First-Trimester Normotension Is a Weak Indicator of Normal Maternal Cardiovascular Function.

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.

Obesity in pregnancy causes a volume overload in third trimester.

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/m2 ) and normal weight, nonobese women (BMI 20-25 kg/m2 ). 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/cm5 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.

Development of a biophysical screening model for gestational hypertensive diseases.

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.

Low Volume Circulation in Normotensive Women Pregnant with Neonates 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.

Gestational hypertensive disorders show unique patterns of circulatory deterioration with ongoing pregnancy.

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.

Body fluid volume homeostasis is abnormal in pregnancies complicated with hypertension and/or poor fetal growth.

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.

Feasibility of Combined Doppler-ECG Assessment of Internal Jugular Veins.

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.

Risk of adverse pregnancy outcomes in women with periodontal disease and the effectiveness of interventions in decreasing this risk: protocol for systematic overview of systematic reviews.

BACKGROUND: Periodontal disease is an inflammatory disease of the tissues supporting the teeth. Women who have periodontal disease while pregnant may be at risk of adverse pregnancy outcomes. Although the association between periodontal disease and adverse pregnancy outcomes has been addressed in a considerable number of systematic reviews and meta-analyses, there are important differences in the conclusions of these reviews. Systematic reviews assessing the effectivity of various therapeutic interventions to treat periodontal disease during pregnancy to try and reduce adverse pregnancy outcomes have also arrived at different conclusions. We aim to provide a systematic overview of systematic reviews comparing the frequency of adverse pregnancy outcomes between women with and without periodontal disease and/or evaluating the effect of preventive and therapeutic interventions for periodontal disease before or during pregnancy on adverse pregnancy outcomes. METHODS: We will include systematic reviews reporting on studies comparing adverse pregnancy outcomes: (i) between women with or without periodontal disease before (<6 months) or during pregnancy and/or (ii) according to preventive or therapeutic interventions for periodontal disease. Eligible interventions include (combinations of) the following: oral hygiene education, use of antibiotics, subgingival scaling, and root planing. For preventive and/or therapeutic reviews, the following comparisons will be considered: no intervention, a placebo intervention, or an alternative intervention. Our primary adverse pregnancy outcomes of interests are maternal mortality, preterm delivery, and perinatal mortality. Two reviewers will independently identify eligible published and unpublished systematic reviews from six electronic databases and using hand searching of reference lists and citations. Data items extracted from included systematic reviews are based on the Cochrane Effective Practice and Organization of Care checklist and the preferred reporting items for systematic review and meta-analysis (PRISMA) statement. In our narrative data synthesis, we will consider risk of bias of individual reviews, focusing mainly on the conclusions of the highest quality reviews using the assessment of multiple systematic reviews (AMSTAR) checklist. Disagreements during search, selection, data extraction, and risk of bias assessment will be resolved through discussion and/or consultation of a third reviewer. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015030132.

Type-specific orthostatic hemodynamic response of hypertensive diseases in pregnancy.

Posture 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.

Maternal venous hemodynamics assessment for prediction of preeclampsia should be longitudinal.

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.