Prior placental bed disorders and later dementia: a retrospective Swedish register‐based cohort study

Andolf, Ellika; Bladh, Marie; Möller, Louise; Sydsjö, Gunilla

doi:10.1111/1471-0528.16201

Cited by 29 publications

(45 citation statements)

References 34 publications

(69 reference statements)

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“…Independently of variations in the expression level, we found that the subset of genes that are alternatively spliced have a disease-specific profile, with marked differences between preeclampsia and IUGR, showing in particular that the first condition but not the second, correlates with brain diseases. This fascinating observation is in accordance with many recent studies showing strong links between preeclampsia and brain vascular diseases (Andolf et al 2020;Patel et al 2020;Miller 2019;Basit et al 2018;Cheng and Sharma 2016). For example, deregulation of alternative splicing of the gene STOX1, involved in preeclampsia and Alzheimer's disease (Dijk et al 2005(Dijk et al ,2010 induces a disequilibrium of its two isoforms and increases the risk of disease (Vaiman and Miralles 2016;Ducat 2020).…”

Section: Discussionsupporting

confidence: 76%

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

et al. 2021

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Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expression deregulations in these diseases, but none has tackled systematically the role of alternative splicing. In the present study, we show that alternative splicing is an essential feature of placental diseases, affecting 1060 and 1409 genes in PE vs controls and IUGR vs controls, respectively, many of those involved in placental function. While in IUGR placentas, alternative splicing affects genes specifically related to pregnancy, in preeclamptic placentas, it impacts a mix of genes related to pregnancy and brain diseases. Also, alternative splicing variations can be detected at the individual level as sharp splicing differences between different placentas. We correlate these variations with genetic variants to define splicing Quantitative Trait Loci (sQTL) in the subset of the 48 genes the most strongly alternatively spliced in placental diseases. We show that alternative splicing is at least partly piloted by genetic variants located either in cis (52 QTL identified) or in trans (52 QTL identified). In particular, we found four chromosomal regions that impact the splicing of genes in the placenta. The present work provides a new vision of placental gene expression regulation that warrants further studies.

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Section: Discussionsupporting

confidence: 76%

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

et al. 2021

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“…Traditional CVD risk factors (eg, obesity, hypertension, diabetes, hyperlipidemia) are associated with increased risk of HDP, 73 but the associations between HDP and future CVD, renal disease, and vascular dementia persist, even after adjustment for such factors. 31,34,36 It is estimated that approximately two-thirds of HDP-associated CVD risk is mediated by established risk factors, and the remainder is likely explained by an HDP-specific pathogenesis. 21,29 Whether treatment of nonsevere hypertension is beneficial for preventing long-term morbidity beyond pregnancy and the puerperium remains to be demonstrated.…”

Section: Treatment Of Hypertension In Pregnancymentioning

confidence: 99%

Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association

Garovic¹,

Dechend²,

Easterling³

et al. 2022

Hypertension

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Hypertensive disorders of pregnancy (HDP) remain one of the major causes of pregnancy-related maternal and fetal morbidity and mortality worldwide. Affected women are also at increased risk for cardiovascular disease later in life, independently of traditional cardiovascular disease risks. Despite the immediate and long-term cardiovascular disease risks, recommendations for diagnosis and treatment of HDP in the United States have changed little, if at all, over past decades, unlike hypertension guidelines for the general population. The reasons for this approach include the question of benefit from normalization of blood pressure treatment for pregnant women, coupled with theoretical concerns for fetal well-being from a reduction in utero-placental perfusion and in utero exposure to antihypertensive medication. This report is based on a review of current literature and includes normal physiological changes in pregnancy that may affect clinical presentation of HDP; HDP epidemiology and the immediate and long-term sequelae of HDP; the pathophysiology of preeclampsia, an HDP commonly associated with proteinuria and increasingly recognized as a heterogeneous disease with different clinical phenotypes and likely distinct pathological mechanisms; a critical overview of current national and international HDP guidelines; emerging evidence that reducing blood pressure treatment goals in pregnancy may reduce maternal severe hypertension without increasing the risk of pregnancy loss, high-level neonatal care, or overall maternal complications; and the increasingly recognized morbidity associated with postpartum hypertension/preeclampsia. Finally, we discuss the future of research in the field and the pressing need to study socioeconomic and biological factors that may contribute to racial and ethnic maternal health care disparities.

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“…The exposure was HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other (ie, hemolysis, elevated liver enzymes, and low platelet count/unspecified HDP). 2,3 We included (1) studies that clearly excluded, or took measures to exclude, women with chronic hypertension at baseline; 30,31 (2) studies that reported or adjusted for pre-pregnancy hypertension; 27,32 and (3) studies that did not address chronic hypertension at baseline (the 2 studies that relied on participant recall of hypertensive pregnancies). 26,28 Outcomes were all-cause dementia and dementia subtypes: Alzheimer's disease, vascular dementia, or other/unspecified dementia (eg, frontotemporal dementia, Lewy body dementia).…”

Section: Exposure and Outcomesmentioning

confidence: 99%

Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis

et al. 2023

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BACKGROUND: Prior meta-analyses report a 2- to 4-fold increased risk of later cardiovascular disease among women with a history of hypertensive disorders of pregnancy (HDP). Given HDP’s vascular underpinnings, it is hypothesized to also be a risk factor for later dementia. We aim to summarize the evidence for the impact of HDP on dementia and consider unique associations between HDP and dementia subtypes. METHODS: Observational studies on the relationship between HDP and dementia were identified from online electronic databases to July 1, 2021 (PROSPERO identifier: CRD42020185630). We included observational studies published in English. Exposure among women was any HDP and HDP subtypes: gestational hypertension, preeclampsia/eclampsia, or other/unspecified HDP. Outcome was any dementia and dementia subtypes: Alzheimer’s disease, vascular dementia, or other/unspecified dementias. RESULTS: For our primary analyses, we included 5 cohort studies with a total of 183 874 women with and 2 309 705 women without HDP. Pooled analysis found a 38% higher risk of all-cause dementia among women with, versus without, any type of HDP (adjusted hazard ratio, 1.38 [95% CI, 1.18–1.61]; P <0.01). When examining association by HDP and dementia subtypes, we found that women with, versus without, any type of HDP had over a 3-fold higher risk of vascular dementia (adjusted hazard ratio, 3.14 [95% CI, 2.32–4.24]; P <0.01). CONCLUSIONS: Our findings indicate that maternal history of HDP is an important risk factor for later development of vascular and all-cause dementia. Further research among more racially/ethnically diverse populations quantifying HDP’s effect on all-cause dementia, and specifically vascular dementia, is warranted. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: CRD42020185630

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Prior placental bed disorders and later dementia: a retrospective Swedish register‐based cohort study

Abstract: Objective To investigate the association between a history of placental bed disorders and later dementia. Design Retrospective population-based cohort study. Setting Sweden.

Cited by 29 publications

References 34 publications

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

Alternative splicing in normal and pathological human placentas is correlated to genetic variants

Hypertension in Pregnancy: Diagnosis, Blood Pressure Goals, and Pharmacotherapy: A Scientific Statement From the American Heart Association

Association Between Hypertensive Disorders of Pregnancy and Dementia: a Systematic Review and Meta-Analysis

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