Reference ranges for third-trimester maternal cardiovascular function parameters measured in normotensive pregnant women using a non-invasive cardiac output monitor: A study based on data from the prospective PEACH cohort study.

OBJECTIVE: We defined reference ranges for maternal cardiac output, systemic vascular resistance, and stroke volume measured in the third trimester of pregnancy using the Ultrasound Cardiac Output Monitor 1A. DESIGN: Based on data from the prospective PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension) cohort study. SETTING: Rigshospitalet and Hvidovre Hospital, Denmark. SAMPLE: Normotensive pregnant women aged 18-45 years with singleton pregnancies, enrolled in the PEACH study in 2016-2018. METHODS: We modelled cardiac output, systemic vascular resistance and stroke volume as a function of gestational age using multilevel linear models with fractional polynomials. MAIN OUTCOME MEASURES: Unconditional and conditional reference ranges for cardiovascular parameters measured in gestational weeks 28-40. RESULTS: Our study cohort included 405 healthy pregnant women who contributed 1210 cardiovascular function measurements for analysis. Maximum cardiac output and stroke volume values were measured in gestational weeks 30-32 and decreased over the third trimester, whereas systemic vascular resistance increased during the same period. We created reference ranges for eight combinations of maternal height, age and parity. We also created a simple calculator to allow for implementation of the reference ranges in clinical practice. CONCLUSIONS: Our reference ranges allow the use of a bedside ultrasound device to non-invasively assess cardiac function in pregnancy and identify women at risk of complications. The unconditional ranges allow clinicians to evaluate isolated measurements and identify women needing follow-up. The conditional ranges incorporate information from previous measurements and improve monitoring over time.

Time trends in preeclampsia and gestational diabetes in Denmark and Alberta, Canada, 2005-2018-A population-based cohort study.

INTRODUCTION: Preeclampsia and gestational diabetes mellitus share risk factors such as obesity and increased maternal age, which have become more prevalent in recent decades. We examined changes in the prevalence of preeclampsia and gestational diabetes between 2005 and 2018 in Denmark and Alberta, Canada, and investigated whether the observed trends can be explained by changes in maternal age, parity, multiple pregnancy, comorbidity, and body mass index (BMI) over time. MATERIAL AND METHODS: This study was a register-based cohort study conducted using data from the Danish National Health Registers and the provincial health registers of Alberta, Canada. We included in the study cohort all pregnancies in 2005-2018 resulting in live-born infants and used binomial regression to estimate mean annual increases in the prevalence of preeclampsia and gestational diabetes in the two populations across the study period, adjusted for maternal characteristics. RESULTS: The study cohorts included 846 127 (Denmark) and 706 728 (Alberta) pregnancies. The prevalence of preeclampsia increased over the study period in Denmark (2.5% to 2.9%) and Alberta (1.7% to 2.5%), with mean annual increases of 0.03 (95% confidence interval [CI] 0.02-0.04) and 0.06 (95% CI 0.05-0.07) percentage points, respectively. The prevalence of gestational diabetes also increased in Denmark (1.9% to 4.6%) and Alberta (3.9% to 9.2%), with average annual increases of 0.20 (95% CI 0.19-0.21) and 0.44 (95% CI 0.42-0.45) percentage points. Changes in the distributions of maternal age and BMI contributed to increases in the prevalence of both conditions but could not explain them entirely. CONCLUSIONS: The prevalence of both preeclampsia and gestational diabetes increased significantly from 2005 to 2018, which portends future increases in chronic disease rates among affected women. Increasing demand for long-term follow up and care will amplify the existing pressure on healthcare systems.

Association between preeclampsia in daughters and risk of cardiovascular disease in parents.

Preeclampsia and cardiovascular disease (CVD) might share heritable underlying mechanisms. We investigated whether preeclampsia in daughters is associated with CVD in parents. In a register-based cohort study, we used Cox regression to compare rates of CVD (ischemic heart disease, ischemic stroke, myocardial infarction) in parents with ≥ 1 daughters who had preeclampsia and parents whose daughters did not have preeclampsia in Denmark, 1978-2018. Our cohort included 1,299,310 parents, of whom 87,251 had ≥ 1 daughters with preeclampsia and 272,936 developed CVD during 20,252,351 years of follow-up (incidence rate 135/10,000 person-years). Parents with one daughter who had preeclampsia were 1.19 times as likely as parents of daughters without preeclampsia to develop CVD at age < 55 years (hazard ratio [HR] 1.19, 95% confidence interval [CI] 1.13-1.25). Having ≥ 2 daughters who had preeclampsia yielded an HR of 1.88 (95% CI 1.39-2.53). The corresponding HRs for CVD at ≥ 55 years of age were 1.13 (95% CI 1.12-1.15) and 1.27 (95% CI 1.16-1.38). Patterns of association were similar for all CVD subtypes. Effect magnitudes did not differ for mothers and fathers (p = 0.52). Analyses by timing of preeclampsia onset in daughters suggested a tendency toward stronger associations with earlier preeclampsia onset, particularly in parents < 55 years. Preeclampsia in daughters was associated with increased risks of CVD in parents. Increasing strength of association with increasing number of affected daughters, equally strong associations for mothers and fathers, and stronger associations for CVD occurring before age 55 years suggest that preeclampsia and CVD share common heritable mechanisms.

Cohort profile: The PreEclampsia, Angiogenesis, Cardiac dysfunction and Hypertension (PEACH) Study.

BACKGROUND: Hypertensive disorders of pregnancy (HDP) remain a leading cause of maternal morbidity and mortality worldwide, with implications for maternal and neonatal well-being in the short term and for long-term maternal cardiovascular health. Although the mechanisms behind HDP remain incompletely understood, evidence suggests that preeclampsia in particular is a syndrome with more than one distinct subtype. OBJECTIVES: The PEACH (PreEclampsia, Angiogenesis, Cardiac dysfunction, Hypertension) Study was established to identify new HDP subtyping systems reflecting aetiology and prognosis and to find markers of later cardiovascular disease risk associated with preeclampsia. POPULATION: The PEACH Study recruited pregnant women referred to two Copenhagen-area hospitals with suspected preeclampsia (mean gestational age at enrolment: 36.7 weeks) and a group of frequency-matched pregnant women planning delivery at the same hospitals and healthy when enrolled mid-pregnancy. DESIGN: Prospective, longitudinal pregnancy cohort. METHODS: Participants underwent repeated third-trimester blood sample collection, longitudinal cardiac function assessments using the USCOM-1A during the third trimester and at 1 year postpartum and collection of placental samples immediately after delivery. Medical information was abstracted from medical records and hospital databases. PRELIMINARY RESULTS: During 2016-2018, we recruited 1149 pregnant women, of whom 1101 were followed to delivery. Among 691 women enrolled with suspected preeclampsia, 310 and 172 developed preeclampsia and gestational hypertension respectively. Among 410 women with healthy pregnancies when enrolled mid-pregnancy, 37 later developed hypertensive disorders of pregnancy. Of 1089 women still in the cohort 1 year postpartum, 578 (53.1%) participated in the follow-up assessment. CONCLUSIONS: The PEACH Study's rich data from women with and without HDP will enable us to identify new, clinically useful HDP subtypes to aid in decision-making regarding monitoring and treatment. Continued postpartum follow-up will help us develop algorithms to identify women at risk of persistent postpartum cardiac dysfunction and later cardiovascular disease after pregnancies complicated by HDP.

Patterns of Antihypertensive Medication Use in the First 2 Years Post Partum.

Importance: Women who had a hypertensive disorder of pregnancy (HDP) have a well-documented risk of chronic hypertension within a few years of delivery, but management of postpartum hypertension among these women remains inconsistent. Objective: To assess the incidence of initiation of antihypertensive medication use in the first 2 years after delivery by HDP status and antenatal antihypertensive medication use. Design, Setting, and Participants: This Danish register-based cohort study used data from women with at least 1 pregnancy lasting 20 or more gestational weeks (only the first pregnancy in the period was considered) who delivered from January 1, 1995, to December 31, 2018. Statistical analysis was conducted from October 2022 to September 2023. Exposure: Hypertensive disorders of pregnancy. Main Outcomes and Measures: Cumulative incidences and hazard ratios of initiating antihypertensive medication use within 2 years post partum (5 postpartum time intervals) by HDP status and antenatal medication use. Results: The cohort included 784 782 women, of whom 36 900 (4.7% [95% CI, 4.7%-4.8%]) had an HDP (HDP: median age at delivery, 29.1 years [IQR, 26.1-32.7 years]; no HDP: median age at delivery, 29.0 years [IQR, 25.9-32.3 years]). The 2-year cumulative incidence of initiating postpartum antihypertensive treatment ranged from 1.8% (95% CI, 1.8%-1.8%) among women who had not had HDPs to 44.1% (95% CI, 40.0%-48.2%) among women with severe preeclampsia who required antihypertensive medication during pregnancy. Most women who required postpartum antihypertensive medication after an HDP initiated use within 3 months of delivery (severe preeclampsia, 86.6% [95% CI, 84.6%-89.4%]; preeclampsia, 75.3% [95% CI, 73.8%-76.2%]; and gestational hypertension, 75.1% [95% CI, 72.9%-77.1%]). However, 13.4% (95% CI, 11.9%-14.1%) of women with severe preeclampsia, 24.7.% (95% CI, 24.0%-26.0%) of women with preeclampsia, 24.9% (95% CI, 22.5%-27.5%) of women with gestational hypertension, and 76.7% (95% CI, 76.3%-77.1%) of those without an HDP first filled a prescription for antihypertensive medication more than 3 months after delivery. Women with gestational hypertension had the highest rate of initiating medication after more than 1 year post partum, with 11.6% (95% CI, 10.0%-13.2%) starting treatment after this period. Among women who filled a prescription in the first 3 months post partum, up to 55.9% (95% CI, 46.2%-66.1%) required further prescriptions more than 3 months post partum, depending on HDP status and antenatal medication use. Conclusions and Relevance: In this cohort study of postpartum women, the incidence of initiation of postnatal antihypertensive medication use varied by HDP status, HDP severity, and antenatal antihypertensive medication use. Up to 24.9% of women initiated antihypertensive medication use more than 3 months after an HDP, with up to 11.6% initiating treatment after 1 year. Routine postpartum blood pressure monitoring might prevent diagnostic delays in initiation of antihypertensive medication use and improve cardiovascular disease prevention among women.

Self-monitoring of blood pressure during pregnancy: an observational study in the obstetrical waiting room.

OBJECTIVE: The aim of this study was to assess the feasibility of self-monitoring of blood pressure with a semiautomatic device in pregnant women. PARTICIPANTS AND METHODS: Women attending routine obstetrical ultrasound scanning were invited to participate. The hospital staff initially demonstrated and instructed each participant in correct measurement and then took three measurements on both arms. The participant then repeated the measurements and filled an evaluation questionnaire. We used a validated semiautomatic device for all measurements. Mean values were calculated for systolic, diastolic and mean arterial blood pressure (MAP) and were compared using the paired sample t-test. Mean values and differences of systolic and diastolic pressure were plotted in Bland-Altman plots to test the agreement of the measurements. Finally, a mean evaluation score was calculated. RESULTS: One hundred pregnant women were included in the study. Mean values of systolic, diastolic and MAP were 110.6, 69.7 and 83.3 mmHg, respectively, as assessed by the hospital staff. The corresponding self-measurements were 111.4, 70.2 and 83.9 mmHg, respectively. Mean differences between hospital and self-measurements were 0.79 mmHg for systolic [P=0.052, 95% confidence interval (CI)=-0.008 to 1.58], 0.49 mmHg for diastolic (P=0.056, 95% CI=-0.01 to 0.99) and 0.59 mmHg for MAP (P=0.019, 95% CI=0.099-1.08). The mean evaluation score was 9.2 of 10. CONCLUSION: Differences between hospital staff and self-measurements in systolic, diastolic and MAP are within acceptable international standards. The semiautomatic device Microlife-VSA is well suited for self-measurement; however, safety studies on the use of home measurements in hypertensive pregnancies are still warranted.

Astroglial c-Myc overexpression predisposes mice to primary malignant gliomas.

Malignant astrocytomas are common human primary brain tumors that result from neoplastic transformation of astroglia or their progenitors. Here we show that deregulation of the c-Myc pathway in developing astroglia predisposes mice to malignant astrocytomas within 2-3 weeks of age. The genetically engineered murine (GEM) gliomas harbor a molecular signature resembling that of human primary glioblastoma multiforme, including up-regulation of epidermal growth factor receptor and Mdm2. The GEM gliomas seem to originate in an abnormal population of glial fibrillary acidic protein-expressing cells in the ventricular zone and, analogous to human glioblastomas, exhibit molecular and morphological heterogeneity. Levels of connexin 43 in the majority of the tumors are unaltered from normal tissue, indicating that GEM tumors have retained the capacity to establish syncytial networks. In line with this, individual glioma foci are composed of a mixture of actively proliferating cells expressing c-Myc and proliferating cell nuclear antigen and less dividing bystander cells that express glial fibrillary acidic protein and the broad complex tramtrack bric-a-brac/poxvirus and zinc finger domain protein HOF. A subset of the transgenic mice harbored, in addition to brain tumors, vestigial cerebellums in which granule cell migration and radial Bergman glial cell differentiation were disturbed. These observations argue for a window of vulnerability during astrocyte development where c-Myc overexpression is sufficient to trigger the neoplastic process, presumably by inducing the sustained growth of early astroglial cells. This is in contrast to most other transgenic studies in which c-Myc overexpression requires co-operating transgenes for rapid tumor induction.