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Introduction Pre-eclampsia (PE) is associated with significant maternal and perinatal mortality and morbidity. Twin pregnancy is at greater risk than singleton for developing PE. It is, however, unclear which risk factors are most strongly associated with the development of PE in a twin gestation. Objectives To establish the risk factors for PE in twin pregnancies and investigate the perinatal outcomes in these complicated pregnancies. Methods This was a cohort study of twin pregnancies cared for at St George’s University Hospital (SGH), London. Maternal, foetal and neonatal data were obtained from the hospital’s computerised database and maternity records. The diagnosis of PE was made following the ISSHP diagnostic criteria. Maternal risk factors were assessed at booking. Pregnancies complicated by aneuploidy, major structural abnormalities, miscarriage and those ending in termination were excluded from the analysis. The statistical analysis was performed using Mann–Whitney U and Chi-square tests for the comparison between the pregnancies that developed PE and those that did not. Logistic regression analyses were performed to identify and adjust for potential confounders. Results A total of 1250 twin pregnancies (2500 fetuses) were included in the analysis [284 (22.72%) were monochorionic and 966 (77.28%) dichorionic]. Of these, 120 (9.6%) were complicated by PE. While univariable analysis found that nulliparity (OR = 0.1.69, 95%CI = 1.13–2.52, p = 0.010), maternal age ⩾40 years (OR = 0.47, 95%CI = 0.27–0.81, p = 0.006), body mass index (BMI) (OR = 1.05, 95%CI = 1.02–1.09, p = 0.004) and chronic hypertension (OR = 3.02, 95%CI = 1.45–6.30, p = 0.003) were significant risk factors for the development of PE, multivariable logistic regression analysis found that only BMI (aOR = 1.06, 95%CI = 1.02–1.10, p = 0.002), chronic hypertension (aOR = 3.13, 95%CI = 1.44–6.79, p = 0.004), and nulliparity (aOR = 1.85, 95%CI = 1.19–2.89, p = 0.007) were independent risk factors for PE in a twin gestation. Chorionicity was not associated with the risk of developing PE ( p = 0.772) compared to normotensive twin pregnancies. Those complicated by PE were more likely to have a number of adverse pregnancy outcomes, including induction of labour (66% vs 47.9%, p = 0.017), emergency Caesarean delivery (38.3% vs 19.4%, p < 0.001), greater blood loss at delivery (725 ml vs 600 ml, p = 0.012), postpartum haemorrhage ⩾500 ml (67.5% vs 54.5%, p = 0.006), lower gestational age at delivery (35 + 6 weeks vs 36 + 5 weeks, p = 0.033), neonatal unit admission (33.8% vs 26.1%, p = 0.011) and lower birth weight (2245 g vs 2420 g, p = 0.001). The differences in stillbirth (0.8% vs 1.8%, p = 0.273) and perinatal mortality (0% vs 0.8%, p = 0.164) were not statistically significant. Conclusions Nulliparity, increased maternal BMI and chronic hypertension were risk factors for PE in twin pregnancies, while monochorionicity, ethnicity and assisted reproductive techniques were not. In common with singleton pregnancies, twin pregnancies complicated by PE are at greater risk of an adverse pregnancy outcome. Prediction models for PE in twin pregnancies are likely to include risk factors that differ from those used in singleton pregnancy models. [ABSTRACT FROM AUTHOR]

Objective While gestational hypertension (GH) and chronic hypertension are usually benign, pre-eclampsia (PE) is more commonly associated with adverse maternal and fetal outcomes. About 15–25% of women initially diagnosed with GH will develop PE, but only 10% of women who develop GH after 36 weeks of gestation will develop PE. Pulse wave velocity (PWV) and augmentation index (AIx) are markers of arterial stiffness and endothelial dysfunction, while uterine artery Doppler pulsatility index (UtA PI) reflects the resistance in the uteroplacental circulation. These parameters have been shown to be associated with the risk of PE. The main aim of this study was to investigate whether maternal cardiovascular changes can discriminate pregnancies which will subsequently develop PE among those presenting with GH. Methods This was a prospective cohort study in women with singleton pregnancies presenting with GH at St George’s Hospital ( n = 112). Another group of uncomplicated singleton pregnancies were recruited as controls. PWV, AIx and aortic systolic blood pressure (SBP Ao ) were recorded using the Arteriograph® (TensionMed Ltd., Budapest, Hungary). The uterine artery Doppler was recorded on both sides and the mean PI was calculated. Mann-Whitney and Chi-Square tests were used to compare the groups, while regression analysis was used to identify and adjust for potential confounders. The predictive accuracy for the development of PE was assessed using the ROC curve analysis. Results The analysis included 105 pregnancies with GH and 356 controls. Compared to the group that remained as GH ( n = 82), the group that developed PE ( n = 23) had significantly higher AIx (25.9%, IQR 12.8–34.3 vs 15.8%, IQR 6.1–25.6; p = 0.019) and SBP Ao (141 mmHg, IQR 130–158 vs 130 mmHg, IQR 123–142; p = 0.005) at the initial assessment. They also had significantly higher UtA mean PI at 20–24 weeks (1.10, IQR 0.78–1.47 vs 0.83, IQR 0.68–1.04; p = 0.008). AIx was significantly associated with the risk of development of PE (odds ratio 1.05; 95% CI 1.01–1.09, p = 0.016). For a cut-off of 31.18%, AIx had sensitivity of 41.2% (95% CI 18.4–67.1%) and specificity of 93.2% (95% CI 83.5–98.1%) and LR 6.07 (AUC 0.69; 95% CI 0.53–0.84, p = 0.019). Conclusion Arterial stiffness and SBP Ao measured at the initial assessment of GH can potentially discriminate the pregnancies that will develop PE. Identification of women who will develop PE among those who initially present with PIH is likely to facilitate targeted antenatal surveillance and possibly intervention. [ABSTRACT FROM AUTHOR]

Objectives Corin, an atrial natriuretic peptide-converting enzyme, has been found to promote trophoblast invasion and spiral artery remodeling. Reduced maternal plasma atrial natriuretic peptide (ANP) levels and elevated corin levels have been reported in pregnancies complicated by PE. The aim of this study was to investigate longitudinal changes in maternal plasma levels of corin and midregional proatrial natriuretic peptide (MR-PANP) in pregnancies that develop preeclampsia (PE) and gestational hypertension (GH). Methods Nested case control study drawn from a larger prospective longitudinal study in singleton pregnancies identified by screening at 11 + 0 − 13 + 6 weeks’ gestation as being at high risk for PE. Blood samples were taken every four weeks until delivery. Values were compared in pregnancies that developed preterm-PE (requiring delivery before 37 weeks), term-PE, GH, and those that remained normotensive. The distribution of maternal plasma corin and PANP were made Gaussian after log 10 transformation. Analysis of repeated measures with multilevel mixed-effects linear model (fixed effects and random effects) was performed. The multilevel model was compared to one-level model by the likelihood radio (LR) test. Results A total of 471 samples were analyzed from 122 women, including 85 that remained normotensive, 12 that developed GH, 13 term-PE and 12 preterm-PE. In the normotensive group, log10corin levels were associated with gestational age ( p < 0.01), while log10MR-PANP levels were not. In the preterm-PE group, compared to the normotensive group, corin was significantly lower until 20 weeks’ gestation ( p = 0.001). In the GH and term-PE groups, corin did not differ significantly from the normotensive group ( p = 0.64 and p = 0.16, respectively). Compared to the normotensive group, MR-PANP levels were significantly higher in the pregnancies that developed preterm-PE and GH ( p = 0.046 and p = 0.019, respectively), but not term-PE ( p = 0.47). Conclusions Maternal plasma corin and MR-PANP could potentially be useful biomarkers for the prediction of preterm-PE. Disclosures A. Khalil: Research Support Recipient; Commercial Interests: USCOM, Roche, Alere, NICOM, Q-fFN; Speaker: Roche. [ABSTRACT FROM AUTHOR]

Introduction Hypertensive disorders complicate 10% of pregnancies and are associated with an increased risk of maternal and fetal morbidity and mortality. Traditional monitoring requires frequent hospital visits and investigations, which are time-consuming and stressful for patients, as well as a burden on maternity services. Home blood pressure monitoring (HBPM) offers an accurate and safe means of monitoring blood pressure and could provide cost-savings. We have introduced HBPM with the adjunct of an innovative smartphone app to record results and give advice to women with hypertension in pregnancy. Patients and methods We conducted a cost analysis for a cohort of hypertensive pregnant women using HBPM with our app using 2 techniques: process modelling and a direct case-control comparison with a cohort of women on traditional monitoring. Models were derived from common scenarios and costs obtained from NICE tariffs and NHS Practice Reports. For the direct comparison, data was collected from case notes and hospital databases. Variables included number of outpatient attendances, inpatient bed days and number of investigations. Results There were 108 patients in the HBPM cohort and 58 patients on the traditional pathway. Using process modelling we estimated that by using HBPM and thereby reducing the number of DAU visits required, costs per patient per week could be reduced from £196.64-£294.96 to £49.16-£98.32. The direct comparison demonstrated average savings of £200.85 per patient, per week of monitoring using HBPM compared to the traditional pathway with savings of £286.59 in some scenarios. There was no statistical difference in adverse outcomes between the groups. Conclusion This pilot study suggests that HBPM is a cost-saving initiative which is acceptable to patients in a hypertensive pregnant population. A larger study is required to confirm these findings. [ABSTRACT FROM AUTHOR]

Introduction Pregnancies resulting in small for gestational age (SGA) newborns are associated with altered Uteroplacental and maternal systemic circulations. However, data on the interaction between these cardiovascular changes are scarce. Whether these pregnancies result from placental insufficiency only, or combined with impaired maternal cardiovascular adaptation, is yet to be established. Objective The aim of this study was to ascertain the interaction between the maternal systemic and uteroplacental circulations in pregnancies resulting in SGA neonates. Methods This was a prospective case-control study including pregnancies resulting in SGA neonates ( n = 142) and a group of pregnancies resulting in appropriate for gestational age (AGA) neonates ( n = 473), recruited after 20 weeks gestation. Maternal cardiac output (CO), stroke volume (SV) and systemic vascular resistance (SVR) were recorded using the USCOM®, while the aortic augmentation index (AIx), heart rate and pulse wave velocity (PWV) were recorded using the Arteriograph®. The uterine artery (UtA) mean pulsatility index (PI) was assessed at the same visit. The Mann–Whitney test was used to compare the two groups and logistic regression analysis was used to investigate and adjust for potential confounding variables. Results Compared to controls, the SGA pregnancies had significantly lower CO (median 6.02 L/min, IQR 5.22–6.98 vs 6.64 L/min, IQR 5.68–7.73, p < 0.001), SV (median 76.99 ml, IQR 63.33–89.17 vs 80.02 ml, IQR 68.26–93.66, p = 0.035), but significantly higher SVR (median 1263 dynes-sec/cm 5 , IQR 1030–1538 vs 1094 dynes-sec/cm 5 , IQR 935.4–1337, p < 0.001) and AIx (median 14.25%, IQR 2.89–28.82 vs 5.71%, IQR 0.49–15.26, p < 0.001). UtA mean PI was significantly higher in the SGA pregnancies compared to controls (median 0.96, IQR 0.71–1.31 vs 0.71, IQR 0.58–0.88, p < 0.001). Multivariable logistic regression analysis adjusting for both gestational age and the parameters of the uteroplacental and maternal circulations, demonstrated that both the CO and the UtA mean PI remained significantly associated with the risk of SGA [adjusted odds ratio (95% CI) 0.74; p = 0.005 (0.63–0.87) and 6.40 (3.31–12.39); p < 0.001, respectively). Conclusion Placental insufficiency and impaired maternal cardiovascular adaptation are independently associated with the risk of delivery of an SGA neonate. [ABSTRACT FROM AUTHOR]

Introduction: Changes in cardiac output (CO) and systemic vascular resistance (SVR) have been shown to precede the clinical onset of pregnancy complications, such as pre-eclampsia and fetal growth restriction. CO and SVR undergo major changes during normal pregnancy. However, assessment of these vascular parameters requires intensive training and expensive techniques, so currently can be performed only in specialised centres. Objectives: The aim of this study was to investigate maternal cardiovascular function measured using an ultrasonic cardiac output monitor (USCOM), a simple non-invasive continuous wave Doppler device, in a cohort of pregnant women and non-pregnant controls. Methods: This was a cross sectional study including 185 women with normal singleton pregnancies at 11–40weeks of gestation and 49 non-pregnant controls. Stroke volume (SV), CO and SVR were measured using the USCOM device. All measurements were performed with the patients in supine position. All women with a gestational age of >20weeks were in a left lateral position by placing a wedge-shaped pillow under their right side to prevent vena cava compression. In a group of 25 pregnant women, each measurement was repeated three times to evaluate the reproducibility of this technique. Cardiac index (CI), SV index (SVI) and SVR index (SVRI) relate CO, SV and SVR to the body surface area. The data were normally distributed after logarithmic transformation. Comparisons between pregnant and non-pregnant women were performed using Studentt-test, Chi-Square test or multiple regression analysis, when adjustment for potential confounders was necessary. Data analysis was performed using SPSS 16.0. Results: In the first trimester, all of the following vascular parameters were higher in pregnant women compared to non-pregnant controls: CO [median (IQR): 4.86 (4.45–5.57) vs 5.57 (4.76–6.52)L/min, P <0.001], CI [median (IQR): 2.69 (2.44–3.07) vs 3.25 (2.80–3.86)L/min/m2, P <0.001], SV [median (IQR): 72.51 (68.10–80.18) vs 80.75 (74.50–99.74)mL/beat, P <0.001], SVI [median (IQR): 41.93 (37.53–46.57) vs 47.01 (43.85–53.79)mL/m2/beat, P <0.001]. Pregnant women had significantly lower SVR [median (IQR): 1458 (1261–1649) vs 1165 (1023–1406)sec/cm−5, P <0.001] and SVRI [median (IQR): 2646 (2307–2963) vs 2006 (1179–2277)dynes-sec/cm−5/m2, P <0.001] at 11–13weeks’ gestation. Conclusion: Using USCOM, maternal cardiac function can be assessed in a simple, non-invasive and reproducible manner. This simple technique is likely to facilitate large scale studies of maternal cardiovascular function in pregnancy. [Copyright &y& Elsevier]

Introduction: Women who develop pregnancy complications are more likely to develop cardiovascular disorders later in life. A history of pre-eclampsia (PE) is associated with a four-fold increased risk of hypertension and twice the risk of future ischaemic heart disease and stroke. Early identification of women at risk of developing pregnancy complications is likely to facilitate targeted antenatal surveillance and possibly intervention. Maternal ethnicity affects the risk of developing some of these complications, and so is likely to be an important variable in the risk assessment. Objectives: The main aim of this study was to quantify the ethnicity-related risk of adverse pregnancy outcomes. Methods: This was a multicentre cohort study in singleton pregnancies at 11+0–13+6 weeks of gestation. Data on maternal characteristics, medical and obstetric history were collected and pregnancy outcomes ascertained. Racial origin was classified into Caucasian, African, South Asian, East Asian and mixed. The adverse pregnancy outcomes in this study included PE, gestational hypertension (GH), gestational diabetes (GDM), preterm delivery (PTD), small for gestational age (SGA), large for gestational age (LGA), stillbirth, obstetric cholestasis (OC) and emergency Caesarean section (CS). The diagnosis of PE and GH was made according to the guidelines of the International Society for the Study of Hypertension in Pregnancy. The neonate was considered SGA if the birthweight was less than the 5th percentile and LGA if the birthweight was more than the 90th percentile for gestation at delivery. The diagnosis of GDM was made if the fasting plasma glucose level was at least 6mmol/L or the plasma glucose level 2h after oral administration of 75g glucose was 7.8mmol/L or more (WHO). Stillbirth was defined as the death of a fetus before birth after the 24th week of pregnancy. The diagnosis of OC was made when there was pruritus in association with abnormal liver function in the absence of any other identifiable liver pathology which resolved after delivery. Multiple regression analysis was used to examine which maternal characteristics provided a significant contribution in the prediction of these adverse pregnancy outcomes. Crude and adjusted odds ratios (ORs) were derived for each pregnancy outcome. Results: Seventy five thousand and four hundred women were included in the study, of whom 57,564 were Caucasian and 11,395 African. Compared to Caucasian ethnic origin, African women were more likely to develop PE [OR (95% CI): 2.77 (2.49–3.09), p <0.0001], GH [OR 1.38 (1.23–1.56), p <0.0001], SGA [OR 3.48 (3.16–3.83), p <0.0001], stillbirth [OR 2.42 (1.87–3.12), p <0.0001], GDM [OR 1.82 (1.59–2.07), p <0.0001], PTD prior to 37 weeks gestation [OR 1.33 (1.23–1.44), p <0.0001], and emergency CS [OR 2.42 (1.87–3.12), p <0.0001]. On the other hand, African women were less likely to develop LGA and OC [OR (95% CI): 0.63 (0.58–0.67) and 0.47 (0.32–0.69) respectively; p <0.0001 for both]. Conclusion: Compared to Caucasian ethnic background, women of African origin have a different risk profile for adverse pregnancy outcomes. This difference should be taken into account when calculating an individualised adjusted risk or when tailoring antenatal care. [Copyright &y& Elsevier]

Background There is growing interest in non-invasive haemodynamic assessment for both clinical and research purposes. In order to allow for application, comparison and interpretation of haemodynamic parameters, there is a need to construct device-specific reference ranges. Furthermore, there is a paucity of data demonstrating the influence of maternal characteristics on central haemodynamic parameters. The purpose of this study was to assess stroke volume (SV), cardiac output (CO) and systemic vascular resistance (SVR) in a low-risk obstetric population, construct gestational-age (GA) specific reference ranges and delineate the effect of maternal characteristics. Methods This was a prospective cohort study of 824 patients with a GA ranging from 5 to 42 weeks. The inclusion criteria were women with a viable, singleton pregnancy, aged 16 and above with an uncomplicated pregnancy. Exclusion criteria included any medical disorder or pregnancy complication. The non-invasive device employed in this study was USCOM-1A®. All measurements were performed under standardised conditions. USCOM-1A® employs continuous wave Doppler, with a non-imaging probe in the suprasternal notch to obtain velocity time integrals of transaortic blood flow at the left ventricular outflow tract. For each haemodynamic variable, a normal distribution with mean conditional on GA was considered first. Once the distribution of the data had been determined with respect to GA, maternal characteristics were added to the model to test whether they provided a significant improvement in prediction of the mean/median value. Improvements in model fit were evaluated using the generalised likelihood ratio test, with statistical significance at p < 0.05. Results Maternal age had an effect on CO ( p < 0.001). The estimated median CO was constant above the age of 32 years, but was around 0.5 L/min higher for women aged 25 or younger. Maternal weight ( p < 0.001), height ( p < 0.001) and their interaction ( p = 0.002) also affected CO. In women with a height less than 1.60 m, there was no association between median CO and weight. In those with a height exceeding 1.60 m, an increase in weight was associated with an increase in CO. SV was primarily associated with height ( p < 0.001), although some positive association with weight ( p < 0.001) can also be observed within the normal BMI range. Greater height ( p < 0.001) was associated with lower median values of SVR with an estimated difference of around 120 dynes·s·cm 5 between 1.60 m and 1.80 m. Advancing maternal age was associated with higher median SVR with an estimated difference of around 50 dynes·s·cm 5 between 25 and 35 years. Smokers had a lower SVR of73.5 dynes·s·cm 5 (95% CI; 8.6–138.4 dynes·s·cm 5 ). Conclusion We provide USCOM-1A® specific reference ranges for SV, CO and SVR in uncomplicated pregnancies. This will enable clinical application and comparison in pathological conditions. Maternal haemodynamics are significantly influenced by maternal age, height, weight and smoking status. [ABSTRACT FROM AUTHOR]

Introduction Many studies investigating long-term vascular disease risk associated with hypertensive pregnancies examined risks in relatively young women among whom coronary heart disease (CHD) is uncommon. Objective We examined the prospective relation between a history of hypertension during pregnancy and CHD in middle-aged women. Methods At study baseline of the UK Million Women study (1996–2001), 1.1 million parous women (mean age = 56 years) without vascular disease reported their medical history including, including information on having had high blood pressure during pregnancy, as well as other factors relating to health and lifestyle. They were followed for incident CHD (hospitalisation or death), and adjusted relative risks were calculated using Cox regression. Results Of the 1.1 million women in the cohort study, 26% reported having had a hypertensive pregnancy. Among these women who reported having had hypertension during pregnancy, 27% also reported being treated for hypertension at baseline; in contrast, among women without a hypertensive pregnancy, only 10% reported being treated for hypertension at baseline. After a mean follow-up of 12 years, over 68,000 women subsequently had a first coronary disease event. Overall, a hypertensive pregnancy compared to those without such history was associated with an increased risk of CHD (relative risk = 1.29, P < 0.001); however, among women who were being treated for hypertension at baseline, the relative risk of incident CHD associated with hypertension during pregnancy was substantially reduced. Conclusion Hypertension during pregnancy was associated with increased risk of incident CHD, mainly because many of these women will have had hypertension in their 50s and 60s, which has a substantially greater effect on coronary disease than hypertension during pregnancy. The high proportion of those who reported having had hypertension during pregnancy in this cohort may suggest that this group included women who experienced hypertensive pregnancy that did not meet clinical criteria for specific disorders such as preeclampsia, the prevalence of which is usually relatively low. [ABSTRACT FROM AUTHOR]

Background Obesity is a global epidemic, which is associated with increased perinatal mortality and morbidity. Despite the significant health and economic impact of maternal obesity, there is a paucity of good quality studies assessing central haemodynamic parameters in morbidly obese pregnant women. Objective To investigate the haemodynamic profile in women with morbid obesity, defined as body mass index (BMI) greater than 40 kg/m 2 , in the absence of hypertensive disorders of pregnancy. Methods A prospective, case-control study of 23 pregnant women with class 3 obesity and 327 controls with a normal BMI, matched for maternal age and gestational age. We planned to recruit 10 control cases for each obese case. Women aged 16 and over with singleton pregnancies of 12 or more weeks’ gestation were recruited from routine antenatal scanning clinics and the maternity day assessment unit at our tertiary centre. Those found to be hypertensive at the time of study recruitment, had a pre-existing diagnosis of hypertensive disorders of pregnancy (ISSHP 2014) or congenital/acquired heart disease, were not included in the analysis. Maternal haemodynamics were investigated using Ultrasound Cardiac Output Monitor (USCOM 1A®). All non-invasive assessments were performed in the same room, under standardised conditions for the entire cohort. Mann Whitney U test, Chi-Square test, or Fisher’s exact test when appropriate, was used to compare the categorical variables between the two groups. Results Women with morbid obesity had raised mean arterial pressure (91 vs 85 mmHg, p < 0.01) and heart rate (92 vs 83 bpm, p < 0.05) compared to controls. We found no significant differences in stroke volume (77 vs 82 mls, p = 0.165), cardiac output (7.04 vs 6.75 L/min, p = 0.325) or total peripheral resistance (TPR: 1106 vs 1052 dyn · s · cm 5 , p = 0.318). When haemodynamic indices were corrected for body surface area, women with morbid obesity had a significantly lower stroke volume index (33 vs 46 mls), lower cardiac index (3.01 vs 3.70 L/min/m 2 ) and higher TPR index (2567 vs 1915 dyn · s · cm 5 /m 2 ); p < 0.01 for all. Conclusions Morbidly obese pregnant women have an adverse haemodynamic profile compared to women of normal weight, even in women who did not develop hypertensive disorders of pregnancy. The abnormal haemodynamics observed in obesity are consistent with findings outside of pregnancy and with the predisposition of obese women to hypertensive disorders of pregnancy. Given the differences in anthropometric parameters. [ABSTRACT FROM AUTHOR]

Objective In pregnancies complicated by hypertension, antihypertensive therapy should be tailored to the type of hypertension, whether cardiogenic or vasogenic. However, current clinical assessment does not allow this differentiation. Inotropy is a measure of the myocardial contractility, while the ratio of potential to kinetic energy (PKR) is a measure of arterial impedance. In a recent report, both Smith-Madigan inotropy index (SMII) and PKR could be derived from a continuous-wave Doppler ultrasound technique. The aim of this study was to investigate these two novel cardiovascular parameters in pregnancies complicated by hypertensive disorders compared to uncomplicated pregnancies. Methods This was a prospective case-control study including a group of women presenting with hypertension in the second half of the pregnancy and a group of uncomplicated pregnancies recruited after 20 weeks’ gestation. Cardiovascular parameters were assessed using a continuous-wave Doppler ultrasound technique (USCOM®). Pregnancies were followed up and the outcome ascertained. Mann–Whitney test and regression analysis were used for statistical analysis. Results We recruited 94 women with hypertensive disorders in pregnancy and 106 controls. Compared to normotensive controls, the cases had significantly higher SMII (median 1.96 W/m 2 , IQR 1.64–2.40 vs 1.75 W/m 2 , IQR 1.47–2.03, p < 0.001), higher PKR (median 26.27, IQR 19.0–37.07 vs 20.94, IQR 15.69–27.73, p < 0.001), higher systemic vascular resistance index (median 2622 dynes-sec/cm 5 /m 2 , IQR 2170–3023 vs 1877 dynes-sec/cm 5 /m 2 , IQR 1561–2233, p < 0.001), but significantly lower cardiac index (median 3.34 L/min/m 2 , IQR 2.97–4.0 vs 3.72 L/min/m 2 , IQR 3.17–4.40, p = 0.003). Conclusion Women presenting with hypertensive disorders in pregnancy demonstrate significant changes in cardiac contractility and dynamic arterial impedance. It remains to be established whether these indices may be used prospectively for the individualized triage and management of these pregnancies. [ABSTRACT FROM AUTHOR]

Objective The literature describing the maternal cardiovascular changes in pregnancies complicated by fetal growth restriction and maternal hypertension is limited, conflicting and does not discriminate the two pathologies. The aim of this study was to investigate maternal cardiovascular changes in pregnancies complicated by small for gestational age (SGA) neonates with or without maternal hypertension. Methods This was a prospective case-control study including pregnancies resulted in SGA neonate ( n = 159) and a group of uncomplicated pregnancies ( n = 473), recruited after 20 weeks’ gestation. The SGA group was further divided according to fetal Doppler to define fetal growth restriction (FGR; n = 51) and maternal hypertension ( n = 51). FGR was defined as estimated fetal weight below the 10th centile with abnormal umbilical artery Doppler (pulsatility index [PI] above the 90th centile or absent or reversed end-diastolic flow). Maternal cardiac output (CO), cardiac index (CI), systemic vascular resistance (SVR), systemic vascular resistance index (SVRI) were recorded using the USCOM®, while the augmentation index (AIx) was assessed using the Arteriograph®.Uterine artery (UtA) mean PI was assessed at the same visit. Mann–Whitney test and regression analysis were used for statistical analysis. Results Compared to controls, the SGA pregnancies had significantly lower CO (median 6.08 L/min, IQR 5.31–6.86 vs 6.65 L/min, IQR 5.68–7.79, p = 0.006), but significantly higher SVR (median 1091 dynes-sec/cm 5 , IQR 998–1359 vs 1040 dynes-sec/cm 5 , IQR 878–1263, p = 0.008). Both AIx and UtA mean PI were significantly higher in the SGA pregnancies compared to controls ( p = 0.002 and p < 0.001, respectively). In normotensive SGA, the results were similar ( p < 0.05). However, after correcting for body surface area, neither cardiac index nor SVR index were significantly different between the two study groups ( p = 0.209 and p = 0.139, respectively). In normotensive FGR pregnancies, SVR, AIx and UtA mean PI were significantly higher ( p < 0.01 for all), while CO was not significantly different ( p = 0.429). Conclusion FGR is associated with maternal cardiovascular changes. The conflicting results reported by previous studies could be explained by failure to correct for maternal body surface area, incorrectly labelling SGA pregnancies as FGR, or lack of distinction between FGR with or without maternal hypertension. [ABSTRACT FROM AUTHOR]

Objective Pre-eclampsia (PE) is associated with marked maternal cardiovascular changes before its clinical onset, at the time of clinical diagnosis, and in the postpartum period. These changes vary according to the timing of onset (early vs late) or the severity (mild vs severe) of PE.The aim of this study was to perform a systematic review and meta-analysis to quantify these cardiovascular changes associated with PE. Methods MEDLINE, EMBASE, CINAHL and The Cochrane Library were searched, using combinations of the terms pre-eclampsia, cardiac, vascular resistance, stroke volume (SV) and pregnancy hypertension. Reference lists within relevant articles and reviews were hand-searched for additional reports. Randomised controlled trials, cohort and case-control studies were included. Studies reporting data on cardiac output (CO), cardiac index (CI), SV, systemic vascular resistance (SVR) and its index (SVRI) were included. Between-study heterogeneity was assessed using the I 2 test. Results The search yielded 1943 citations, of which 56 studies were included in the review. A significant increase in SVR (weighted mean difference [WMD] 446.42, p < 0.001) and SVRI (WMD 923.34, p < 0.001) and a decrease in the CI (WMD −0.54, p < 0.001) were observed in women with PE compared with women with normotensive pregnancies. SVR was significantly higher (WMD 866, p < 0.001) while the SV was significantly lower (WMD −2.6, p < 0.001) in early-onset compared to late-onset PE. Screening studies have reported significantly higher SV in the first trimester in pregnancies that later developed PE compared to those which remained normotensive (WMD 1195, p < 0.001). Both the heart rate (WMD 5.87, p = 0.002) and SVR (WMD 317.33, p = 0.004) were significantly lower, while the SV (WMD −9.00, p = 0.002) was significantly higher after the incident pregnancy (postpartum), when complicated by PE. Conclusion Women who develop PE have significantly elevated SVR, both at the time of the clinical diagnosis and postpartum. SV may also be useful in first trimester screening for PE. However, changes in CO were not significantly different in PE before its clinical onset, at the time of diagnosis, or postpartum. [ABSTRACT FROM AUTHOR]

Objectives Maternal cardiac adaptation to pregnancy is important in maintaining normal uteroplacental perfusion. These changes could potentially explain the different clinical phenotypes associated with impaired placentation and could potentially be used to guide therapy. The aim of this study was to investigate the changes in the maternal systemic circulation in normotensive pregnancies and those complicated by pre-eclampsia (PE). Methods This was a prospective case-control study in singleton pregnancies recruited after 20 weeks’ gestation, some of whom developed PE and some of whom remained normotensive. The diagnosis of PE was made according to the guidelines of the International Society for the Study of Hypertension in Pregnancy. Maternal cardiac index (CI), systemic vascular resistance index (SVRI) and inotropy, which is a measure of myocardial contractility, were assessed using a continuous-wave Doppler ultrasound technique (USCOM®). Mann–Whitney test and regression analysis were used for statistical analysis. Results We recruited 153 women with pregnancies complicated by PE and 458 normotensive controls. In the normotensive pregnancies, CI and inotropy were negatively correlated with gestational age (GA) ( r = 0.21; p < 0.001 and r = −0.15; p = 0.003, respectively), while SVRI was positively correlated with GA ( r = 0.20; p < 0.001). Compared to controls, pregnancies complicated by PE had significantly lower CI (median 3.30 L/min, IQR 2.73–3.81 vs. 3.50 L/min, IQR 3.0–4.07, p < 0.001), higher inotropy (median 1.87 W/m2, IQR 1.61–2.25 vs. 1.65 W/m 2 , IQR 1.42–1.93, p < 0.001) and higher SVRI (median 2678 dynes-s/cm 5 , IQR 2238–3269 vs. 2027 dynes-s/cm 5 , IQR 1667–2413, p < 0.001). Conclusions These findings suggest that in normal pregnancy the maternal myocardial contractility and function correlates with gestational age in the second half of pregnancy. Using this non-invasive technique of assessing maternal systemic cardiovascular function, we demonstrated the changes in pregnancies complicated by PE, including an increase in systemic vascular resistance and decline in cardiac function. These findings suggest that beta-blockade as antihypertensive therapy should be avoided in these cases. Disclosures A. Khalil: d. Research Support Recipient; Commercial Interest(s):; USCOM, Roche, Alere, Q-fFN, NICOM. f. Speaker; Commercial Interest: Roche. [ABSTRACT FROM AUTHOR]

Introduction: Pre-eclampsia (PE), particularly early-onset PE (PE requiring delivery before 34 weeks), is commonly associated with fetal growth restriction (FGR). The evidence for an association between FGR and a more severe PE phenotype is controversial. Objectives: The main aim of this study was to investigate whether the presence of FGR in women with early-onset PE is associated with more severe maternal disease compared to those with appropriately grown fetuses (AGA). Methods: This was a retrospective cohort study of women with early-onset PE between 2001 and 2010 at University College London Hospital. The diagnosis of PE was made according to the criteria defined by the International Society of the Study of Hypertension in Pregnancy (ISSHP). PE was diagnosed when the systolic blood pressure was 140mmHg or more and/or the diastolic blood pressure 90mmHg or more on at least two occasions four hours apart developing after 20 weeks of gestation in previously normotensive women with proteinuria of 300 mg or more in 24h or two readings of at least ++ on dipstick analysis of midstream or catheter urine specimens if no 24-h collection is available. FGR was defined as birthweight less than the 5th centile, with abnormal umbilical artery Doppler (raised pulsatility index, absent or reversed end-diastolic flow). Maternal, fetal and neonatal data were collected and study groups compared using Chi-square test or Fisher’s exact test (categorical variables), and Mann Whitney-U test (continuous variables). Data analysis was performed using SPSS 16.0. Results: In women with early-onset PE (n =134), FGR (n =66, 49%) was associated with significantly higher perinatal mortality (p =0.02). Gestational age at delivery was significantly lower in the FGR group (median, IQR: 29.0 weeks, 28.0–32.8 vs 32.0, 30.0–33.2, p =0.01). However, maternal indicators of PE severity, including blood pressure 3160mmHg systolic or 3110mmHg diastolic, ALT>100U/L, platelet count <100×109/L, use of magnesium sulphate or use of antihypertensive therapy, were similar in the two groups. Conclusion: In women with early onset PE, FGR was associated with worse perinatal outcome, but was not associated with a more severe maternal PE phenotype. This may be because the presence of FGR in these women leads to earlier iatrogenic delivery, before the maternal condition deteriorates, but further studies are needed to investigate this. [Copyright &y& Elsevier]