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Pre-eclampsia and risk of dementia later in life: nationwide cohort study.

ABSTRACT: OBJECTIVE:To explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset. DESIGN:Nationwide register based cohort study. SETTING:Denmark. POPULATION:All women with at least one live birth or stillbirth between 1978 and 2015. MAIN OUTCOME MEASURE:Hazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression. RESULTS:The cohort consisted of 1?178?005 women with 20?352?695 person years of follow-up. Women with a history of pre-eclampsia had more than three times the risk of vascular dementia (hazard ratio 3.46, 95% confidence interval 1.97 to 6.10) later in life, compared with women with no history of pre-eclampsia. The association with vascular dementia seemed to be stronger for late onset disease (hazard ratio 6.53, 2.82 to 15.1) than for early onset disease (2.32, 1.06 to 5.06) (P=0.08). Adjustment for diabetes, hypertension, and cardiovascular disease attenuated the hazard ratios only moderately; sensitivity analyses suggested that body mass index was unlikely to explain the association with vascular dementia. In contrast, only modest associations were observed for Alzheimer's disease (hazard ratio 1.45, 1.05 to 1.99) and other/unspecified dementia (1.40, 1.08 to 1.83). CONCLUSIONS:Pre-eclampsia was associated with an increased risk of dementia, particularly vascular dementia. Cardiovascular disease, hypertension, and diabetes were unlikely to mediate the associations substantially, suggesting that pre-eclampsia and vascular dementia may share underlying mechanisms or susceptibility pathways. Asking about a history of pre-eclampsia could help physicians to identify women who might benefit from screening for early signs of disease, allowing for early clinical intervention.

SUBMITTER: Basit S

PROVIDER: S-EPMC6191824 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Pre-eclampsia and risk of dementia later in life: nationwide cohort study.

Basit Saima S Wohlfahrt Jan J Boyd Heather A HA

BMJ (Clinical research ed.) 20181017

<h4>Objective</h4>To explore associations between pre-eclampsia and later dementia, overall and by dementia subtype and timing of onset.<h4>Design</h4>Nationwide register based cohort study.<h4>Setting</h4>Denmark.<h4>Population</h4>All women with at least one live birth or stillbirth between 1978 and 2015.<h4>Main outcome measure</h4>Hazard ratios comparing dementia rates among women with and without a history of pre-eclampsia, estimated using Cox regression.<h4>Results</h4>The cohort consisted ...[more]

PMID: 30333106

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Project description:ObjectiveTo investigate associations between pre-eclampsia and later risk of kidney disease.DesignNationwide register based cohort study.SettingDenmark.PopulationAll women with at least one pregnancy lasting at least 20 weeks between 1978 and 2015.Main outcome measureHazard ratios comparing rates of kidney disease between women with and without a history of pre-eclampsia, stratified by gestational age at delivery and estimated using Cox regression.ResultsThe cohort consisted of 1 072 330 women followed for 19 994 470 person years (average 18.6 years/woman). Compared with women with no previous pre-eclampsia, those with a history of pre-eclampsia were more likely to develop chronic renal conditions: hazard ratio 3.93 (95% confidence interval 2.90 to 5.33, for early preterm pre-eclampsia (delivery <34 weeks); 2.81 (2.13 to 3.71) for late preterm pre-eclampsia (delivery 34-36 weeks); 2.27 (2.02 to 2.55) for term pre-eclampsia (delivery ≥37 weeks). In particular, strong associations were observed for chronic kidney disease, hypertensive kidney disease, and glomerular/proteinuric disease. Adjustment for cardiovascular disease and hypertension only partially attenuated the observed associations. Stratifying the analyses on time since pregnancy showed that associations between pre-eclampsia and chronic kidney disease and glomerular/proteinuric disease were much stronger within five years of the latest pregnancy (hazard ratio 6.11 (3.84 to 9.72) and 4.77 (3.88 to 5.86), respectively) than five years or longer after the latest pregnancy (2.06 (1.69 to 2.50) and 1.50 (1.19 to 1.88). By contrast, associations between pre-eclampsia and acute renal conditions were modest.Conclusions Pre-eclampsia, particularly early preterm pre-eclampsia, was strongly associated with several chronic renal disorders later in life. More research is needed to determine which women are most likely to develop kidney disease after pre-eclampsia, what mechanisms underlie the association, and what clinical follow-up and interventions (and in what timeframe post-pregnancy) would be most appropriate and effective.

Project description:OBJECTIVES:Abnormal placentation in early pregnancy may play a role in the pathogenesis of pre-eclampsia. Human chorionic gonadotropin (hCG) regulates placental development and angiogenesis and may affect the ratio of soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF) in the serum. The aims of this study were to investigate the association of total hCG with the risk of pre-eclampsia and to examine the potential effect of pro- and anti-angiogenic factors on this association. METHODS:This was a population-based prospective cohort study of 7754 women with a singleton pregnancy. Total hCG was measured in the first available sample (median gestational age, 14.4 weeks; 95% range, 10.1-26.1 weeks) and sFlt-1 and PlGF concentrations in early (< 18 weeks; median, 13.2 weeks; 95% range, 9.6-17.6 weeks) and in mid- (18-25 weeks; median, 20.4 weeks; 95% range, 18.5-23.5 weeks) pregnancy. We tested the association of hCG concentration and risk of pre-eclampsia using regression analysis, adjusting for maternal age, ethnicity, body mass index, parity, education level, smoking status and fetal sex. Additionally, we assessed whether this association was affected by the sFlt-1/PlGF ratio. RESULTS:High hCG concentration was associated with a 1.5-2.7-fold increased risk of pre-eclampsia (P = 0.0001), depending on the cut-off used, and with increased sFlt-1/PlGF ratio during early pregnancy (P < 0.0001). The association between high hCG and pre-eclampsia attenuated by roughly 40% after adjustment for early-pregnancy sFlt-1/PlGF ratio (β-estimate change from 0.19 ± 0.10 (P = 0.052) to 0.12 ± 0.10 (P = 0.22)). CONCLUSIONS:High total hCG concentration in early pregnancy is associated with an increased risk of pre-eclampsia. The effect of high hCG concentration on the balance between pro- and anti-angiogenic factors during pregnancy may have a role in the pathophysiology of pre-eclampsia. © 2019 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of the International Society of Ultrasound in Obstetrics and Gynecology.

Dataset Information

Pre-eclampsia and risk of dementia later in life: nationwide cohort study.

Publications

Pre-eclampsia and risk of dementia later in life: nationwide cohort study.

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