved.