ObjectiveTo compare longitudinal maternal hemodynamic changes throughout gestation between differ... more ObjectiveTo compare longitudinal maternal hemodynamic changes throughout gestation between different age groups.MethodsThis 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.ResultsThe 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), an...
Objective To compare maternal haemodynamics in women at low and high risk for preterm pre-eclamps... more 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.
Bjog: An International Journal Of Obstetrics And Gynaecology, Mar 25, 2020
ObjectiveTo compare maternal haemodynamics in women at low and high risk for preterm pre‐eclampsi... more ObjectiveTo 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.DesignProspective, longitudinal observational study.SettingMaternity units in six UK hospitals.PopulationWomen 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).MethodsWomen 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 measuresLongitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR).ResultsThe 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.ConclusionsWomen 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 abstractIn women at high risk of pre‐eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation.
Acta Obstetricia et Gynecologica Scandinavica, Mar 17, 2021
IntroductionThe aim of this study was to assess perinatal outcomes in women with chronic hyperten... more IntroductionThe 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 methodsThis 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 &gt;140/90 mmHg (n = 100). Groups 2‐4 had prepregnancy CH; group 2 had BP &lt;140/90 mmHg without antihypertensives (n = 234), group 3 had BP &lt;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.ResultsThere 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.ConclusionsIn 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.
American Journal of Obstetrics and Gynecology, Jun 1, 2021
BACKGROUND Pregnancies with small for gestational age fetuses are at increased risk of adverse ma... more 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 To evaluate the trends in maternal cardiac function, fetal growth and oxygenation with advancing gestational age in a routine obstetric 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+0-13+6, 19+0-24+0, 30+0-34+0 and 35+0-37+0 weeks' gestation, sonographic estimated fetal weight in the last three visits and the ratio of the middle cerebral artery by the umbilical artery pulsatility indices or cerebroplacental ratio in the last two visits. Women were divided into five groups according to birthweight percentile: Group 1 <10th percentile (n=261); group 2, 10-19.9 percentile (n=180), group 3, 20-29.9 percentile (n=189); group 4, 30-69.9 percentile (n=651) and group 5, >70th centile (n=508). Multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z-scores of estimated fetal weight and cerebroplacental ratio. RESULTS In visit 2, compared to visit 1, in all groups cardiac output increased and peripheral vascular resistance decreased. At visit 3, groups 1, 2 and 3, compared to 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, whilst groups 1 and 2 demonstrated a significant decline. CONCLUSION in a general obstetric population, maternal cardiac adaptation from 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.
Ultrasound in Obstetrics & Gynecology, Oct 1, 2022
OBJECTIVES To compare the longitudinal maternal hemodynamic changes throughout gestation between ... more OBJECTIVES To compare the longitudinal maternal hemodynamic changes throughout gestation between different groups stratified according to booking weight and assess the relative influence of height, booking weight and gestational weight gain on cardiac adaptation. METHODS This was a prospective, longitudinal study assessing maternal hemodynamics by bioreactance technique at 11+0 -13+6 , 19+0 -24+0 , 30+0 -34+0 and 35+0 -37+0 weeks' gestation. Women were divided into three groups according to maternal booking weight at the first visit at 11+0 -13+6 weeks: Group 1 <60.0 kg (n=421); group 2, 60.0-79.7 kg (n=904), group 3, >79.7 kg (n=427). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables correcting for demographics, medical and obstetric history, pregnancy complications, maternal weight and time. The linear mixed-effect model was then repeated with maternal height, booking weight and gestational weight gain z-scores, and the standardised coefficients used to depict the relative influence of each of these demographic parameters in longitudinal changes of maternal hemodynamics. RESULTS Compared to group 1, women in group 3 demonstrated higher cardiac output (CO), heart rate (HR), peripheral vascular resistance (PVR) and mean arterial pressure (MAP) throughout pregnancy. Group 2 and 3 had higher stroke volume (SV) than group 1 in the first visit, but their SV plateaued and demonstrated an earlier decrease from visit 2 to 3 when compared to group 1. Compared to group 1 and 2, there is a higher prevalence of pre-eclampsia, gestational hypertension and gestational diabetes in group 3. Maternal height is the most important contributor to CO, PVR, SV and HR, and weight to MAP. Gestational weight gain is the second most important characteristic influencing the longitudinal changes of PVR and SV. CONCLUSIONS Women with greater booking weight have a pathological hemodynamic profile with high CO, PVR and MAP compared to those of lesser weight. 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 influencer for SV and PVR. This article is protected by copyright. All rights reserved.
Bjog: An International Journal Of Obstetrics And Gynaecology, Aug 5, 2021
ObjectivesTo assess first trimester serum placental growth factor (PLGF), soluble fms‐like tyrosi... more ObjectivesTo 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.DesignCase–control.SettingTertiary referral centre.Population650 women with CH, 142 normotensive controls.MethodsIn 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 &lt;140/90 mmHg without antihypertensive medication, in group 3 the BP was &lt;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 measureComparisons 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.ResultsCompared 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.ConclusionIn 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 abstractFirst trimester blood pressure control impacts on serum PLGF, sFLT‐1, endothelin and IL‐6 in women with chronic hypertension.
Prenatal recognition of dilated aortic root is extremely rare and there are significant challenge... more Prenatal recognition of dilated aortic root is extremely rare and there are significant challenges in counselling these patients. The primary aim of this case series is to describe the prevalence, associations and outcome of dilated ascending aorta diagnosed during fetal life.
IntroductionThe aim of this study was to assess perinatal outcomes in women with chronic hyperten... more IntroductionThe 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 methodsThis 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 ho...
American Journal of Obstetrics and Gynecology, 2022
Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension... more 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.
ABSTRACTObjectiveTo compare the predictive performance for delivery with pre‐eclampsia (PE) at &l... more ABSTRACTObjectiveTo 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.MethodsThis 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...
American Journal of Obstetrics and Gynecology, 2021
BACKGROUND Pregnancies with small for gestational age fetuses are at increased risk of adverse ma... more 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 To evaluate the trends in maternal cardiac function, fetal growth and oxygenation with advancing gestational age in a routine obstetric 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+0-13+6, 19+0-24+0, 30+0-34+0 and 35+0-37+0 weeks' gestation, sonographic estimated fetal weight in the last three visits and the ratio of the middle cerebral artery by the umbilical artery pulsatility indices or cerebroplacental ratio in the last two visits. Women were divided into five groups according to birthweight percentile: Group 1 <10th percentile (n=261); group 2, 10-19.9 percentile (n=180), group 3, 20-29.9 percentile (n=189); group 4, 30-69.9 percentile (n=651) and group 5, >70th centile (n=508). Multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z-scores of estimated fetal weight and cerebroplacental ratio. RESULTS In visit 2, compared to visit 1, in all groups cardiac output increased and peripheral vascular resistance decreased. At visit 3, groups 1, 2 and 3, compared to 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, whilst groups 1 and 2 demonstrated a significant decline. CONCLUSION in a general obstetric population, maternal cardiac adaptation from 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.
ObjectiveTo compare longitudinal maternal hemodynamic changes throughout gestation between differ... more ObjectiveTo compare longitudinal maternal hemodynamic changes throughout gestation between different age groups.MethodsThis 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.ResultsThe 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), an...
Objective To compare maternal haemodynamics in women at low and high risk for preterm pre-eclamps... more 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.
Bjog: An International Journal Of Obstetrics And Gynaecology, Mar 25, 2020
ObjectiveTo compare maternal haemodynamics in women at low and high risk for preterm pre‐eclampsi... more ObjectiveTo 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.DesignProspective, longitudinal observational study.SettingMaternity units in six UK hospitals.PopulationWomen 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).MethodsWomen 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 measuresLongitudinal changes of cardiac output (CO), mean arterial pressure (MAP), and peripheral vascular resistance (PVR).ResultsThe 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.ConclusionsWomen 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 abstractIn women at high risk of pre‐eclampsia, prophylactic use of aspirin may not alter the impaired maternal cardiac adaptation.
Acta Obstetricia et Gynecologica Scandinavica, Mar 17, 2021
IntroductionThe aim of this study was to assess perinatal outcomes in women with chronic hyperten... more IntroductionThe 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 methodsThis 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 &gt;140/90 mmHg (n = 100). Groups 2‐4 had prepregnancy CH; group 2 had BP &lt;140/90 mmHg without antihypertensives (n = 234), group 3 had BP &lt;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.ResultsThere 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.ConclusionsIn 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.
American Journal of Obstetrics and Gynecology, Jun 1, 2021
BACKGROUND Pregnancies with small for gestational age fetuses are at increased risk of adverse ma... more 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 To evaluate the trends in maternal cardiac function, fetal growth and oxygenation with advancing gestational age in a routine obstetric 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+0-13+6, 19+0-24+0, 30+0-34+0 and 35+0-37+0 weeks' gestation, sonographic estimated fetal weight in the last three visits and the ratio of the middle cerebral artery by the umbilical artery pulsatility indices or cerebroplacental ratio in the last two visits. Women were divided into five groups according to birthweight percentile: Group 1 <10th percentile (n=261); group 2, 10-19.9 percentile (n=180), group 3, 20-29.9 percentile (n=189); group 4, 30-69.9 percentile (n=651) and group 5, >70th centile (n=508). Multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z-scores of estimated fetal weight and cerebroplacental ratio. RESULTS In visit 2, compared to visit 1, in all groups cardiac output increased and peripheral vascular resistance decreased. At visit 3, groups 1, 2 and 3, compared to 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, whilst groups 1 and 2 demonstrated a significant decline. CONCLUSION in a general obstetric population, maternal cardiac adaptation from 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.
Ultrasound in Obstetrics & Gynecology, Oct 1, 2022
OBJECTIVES To compare the longitudinal maternal hemodynamic changes throughout gestation between ... more OBJECTIVES To compare the longitudinal maternal hemodynamic changes throughout gestation between different groups stratified according to booking weight and assess the relative influence of height, booking weight and gestational weight gain on cardiac adaptation. METHODS This was a prospective, longitudinal study assessing maternal hemodynamics by bioreactance technique at 11+0 -13+6 , 19+0 -24+0 , 30+0 -34+0 and 35+0 -37+0 weeks' gestation. Women were divided into three groups according to maternal booking weight at the first visit at 11+0 -13+6 weeks: Group 1 <60.0 kg (n=421); group 2, 60.0-79.7 kg (n=904), group 3, >79.7 kg (n=427). A multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables correcting for demographics, medical and obstetric history, pregnancy complications, maternal weight and time. The linear mixed-effect model was then repeated with maternal height, booking weight and gestational weight gain z-scores, and the standardised coefficients used to depict the relative influence of each of these demographic parameters in longitudinal changes of maternal hemodynamics. RESULTS Compared to group 1, women in group 3 demonstrated higher cardiac output (CO), heart rate (HR), peripheral vascular resistance (PVR) and mean arterial pressure (MAP) throughout pregnancy. Group 2 and 3 had higher stroke volume (SV) than group 1 in the first visit, but their SV plateaued and demonstrated an earlier decrease from visit 2 to 3 when compared to group 1. Compared to group 1 and 2, there is a higher prevalence of pre-eclampsia, gestational hypertension and gestational diabetes in group 3. Maternal height is the most important contributor to CO, PVR, SV and HR, and weight to MAP. Gestational weight gain is the second most important characteristic influencing the longitudinal changes of PVR and SV. CONCLUSIONS Women with greater booking weight have a pathological hemodynamic profile with high CO, PVR and MAP compared to those of lesser weight. 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 influencer for SV and PVR. This article is protected by copyright. All rights reserved.
Bjog: An International Journal Of Obstetrics And Gynaecology, Aug 5, 2021
ObjectivesTo assess first trimester serum placental growth factor (PLGF), soluble fms‐like tyrosi... more ObjectivesTo 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.DesignCase–control.SettingTertiary referral centre.Population650 women with CH, 142 normotensive controls.MethodsIn 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 &lt;140/90 mmHg without antihypertensive medication, in group 3 the BP was &lt;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 measureComparisons 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.ResultsCompared 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.ConclusionIn 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 abstractFirst trimester blood pressure control impacts on serum PLGF, sFLT‐1, endothelin and IL‐6 in women with chronic hypertension.
Prenatal recognition of dilated aortic root is extremely rare and there are significant challenge... more Prenatal recognition of dilated aortic root is extremely rare and there are significant challenges in counselling these patients. The primary aim of this case series is to describe the prevalence, associations and outcome of dilated ascending aorta diagnosed during fetal life.
IntroductionThe aim of this study was to assess perinatal outcomes in women with chronic hyperten... more IntroductionThe 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 methodsThis 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 ho...
American Journal of Obstetrics and Gynecology, 2022
Superimposed preeclampsia complicates about 20% of pregnancies in women with chronic hypertension... more 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.
ABSTRACTObjectiveTo compare the predictive performance for delivery with pre‐eclampsia (PE) at &l... more ABSTRACTObjectiveTo 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.MethodsThis 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...
American Journal of Obstetrics and Gynecology, 2021
BACKGROUND Pregnancies with small for gestational age fetuses are at increased risk of adverse ma... more 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 To evaluate the trends in maternal cardiac function, fetal growth and oxygenation with advancing gestational age in a routine obstetric 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+0-13+6, 19+0-24+0, 30+0-34+0 and 35+0-37+0 weeks' gestation, sonographic estimated fetal weight in the last three visits and the ratio of the middle cerebral artery by the umbilical artery pulsatility indices or cerebroplacental ratio in the last two visits. Women were divided into five groups according to birthweight percentile: Group 1 <10th percentile (n=261); group 2, 10-19.9 percentile (n=180), group 3, 20-29.9 percentile (n=189); group 4, 30-69.9 percentile (n=651) and group 5, >70th centile (n=508). Multilevel linear mixed-effects model was performed to compare the repeated measures of hemodynamic variables and z-scores of estimated fetal weight and cerebroplacental ratio. RESULTS In visit 2, compared to visit 1, in all groups cardiac output increased and peripheral vascular resistance decreased. At visit 3, groups 1, 2 and 3, compared to 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, whilst groups 1 and 2 demonstrated a significant decline. CONCLUSION in a general obstetric population, maternal cardiac adaptation from 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.
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