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Objective: To investigate maternal cardiac function in twin pregnancy.Methods: We conducted a cross-sectional study of 119 pregnant women with twin pregnancies at 10-40 weeks' gestation. Two-dimensional and M-mode echocardiography of the left ventricle was performed in the left lateral decubitus position to assess left ventricular longitudinal and transverse systolic function. The measurements were compared with those obtained from 128 women with singleton pregnancies previously reported.Results: In twin pregnancies, compared with singletons, maternal cardiac output was greater by 20% (P <.001), because of a greater stroke volume (15%, P <.001) and heart rate (3.5%; P =.04). Furthermore, in women with twins there were greater left ventricular end-diastolic and left ventricular end-systolic dimensions, left ventricular mass (13.5%; P <.001), fractional shortening (3%; P =.04), and ejection fraction (2.5%; P =.04). Mean arterial pressure and global time to shortening in women with twins, compared with singletons, were less in the first trimester by approximately 2%, but after midpregnancy they increased progressively, so that at term the measurements were greater by 3% and 5.7%, respectively (P =.03). Conversely, long axis shortening in women with twins, compared with singletons, was greater in the first trimester by approximately 6.5%, but at term it was 3% less (P =.01). Twin pregnancies that subsequently developed preeclampsia had a hemodynamic profile similar to the rest of the twin population.Conclusion: Twin pregnancy is characterized by an even more hyperdynamic circulation than singleton pregnancy. Left ventricle longitudinal systolic function and mean arterial pressure are more abruptly affected after 20 weeks compared with singleton pregnancies. [ABSTRACT FROM AUTHOR]

Objectives: To examine the postnatal course of ophthalmic artery (OA) Doppler in women with hypertensive disorders of pregnancy (HDP) and to evaluate the correlation between OA Doppler parameters and poor postnatal blood pressure control and renal dysfunction at 2-3 weeks and 6-9 weeks postnatally., Methods: This was a prospective cohort study of women with a singleton pregnancy and HDP seen at a tertiary pregnancy hypertension clinic between 2019 and 2021. Three visits were included: Visit 1, the last visit to the antenatal hypertension clinic within 2 weeks prior to delivery; Visit 2, at 2-3 weeks postnatally; and Visit 3, at 6-9 weeks postnatally. At each visit, maternal demographic characteristics, medical history, blood pressure and OA Doppler were obtained. In addition, fetal growth and fetal Dopplers were examined antenatally and, at 6-9 weeks postnatally, estimated glomerular filtration rate and proteinuria were quantified. Study participants were divided into four hypertension groups, according to longitudinal changes in blood pressure at the three visits. For the postnatal visits, hypertension was defined as systolic blood pressure (SBP) ≥ 140 mmHg and/or diastolic blood pressure (DBP) ≥ 90 mmHg in the absence of antihypertensive medication, and SBP ≥ 130 mmHg and/or DBP ≥ 80 mmHg whilst taking antihypertensives. Group 1 was hypertensive at all three visits; Group 2 was hypertensive at Visits 1 and 2 but normotensive at Visit 3; Group 3 was hypertensive at Visits 1 and 3 but normotensive at Visit 2; and Group 4 was hypertensive at Visit 1 but normotensive at Visits 2 and 3. The longitudinal changes in mean arterial pressure (MAP), peak systolic velocity (PSV) 1, PSV2 and the ratio of PSV2/PSV1 over the three timepoints were examined by a repeated-measures, multilevel, linear mixed-effects analysis, controlling for maternal age, weight at presentation and use of antihypertensive medication. In addition, we examined the longitudinal change in OA Doppler parameters in women with different degrees of postnatal blood pressure control and in those with and those without renal dysfunction at 6-9 weeks postnatally., Results: A total of 108 women were recruited to the study, of whom 86 had new-onset hypertension and 22 had chronic hypertension. When controlling for maternal age, weight at presentation and use of antihypertensive medication, a significant decline in log 10 MAP (P < 0.001), log 10 PSV1 (P < 0.001) and log 10 PSV2 (P = 0.01) was seen between Visits 1 and 3. Log 10 PSVR did not change with time. When assessing OA Doppler against hypertension group, log 10 PSV1 and log 10 PSV2 did not differ between the hypertension groups, whilst Group 4 had a lower log 10 PSVR compared with Group 1 (P < 0.01), Group 2 (P = 0.03) and Group 3 (P < 0.01). At 6-9 weeks postnatally, log 10 PSVR was lower in those without compared to those with renal dysfunction (-0.021, P = 0.01), whilst log 10 MAP, log 10 PSV1 and log 10 PSV2 values did not differ. Log 10 PSVR did not change with time and remained at -0.12 (95% CI, -0.13 to -0.11) across the three visits., Conclusions: In women with HDP, the OA-PSVR was significantly higher in those with labile or persistently raised blood pressure postnatally compared to women whose blood pressure normalized. Similarly, the OA-PSVR at 6-9 weeks postnatally was significantly higher in women with renal dysfunction vs those without dysfunction. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To compare the predictive performance for delivery with pre-eclampsia (PE) within 2 weeks of assessment in women with chronic hypertension at 24-41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio., Methods: This was a prospective study of 104 women with a singleton pregnancy and chronic hypertension presenting at 24-41 weeks' gestation. Twenty-six (25.0%) cases developed superimposed PE within 2 weeks of sampling. We compared the predictive performance for superimposed PE between GlyFn, PlGF and the sFlt-1/PlGF ratio at a fixed screen-positive rate of approximately 10%., Results: The median gestational age at sampling was 34.1 (interquartile range, 31.5-35.6) weeks and 84.6% (88/104) of cases were sampled at < 36 weeks. The predictive performance for superimposed PE of the three methods of screening was similar, with detection rates of about 23-27%, at a screen-positive rate of 11% and a false-positive rate of about 5%., Conclusions: Measurement of GlyFn is a simple point-of-care test that can be carried out without need for a laboratory and provide results within 10 min of testing. In this respect, it could potentially replace the angiogenic markers that are used currently in the prediction of imminent PE in high-risk women. However, neither GlyFn nor angiogenic factors are likely to improve the management of women with chronic hypertension because their predictive performance for superimposed PE is poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Objectives: To compare the ophthalmic artery Doppler peak systolic velocity ratio (OA PSV-ratio) and soluble fms-like tyrosine kinase-1/placental growth factor ratio (sFlt-1/PlGF ratio) in predicting adverse maternal and perinatal outcomes in women presenting with new onset hypertension., Study Design: Prospective cohort study in a specialist hypertension clinic, within a tertiary referral centre., Main Outcome Measures: Comparison between the OA PSV-ratio and sFlt-1/PlGF ratio in predicting delivery within one week from presentation and adverse maternal and perinatal outcomes e.g. severe hypertension, neonatal unit admission, small for gestational age., Results: Women who delivered within one week, compared to those who did not, had a higher OA PSV-ratio (0.82 vs 0.71, p < 0.01) and sFlt-1/PlGF ratio (93.3 vs 40.5, p = 0.08). Independent predictors of the OA PSV-ratio included mean arterial pressure and maternal weight and predictors of the sFlt-1/PlGF ratio included diastolic blood pressure and use of antihypertensive medications. Prediction of adverse outcomes with both ratios were similar and only modest e.g. AUROC for predicting delivery within one week for OA PSV-ratio was 0.57 (95% CI 0.47-0.67) and for sFlt-1/PlGF ratio was 0.61 (95% CI 0.52-0.70) (p = 0.53)., Conclusions: In women presenting with new onset hypertension, the OA PSV-ratio and sFlt-1/PlGF ratio have similar and modest performance in predicting adverse outcomes., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To compare the predictive performance for delivery with pre-eclampsia (PE) within 2 weeks after assessment in women with new-onset hypertension at 24-41 weeks' gestation between serum glycosylated fibronectin (GlyFn) concentration, serum placental growth factor (PlGF) concentration and soluble fms-like tyrosine kinase-1 (sFlt-1) to PlGF concentration ratio., Methods: This was a prospective observational study of 409 women with a singleton pregnancy presenting at 24-41 weeks' gestation with new-onset hypertension. The recommended cut-off for sFlt-1/PlGF ratio for the prediction of PE in the platform used in this study is 85; the appropriate cut-offs for GlyFn and PlGF were determined to achieve the same screen-positive rate as that of sFlt-1/PlGF ratio > 85. We then compared the predictive performance for delivery with PE within 2 weeks after presentation between GlyFn, PlGF and sFlt-1/PlGF, both overall and in subgroups according to gestational age at presentation., Results: Delivery with PE within 2 weeks occurred in 93 (22.7%) cases. The screen-positive rate for sFlt-1/PlGF ratio > 85 was 46.2%. The cut-off corresponding to a screen-positive rate of 46.2% was 75 pg/mL for PlGF and 510 µg/mL for GlyFn. The overall detection rate for delivery with PE within 2 weeks after presentation was 62.4% (95% CI, 51.7-72.2%) for GlyFn and sFlt-1/PlGF and 60.2% (95% CI, 49.5-70.2%) for PlGF. In all women who delivered with PE within 2 weeks after presentation at < 34 weeks' gestation and in about 60-70% of those presenting at < 38 weeks, GlyFn and sFlt-1/PlGF were increased and PlGF was reduced. However, the screen-positive rate for these tests was very high at about 45%. The predictive performance for delivery with PE within 2 weeks after presentation at ≥ 38 weeks' gestation was poorer for all three methods of screening, with detection rates of 47-63% at screen-positive rates of 40-50%., Conclusions: In women with new-onset hypertension, the predictive performance for delivery with PE within 2 weeks after presentation for serum GlyFn is similar to that of PlGF and the sFlt-1/PlGF ratio, but GlyFn may be the preferred option because it is a rapid point-of-care test. However, the predictive performance for all tests is relatively poor. © 2023 International Society of Ultrasound in Obstetrics and Gynecology., (© 2023 International Society of Ultrasound in Obstetrics and Gynecology.)

Background: Compared with gestational hypertension, preeclampsia has traditionally been considered the worse end of the spectrum of hypertensive disorders of pregnancy. It is associated with worse pregnancy outcomes and future cardiovascular morbidities. Both hypertensive disorders may be associated with cardiac maladaptation in pregnancy. However, previous studies were limited by small numbers and a paucity of longitudinal data and unaccounted for the contribution of maternal characteristics that can affect hemodynamics., Objective: This study aimed to assess, in an unselected population, the maternal cardiac adaptation in normotensive and hypertensive pregnancies after controlling for important maternal characteristics that affect maternal cardiac function and the interaction among these covariates., Study Design: This was a prospective, multicenter longitudinal study of maternal hemodynamics, assessed by a noninvasive bioreactance technology, measured at 11 0/7 to 13 6/7, 19 0/7 to 24 0/7, 30 0/7 to 34 0/7, and 35 0/7 to 37 0/7 weeks of gestation in 3 groups of women. Group 1 was composed of women with preeclampsia (n=45), group 2 was composed of women with gestational hypertension (n=61), and group 3 was composed of normotensive women (n=1643). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal age, height, weight, weight gain, race, previous obstetrical history, and birthweight., Results: After adjusting for confounders that significantly affect maternal hemodynamics, both group 1 and group 2, compared with group 3, had pathologic cardiac adaptation. Group 1, compared with group 3, demonstrated hyperdynamic circulation with significantly higher cardiac output driven by greater stroke volume in the first trimester of pregnancy. As the pregnancies progressed to after 20 0/7 weeks of gestation, this hyperdynamic state transitioned to hypodynamic state with low cardiac output and high peripheral vascular resistance. Group 2, compared with group 3, had no significant differences in cardiac output, stroke volume, and heart rate before 20 0/7 weeks of gestation but thereafter demonstrated a continuous decline in cardiac output and stroke volume, similar to group 1. Both groups 1 and 2, compared with group 3, had persistently elevated mean arterial pressure and uterine artery pulsatility index throughout pregnancy., Conclusion: After adjusting for confounders that affect maternal hemodynamics in an unselected pregnant population, women with preeclampsia and gestational hypertension, compared with normotensive women, demonstrated similar cardiac maladaptation. This pathologic profile was evident after 20 0/7 weeks of gestation and at least 10 weeks before the clinical manifestation of the disease., (Crown Copyright © 2022. Published by Elsevier Inc. All rights reserved.)

Objective: To compare longitudinal maternal hemodynamic changes throughout gestation between different groups stratified according to weight at presentation and assess the relative influence of height, weight at presentation and gestational weight gain on cardiac adaptation., Methods: This was a prospective, longitudinal study assessing maternal hemodynamics using bioreactance technology at 11 + 0 to 13 + 6, 19 + 0 to 24 + 0, 30 + 0 to 34 + 0 and 35 + 0 to 37 + 0 weeks' gestation. Women were divided into three groups according to maternal weight at presentation at the first visit at 11 + 0 to 13 + 6 weeks: Group 1, &lt; 60.0 kg (n = 421); Group 2, 60.0-79.7 kg (n = 904); Group 3, &gt; 79.7 kg (n = 427). A multilevel linear mixed-effects model was used to compare the repeated measures of hemodynamic variables, correcting for demographics, medical and obstetric history, pregnancy complications, maternal weight and time of evaluation. The linear mixed-effects model was then repeated using maternal height, weight at presentation and gestational weight gain Z-scores, and the standardized coefficients were used to evaluate the relative impact of each of these demographic parameters on longitudinal changes of maternal hemodynamics., Results: Compared with Group 1, women in Group 3 demonstrated higher cardiac output (CO), heart rate (HR) and mean arterial pressure (MAP) throughout pregnancy. Groups 2 and 3 had higher stroke volume (SV) than Group 1 at the first visit, but their SV plateaued between the first and second visits and demonstrated an earlier significant decrease from the second visit to the third visit when compared with Group 1. Compared with Groups 1 and 2, there was a higher prevalence of pre-eclampsia, gestational hypertension and gestational diabetes in Group 3. Maternal height was the most important contributor to CO, peripheral vascular resistance (PVR), SV and HR, while weight at presentation was the most important contributor to MAP. Gestational weight gain was the second most important characteristic influencing the longitudinal changes of PVR and SV., Conclusions: Women with greater weight at presentation have a pathological hemodynamic profile, with higher CO, HR and MAP compared to women with lower weight at presentation. Height is the main determinant of CO, SV, HR and PVR, weight is the main determinant of MAP, and gestational weight gain is the second most important determinant of SV and PVR. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To examine whether the ophthalmic artery peak systolic velocity ratio (OA PSV-ratio) is higher in women with pre-eclampsia compared with gestational hypertension (GH) and chronic hypertension (CH), after controlling for confounding variables., Design: Prospective cohort., Setting: Specialist hypertension clinic in a tertiary referral centre., Population: Singleton pregnancies presenting between 32 +0 and 36 +6  weeks of gestation with pre-eclampsia (n = 50), GH (n = 54) and CH (n = 56)., Methods: Paired measurements of maternal mean arterial pressure (MAP) and OA PSV-ratio were performed by trained sonographers. Multiple linear regression was fitted to the OA PSV-ratio, including maternal characteristics and medical history, GH, pre-eclampsia and MAP and use of antihypertensive medication., Main Outcome Measure: Whether pre-eclampsia is independently associated with higher OA PSV-ratio., Results: MAP was significantly higher in both GH (p = 0.0015) and pre-eclampsia (p = 0.008) than in CH pregnancies. There was no significant difference between pre-eclampsia and GH (0.670). The OA PSV-ratio was significantly higher in pre-eclampsia than CH (p = 0.0008) and GH (p = 0.015). There was no significant difference between the OA PSV-ratio in CH and GH (p = 0.352). Multiple linear regression modelling showed that the OA PSV-ratio was influenced by maternal weight (p = 0.005), maternal age (p = 0.014), antihypertensive medications (p = 0.007) and MAP (p < 0.0001). After controlling for these variables, the OA PSV-ratio was still significantly higher in those with pre-eclampsia (p = 0.0002)., Conclusions: The OA PSV-ratio is influenced by maternal weight, age, antihypertensive medications and MAP. Pre-eclampsia is an independent predictor of OA PSV-ratio, which therefore may be a useful point-of-care test when assessing women presenting with hypertension., (© 2021 John Wiley & Sons Ltd.)

Objective: To compare the predictive performance for delivery with pre-eclampsia (PE) at < 3 weeks and at any stage after assessment at 35 + 0 to 36 + 6 weeks' gestation of serum placental growth factor (PlGF) and soluble fms-like tyrosine kinase-1 (sFlt-1)/PlGF ratio with that of a competing-risks model utilizing maternal risk factors, mean arterial pressure (MAP) and ophthalmic artery peak systolic velocity (PSV) ratio., Methods: This was a prospective observational study of women attending for a routine hospital visit at 35 + 0 to 36 + 6 weeks' gestation. This visit included recording of maternal demographic characteristics and medical history, ultrasound examination of fetal anatomy and growth, assessment of flow velocity waveforms from the maternal ophthalmic arteries and measurement of MAP, serum PlGF and serum sFlt-1. The performance of screening for delivery with PE at < 3 weeks and at any time after the examination was assessed using areas under the receiver-operating-characteristics curves and detection rates (DRs), at a 10% false-positive rate (FPR). McNemar's test was used to compare DRs, at a 10% FPR, between screening by PlGF concentration, the sFlt-1/PlGF concentration ratio and the competing-risks model utilizing maternal risk factors, MAP and ophthalmic artery PSV ratio. Model-based estimates of screening performance for different methods of screening were also produced., Results: The study population of 2338 pregnancies contained 75 (3.2%) cases that developed PE, including 30 (1.3%) that delivered with PE at < 3 weeks from assessment, and 2263 cases unaffected by PE. The DR of PE at < 3 weeks from assessment, at a 10% FPR, of sFlt-1/PlGF ratio (70.0% (95% CI, 50.6-85.3%)) was superior to that of PlGF (50.0% (95% CI, 31.3-68.7%)) or PSV ratio (56.7% (95% CI, 37.4-74.5%)) but inferior to that of the combination of maternal risk factors, MAP multiples of the median (MoM) and PSV ratio delta (96.7% (95% CI, 82.8-99.9%)). Similarly, the DR of PE at any stage after assessment of sFlt-1/PlGF ratio (62.7% (95% CI, 50.7-73.6%)) was superior to that of PlGF (52.0% (95% CI, 40.2-63.7%)) or PSV ratio (41.3% (95% CI, 30.1-53.3%)) but inferior to that of the combination of maternal risk factors, MAP MoM and PSV ratio delta (78.7% (95% CI, 67.7-87.3%)). The empirical results for DR at a 10% FPR were consistent with the modeled results, both for delivery with PE at < 3 weeks and at any time after assessment., Conclusion: Ophthalmic artery Doppler in combination with maternal risk factors and blood pressure could potentially replace measurement of PlGF and sFlt-1/PlGF ratio in the prediction of imminent PE. © 2022 International Society of Ultrasound in Obstetrics and Gynecology., (© 2022 International Society of Ultrasound in Obstetrics and Gynecology.)

Objective: To examine the changes in ophthalmic artery Doppler indices and their association with changes in mean arterial blood pressure (MAP) and systolic (SBP) and diastolic (DBP) blood pressure, following acute antihypertensive treatment in women with hypertensive disorders of pregnancy presenting with high blood pressure., Methods: This was a prospective cohort study of 31 pregnant women presenting at 30 + 0 to 39 + 6 weeks' gestation for management of their hypertension. Paired maternal blood-pressure and ophthalmic-artery-Doppler measurements were performed prior to and at 30 min and 60 min after starting antihypertensive medication. In patients who did not achieve blood-pressure control (i.e. when blood pressure was < 140/90 mmHg) by 60 min, paired readings were continued up to 120 min. If blood-pressure control was still not achieved at that point, patients were admitted to hospital. Univariate linear regression was performed to determine the association of ophthalmic artery peak systolic velocity (PSV) ratio with SBP, DBP and MAP before treatment and after blood-pressure control. The longitudinal changes in MAP, SBP, DBP and PSV ratio from pretreatment to 30 min and 60 min after commencement of antihypertensives were examined by repeated measure, multilevel, linear mixed-effects analysis., Results: Antihypertensive treatment was associated with a decrease in SBP, DBP, MAP and PSV ratio. At 60 min following antihypertensive treatment, the decrease in SBP, DBP, MAP and PSV ratio was 12.1 mmHg (95% CI, 9.0-15.1 mmHg; P < 0.0001), 9.1 mmHg (95% CI, 6.5-11.5 mmHg; P < 0.0001), 10.0 mmHg (95% CI, 7.6-12.4 mmHg; P < 0.0001) and 0.07 (95% CI, 0.03-0.11 mmHg; P < 0.001), respectively. From the total cohort, 20 (64.5%) women had achieved blood-pressure control at 60 min and another seven (22.6%) by 120 min from commencement of antihypertensive treatment. Four (12.9%) women did not achieve blood-pressure control during this period and were admitted to hospital. The relationship between PSV ratio and SBP, DBP and MAP was assessed before treatment (n = 31) and at the point of blood-pressure control in women in whom this was achieved by 120 min (n = 27). Prior to treatment, there was a significant association between PSV ratio and MAP (P < 0.0001, R 2  = 0.39). This was primarily due to the association of PSV ratio with DBP (P < 0.0001, R 2  = 0.39) and less so due to its association with SBP (P = 0.02, R 2  = 0.16). At the point of achieving blood-pressure control, there was no significant association between PSV ratio and MAP (P = 0.7), DBP (P = 0.5) or SBP (P = 0.7)., Conclusions: Acute blood-pressure control in pregnancy is associated with a concomitant reduction in blood pressure and ophthalmic artery PSV ratio. In hypertensive pregnant women, there is a significant association of PSV ratio with MAP, SBP and DBP, which disappears after blood pressure is reduced to < 140/90 mmHg following antihypertensive treatment. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension and is associated with increased maternal and perinatal morbidity compared with preeclampsia alone. Distinguishing superimposed preeclampsia from chronic hypertension can be challenging because, in chronic hypertension, the traditional criteria for the diagnosis of preeclampsia, hypertension, and significant proteinuria can often predate the pregnancy. Furthermore, the prevalence of superimposed preeclampsia is unlikely to be uniformly distributed across this high-risk group but is related to the severity of preexisting endothelial dysfunction. This has led to interest in identifying biomarkers that could help in screening and diagnosis of superimposed preeclampsia and in the stratification of risk in women with chronic hypertension. Elevated levels of uric acid and suppression of other renal biomarkers, such as the renin-angiotensin aldosterone system, have been demonstrated in women with superimposed preeclampsia but perform only modestly in its prediction. In addition, central to the pathogenesis of preeclampsia is a tendency toward an antiangiogenic state thought to be triggered by an impaired placenta and, ultimately, contributing to the endothelial dysfunction pathognomonic of the disease. In the general obstetrical population, angiogenic factors, such as soluble fms-like tyrosine kinase-1 and placental growth factor, have shown promise in the prediction of preeclampsia. However, soluble fms-like tyrosine kinase-1 and placental growth factor are impaired in women with chronic hypertension irrespective of whether they develop superimposed preeclampsia. Therefore, the differences in levels are less discriminatory in the prediction of superimposed preeclampsia compared with the general obstetrical population. Alternative biomarkers to the angiogenic and renal factors include those of endothelial dysfunction. A characteristic of both preeclampsia and chronic hypertension is an exaggerated systemic inflammatory response causing or augmenting endothelial dysfunction. Thus, proinflammatory mediators, such as tumor necrosis factor-α, interleukin-6, cell adhesion molecules, and endothelin, have been investigated for their role in the screening and diagnosis of superimposed preeclampsia in women with chronic hypertension. To date, the existing limited evidence suggests that the differences between those who develop superimposed preeclampsia and those who do not are, as with angiogenic factors, also modest and not clinically useful for the stratification of women with chronic hypertension. Finally, pro-B-type natriuretic peptide is regarded as a sensitive marker of early cardiac dysfunction that, in women with chronic hypertension, may predate the pregnancy. Thus, it has been proposed that pro-B-type natriuretic peptide could give insight as to the ability of women with chronic hypertension to adapt to the hemodynamic requirements of pregnancy and, subsequently, their risk of developing superimposed preeclampsia. Although higher levels of pro-B-type natriuretic peptide have been demonstrated in women with superimposed preeclampsia compared with those without, current evidence suggests that pro-B-type natriuretic peptide is not a predictor for the disease. The objectives of this review are to, first, discuss the current criteria for the diagnosis of superimposed preeclampsia and, second, to summarize the evidence for these potential biomarkers that may assist in the diagnosis of superimposed preeclampsia., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Objectives: To assess first trimester serum placental growth factor (PLGF), soluble fms-like tyrosine kinase-1 (sFLT-1), interleukin-6 (IL-6), tumour necrosis factor-α (TNF-α), endothelin and vascular cell adhesion molecule (VCAM) in women with chronic hypertension (CH) stratified according to blood pressure (BP) control., Design: Case-control., Setting: Tertiary referral centre., Population: 650 women with CH, 142 normotensive controls., Methods: In the first trimester, patients with CH were subdivided into four groups. Group 1 included women without pre-pregnancy CH presenting with BP ≥140/90 mmHg. Groups 2-4 had pre-pregnancy CH; in group 2 the BP was <140/90 mmHg without antihypertensive medication, in group 3 the BP was <140/90 mmHg with antihypertensive medication, and in group 4 the BP was ≥140/90 mmHg despite antihypertensive medication. PLGF, sFLT-1, IL-6, TNF-α, endothelin and VCAM were measured at 11 +0 -13 +6  weeks' gestation and converted into multiples of the expected median (MoM) using multivariate regression analysis in the controls., Main Outcome Measure: Comparisons of MoM values of PLGF, sFLT-1, endothelin, IL-6, TNF-α and VCAM between the entire cohort of women with CH and the control group were made using Student's t-test or Mann-Whitney U-test. Comparisons between the four CH groups were made using analysis of variance or Kruskal-Wallis tests., Results: Compared with the control group, women with CH had significantly lower MoM of PLGF, sFLT-1 and IL-6 and a significantly higher MoM of endothelin. Between the four groups of women with CH, there were no significant differences in the MoM of sFLT-1, PLGF, sFLT-1/PLGF ratio, endothelin, IL-6 or VCAM, or in the levels of TNF- α., Conclusion: In women with CH, differences exist in first trimester angiogenic and inflammatory profiles when compared with normotensive pregnancies. However, these differences do not assist in the stratification of women with CH to identify those with more severe underlying disease and worse pregnancy outcomes., Tweetable Abstract: First trimester blood pressure control impacts on serum PLGF, sFLT-1, endothelin and IL-6 in women with chronic hypertension., (© 2021 John Wiley & Sons Ltd.)

Background: Hypertensive disorders of pregnancy are associated with chronic kidney disease. Early detection of renal dysfunction enables implementation of strategies to prevent progression. International guidelines recommend review at 6-8 weeks postpartum to identify persistent hypertension and abnormal renal function, but evidence for the efficacy of this review is limited., Methods: All women attending a specialist fetal-maternal medicine clinic for hypertensive disorders of pregnancy (pre-eclampsia, chronic hypertension, gestational hypertension) were invited for a 6-8 weeks postpartum review of their blood pressure and renal function in order to establish the prevalence and independent predictors of renal dysfunction. Renal dysfunction was defined as low estimated Glomerular Filtration Rate (eGFR < 60 ml/min/1.73 m 2 ) or proteinuria (24-h protein excretion > 150 mg or urinary albumin-to-creatinine ratio > 3 mg/mmol). All women attending a specialist clinic for hypertensive disorders were invited for a 6-8 weeks postpartum review of their blood pressure and renal function. Demographics, pregnancy and renal outcomes were prospectively collected., Results: Between 2013 and 2019, 740 of 1050 (70.4%) women who had a pregnancy complicated by a hypertensive disorder attended their 6-8 weeks postpartum visit. Renal dysfunction was present in 32% of the total cohort and in 46% and 22% of women with and without pre-eclampsia, respectively. Multivariate logistic regression demonstrated that independent predictors were pre-eclampsia, chronic hypertension, highest measured antenatal serum creatinine, highest measured antenatal 24-h urinary protein, and blood pressure ≥ 140/90 mmHg at the postnatal visit., Conclusions: Renal dysfunction was present in one in three women with hypertensive disorders of pregnancy at 6-8 weeks postpartum. This includes women with gestational hypertension and chronic hypertension without superimposed pre-eclampsia, and thus these women should also be offered postnatal review., (© 2021. The Author(s).)

Objective: To compare longitudinal maternal hemodynamic changes throughout gestation between different age groups., Methods: This was a prospective longitudinal study assessing maternal hemodynamics using a bioreactance technique at 11 + 0 to 13 + 6, 19 + 0 to 24 + 0, 30 + 0 to 34 + 0 and 35 + 0 to 37 + 0 weeks' gestation. Women were divided into four groups according to maternal age at the first visit at 11 + 0 to 13 + 6 weeks: Group 1, < 25.0 years; Group 2, 25.0-30.0 years; Group 3, 30.1-34.9 years; and Group 4, ≥ 35.0 years. A multilevel linear mixed-effects model was performed to compare the repeat measurements of hemodynamic variables, correcting for demographics, medical and obstetric history, pregnancy complications, maternal age and gestational-age window., Results: The study population included 254 women in Group 1, 442 in Group 2, 618 in Group 3 and 475 in Group 4. Younger women (Group 1) had the highest cardiac output (CO) and lowest peripheral vascular resistance (PVR), and older women (Group 4) had the lowest CO and highest PVR throughout pregnancy. The higher CO seen in younger women was achieved through an increase in heart rate alone and not with a concomitant rise in stroke volume. Although the youngest age group demonstrated an apparently more favorable hemodynamic profile, it had the highest incidence of a small-for-gestational-age neonate. There was no significant difference between the groups in the incidence of pre-eclampsia., Conclusion: Age-specific differences in maternal hemodynamic adaptation do not explain the differences in the incidence of a small-for-gestational-age neonate between age groups. © 2021 International Society of Ultrasound in Obstetrics and Gynecology., (© 2021 International Society of Ultrasound in Obstetrics and Gynecology.)

Introduction: The aim of this study was to assess perinatal outcomes in women with chronic hypertension (CH) stratified into four groups according to their blood pressure (BP) control in the first trimester of pregnancy., Material and Methods: This was a prospective cohort study between January 2011 and June 2017, based in a university hospital in London, UK. The population consisted of four groups: group 1 included women without history of CH, presenting in the first trimester with BP >140/90 mmHg (n = 100). Groups 2-4 had prepregnancy CH; group 2 had BP <140/90 mmHg without antihypertensives (n = 234), group 3 had BP <140/90 mmHg with antihypertensives (n = 272), and group 4 had BP ≥140/90 mmHg despite antihypertensives (n = 194). The main outcome measures were: fetal growth restriction, admission to neonatal (NNU) or neonatal intensive care unit (NICU) for ≥2 days, composite neonatal morbidity, and composite serious adverse neonatal outcome. Outcomes were collected from the hospital databases and for up to 6 weeks postnatally. Differences between groups were assessed using chi-squared test and multivariate logistic regression was used to assess the independent contribution of the four groups to the prediction of pertinent outcomes, after controlling for maternal characteristics., Results: There was a higher incidence of fetal growth restriction in groups 3 (17.6%) and 4 (18.2%), compared with groups 1 (10.0%) and 2 (11.1%) (P = .04). There were more admissions to the NNU for ≥2 days in groups 3 (23.2%) and 4 (25.0%), compared with groups 1 (17.0%) and 2 (13.2%) (P = .008); and more admissions to NICU for ≥2 days in groups 3 (9.2%) and 4 (9.4%), compared with groups 1 (3.0%) and 2 (3.4%) (P = .01). Composite neonatal morbidity was higher in groups 3 (22.4%) and 4 (21.4%), compared with groups 1 (17.0%) and 2 (11.5%) (P = .009). Composite serious adverse postnatal outcome was higher in groups 3 (3.3%) and 4 (4.2%), compared with groups 1 (1.0%) and 2 (0.9%) but the difference did not reach statistical significance (P = .09). These results were also observed when values were adjusted for maternal characteristics., Conclusions: In CH adverse perinatal outcomes are worse in women who are known to have CH and need antihypertensives in the first trimester of pregnancy. Women with newly diagnosed CH in the first trimester have similar outcomes to those with known CH who have antihypertensive treatment discontinued., (© 2021 Nordic Federation of Societies of Obstetrics and Gynecology.)

Background: Pregnancies with small-for-gestational-age fetuses are at increased risk of adverse maternal-fetal outcomes. Previous studies examining the relationship between maternal hemodynamics and fetal growth were mainly focused on high-risk pregnancies and those with fetuses with extreme birthweights, such as less than the 3rd or 10th percentile and assumed a similar growth pattern in fetuses above the 10th percentile throughout gestation., Objective: This study aimed to evaluate the trends in maternal cardiac function, fetal growth, and oxygenation with advancing gestational age in a routine obstetrical population and all ranges of birthweight percentiles., Study Design: This was a prospective, longitudinal study assessing maternal cardiac output and peripheral vascular resistance by bioreactance at 11 +0 to 13 +6 , 19 +0 to 24 +0 , 30 +0 to 34 +0 , and 35 +0 to 37 +0 weeks' gestation, sonographic estimated fetal weight in the last 3 visits and the ratio of the middle cerebral artery by umbilical artery pulsatility indices or cerebroplacental ratio in the last 2 visits. Women were divided into the following 5 groups according to birthweight percentile: group 1, <10th percentile (n=261); group 2, 10 to 19.9 percentile (n=180); group 3, 20 to 29.9 percentile (n=189); group 4, 30 to 69.9 percentile (n=651); and group 5, ≥70th percentile (n=508). The multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z scores of the estimated fetal weight and cerebroplacental ratio., Results: In visit 2, compared with visit 1, in all groups, cardiac output increased, and peripheral vascular resistance decreased. At visit 3, groups 1, 2, and 3, compared with 4 and 5, demonstrated an abrupt decrease in cardiac output and increase in peripheral vascular resistance. From visit 2, group 1 had a constant decline in estimated fetal weight, coinciding with the steepest decline in maternal cardiac output and rise in peripheral vascular resistance. In contrast, in groups 4 and 5, the estimated fetal weight had a stable or accelerative pattern, coinciding with the greatest increase in cardiac output and lowest peripheral vascular resistance. Groups 2 and 3 showed a stable growth pattern with intermediate cardiac output and peripheral vascular resistance. Increasing birthweight was associated with higher cerebroplacental ratio. Groups 3, 4, and 5 had stable cerebroplacental ratio across visits 3 and 4, whereas groups 1 and 2 demonstrated a significant decline (P<.001)., Conclusion: In a general obstetrical population, maternal cardiac adaptation at 32 weeks' gestation parallels the pattern of fetal growth and oxygenation; babies with birthweight<20th percentile have progressive decline in fetal cerebroplacental ratio, decline in maternal cardiac output, and increase in peripheral vascular resistance., (Crown Copyright © 2021. Published by Elsevier Inc. All rights reserved.)

Maternal cardiac dysfunction is associated with pre-eclampsia, fetal growth restriction and haemodynamic instability during obstetric anaesthesia. There is growing interest in the use of non-invasive cardiac output monitoring to guide antihypertensive and fluid therapies in obstetrics. The aim of this study was to validate thoracic bioreactance using the NICOM® instrument against transthoracic echocardiography in pregnant women, and to assess the effects of maternal characteristics on the absolute difference of stroke volume, cardiac output and heart rate. We performed a prospective study involving women with singleton pregnancies in each trimester. We recruited 56 women who were between 11 and 14 weeks gestation, 57 between 20 and 23 weeks, and 53 between 35 and 37 weeks. Cardiac output was assessed repeatedly and simultaneously over 5 min in the left lateral position with NICOM and echocardiography. The performance of NICOM was assessed by calculating bias, 95% limits of agreement and mean percentage difference relative to echocardiography. Multivariate regression analysis evaluated the effect of maternal characteristics on the absolute difference between echocardiography and NICOM. The mean percentage difference of cardiac output measurements between the two methods was ±17%, with mean bias of -0.13 l.min -1 and limits of agreement of -1.1 to 0.84; stroke volume measurements had a mean percentage difference of ±15%, with a mean bias of -0.8 ml (-10.9 to 12.6); and heart rate measurements had a mean percentage difference of ±6%, with a mean bias of -2.4 beats.min -1 (-6.9 to 2.0). Similar results were found when the analyses were confined to each individual trimester. The absolute difference between NICOM and echocardiography was not affected by maternal age, weight, height, race, systolic or diastolic blood pressure. In conclusion, NICOM demonstrated good agreement with echocardiography, and can be used in pregnancy for the measurement of cardiac function., (© 2020 Association of Anaesthetists.)

Introduction: Chronic hypertension complicates 1%-2% of pregnancies and is one of the most significant risk factors for the development of preeclampsia. Inflammatory mediators, such as interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), vascular cell adhesion molecule (VCAM) and endothelin have been implicated in the endothelial dysfunction that is pathognomonic of preeclampsia and may serve as useful first trimester biomarkers for the prediction of preeclampsia. The objectives of this study are: first, to investigate differences in serum levels of IL-6, TNF-α, VCAM and endothelin at 11 +0 to 13 +6 weeks' gestation in women with chronic hypertension who developed superimposed preeclampsia with those who did not and normotensive controls and, second, to evaluate the performance of these biomarkers in the prediction of preeclampsia., Material and Methods: The study population was comprised of 650 women with chronic hypertension, including 202 who developed superimposed preeclampsia and 448 who did not, and 142 normotensive controls matched to the chronic hypertension group for storage time and racial origin. Serum concentrations of IL-6, TNF-α, VCAM and endothelin were measured and the values were converted into multiples of the expected median using multivariate regression analysis in the control group. The multiples of the median values of the biomarkers between the two groups of women with chronic hypertension and the controls were compared, and the receiver operating characteristic curve (ROC) was used to assess the performance of these variables for the prediction of preeclampsia., Results: In women with chronic hypertension, compared with the normotensive controls, there was a significantly higher first trimester median concentration of endothelin but not of VCAM, IL-6 or TNF-α. Within the cohort of women with chronic hypertension, those who developed superimposed preeclampsia, compared with those who did not, had higher first trimester serum concentration of VCAM but not of endothelin, IL-6 or TNF-α. However, serum VCAM provided a poor prediction of superimposed preeclampsia (area under the ROC curve 0.537, 95% CI 0.487-0.587)., Conclusions: Women with chronic hypertension have increased serum endothelin in the first trimester of pregnancy and those who develop superimposed preeclampsia have higher levels of VCAM. None of the inflammatory mediators performed well in the first trimester in the prediction of preeclampsia., (© 2020 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objective: To compare central hemodynamics between white, black and Asian women in pregnancy., Methods: This was a prospective, longitudinal study of maternal central hemodynamics in white, black and Asian women with a singleton pregnancy, assessed using a bioreactance method at 11 + 0 to 13 + 6, 19 + 0 to 24 + 0, 30 + 0 to 34 + 0 and 35 + 0 to 37 + 0 weeks' gestation. At each visit, cardiac output (CO), stroke volume (SV), heart rate (HR), peripheral vascular resistance (PVR) and mean arterial pressure were recorded. Multilevel linear mixed-effects analysis was performed to compare the repeated measures of the cardiac variables between white, black and Asian women, controlling for maternal characteristics, medical history and medication use., Results: The study population included 1165 white, 247 black and 116 Asian women. CO increased with gestational age to a peak at 32 weeks and then decreased; the highest CO was observed in white women and the lowest in Asian women. SV initially increased after the first visit but subsequently declined with gestational age in white women, decreased with gestational age in black women and remained static in Asian women. In all three study groups, HR increased with gestational age until 32 weeks and then remained constant; HR was highest in black women and lowest in white women. PVR showed a reversed pattern to that of CO; the highest values were in Asian women and the lowest in white women. The least favorable hemodynamic profile, which was observed in black and Asian women, was reflected in higher rates of a small-for-gestational-age infant., Conclusions: There are race-specific differences in maternal cardiac adaptation to pregnancy. White women have the most favorable cardiac adaptation by increasing SV and HR, achieving the highest CO and lowest PVR. In contrast, black and Asian women have lower CO and higher PVR than do white women, with CO increasing through a rise in HR due to declining or static SV. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: To compare maternal haemodynamics in women at low and high risk for preterm pre-eclampsia (PE), and between those at high risk who are randomised to aspirin or placebo., Design: Prospective, longitudinal observational study., Setting: Maternity units in six UK hospitals., Population: Women participating in the Aspirin for Prevention of Preterm Pre-eclampsia (ASPRE) trial. The population comprised three groups of women: low risk for preterm PE (n = 1362), high risk for preterm PE treated with aspirin (n = 208) and high risk for preterm PE on placebo (n = 220)., Methods: Women had four visits during pregnancy: 11-14, 19-24, 30-34, and 35-37 weeks' gestation. Blood pressure was measured with a device validated for pregnancy, and PE and maternal haemodynamics were assessed with a bioreactance monitor at each visit. A multilevel linear mixed-effects analysis was performed to examine longitudinal changes of maternal haemodynamic variables, controlling for demographic characteristics, past medical history and medication use., Main Outcome Measures: Longitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR)., Results: The low-risk group demonstrated the expected changes with an increase in CO and reduction in MAP and PVR, with a quadratic change across gestation. In contrast, the high-risk groups had a declining CO, and higher MAP and PVR during pregnancy. The administration of aspirin did not appear to affect maternal haemodynamics., Conclusions: Women screened as high risk for preterm PE have a pathological cardiac adaptation to pregnancy and the prophylactic use of aspirin (150 mg oral daily from the first trimester) in this group may not alter this haemodynamic profile., Tweetable Abstract: In women at high risk of pre-eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation., (© 2020 Royal College of Obstetricians and Gynaecologists.)

Background: An imbalance between angiogenic and antiangiogenic factors is thought to be a central pathogenetic mechanism in preeclampsia. In pregnancies that subsequently experience preeclampsia, the maternal serum concentration of the angiogenic placental growth factor is decreased from as early as the first trimester of pregnancy, and the concentration of the antiangiogenic soluble fms-like tyrosine kinase-1 is increased in the last few weeks before the clinical presentation of the disease. Chronic hypertension, which complicates 1-2% of pregnancies, is the highest risk factor for the development of preeclampsia among all other factors in maternal demographic characteristics and medical history. Two previous studies in women with chronic hypertension reported that first-trimester serum placental growth factor and soluble fms-like tyrosine kinase-1 levels were not significantly different between those who experienced superimposed preeclampsia and those who did not, whereas a third study reported that concentrations of placental growth factor were decreased., Objective: The purpose of this study was to investigate whether, in women with chronic hypertension, serum concentrations of placental growth factor and soluble fms-like tyrosine kinase-1 and soluble fms-like tyrosine kinase-1/placental growth factor ratio at 11 +0 -13 +6 weeks gestation are different between those women who experienced superimposed preeclampsia and those who did not and to compare these values with those in normotensive control subjects., Study Design: The study population comprised 650 women with chronic hypertension, which included 202 women who experienced superimposed preeclampsia and 448 women who did not experience preeclampsia, and 142 normotensive control subjects. Maternal serum concentration of placental growth factor and soluble fms-like tyrosine kinase-1 were measured by an automated biochemical analyzer and converted into multiples of the expected median with the use of multivariate regression analysis in the control group. Comparisons of placental growth factor and soluble fms-like tyrosine kinase-1 levels and soluble fms-like tyrosine kinase-1/placental growth factor ratio in multiples of the expected median values between the 2 groups of chronic hypertension and the control subjects were made with the analysis of variance or the Kruskal-Wallis test., Results: In the group of women with chronic hypertension who experienced preeclampsia compared with those women who did not experience preeclampsia, there were significantly lower median concentrations of serum placental growth factor multiples of the expected median (0.904 [interquartile range, 0.771-1.052] vs 0.948 [interquartile range, 0.814-1.093]; P=.014) and soluble fms-like tyrosine kinase-1 multiples of the expected median (0.895 [interquartile range, 0.760-1.033] vs 0.938 [interquartile range, 0.807-1.095]; P=.013); they were both lower than in the normotensive control subjects (1.009 [interquartile range, 0.901-1.111] and 0.991 [interquartile range, 0.861-1.159], respectively; P<.01 for both). There were no significant differences among the 3 groups in soluble fms-like tyrosine kinase-1/placental growth factor ratios. In women with chronic hypertension, serum placental growth factor and soluble fms-like tyrosine kinase-1 levels provided poor prediction of superimposed preeclampsia (area under the curve, 0.567 [95% confidence interval, 0.537-0.615] and 0.546 [95% confidence interval, 0.507-0.585], respectively)., Conclusion: Women with chronic hypertension, and particularly those who subsequently experienced preeclampsia, have reduced first-trimester concentrations of both placental growth factor and soluble fms-like tyrosine kinase-1., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Pregnancy after liver transplantation (LT) is increasingly common and is a frequent scenario that transplant physicians, obstetricians, and midwives encounter. This review summarizes the key issues surrounding preconception, pregnancy-related outcomes, immunosuppression, and breastfeeding in female LT recipients. Prepregnancy counseling in these patients should include recommendations to delay conception for at least 1-2 years after LT and discussions about effective methods of contraception. Female LT recipients are generally recommended to continue immunosuppression during pregnancy to prevent allograft rejection; however, individual regimens may need to be altered. Although pregnancy outcomes are overall favorable, there is an increased risk of maternal and fetal complications. Pregnancy in this cohort remains high risk and should be managed vigilantly in a multidisciplinary setting. We aim to review the available evidence from national registries, population-based studies, and case series and to provide recommendations for attending clinicians., (Copyright © 2019 by the American Association for the Study of Liver Diseases.)

Competing Interests: None.

Objectives: To evaluate fetal growth in pregnancies complicated by placenta previa with or without placenta accreta spectrum (PAS) disorder, compared with in pregnancies with a low-lying placenta., Methods: This was a multicenter retrospective cohort study of singleton pregnancies complicated by placenta previa with or without PAS disorder, for which maternal characteristics, ultrasound-estimated fetal weight and birth weight were available. Four maternal-fetal medicine units participated in data collection of diagnosis, treatment and outcome. The control group comprised singleton pregnancies with a low-lying placenta (0.5-2 cm from the internal os). The diagnosis of PAS and depth of invasion were confirmed at delivery using both a predefined clinical grading score and histopathological examination. For comparison of pregnancy characteristics and fetal growth parameters, the study groups were matched for smoking status, ethnic origin, fetal sex and gestational age at delivery., Results: The study included 82 women with placenta previa with PAS disorder, subdivided into adherent (n = 35) and invasive (n = 47) PAS subgroups, and 146 women with placenta previa without PAS disorder. There were 64 controls with a low-lying placenta. There was no significant difference in the incidence of small-for-gestational age (SGA) (birth weight ≤ 10 th percentile) and large-for-gestational age (LGA) (birth weight ≥ 90 th  percentile) between the study groups. Median gestational age at diagnosis was significantly lower in pregnancies with placenta previa without PAS disorder than in the low-lying placenta group (P = 0.002). No significant difference was found between pregnancies complicated by placenta previa with PAS disorder and those without for any of the variables. Median estimated fetal weight percentile was significantly lower in the adherent compared with the invasive previa-PAS subgroup (P = 0.047). Actual birth weight percentile at delivery did not differ significantly between the subgroups (P = 0.804)., Conclusions: No difference was seen in fetal growth in pregnancies complicated by placenta previa with PAS disorder compared with those without and compared with those with a low-lying placenta. There was also no increased incidence of either SGA or LGA neonates in pregnancies with placenta previa and PAS disorder compared with those with placenta previa with spontaneous separation of the placenta at birth. Adverse neonatal outcome in pregnancies complicated by placenta previa and PAS disorder is linked to premature delivery and not to impaired fetal growth. Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2019 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Parous women have a lower risk for pregnancy complications, such as preeclampsia or delivery of small-for-gestational-age neonates. However, parous women are a heterogeneous group of patients because they contain a low-risk cohort with previously uncomplicated pregnancies and a high-risk cohort with previous pregnancies complicated by preeclampsia and/or small for gestational age. Previous studies examining the effect of parity on maternal hemodynamics, including cardiac output and peripheral vascular resistance, did not distinguish between parous women with and without a history of preeclampsia or small for gestational age and reported contradictory results., Objective: The objective of the study was to compare maternal hemodynamics in nulliparous women and in parous women with and without previous preeclampsia and/or small for gestational age., Study Design: This was a prospective, longitudinal study of maternal hemodynamics, assessed by a bioreactance method, measured at 11 +0 to 13 +6 , 19 +0 to 24 +0 , 30 +0 to 34 +0 , and 35 +0 to 37 +0 weeks' gestation in 3 groups of women. Group 1 was composed of parous women without a history of preeclampsia and/or small for gestational age (n = 632), group 2 was composed of nulliparous women (n = 829), and group 3 was composed of parous women with a history of preeclampsia and/or small for gestational age (n = 113). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables controlling for maternal characteristics, medical history, and development of preeclampsia or small for gestational age in the current pregnancy., Results: In groups 1 and 2, cardiac output increased with gestational age to a peak at 32 weeks and peripheral vascular resistance showed a reversed pattern with its nadir at 32 weeks; in group 1, compared with group 2, there was better cardiac adaptation, reflected in higher cardiac output and lower peripheral vascular resistance. In group 3 there was a hyperdynamic profile of higher cardiac output and lower peripheral vascular resistance at the first trimester followed by an earlier sharp decline of cardiac output and increase of peripheral vascular resistance from midgestation. The incidence of preeclampsia and small for gestational age was highest in group 3 and lowest in group 1., Conclusion: There are parity-specific differences in maternal cardiac adaptation in pregnancy., (Crown Copyright © 2019. Published by Elsevier Inc. All rights reserved.)

Objective: To compare maternal hemodynamics and perinatal outcome, in pregnancies that do not develop pre-eclampsia (PE) or deliver a small-for-gestational-age (SGA) neonate, between those identified at 11-13 weeks' gestation as being screen positive or negative for preterm PE, by a combination of maternal factors, mean arterial pressure, uterine artery pulsatility index, serum placental growth factor and pregnancy associated plasma protein-A., Methods: This was a prospective longitudinal cohort study of maternal cardiovascular function, assessed using a bioreactance method, in women undergoing first-trimester screening for PE. Maternal hemodynamics and perinatal outcome were compared between screen-positive and screen-negative women who did not have a medical comorbidity, did not develop PE or pregnancy-induced hypertension and delivered at term a live neonate with birth weight between the 5 th and 95 th percentiles. A multilevel linear mixed-effects model was used to compare the repeated measures of cardiac variables, controlling for maternal characteristics., Results: The screen-negative group (n = 926) had normal cardiac function changes across gestation, whereas the screen-positive group (n = 170) demonstrated static or reduced cardiac output and stroke volume and higher mean arterial pressure and peripheral vascular resistance with advancing gestation. In the screen-positive group, compared with screen-negative women, birth-weight Z-score was shifted toward lower values, with prevalence of delivery of a neonate below the 35 th , 30 th or 25 th percentile being about 70% higher, and the rate of operative delivery for fetal distress in labor also being higher., Conclusion: Women who were screen positive for impaired placentation, even though they did not develop PE or deliver a SGA neonate, had pathological cardiac adaptation in pregnancy and increased risk of adverse perinatal outcome. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Background: Hypoglycaemia accounts for approximately one-tenth of term admissions to neonatal units can cause long-term neurodevelopmental impairment and is associated with the significant burden to the affected infants, families and the health system., Objective: To define the prevalence, length and cost of admissions for hypoglycaemia in infants born at greater than 35 weeks gestation and to identify antenatal and perinatal predictors of those outcomes., Materials and Methods: This was a retrospective audit of infants admitted for hypoglycaemia between 1 January 2012 and 31 December 2015, in a level three neonatal intensive care unit at King's College Hospital NHS Foundation Trust, London. The main outcome measures were the prevalence, length and cost of admissions for hypoglycaemia and antenatal and postnatal predictors of the length and cost of the stay., Results: There were 474 admissions for hypoglycaemia (17.8% of total admissions). Their median (IQR) blood glucose on admission was 2.1 (1.7-2.4) mmol/l, gestation at delivery 38.1 (36.7-39.3) weeks, birthweight percentile 31.4 (5.4-68.9), their length of stay was 3.0 (2.0-5.0). Admissions equated to a total of 2107 hospital days. The total cost of the stay was 1,316,591 Great Britain pound. The antenatal factors associated with admission for hypoglycaemia were maternal hypertension (19.8%), maternal diabetes (24.5%), foetal growth restriction (FGR) (25.9%) and pathological intrapartum cardiotocograph (23.4%). In 13.7% of cases, there was no associated pregnancy complication. Multivariate logistic regression analysis demonstrated lower gestational age, z-score birthweight squared, exclusive breastfeeding and maternal prescribed nifedipine were independently associated with the length and cost of the stay., Conclusion: Hypoglycaemia accounted for approximately one-fifth of admissions after 35-week gestation. Lower gestational age and admission blood glucose, low and high z-score birthweight, maternal nifedipine and exclusive breastfeeding are associated with longer duration of stay.

Objective: The aim of this study was to validate the Omron HBP-1300 oscillometric blood pressure (BP) device according to the British Hypertension Society validation protocol, in pregnant women of both medium-arm and large-arm circumferences., Participants and Methods: BP was measured sequentially in 72 women of any gestation requiring the use of a large-size (N=36, arm circumference ≥33 cm) or medium-size cuff (N=36, arm circumference <33 cm) alternating between a mercury sphygmomanometer and the Omron HBP-1300 device., Results: The Omron HBP-1300 is accurate in pregnancy with a mean device-observer difference of 3±6 and 1±6 mmHg for systolic BP and 2±5 and 3±6 mmHg for diastolic BP in women requiring the use of the medium and large cuff, respectively., Conclusion: The Omron HBP-1300-automated BP device can be recommended for use in pregnant women with medium-arm or large-arm circumferences.

Objectives: To compare rates of severe hypertension (SH), preeclampsia (PE) birth of small for gestational age (SGA) neonates between women with chronic hypertension (CH) diagnosed during the first trimester of pregnancy and those with pre-pregnancy CH., Study Design: Prospective cohort study of women with CH and singleton pregnancies referred to an Antenatal Hypertension Clinic at 8-14 weeks' gestation. At presentation the patients were subdivided into four groups based on blood pressure (BP) control. Group 1 included women without a preceding history of CH presenting with BP of ≥140/90 mmHg (n = 86). Groups 2-4 had pre-pregnancy CH; in group 2 the BP was <140/90 mmHg without antihypertensive medication (n = 200), in group 3 the BP was <140/90 mmHg with antihypertensive medication (n = 231) and in group 4 the BP was ≥140/90 mmHg despite antihypertensive medication (n = 173)., Main Outcome Measures: PE, SH (BP ≥ 160/110 mmHg), SGA (birthweight < 10th percentile)., Results: In group 1, the rate of SH (15.1%), was similar to that in group 2 (10.5%) and group 3 (23.8%) but significantly lower than in group 4 (52.6%). In group 1, the rate of PE (12.8%) and SGA <10th centile (18.6%) were similar to those in group 2 (16.5% and 21.0%) and significantly lower than in group 3 (26.0 and 30.7%) and group 4 (26.6% and 31.8)., Conclusion: In women diagnosed with CH in the first trimester of pregnancy, the rates of SH, PE and SGA are similar to those with pre-pregnancy CH who present with BP below 140/90 without the need for antihypertensive medication., (Copyright © 2018 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Objectives: To assess whether, in a cohort of patients with a small-for-gestational-age (SGA) fetus with estimated fetal weight ≤ 10 th percentile, maternal hemodynamics, fetal biometry and Doppler indices at presentation can predict the subsequent development of an abnormal fetal Doppler index or delivery of a baby with birth weight < 3 rd percentile., Methods: This was a prospective observational cohort study conducted at a specialist clinic for the management of pregnancies with a SGA fetus at King's College Hospital, London, UK. The study population comprised 86 singleton pregnancies with a SGA fetus, presenting at a median gestational age of 32 (range, 26-35) weeks. We measured maternal cardiac function using a non-invasive transthoracic bioreactance monitor, as well as mean arterial pressure, fetal biometry, and umbilical artery (UA), fetal middle cerebral artery (MCA) and uterine artery (UtA) pulsatility indices (PI), and the deepest vertical pool of amniotic fluid. Z-scores of these variables were calculated based on reported reference ranges and the values were compared between pregnancies with evidence of an abnormal fetal Doppler index at presentation (Group 1), those that had developed an abnormal Doppler index at a subsequent visit (Group 2) and those that did not develop an abnormal Doppler index throughout pregnancy (Group 3). Abnormal fetal Doppler was defined as UA-PI > 95 th percentile and/or MCA-PI < 5 th percentile. Differences in measured variables at presentation were also compared between pregnancies delivering a baby with birth weight < 3 rd percentile and those delivering a baby with birth weight ≥ 3 rd percentile. Multivariate logistic regression analysis was used to determine significant predictors of birth weight < 3 rd percentile and evolution from normal to abnormal fetal Doppler., Results: In the study population, 14 (16%) cases were in Group 1, 19 (22%) in Group 2 and 53 (62%) in Group 3. Birth weight was < 3 rd percentile in 39 (45%) cases and ≥ 3 rd percentile in 47 (55%). There was decreased cardiac output and stroke volume and increased peripheral vascular resistance compared with a normal population, and the deviations from normal were most marked in Group 1. Pregnancies with birth weight < 3 rd percentile, compared with those with birth weight ≥ 3 rd percentile, had greater deviations from normal in fetal biometry, maternal cardiac output, stroke volume, heart rate, peripheral vascular resistance and UtA-PI. Multivariate logistic regression analysis demonstrated that, in the prediction of birth weight < 3 rd percentile, maternal hemodynamic profile provided significant improvement to the prediction provided by maternal demographics, fetal biometry, UtA-PI, UA-PI and MCA-PI (difference between areas under receiver-operating characteristics curves, 0.18 (95% CI, 0.06-0.29); P = 0.002). In contrast, there was no significant independent contribution from maternal hemodynamics in the prediction of the subsequent development of abnormal fetal Doppler., Conclusions: In pregnancies with a SGA fetus, there is decreased maternal cardiac output and stroke volume and increased peripheral vascular resistance, and the deviations from normal are most marked in cases of redistribution in the fetal circulation and reduced amniotic fluid volume. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.)

Objectives: To determine if, in a high-risk group of women in the first half of pregnancy, those who develop pre-eclampsia (PE) with fetal growth restriction (FGR) demonstrate distinct hemodynamics compared with those with PE in the absence of FGR (PE only)., Methods: Cardiac output (CO), peripheral vascular resistance (PVR) and mean arterial pressure (MAP) were measured at the first hospital visit at 9-24 weeks' gestation in 69 women who had chronic hypertension and 67 who had had a hypertensive disorder in a previous pregnancy. These women were divided into five groups according to pregnancy outcome. In total, 19 subsequently developed PE only, 22 developed PE with FGR, 17 developed pregnancy-induced hypertension, 39 had chronic hypertension without PE or FGR and 39 had had a hypertensive disorder in a previous pregnancy without PE, pregnancy-induced hypertension or FGR in the index pregnancy. The hemodynamic values in each of these groups were compared with those in a cohort of 300 low-risk women with normal pregnancy., Results: In all the high-risk groups, PVR and MAP were higher than in women with a normal pregnancy, but CO was lower in the group of women with PE and FGR, whereas in the other high-risk groups, it was not significantly different from normal., Conclusions: In women who develop PE, there is evidence of high PVR and MAP from the first half of pregnancy, whilst PE and FGR are associated with failure in physiological expansion of CO. Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2017 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The Microlife WatchBP Home automated blood pressure device was assessed for accuracy in pregnant women of medium (<32 cm) and large (≥32 cm) arm circumference., Materials and Methods: The British Hypertension Society validation protocol was modified for the purpose of this study to include women with arm circumference of less than 32 cm (N=51) and greater than or equal to 32 cm (N=46) as two separate arms., Results: The device achieved an overall A/A grade for medium arm circumference and B/A grade for large arm circumference. The mean±SD device-observer difference was 1.7±6.2 and -0.4±4.4 for systolic and diastolic blood pressure, respectively, for medium arm circumference and 3.0±8.5 and 1.5±5.1, respectively, for large arm circumference. When all women with pre-eclampsia from both groups were pooled (N=23), the device achieved an overall grade of A/A with mean differences of 2.1±7.2 for systolic blood pressure and 1.0±5.6 for diastolic blood pressure., Conclusion: The Microlife WatchBP Home automated blood pressure device can be recommended for use in pregnant women of all gestations, including those with pre-eclampsia. However, caution is needed for women with large arm circumferences.

Introduction: The replacement of 24-h urine collection by protein-creatinine ratio (PCR) for the diagnosis of preeclampsia has been recently recommended. However, the literature is conflicting and there are concerns about the impact of demographic characteristics on the performance of PCR., Material and Methods: This was an implementation audit of the introduction of PCR in a London Tertiary obstetric unit. The performance of PCR in the prediction of proteinuria ≥300 mg/day was assessed in 476 women with suspected preeclampsia who completed a 24-h urine collection and an untimed urine sample for PCR calculation. Multivariate logistic regression was used to assess the independent predictors of significant proteinuria., Results: In a pregnant population, ethnicity and PCR are the main predictors of ≥300 mg proteinuria in a 24-h urine collection. A PCR cut-off of 30 mg/mmol would have incorrectly classified as non-proteinuric, 41.4% and 22.9% of black and non-black women, respectively. Sensitivity of 100% is achieved at cut-offs of 8.67 and 20.56 mg/mmol for black and non-black women, respectively. Applying these levels as a screening tool to inform the need to perform a 24-h urine collection in 1000 women, would lead to a financial saving of €2911 in non-black women and to an additional cost of €3269 in black women., Conclusions: Our data suggest that a move from screening for proteinuria with a 24-h urine collection to screening with urine PCR is not appropriate for black populations. However, the move may lead to cost-saving if used in the white population with a PCR cut-off of 20.5., (© 2018 Nordic Federation of Societies of Obstetrics and Gynecology.)

Objectives: In pregnant women with previous gestational hypertension: to compare the prevalence of preeclampsia as defined by the 2001 versus the 2014 International Society for the Study of Hypertension in Pregnancy (ISSHP) criteria, to determine the rates of fetal growth restriction (FGR) as defined, not only by birthweight centile, but in combination with fetal ultrasound studies and, finally, to determine rates of other related outcomes such as gestational diabetes (GDM) and obstetric cholestasis (OC)., Study Design: This was a retrospective observational study based at the Antenatal Hypertension Clinic, Kings College Hospital, London. Routinely collected data of 773 women booked between 2011 and 2016 with a history of gestational hypertension was analysed. All women were normotensive at booking and those with chronic hypertension were excluded., Main Outcomes Measures: Hypertensive disorders of pregnancy (ISSHP-2014), FGR, GDM., Results: Forty-nine percent developed one or more pregnancy complications, of which 72% were hypertensive disorders of pregnancy, 25.8% preeclampsia, 25% GDM and 19% FGR. Overall recurrence rate of preeclampsia was 12.5% (ISSHP-2014). Higher blood pressure and body mass index at booking were associated with higher risk of preeclampsia and GDM. Earlier gestation of previous hypertension was associated with higher risk of preeclampsia and FGR. The ISSHP-2014 compared to the 2001 guidelines classified 56% more women as having preeclampsia., Conclusion: Pregnant women with a history of gestational hypertension have a 49% chance of developing a complication related to a hypertensive disorder, GDM and OC. The rate of preeclampsia was more than doubled if the updated ISSHP-2014 definition was used., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Background: There is extensive evidence that prepregnancy chronic hypertension is associated with a high risk of development of severe hypertension and preeclampsia and birth of small-for-gestational-age neonates. However, previous studies have not reported whether antihypertensive use, blood pressure control, or normalization of blood pressure during early pregnancy influences the rates of these pregnancy complications., Objective: The purpose of this study was to stratify women with prepregnancy chronic hypertension according to the use of antihypertensive medications and level of blood pressure control at the first hospital visit during the first trimester of pregnancy and to examine the rates of severe hypertension, preeclampsia, and birth of small-for-gestational-age neonates according to such stratification., Study Design: We conducted a prospective study of 586 women with prepregnancy chronic hypertension, in the absence of renal or liver disease, that was booked at a dedicated clinic for the management of hypertension in pregnancy. The patients had singleton pregnancies and were subdivided according to findings in their first visit: group 1 (n=199), blood pressure <140/90 mm Hg without antihypertensive medication; group 2 (n=220), blood pressure <140/90 mm Hg with antihypertensive medication; and group 3 (n=167), systolic blood pressure ≥140 mm Hg and/or diastolic blood pressure ≥90 mm Hg, despite antihypertensive medication. In the subsequent management of these pregnancies, our policy was to maintain the blood pressure at 130-140/80-90 mm Hg with the use of antihypertensive medication; antihypertensive drugs were stopped if the blood pressure was persistently <130/80 mm Hg. The outcome measures were severe hypertension (systolic blood pressure ≥160 mm Hg and/or diastolic blood pressure ≥110 mm Hg), preterm and term preeclampsia (in addition to hypertension at least 1 of renal involvement, liver impairment, neurologic complications, or thrombocytopenia), and birth of small-for-gestational-age neonates (birthweight <5th percentile for gestational age). The incidence of these complications was compared in the 3 strata., Results: The median gestational age at presentation was 10.0 weeks (interquartile range, 9.1-11.0 weeks). In groups 2 and 3, compared with group 1, there was a significantly higher body mass index, incidence of black racial origin, and history of preeclampsia in a previous pregnancy. There was a significant increase from group 1 to group 3 in the incidence of severe hypertension (10.6%, 22.2%, and 52.1%), preterm preeclampsia with onset at <37 weeks of gestation (7.0%, 15.9%, and 20.4%), and small for gestational age (13.1%, 17.7%, and 21.1%), but not term preeclampsia with onset at ≥37 weeks of gestation (9.5%, 9.1%, and 6.6%)., Conclusions: In women with prepregnancy chronic hypertension, the rates of development of severe hypertension, preterm preeclampsia, and small for gestational age are related to the use of antihypertensive medications and the level of blood pressure control at the first hospital visit during the first trimester of pregnancy., (Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.)

Objectives: Automated blood pressure devices are frequently introduced in maternity care without prior validation for their accuracy in pregnancy. Our objectives were to, firstly, establish the accuracy in pregnancy of a locally used device (Welch Allyn 300) and, secondly, to audit its impact on the diagnosis and treatment of hypertension., Study Design: Validation study: The device was evaluated using the grading criteria of the European Society of Hypertension International Protocol (ESH-IP) (2010). Two observers took nine same-arm measurements alternating between the Welch Allyn and the mercury sphygmomanometer. Thirty-three women of any gestation were included. Clinical audit: One observer took three same-arm measurements alternating between the Welch Allyn and the mercury sphygmomanometer. One hundred women of any gestation referred with suspected hypertension were included. The main outcome measures were the proportion diagnosed with hypertension or commenced on anti-hypertensive treatment on the presenting visit when using either the manual or the automated device., Main Outcome Measures: Grading criteria of the ESH-IP (2010) and proportion of women diagnosed with hypertension or commenced on antihypertensive therapy at the presenting visit when using either manual sphygmomanometry or the Welch Allyn device., Results: The Welch Allyn 300 series failed to meet the criteria of the ESH-IP (2010) for pregnancy. Compared to the mercury device, it under diagnosed hypertension by 48% and need for treatment by 80%., Conclusions: The Welch Allyn 300 cannot be recommended for the measurement of blood pressure in pregnancy. Its use leads to the under-diagnosis and under-treatment of gestational hypertension., (Crown Copyright © 2017. Published by Elsevier B.V. All rights reserved.)

Objective: Fetal growth restriction (FGR) is a powerful determinant of poor perinatal outcome. From our previous work in pregnancies at high risk of development of hypertension we found impaired cardiovascular adaptation early in gestation in those destined to deliver growth-restricted infants. In this study, we monitored serially maternal hemodynamics from the first to third trimester in a similar high-risk cohort, in order to determine whether this distinct hemodynamic profile found at presentation persisted throughout pregnancy in those complicated by FGR., Methods: This was a prospective observational study based at a specialist antenatal hypertension clinic at a tertiary hospital in London. Maternal hemodynamics were evaluated serially using a non-invasive bioreactance method in pregnant women referred to the clinic with a history of chronic hypertension or a history of hypertensive disorder in a previous pregnancy. Differences in maternal hemodynamic parameters were compared between women who delivered a baby with a birth weight ≥ 10 th vs < 10 th percentile and ≥ 5 th vs < 5 th percentile., Results: Eighty-four pregnant women were included in the study. Mean gestational age at presentation was 14.3 weeks. Sixteen women delivered babies with a birth weight < 10 th percentile and 11 with a birth weight < 5 th percentile. In pregnancies with a birth weight ≥ 10 th percentile, longitudinal maternal hemodynamics showed a pattern consistent with well-established physiological changes in pregnancy, i.e. a reduction in vascular resistance and an increase in cardiac output with advancing gestation until mid-pregnancy. However, women who delivered babies with a birth weight < 10 th percentile showed a static pattern with no change during gestation and lower cardiac output and higher peripheral vascular resistance. Similar differences were seen when the 5 th percentile was used to discriminate between appropriately-grown and growth-restricted babies., Conclusion: Serial assessment of maternal hemodynamics in high-risk women identifies distinctive trends associated with pregnancies destined to deliver babies with birth weights < 10 th and < 5 th percentiles. These pregnancies have a suppressed and static maternal cardiac output and stroke volume, and have consistently raised peripheral vascular resistance. This suggests that, in women with chronic hypertension or a history of hypertensive disorder in a previous pregnancy, FGR is associated with a primary and persistent failure of maternal cardiovascular adaptation in pregnancy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: The aim of this study was to evaluate the accuracy of the Omron MIT Elite automated device in pregnant women with an arm circumference of or above 32 cm, using the British Hypertension Society validation protocol., Methods: Blood pressure was measured sequentially in 46 women of any gestation requiring the use of a large cuff (arm circumference ≥32 cm) alternating between the mercury sphygmomanometer and the Omron MIT Elite device., Results: The Omron MIT Elite achieved an overall D/D grade with a mean of the device-observer difference being 7.17±6.67 and 9.31±6.59 for systolic and diastolic blood pressure respectively. Interobserver accuracy was 94.6% for systolic and 95% for diastolic readings within 5 mmHg., Conclusion: The Omron MIT Elite overestimates blood pressure and has failed the British Hypertension Society protocol requirements. Therefore, it cannot be recommended for use in pregnant women with an arm circumference of or above 32 cm.

This prospective observational study aimed to identify at presentation the maternal hemodynamic and demographic variables associated with a therapeutic response to oral labetalol and to use these variables to develop a prediction model to anticipate the response to labetalol monotherapy in women with hypertension. It was set at a maternity unit in a UK teaching hospital. Maternal demographic data from 50 pregnant women, presenting with hypertension between January and August 2013, was collected and blood pressure measured with a device validated for pregnancy and pre-eclampsia. Maternal haemodynamics were assessed with a bioreactance monitor. Participants were commenced on oral labetalol, and reviewed until delivery and discharge home. Logistic regression analysis was performed to assess the prediction of response to labetalol according to the maternal demographic and hemodynamic variables. Main outcome measures were the response to labetalol monotherapy up to delivery and discharge home, defined as sustained blood pressure control <140/90, and the rates of severe hypertension. Thirty-seven women (74%) had their blood pressure well controlled with labetalol monotherapy, 13 (26%) failed to achieve control with labetalol alone, of whom 9 developed severe hypertension. Multivariate logistic regression showed that heart rate, ethnicity and stroke volume index were independent predictors of the response to labetalol. The predictive accuracy of the model was 96% (95% confidence interval (CI) 86-99%). Maternal demographics and haemodynamics are potent predictors for the response to labetalol, and these parameters may guide therapy to enable effective blood pressure control and a lowering of severe hypertension rates.

Objectives: To examine whether treatment for hypertension in pregnancy that is guided by serial monitoring of maternal central hemodynamics leads to a reduction in the rate of severe hypertension, defined as blood pressure ≥ 160/110 mmHg; and to assess the distinct longitudinal hemodynamic profiles associated with beta-blocker monotherapy, vasodilator monotherapy and dual agent therapy, and their relationships with outcomes, including fetal growth restriction., Methods: This was a prospective observational study at a dedicated antenatal hypertension clinic in a tertiary UK hospital. Fifty-two untreated women presenting with hypertension were recruited consecutively and started on treatment, either with a beta-blocker or a vasodilator. The choice of initial antihypertensive agent was determined according to a model constructed previously to predict the response to the beta-blocker labetalol in pregnant women needing antihypertensive treatment. At presentation, the demographic and maternal hemodynamic variables associated with a therapeutic response to labetalol, defined as blood pressure control < 140/90 mmHg with labetalol monotherapy throughout pregnancy, were ascertained and analyzed with logistic regression to create a model to predict sustained blood pressure control as described above. The women were reviewed regularly until delivery and underwent serial hemodynamic monitoring throughout pregnancy. If their blood pressure was elevated, the prediction model was referred to again to determine if alternative antihypertensive therapy, either with additional beta-blocker or a vasodilator, should be added., Results: Treatment by referring to results of serial hemodynamic monitoring reduced the rate of severe antenatal hypertension from 18% to 3.8%. Seventy-seven percent of women were initially prescribed a beta-blocker and 23% a vasodilator. The group that maintained good blood pressure control with beta-blocker monotherapy had the best fetal and maternal outcomes. They had lower blood pressures at presentation and throughout gestation, demonstrated well-maintained cardiac output and had the lowest rates of fetal growth restriction. The groups that required dual therapy to control their blood pressure had persistently higher blood pressure and rate of fetal growth restriction. The groups that required vasodilator therapy due to high levels of peripheral vascular resistance, either at presentation or later in pregnancy, accounted for 81% of cases with fetal growth restriction., Conclusion: Using serial hemodynamic monitoring in pregnancy to guide treatment of hypertension significantly reduces the rate of severe hypertension and allows identification of high-resistance, low-output hypertensive pregnancies that are associated with an increased rate of fetal growth restriction. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., Resumen Objetivos: Examinar si el tratamiento para la hipertensión en el embarazo guiado por un seguimiento en serie de las principales constantes hemodinámicas de la madre conduce a una reducción en la tasa de hipertensión grave, definida como presión arterial ≥ 160/110 mmHg; y evaluar los diferentes perfiles hemodinámicos longitudinales asociados a la monoterapia con beta-bloqueantes, la monoterapia con vasodilatadores y la terapia dual, y su relación con los resultados, como la restricción del crecimiento fetal. MÉTODOS: Se realizó un estudio observacional prospectivo en una clínica especializada en hipertensión prenatal de un hospital de atención terciaria del Reino Unido. Se reclutaron consecutivamente a cincuenta y dos mujeres no tratadas que presentaban hipertensión y se comenzó a tratarlas, bien con un beta-bloqueante o bien con un vasodilatador. La elección del agente antihipertensivo inicial se determinó de acuerdo con un modelo elaborado previamente para predecir la respuesta al beta-bloqueante labetalol en mujeres embarazadas que necesitaban tratamiento antihipertensivo. Al inicio se registraron las características demográficas y las variables hemodinámicas maternas asociadas con una respuesta terapéutica al labetalol, definida como un control de la presión arterial < 140/90 mmHg con monoterapia de labetalol durante todo el embarazo que se analizó mediante regresión logística para crear un modelo con el que pronosticar un control sostenido de la presión arterial, como se describe arriba. Las mujeres fueron sometidas a revisiones regulares hasta el momento del parto y se les hizo un seguimiento hemodinámico en serie durante todo el embarazo. Si la presión arterial era elevada, se empleó de nuevo el modelo de predicción para determinar si se debería añadir un tratamiento antihipertensivo alternativo, ya sea con un beta-bloqueante adicional o con un vasodilatador., Resultados: El tratamiento que tuvo en cuenta los resultados del seguimiento hemodinámico en serie redujo la tasa de hipertensión prenatal grave del 18% al 3,8%. Al 77% de las mujeres se les recetó inicialmente un y al 23% un vasodilatador. El grupo que mantuvo un buen control de la presión arterial con monoterapia de beta-bloqueantes logró mejores resultados fetales y maternos. Este grupo tuvo menor presión arterial al inicio y durante toda la gestación, mostró un gasto cardíaco en buen estado y tuvo las tasas más bajas de restricción del crecimiento fetal. Los grupos que requirieron terapia dual para controlar su presión arterial mostraron persistentemente una mayor presión arterial y un mayor ritmo de restricción del crecimiento fetal. Los grupos que requirieron tratamiento vasodilatador debido a los altos niveles de resistencia vascular periférica, tanto al inicio como durante el embarazo, representaron el 81% de los casos con restricción del crecimiento fetal. CONCLUSIÓN: El uso de un seguimiento hemodinámico en serie en el embarazo como guía para el tratamiento de la hipertensión reduce significativamente la tasa de hipertensión severa y permite la identificación de embarazos con hipertensión de alta resistencia y malos resultados, asociados con una mayor tasa de restricción del crecimiento fetal. : (≥ 160/110 mmHg);β、,()。 : 。52、,β。β。,(<140/90 mmHg),logistic,。,。,(β)。 : ,18%3.8%。77%β,23%。β。,,。,。,81%。 : ,,、。., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Hypertensive pregnant women who do not respond to treatment with labetalol to control blood pressure (BP), but require vasodilatory therapy, progress rapidly to severe hypertension. This could be delayed by early recognition and individualized treatment. In this study, we sought to create prediction models from data at presentation and at 1 h and 24 h after commencement of treatment to identify patients who will not have a sustained response to labetalol and therefore need vasodilatory therapy., Methods: The study population comprised 134 women presenting with hypertension at a UK hospital. Treatment with oral labetalol was administered when BP was > 150/100 mmHg or > 140/90 mmHg with systemic disease. BP and hemodynamic parameters were recorded at presentation and at 1 h and 24 h after commencement of treatment. Labetalol doses were titrated to maintain BP around 135/85 mmHg. Women with unresponsive BP, despite labetalol dose maximization (2400 mg/day), received additional vasodilatory therapy with nifedipine. Binary logistic and longitudinal (mixed-model) data analyses were performed to create prediction models anticipating the likelihood of hypertensive women needing vasodilatory therapy. The prediction models were created from data at presentation and at 1 h and 24 h after treatment, to assess the value of central hemodynamics relative to the predictive power of BP, heart rate and demographic variables at these intervals., Results: Twenty-two percent of our cohort required additional vasodilatory therapy antenatally. These women had higher rates of severe hypertension and delivered smaller babies at earlier gestational ages. The unresponsive women were more likely to be of black ethnicity, had higher BP and peripheral vascular resistance (PVR), and lower heart rate and cardiac output (CO) at presentation. Those who needed vasodilatory therapy showed an initial decrease in BP and PVR, which rebounded at 24 h, whereas BP and PVR in those who responded to labetalol showed a sustained decrease at 1 h and 24 h. Stroke volume and CO did not decrease during the acute phase of treatment in either group. The best model for prediction of the need for vasodilators was provided at 24 h by combining ethnicity and longitudinal BP and heart rate changes. The model achieved a detection rate of 100% for a false-positive rate of 20% and an area under the receiver-operating characteristics curve of 0.97., Conclusion: Maternal demographics and hemodynamic changes in the acute phase of labetalol monotherapy provide a powerful tool to identify hypertensive pregnant patients who are unlikely to have their BP controlled by this therapy and will consequently need additional vasodilatory therapy. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd., Resumen Objetivo: Las embarazadas hipertensas que no responden al tratamiento con labetalol para el control de la presión arterial (PA), pero que requieren terapia vasodilatadora, evolucionan rápidamente hacia una hipertensión severa. Ésta se puede retrasar mediante un diagnóstico precoz y un tratamiento individual. En este estudio se ha tratado de crear modelos de predicción a partir de datos al inicio del tratamiento y al cabo de 1 hora y de 24 horas después del mismo, para identificar a las pacientes que no mostrarán una respuesta constante al labetalol y que por lo tanto necesitarán terapia vasodilatadora. MÉTODOS: La población de estudio incluyó 134 mujeres con hipertensión en un hospital del Reino Unido. El tratamiento con labetalol por vía oral se administró cuando la PA fue >150/100 mm de Hg o >140/90 mm de Hg con enfermedad multisistémica. Se registró la PA y los parámetros hemodinámicos tanto al inicio como al cabo de 1 h y de 24 h después del inicio del tratamiento. Las dosis de Labetalol se ajustaron para mantener la PA en torno a los 135/85 mm de Hg. Las mujeres cuya PA no produjo respuesta, a pesar de haberles administrado la dosis máxima de labetalol (2400 mg/día), recibieron terapia vasodilatadora adicional con nifedipino. Se realizaron análisis de datos mediante logística binaria y longitudinal (modelo mixto), para crear modelos de predicción con los que pronosticar la probabilidad de la necesidad de terapia vasodilatadora en mujeres hipertensas. Los modelos de predicción se crearon a partir de datos al inicio y al cabo de 1 hora y 24 horas del tratamiento, para evaluar el valor de los parámetros hemodinámicos principales con respecto a la capacidad predictiva de la PA, la frecuencia cardíaca y las variables demográficas en estos intervalos., Resultados: El 22 % de la cohorte necesitó terapia vasodilatadora adicional antes del parto. Estas mujeres tuvieron tasas más altas de hipertensión grave y neonatos más pequeños en edades gestacionales más tempranas. Las mujeres que no respondieron al tratamiento fueron con más frecuencia de raza negra, tuvieron la PA y la resistencia vascular periférica (RVP) más alta, y la frecuencia cardíaca y el gasto cardíaco (GC) más bajos al inicio del tratamiento. Aquellas que necesitaron terapia vasodilatadora mostraron un descenso inicial de la PA y la RVP, que se recuperó al cabo de 24 h, mientras que la PA y la RVP en las que respondieron al labetalol mostraron una disminución constante al cabo de 1 h y de 24 h. El volumen sistólico y el GC no disminuyeron durante la fase aguda del tratamiento en ninguno de los grupos. El mejor modelo para la predicción de la necesidad de vasodilatadores se obtuvo a las 24 h mediante la combinación de la etnia con los cambios longitudinales de la PA y la frecuencia cardíaca. El modelo alcanzó una tasa de detección del 100% para una tasa de falsos positivos del 20% y un área bajo la curva de características operativas del receptor de 0,97. CONCLUSIÓN: Los datos demográficos maternos y los cambios hemodinámicos en la fase aguda de la monoterapia con labetalol constituyen una herramienta poderosa para identificar a las pacientes embarazadas hipertensas con pocas probabilidades de que se les pueda controlar su PA mediante esta terapia y que por lo tanto necesitarán terapia vasodilatadora adicional. : 、(blood pressure,BP),。。,1 h24 h,。 : 134。BP>150/100 mmHgBP>140/90 mmHg。1 h24 hBP。,BP135/85 mmHg。BP,()。logistic(),。1 h24 h,,BP、。 : 22%。。,BP(peripheral vascular resistance,PVR),(cardiac output,CO)。BPPVR,24 h,1 h24 hBPPVR。CO。24hBP。100%,20%,0.97。 : ,BP。., (Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.)

Objective: Firstly, to validate the Withings BP-800 automated device for use in pregnancy and, secondly, to assess the impact of maternal somatometric and demographic variables on the accuracy of the device., Design: Prospective observational study., Setting: Kings College Hospital, London, UK., Population: Forty-seven women of any gestation., Methods: Validation: The British Hypertension Society (BHS) Protocol (1993) was used for the validation of the Withings BP-800. Two trained observers took nine sequential same arm measurements alternating between the Withings BP-800 and the mercury sphygmomanometer. Assessment of factors affecting the disagreement between the two devices: The associations between discrepancies in the measured systolic and diastolic blood pressure by the two devices and potential predictors of discrepancy and/or possible confounders of associations including age, gestational age, ethnicity, body mass index and arm circumference were investigated using two-level mixed effects models to take into account the repeated measurements., Main Outcome Measures: Accuracy of the Withings BP-800 based on the grading criteria of the BHS Protocol (1993)., Results: The Withings BP-800 failed to meet the validation criteria of the BHS protocol for pregnancy and preeclampsia. Inter-device discrepancy was significantly associated with larger arm circumferences and was more pronounced with diastolic blood pressure. This relationship was independent of other maternal characteristics., Conclusions: The Withings BP-800 cannot be recommended for the measurement of blood pressure in pregnancy or preeclampsia. The inaccuracy of the Withings BP-800 increases when used in patients with larger arm circumferences with a propensity to over-read., (Crown Copyright © 2016. Published by Elsevier B.V. All rights reserved.)