Periodontal Disease and Pregnancy Outcomes: Overview of Systematic Reviews.

Periodontal disease is very common during pregnancy. Although it has been linked to adverse pregnancy outcomes, systematic reviews have reached discrepant conclusions on these links. Therefore, we conducted a systematic overview of systematic reviews studying the association between periodontal disease and adverse pregnancy outcomes. We searched 6 online databases up to November 2016 and hand-searched references and citations of eligible papers. Systematic reviews of studies comparing pregnancy outcomes among women with and without periodontal disease were eligible for inclusion. Primary outcomes were maternal mortality, preterm birth, and perinatal mortality. Two reviewers extracted data and assessed risk of bias of individual systematic reviews. Findings are described in tabular and narrative form. Twenty-three systematic reviews (including between 3 and 45 studies) were included. None reported the association between periodontal disease and maternal or perinatal mortality. Systematic reviews with the lowest risk of bias consistently demonstrated positive associations between periodontal disease and preterm birth (relative risk, 1.6; 95% confidence interval, 1.3 to 2.0; 17 studies, 6,741 participants), low birth weight (LBW; relative risk, 1.7; 95% CI, 1.3 to 2.1; 10 studies, 5,693 participants), preeclampsia (odds ratio, 2.2; 95% CI, 1.4 to 3.4; 15 studies, 5,111 participants), and preterm LBW (relative risk 3.4; 95% CI, 1.3 to 8.8; 4 studies, 2,263 participants). Based on these figures, estimated population-attributable fractions for periodontal disease were 5% to 38% for preterm birth, 6% to 41% for LBW, and 10% to 55% for preeclampsia. In terms of limitations, as several primary studies did not adjust for confounding, meta-analyses may have overestimated the strength of the associations under study. Due to substantial overlap in included primary studies, we could not aggregate results across reviews. Consistent evidence from systematic reviews with low risk of bias indicates that pregnant women with periodontal disease are at increased risk of developing preeclampsia and delivering a preterm and/or LBW baby (PROSPERO: CRD42015030132). Knowledge Transfer Statement: This study highlights that periodontal disease is an important risk factor for several common adverse pregnancy outcomes. Clinicians should be aware of this link to guide risk selection. Research is needed to develop novel preventive and treatment strategies.

Maternal venous Doppler characteristics are abnormal in pre-eclampsia but not in gestational hypertension.

OBJECTIVE: To compare functional characteristics of maternal thoraco-abdominal arteries and veins in proteinuric and non-proteinuric hypertension in pregnancy. METHODS: This retrospective study included women with singleton pregnancies during the third trimester, which were either uncomplicated or complicated with different clinical types of hypertension: non-proteinuric gestational hypertension (GH), early-onset pre-eclampsia (PE) diagnosed < 34 weeks or late-onset PE diagnosed ≥ 34 weeks. Demographic maternal and neonatal data were recorded, together with maternal serum and urine analytes. All women underwent standardized automated blood-pressure measurement, together with non-invasive impedance cardiography (ICG), for measurement of cardiac output (CO), aortic flow velocity index (VI) and aortic flow acceleration index (ACI). A standardized combined Doppler-electrocardiography assessment of maternal venous hemodynamics was performed to measure renal interlobar vein impedance index (RIVI), hepatic vein impedance index (HVI) and venous pulse transit time (VPTT) in liver and kidneys. Finally, resistance index (RI), pulsatility index (PI) and arterial pulse transit time (APTT) were measured in the uterine arcuate arteries. Mann-Whitney U-tests and Fisher's exact tests were used for intergroup comparisons, and linear dependence between variables was assessed using Pearson's correlation coefficient (r). RESULTS: A total of 150 pregnancies were evaluated: 22 with uncomplicated pregnancy, 41 GH, 31 early PE and 56 late PE. Aortic VI and ACI were lower in GH, early PE and late PE than in uncomplicated pregnancy. Both early PE and late PE differed from GH by having shorter APTT in the uterine arcuate arteries and higher RIVI. Hemodynamic abnormalities were most pronounced in early PE, during which uterine arcuate artery RI was higher and VPTT in kidneys was shorter than in late PE. There was a significant correlation between degree of proteinuria and RIVI for the left (r = 0.381) and right (r = 0.347) kidney in late PE, but this was not true for early PE. CONCLUSIONS: There is a gradient of worsening arterial and venous hemodynamic abnormalities from GH to late PE and then to early PE. Venous hemodynamic abnormalities are present only in PE, with a linear correlation between proteinuria and RIVI in late PE. The role of the maternal venous compartment in the pathophysiology and etiology of PE-related symptoms may be much more important than considered at present.

Validation of 3D power Doppler and VOCAL software in the sonographic assessment of hepatic venous flow.

UNLABELLED:  AIM: To evaluate the reproducibility of three-dimensional power Doppler ultrasonography (3D-PDU) and the repeatability of Virtual Organ Computer-aided AnaLysis (VOCAL) software in the assessment of hepatic venous flow in ten healthy non-pregnant individuals. METHODS: Visualization of hepatic veins was performed using both intra- and subhepatic approaches; These examinations were repeated twice. Vascular indices were obtained for each examination in a reference point using both small and large volume samples (3 times per type of volume sample). Intraclass Correlation Coefficients and Pearson's Product-Moment Correlation Coefficient were calculated to assess reproducibility and repeatability, respectively. RESULTS: Intraclass Correlation Coefficients were more than 0.60 in small volumes, but variable in large volumes for both approaches. However, re-identification of the reference point failed in 30% using the subhepatic approach. Repeatability was high for all VOCAL analyses (Pearson's Product-Moment Correlation Coefficient > 0.98). CONCLUSIONS: These results indicate reliable use of intrahepatic small volume samples in clinical application and invite to explore the role of this technology in the assessment of hepatic venous hemodynamics.

The maternal venous system: the ugly duckling of obstetrics.

In pregnancy, both maternal vascular tone and cardiac function are considered key players to reach a normal outcome for both mother and child. This complex story of maternal hemodynamics is intensely discussed in current scientific literature, however the role of the maternal veins has been strongly underestimated. We developed and evaluated a set of measurable objective parameters which give an indication of venous function, i.e. the venous impedance index and the venous pulse transit time. These parameters turned out to be subject to changes throughout normal pregnancy and in preeclampsia enabling their use in gestational hemodynamic -studies. From our studies, we concluded that the venous system is a crucial determinant of cardiac output, which can be estimated by impedance cardiography. The introduction of these non-invasive techniques in obstetrics enables profiling the maternal cardiovascular system, integrating both arteries and veins, as well as maternal cardiac -function. Studying the cascade of cardiovascular changes throughout pregnancy using such non-invasive, easily applicable, and highly accessible methods opens perspectives to introduce this maternal cardiovascular profile in several -clinical settings. The early discrimination between low and high risk patients, together with the classification of different pregnancy disorders may help guiding the clinical work-up of the pregnant population regarding both prevention and treatment, as well as follow-up. We illustrate that the venous system, being an "ugly duckling" at first neglected by the medical world, transforms and matures into a beautiful swan, accepted by the obstetric world. We are confident that this is the beginning of many other studies regarding the maternal venous system, an important piece of the gestational physiology puzzle.

Impedance cardiography in uncomplicated pregnancy and pre-eclampsia: a reliability study.

It has been reported that cardiac contractility is altered in pre-eclampsia compared with normal pregnancy. Because of the non-invasive nature of impedance cardiography (ICG), this method is gaining popularity in the obstetric field. We assessed the reliability of ICG measurements in uncomplicated 3rd trimester pregnancies (UP) and pre-eclamptic pregnancies (PE). ICG measurements were recorded before and after three position changes, and this examination was done twice (session 1 and 2) per subject. For each of the 22 haemodynamic parameters, inter- and intrasession Pearson's correlation coefficients (PCC) were calculated for mean values of 30 measurements per position per subject. PCC was consistently ≥ 0.80 for contractility parameters 'acceleration-', 'velocity-' and 'heather-index' in both UP and PE. These data illustrate that correlation between repeated ICG measurements of cardiac contractility is high under standardised conditions, and that ICG may be useful to study changes of cardiac contractility in pregnancy.

Time interval between maternal electrocardiogram and venous Doppler waves in normal pregnancy and preeclampsia: a pilot study.

PURPOSE: To evaluate the time interval between maternal electrocardiogram (ECG) and venous Doppler waves at different stages of uncomplicated pregnancy (UP) and in preeclampsia (PE). MATERIALS AND METHODS: Cross-sectional pilot study in 40 uncomplicated singleton pregnancies, categorized in four groups of ten according to gestational age: 10 - 14 weeks (UP1), 18 - 23 weeks (UP2), 28 - 33 weeks (UP3) and ≥ 37 weeks (UP4) of gestation. A fifth group of ten women with PE was also included. A Doppler flow examination at the level of renal interlobar veins (RIV) and hepatic veins (HV) was performed according to a standard protocol, in association with a maternal ECG. The time interval between the ECG P-wave and the corresponding A-deflection of the venous Doppler waves was measured (PA), and expressed relative to the duration of the cardiac cycle (RR), and labeled PA/RR. RESULTS: In hepatic veins, the PA/RR is longer in UP 4 than in UP 1 (0.48 ± 0.15 versus 0.29 ± 0.09, p ≤ 0.001). When all UP groups were compared, the PA/RR increased gradually with gestational age. In PE, the HV PA/RR is shorter than in UP 3 (0.25 ± 0.09 versus 0.42 ± 0.14, p < 0.01) and this difference persisted under anti-hypertensive treatment (0.28 ± 0.06 versus 0.42 ± 0.14, p ≤ 0.01, n = 6). Similar results were found in both kidneys. In UP 1 but not in UP 3 or UP 4, the HV PA/RR is shorter in the liver than in the left and right kidney (0.29 ± 0.09 versus 0.38 ± 0.12, p < 0.01, and versus 0.36 ± 0.09, p ≤ 0.01). CONCLUSION: The PA/RR is organ-specific and gestation-dependent, and is considered to relate to venous vascular tone and/or intravascular filling. Increased values at advanced gestational stages are consistent with known features of maternal cardiovascular adaptation. Shorter values in preeclampsia are consistent with maternal cardiovascular maladaptation mechanisms. Our pilot study invites more research of the relevance of the time interval between maternal ECG and venous Doppler waves as a new parameter for studying the gestational cardiovascular (patho)physiology of the maternal venous compartment by duplex sonography.

OS095. Impedance cardiography: A straightforward and reliable tool to evaluate differences of cardiac reflex response between normal pregnancy and pre-eclampsia.

INTRODUCTION: Reflex responses of cardiac cycle time intervals (CCTI) can be measured by echocardiography, and are reported to differ between uneventful pregnancy (UP) and pre-eclampsia (PE). It is unknown whether impedance cardiography (ICG) is a useful method to measure CCTI during pregnancy. OBJECTIVES: ICG measurements of CCTI before and after orthostatic challenge are evaluated in UP and in the clinical phase of PE. METHODS: Examinations were performed twice in 16 UP (30-36 weeks), and once in 30 early PE (EPE, <34 weeks) and in 32 late PE (LPE, ⩾34 weeks). A 3rd generation ICG device using a 4 electrode arrangement (NICCOMO, Medis, Germany) was used to measure CCTI in supine position and after moving to upright position. The pre-ejection period (PEP) is the time-interval between ventricular depolarisation and start of aortic flow. The left ventricular ejection time (LVET) is the time-interval between opening and closing of the aortic valve. Diastolic time (DT) is heart period duration - (PEP+LVET). Orthostatic-induced changes from supine to upright position (cardiac reflex response or CRR) were evaluated using One-sample Wilcoxon Signed Rank Tests. All CRRs in EPE and LPE were compared to UP using Mann-Whitney U tests. Data are represented as medians (interquartile ranges). RESULTS: Maternal age was comparable between all groups [29 (26-32) years; p⩾0.47]. Gestational age was comparable between both early [31 (28-32) vs 31 (27-33) weeks] and late [37 (36-39) vs 38 (36-39) weeks] third trimester UP and PE [p⩾0.38]. Pre-gestational BMI was higher in EPE compared to UP [26 (24-32) vs 23 (21-24); p<0.01]. This was not true for LPE [25 (23-28); p=0.06]. Birth weight percentiles were lower in both EPE and LPE compared to UP [UP: 44 (38-78), EPE: 18 (5-28), LPE: 31 (18-59); p<0.05], and also lower in EPE compared to LPE [p=0.03]. CRRs within each group are shown in Table 1. The CRRs of PEP were significantly different between UP and both EPE and LPE [p⩽0.01], due to orthostatic-induced increase in PE but not in UP . CONCLUSION: Our study confirms that orthostasis does not change PEP in UP but induces a significant increase of PEP in PE. The increased reflex-induced duration of isovolumetric contraction time can be explained by a decreased left ventricular performance in the clinical phase of PE as compared to UP. ICG turns out to be a straightforward and useful method to evaluate these hemodynamic features.

PP018 Cardiac reflex responses measured by impedance cardiography are different between low and high cardiac output pre-eclampsia.

INTRODUCTION: Pre-eclampsia (PE) has been categorised into subtypes depending on low or high cardiac output (CO) states. Are cardiac reflex responses (CRR) different between these two subtypes? OBJECTIVES: Impedance cardiography (ICG) measurements of cardiac cycle time intervals (CCTI) before and after orthostatic challenge are evaluated in the clinical phase of PE with low and high CO (LPE and HPE, respectively). METHODS: Examinations were performed in 25 LPE (CO⩽7l/min) and 16 HPE (CO⩾9l/min). A third generation ICG device using a four electrode arrangement (NICCOMO, Medis, Germany) was used to measure CCTI in supine position and after moving to upright position. The pre-ejection period (PEP) is the time-interval between ventricular depolarisation and start of aortic flow. The left ventricular ejection time (LVET) is the time-interval between opening and closing of the aortic valve. Systolic time ratio (STR) is PEP/LVET. Diastolic time (DT) is the heart period duration - (PEP+LVET). Time intervals were expressed as a percentage of the heart period duration, i.e. PEPi, LVETi and DTi. Orthostatic-induced changes from supine to upright position (cardiac reflex response or CRR) were evaluated using One-sample Wilcoxon Signed Rank Tests. All CRRs were compared between LPE and HPE using Mann-Whitney U tests. Data are presented as medians (interquartile ranges). RESULTS: Maternal age was comparable between LPE and HPE [29 (26-34) vs 28 (26-33) years; p=0.55]. This was also true for gestational age [34 (30-38) vs 36 (31-39) weeks; p=0.50], and pre-gestational BMI [24 (22-30) vs 25 (24-32); p=0.21]. Birth weight percentiles were lower in LPE compared to HPE [18 (5-31) vs 44 (18-83); p<0.01]. CRRs within each group are shown in Table 1. CRRs of PEP, PEPi and DT were different between LPE and HPE [p⩽0.04], whereas changes in LVET, LVETi, DTi and STR were not [p⩾0.09]. Reflex-induced changes of diastolic blood pressure and heart rate (HR) were not significantly different between LPE and HPE [p⩾0.41]. CONCLUSION: Orthostasis does not change PEP in HPE, but induces a significant increase of PEP in LPE. PEP is dependent on HR, preload, afterload and sympathetic activity. There is no difference in the reflex-induced response of HR, DBP (∼afterload), and STR (∼sympathetic activity) between the two groups. This suggests that the orthostatic-induced change in the isovolumetric contraction time in LPE is preload-induced. Our observations suggest that hemodynamic background mechanisms behind LPE and HPE are different, and support the view that these subtypes are two different clinical entities.

Role of dysfunctional maternal venous hemodynamics in the pathophysiology of pre-eclampsia: a review.

The venous compartment has an important function in regulation and control of cardiac output. Abnormalities of cardiac output have been found in early gestational stages of both early- and late-onset pre-eclampsia. The venous compartment also maintains the balance between circulating and non-circulating blood volumes and regulates the amount of reserve blood stored in the splanchnic venous bed. It is well known that adaptive regulation of maternal blood volume is disturbed in pre-eclampsia. Abnormal venous hemodynamics and venous congestion are responsible for secondary dysfunction of several organs, such as the kidneys in cardiorenal syndrome and the liver in cardiac cirrhosis. Renal and liver dysfunctions are among the most relevant clinical features of pre-eclampsia. Doppler sonography studies have shown that the maternal venous compartment is subject to gestational adaptation, and that blood flow characteristics at the level of renal interlobar and hepatic veins are different in pre-eclampsia compared with uncomplicated pregnancy. In comparison to late-onset pre-eclampsia, in early-onset pre-eclampsia venous Doppler flow abnormalities are more prominent and present up to weeks before clinical symptoms. This paper reviews the growing evidence that dysfunction of maternal venous hemodynamics is part of the pathophysiology of pre-eclampsia and may perhaps be more important than is currently considered. Doppler sonography is a safe and easily performed method with which to study maternal venous hemodynamics. Therefore, exploring the role of maternal venous hemodynamics using Doppler sonography is an exciting new research topic for those who are interested in cardiovascular background mechanisms, as well as prediction and clinical work-up of pre-eclampsia.

Maternal renal interlobar vein impedance index is higher in early- than in late-onset pre-eclampsia.

OBJECTIVES: To test the hypothesis that Doppler characteristics of maternal renal interlobar veins (RIV) are different between pregnancies affected by early-onset pre-eclampsia (EP) and those affected by late-onset pre-eclampsia (LP). METHODS: A gestational age of 34 weeks was considered to differentiate EP from LP. All women had a renal duplex scan according to a standard protocol, with known intraobserver correlation coefficient (0.88). Maximum (Vmax) and minimum (Vmin) RIV velocities were measured on two occasions (between 28 and 32 and between 34 and 37 weeks) in 18 women with uncomplicated pregnancy (UP). In women with EP (n = 32) or LP (n = 41), these variables were measured once, within 3 days following hospital admission. Delta velocity (DeltaV) was calculated as Vmax - Vmin and the RIV impedance index (RIVI) was calculated as DeltaV/Vmax. Data on neonatal outcome and maternal renal function were obtained for UP and those with EP and LP, and group-specific means +/- SD were calculated and compared. RESULTS: Compared with UP, the RIVI of both left and right kidneys was higher in those with EP (0.49 +/- 0.13 vs. 0.36 +/- 0.04, P = 0.0001, and 0.46 +/- 0.15 vs. 0.33 +/- 0.04, P = 0.0008) and in those with LP (0.41 +/- 0.07 vs. 0.37 +/- 0.06, P = 0.04, and 0.38 +/- 0.12 vs. 0.30 +/- 0.05, P = 0.009). RIVI was higher in pregnancies with EP than in those with LP (P < or = 0.01), and this difference was associated with lower median birth-weight percentiles (22.5 (interquartile range (IQR), 15-35) vs. 40.0 (IQR, 12-55), P = 0.01), higher maternal serum uric acid concentrations (419 +/- 84 vs. 374 +/- 85 micromol/L, P = 0.03) and higher proteinuria (4131 +/- 3885 vs. 1190 +/- 1133 mg/24 h, P < 0.0001). CONCLUSION: Maternal vascular maladaption in pre-eclampsia is associated with abnormal Doppler findings in the venous compartment. RIVI is higher in EP than in LP pregnancies and this is associated with lower birth-weight percentiles and higher proteinuria.