Cohort profile: the Olmsted County hypertensive disorders of pregnancy (HDP) cohort using the Rochester Epidemiology Project.

Purpose: The Olmsted County hypertensive disorders of pregnancy (HDP) cohort is a population-based retrospective study designed to compare the incidence of HDP on a per-pregnancy and per-woman basis and to identify associations between HDP with ageing-related diseases, as well as accumulation of multimorbidity.

Participants: Using the Rochester Epidemiology Project (REP) medical records-linkage system, a cohort was collected consisting of women who gave birth in Olmsted County between 1976 and 1982. After exclusions, a per-pregnancy cohort of 7544 women with 9862 pregnancies between 1976 and 1982 was identified, and their delivery information was manually reviewed.

Buffy Coat DNA Methylation Profile Is Representative of Methylation Patterns in White Blood Cell Types in Normal Pregnancy.

We aimed to assess the extent to which the buffy coat DNA methylome is representative of methylation patterns in constitutive white blood cell (WBC) types in normal pregnancy. A comparison of differential methylation of buffy coat DNA vs DNA isolated from polymorphonuclear (PMN) and lymphocytic fractions was performed for each blood sample obtained within 24 h prior to delivery from 29 normotensive pregnant women. Methylation profiles were obtained using an Illumina Human Methylation 450 BeadChip and CHaMP bioinformatics pipeline.

Epigenetic and senescence markers indicate an accelerated ageing-like state in women with preeclamptic pregnancies.

Background: Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria and/or multisystem involvement. Disease-specific therapy has yet to be developed due to the lack of understanding of underlying mechanism(s). We postulate that accelerated ageing in general, and particularly cellular senescence, play a role in its pathophysiology.

Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation.

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria, and vascular injury in the second half of pregnancy. We hypothesized that endothelium-dependent vascular dysfunction is present in a murine model of preeclampsia based on administration of human preeclamptic sera to interleukin-10-/- mice and studied mechanisms that underlie vascular injury. Pregnant wild type and IL-10-/- mice were injected with either normotensive or severe preeclamptic patient sera (sPE) during gestation.

Incidence and Long-Term Outcomes of Hypertensive Disorders of Pregnancy.

Background: Hypertensive disorders of pregnancy (HDP) are associated with increased risks for cardiovascular disease later in life. The HDP incidence is commonly assessed using diagnostic codes, which are not reliable; and typically are expressed per-pregnancy, which may underestimate the number of women with an HDP history after their reproductive years.

Objectives: This study sought to determine the incidence of HDP expressed as both per-pregnancy and per-woman, and to establish their associations with future chronic conditions and multimorbidity, a measure of accelerated aging, in a population-based cohort study.

Amphetamine-Dextroamphetamine and Pregnancy: Neonatal Outcomes After Prenatal Prescription Mixed Amphetamine Exposure.

A retrospective cohort study was performed to evaluate whether birthweight was less among infants of women taking amphetamine-dextroamphetamine during pregnancy at our academic institution. We identified mother-infant pairs with documented exposure to amphetamine-dextroamphetamine in pregnancy from 2005 through 2015. Patients were matched 2:1 with unexposed controls.

Targeting senescence improves angiogenic potential of adipose-derived mesenchymal stem cells in patients with preeclampsia.

Background: Preeclampsia is a pregnancy-specific hypertensive disorder characterized by impaired angiogenesis. We postulate that senescence of mesenchymal stem cells (MSC), multipotent cells with pro-angiogenic activities, is one of the mechanisms by which systemic inflammation exerts inhibitory effects on angiogenesis in preeclampsia.

Methods: MSC were isolated from abdominal fat tissue explants removed during medically indicated C-sections from women with preeclampsia (PE-MSC, n = 10) and those with normotensive pregnancies (NP-MSC, n = 12).

Early Onset Preeclampsia Is Associated With Glycocalyx Degradation and Reduced Microvascular Perfusion.

Background The endothelial glycocalyx is a vasoprotective barrier between the blood and endothelium. We hypothesized that glycocalyx degradation is present in preeclampsia, a pregnancy-specific hypertensive disorder characterized by endothelial dysfunction and activation. Methods and Results We examined the sublingual glycocalyx noninvasively using sidestream dark field imaging in the third trimester among women with normotensive pregnancies (n=73), early (n=14) or late (n=29) onset preeclampsia, or gestational diabetes mellitus (n=21).

Electronic Algorithm Is Superior to Hospital Discharge Codes for Diagnoses of Hypertensive Disorders of Pregnancy in Historical Cohorts.

Objectives: To develop and validate criteria for the retrospective diagnoses of hypertensive disorders of pregnancy that would be amenable to the development of an electronic algorithm, and to compare the accuracy of diagnoses based on both the algorithm and diagnostic codes with the gold standard, of physician-made diagnoses based on a detailed review of medical records using accepted clinical criteria.

Patients And Methods: An algorithm for hypertensive disorders of pregnancy was developed by first defining a set of criteria for retrospective diagnoses, which included relevant clinical variables and diagnosis of hypertension that required blood pressure elevations in greater than 50% of readings ("the 50% rule"). The algorithm was validated using the Rochester Epidemiology Project (Rochester, Minnesota).

Impact of a History of Hypertension in Pregnancy on Later Diagnosis of Atrial Fibrillation.

Background: Atrial fibrillation/flutter (AF) produces significant morbidity in women and is typically attributed to cardiac remodeling from multiple causes, particularly hypertension. Hypertensive pregnancy disorders (HPDs) are associated with future hypertension and adverse cardiac remodeling. We evaluated whether women with AF were more likely to have experienced a HPD compared with those without.

Carotid Artery Intima-Media Thickness and Subclinical Atherosclerosis in Women With Remote Histories of Preeclampsia: Results From a Rochester Epidemiology Project-Based Study and Meta-analysis.

Objective: To measure carotid artery intima-media thickness (CIMT), a marker of subclinical atherosclerosis, in postmenopausal women with and without histories of preeclampsia and to synthesize these results with those from prior studies of CIMT performed 10 or more years after preeclamptic pregnancies.

Patients And Methods: Forty women (median age, 59 years) with histories of preeclampsia and 40 with histories of normotensive pregnancy (confirmed by medical record review) were selected from women who resided and gave birth in Olmsted County, Minnesota, between January 1, 1976, and December 31, 1982. The participants were identified and recruited in 2014-2015, and CIMT was measured by B-mode ultrasonography.

Influence of preeclampsia and late-life hypertension on MRI measures of cortical atrophy.

Objective: Women with a history of preeclampsia are at an increased risk of hypertension and structural brain changes. However, the combined effect of both preeclampsia and late-life hypertension on brain structural changes is not known and was investigated in this study.

Methods: Participants were identified from the population-based Rochester Epidemiology Project cohort.

Urinary Extracellular Vesicles of Podocyte Origin and Renal Injury in Preeclampsia.

Renal histologic expression of the podocyte-specific protein, nephrin, but not podocin, is reduced in preeclamptic compared with normotensive pregnancies. We hypothesized that renal expression of podocyte-specific proteins would be reflected in urinary extracellular vesicles (EVs) of podocyte origin and accompanied by increased urinary soluble nephrin levels (nephrinuria) in preeclampsia. We further postulated that podocyte injury and attendant formation of EVs are related mechanistically to cellfree fetal hemoglobin (HbF) in maternal plasma.

Preeclampsia and cognitive impairment later in life.

Background: Hypertension is a risk factor for cerebrovascular disease and cognitive impairment. Women with hypertensive episodes during pregnancy report variable neurocognitive changes within the first decade following the affected pregnancy. However, long-term follow-up of these women into their postmenopausal years has not been conducted.

Pregnancy history and blood-borne microvesicles in middle aged women with and without coronary artery calcification.

Background And Aims: Having a history of preeclampsia increases the risk for future coronary artery calcification (CAC). This study evaluated the association of blood-borne, cell-derived microvesicles (MV) with CAC in middle-aged women.

Methods: Twelve pre-selected, antigen-specific MV were measured by digital flow cytometry in the blood of age- and parity-matched women (median age 60 years) without a history of cardiovascular events, but with either a history of preeclampsia (PE, n = 39) or normotensive pregnancy (NP, n = 40).

Expected probability of congenital heart disease and clinical utility of fetal echocardiography in pregnancies with pre-gestational diabetes.

Objectives: To establish a prediction model for fetal congenital heart disease (CHD) that could facilitate selective fetal echocardiography screening for diabetic women, and to provide cost analysis of selective versus global screening of these women.

Study Design: A historical cohort study included women with pre-gestational diabetes who received perinatal care at Mayo Clinic, Minnesota from 2007 through 2013. Anatomical scans and fetal echocardiograms were reviewed and charts for postnatal outcomes were abstracted.

Preeclampsia/Eclampsia candidate genes show altered methylation in maternal leukocytes of preeclamptic women at the time of delivery.

Objective: To analyze methylation profiles of known preeclampsia/eclampsia (PE) candidate genes in normal (NL) and preeclamptic (PE) women at delivery.

Methods: A matched case-control study comparing methylation in 79 CpG sites/33 genes from an independent gene set in maternal leukocyte DNA in PE and NL (n = 14 each) on an Illumina BeadChip platform. Replication performed on second cohort (PE = 12; NL = 32).

Impaired Cognition and Brain Atrophy Decades After Hypertensive Pregnancy Disorders.

Background: Hypertensive pregnancy disorders have been associated with subjective cognitive complaints or brain white-matter lesions 5 to 10 years after the hypertensive pregnancy. The long-term effects of hypertensive pregnancies on brain structure and cognitive function remain unknown.

Methods And Results: This study included 1279 women who participated in the Family Blood Pressure Project Genetic Epidemiology Network of Arteriopathy (GENOA) study.

A history of preeclampsia is associated with a risk for coronary artery calcification 3 decades later.

Background: A history of preeclampsia is an independent risk factor for cardiac events and stroke. Changes in vasculature structure that contribute to these associations are not well understood.

Objective: The aim of this study was to quantify coronary artery calcification (CAC), a known risk factor for cardiac events, in a prospective cohort of women with and without histories of preeclampsia.

Pregnancy outcomes in autosomal dominant polycystic kidney disease: a case-control study.

Objectives: To determine whether autosomal dominant polycystic kidney disease (ADPKD) is associated with adverse fetal outcomes and maternal complications.

Methods: We identified a cohort of 146 patients seen for pregnancy and cystic kidney disease at Mayo Clinic from 1975 to 2010. From this cohort, 54 patients met the ultrasound diagnostic criteria for ADPKD (ADPKD group), while the other 92 patients were diagnosed as "Simple Cyst" (control group).

Persistent urinary podocyte loss following preeclampsia may reflect subclinical renal injury.

Objective: Studies have shown that podocyturia, i.e., urinary loss of viable podocytes (glomerular epithelial cells), is associated with proteinuria in preeclampsia.

Methodological differences account for inconsistencies in reported free VEGF concentrations in pregnant rats.

Free vascular endothelial growth factor (VEGF) is undetectable in plasma during human pregnancy. However, studies examining pregnant rats have reported both low (8-29 pg/ml) and high (527-1,030 pg/ml) free VEGF. These discrepancies cast uncertainty over the use of rat models to study angiogenic factors in pregnancy and preeclampsia.