Pregnancy loss and risk of later dementia: A nationwide cohort study, Denmark, 1977-2017.
Ontology highlight
ABSTRACT: Introduction
Pregnancy losses may be associated with increased risks of dementia.Methods
We conducted a register-based cohort study in 1,243,957 women with ?1 pregnancy in Denmark in the period 1977-2015. Using Cox regression, we estimated hazard ratios (HRs) comparing risks of dementia in women with and without pregnancy losses.Results
During 21,672,433 person-years of follow-up, 261,279 women experienced a pregnancy loss, and 2188 women were diagnosed with dementia. Stillbirth was associated with an 86% increased risk of dementia overall (HR 1.86, 95% confidence interval [CI] 1.28-2.71). By contrast, miscarriage was not associated with later risk of dementia overall (single miscarriage, HR 0.99, 95% CI 0.87-1.12; recurrent miscarriages, HR 1.06, 95% CI 0.84-1.35). Adjustment for cardiovascular disease, hypertension, and diabetes did not meaningfully alter the association magnitudes.Discussion
Stillbirth and dementia may share underlying mechanisms, suggesting that a history of stillbirth should be considered when assessing dementia risk in women.
SUBMITTER: Basit S
PROVIDER: S-EPMC6495073 | biostudies-literature | 2019
REPOSITORIES: biostudies-literature
Publications
Pregnancy loss and risk of later dementia: A nationwide cohort study, Denmark, 1977-2017.
Basit Saima S Wohlfahrt Jan J Boyd Heather A HA
Alzheimer's & dementia (New York, N. Y.) 20190430
<h4>Introduction</h4>Pregnancy losses may be associated with increased risks of dementia.<h4>Methods</h4>We conducted a register-based cohort study in 1,243,957 women with ≥1 pregnancy in Denmark in the period 1977-2015. Using Cox regression, we estimated hazard ratios (HRs) comparing risks of dementia in women with and without pregnancy losses.<h4>Results</h4>During 21,672,433 person-years of follow-up, 261,279 women experienced a pregnancy loss, and 2188 women were diagnosed with dementia. Sti ...[more]
Similar Datasets
Project description: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.
| S-EPMC6191824 | biostudies-other
Project description:Background The aim of this study was to investigate the associations between pregnancy complications and cardiovascular mortality and hospitalizations of cardiovascular disease (CVD) after adjustment for major confounding. Methods and Results In a nationwide register-based cohort study, women with singleton births between 1973 and 2014 were included from the Swedish Medical Birth Register. Outcomes of mortality and hospitalizations of CVD were collected from the Cause of Death Register and the National Inpatient Register. The cohort was followed from the date of the first delivery until death or end of follow-up, whichever occurred first. The pregnancy complications studied were preeclampsia or eclampsia, gestational hypertension, gestational diabetes, preterm birth, small for gestational age, and stillbirth. Among the 2 134 239 women (mean age at first pregnancy, 27.0 [SD, 5.1] and mean parity 1.96 [SD, 0.9]), 19.1% (N=407 597) had 1 of the studied pregnancy complications. All pregnancy complications were associated with all-cause and cardiovascular mortality and hospitalization for CVD (ischemic heart disease, ischemic stroke, and peripheral artery disease) after adjustment for major confounding in a Cox proportional hazard regression model. The adjusted hazard ratio for cardiovascular mortality was 1.84 (95% CI, 1.38-2.44) for preterm birth and 3.14 (95% CI, 1.81-5.44) for stillbirth. Conclusions In this large cohort study, pregnancy complications were associated with all-cause mortality, cardiovascular mortality, and hospitalizations for CVD, also after adjusting for confounding, including overweight, smoking, and comorbidities. The study highlights that less established pregnancy complications such as preterm birth and stillbirth are also associated with cardiovascular mortality and CVD.
| S-EPMC9238523 | biostudies-literature
Project description:BackgroundThe prevalence of depression and the exposure to antidepressants are high among women of reproductive age and during pregnancy. Duloxetine is a selective serotonin-norepinephrine reuptake inhibitor (SNRI) approved in the United States and Europe in 2004 for the treatment of depression. Fetal safety of duloxetine is not well established. The present study evaluates the association of exposure to duloxetine during pregnancy and the risk of major and minor congenital malformations and the risk of stillbirths.Methods and findingsA population-based observational study was conducted based on data from registers in Sweden and Denmark. All registered births and stillbirths in the medical birth registers between 2004 and 2016 were included. Malformation diagnoses were identified up to 1 year after birth. Logistic regression analyses were used. Potential confounding was addressed through multiple regression, propensity score (PS) matching, and sensitivity analyses. Confounder variables included sociodemographic information (income, education, age, year of birth, and country), comorbidity and comedication, previous psychiatric contacts, and birth-related information (smoking during pregnancy and previous spontaneous abortions and stillbirths). Duloxetine-exposed women were compared with 4 comparators: (1) duloxetine-nonexposed women; (2) selective serotonin reuptake inhibitor (SSRI)-exposed women; (3) venlafaxine-exposed women; and (4) women exposed to duloxetine prior to, but not during, pregnancy. Exposure was defined as redemption of a prescription during the first trimester and throughout pregnancy for the analyses of malformations and stillbirths, respectively. Outcomes were major and minor malformations and stillbirths gathered from the national patient registers. The cohorts consisted of more than 2 million births with 1,512 duloxetine-exposed pregnancies. No increased risk for major malformations, minor malformations, or stillbirth was found across comparison groups in adjusted and PS-matched analyses. Duloxetine-exposed versus duloxetine-nonexposed PS-matched analyses showed odds ratio (OR) 0.98 (95% confidence interval [CI] 0.74 to 1.30, p = 0.909) for major malformations, OR 1.09 (95% CI 0.82 to 1.45, p = 0.570) for minor malformation, and 1.18 (95% CI 0.43 to 3.19, p = 0.749) for stillbirths. For the individual malformation subtypes, some findings were statistically significant but were associated with large statistical uncertainty due to the extremely small number of events. The main limitations for the study were that the indication for duloxetine and a direct measurement of depression severity were not available to include as covariates.ConclusionsBased on this observational register-based nationwide study with data from Sweden and Denmark, no increased risk of major or minor congenital malformations or stillbirth was associated with exposure to duloxetine during pregnancy.
| S-EPMC8654175 | biostudies-literature
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.
| S-EPMC6487675 | biostudies-literature
Project description:BackgroundCancer is the second leading cause of death worldwide. Few studies have investigated if recurrent pregnancy loss is associated with an increased risk of cancer. We aimed to assess whether pregnancy loss is associated with later cancer development.MethodsWe identified all invasive cancers after age 40, among all Danish women born between January 1957 and December 1972, ensuring a full reproductive history. Cases were matched by birth year 1:10 to cancer-free controls. Women were followed until the end of 2017. The number of pregnancy losses (miscarriages or still births) was correlated to long-term cancer risk using conditional logistic regression, providing odds ratios for specific cancers with different numbers of pregnancy losses, all adjusted for age, education, and other potential confounders.FindingsThe study included 28,785 women with cancer (mean age 48.7 [SD 5.0]) and 283,294 matched controls (mean age 48.6 [SD 5.0]). We found no overall association between pregnancy loss and later development of 11 site-specific types of cancer or cancer overall. Taking the sequence of pregnancy losses into account, primary recurrent pregnancy loss (three consecutive pregnancy losses without prior live birth) was associated with later overall cancer by an odds ratio of 1.27 (1.04-1.56). Secondary recurrent pregnancy loss showed no association to cancer.InterpretationPregnancy loss was not associated with later cancer development. Women with primary recurrent pregnancy loss had a borderline significant association to later cancer overall, this may be a chance finding.FundingOle Kirk's Foundation and Copenhagen University Hospital Rigshospitalet's Research Grant.
| S-EPMC6833468 | biostudies-literature
Project description:ObjectiveTo explore the association between pregnancy duration and risk of endometrial cancer.DesignNationwide register based cohort study.SettingDenmark.ParticipantsAll Danish women born from 1935 to 2002.Main outcome measuresRelative risk (incidence rate ratio) of endometrial cancer by pregnancy number, type, and duration, estimated using log-linear Poisson regression.ResultsAmong 2?311?332 Danish women with 3?947?650 pregnancies, 6743 women developed endometrial cancer during 57?347?622 person years of follow-up. After adjustment for age, period, and socioeconomic factors, a first pregnancy was associated with a noticeably reduced risk of endometrial cancer, whether it ended in induced abortion (adjusted relative risk 0.53 (95% confidence interval 0.45 to 0.64) or childbirth (0.66, 0.61 to 0.72). Each subsequent pregnancy was associated with an additional reduction in risk, whether it ended in induced abortion (0.81, 0.77 to 0.86) or childbirth (0.86, 0.84 to 0.89). Duration of pregnancy, age at pregnancy, spontaneous abortions, obesity, maternal birth cohort, fecundity, and socioeconomic factors did not modify the results.ConclusionsThe risk of endometrial cancer is reduced regardless of whether a pregnancy ends shortly after conception or at 40 weeks of gestation. This reduction in risk could be explained by a biological process occurring within the first weeks of pregnancy, as pregnancies ending in induced abortions were associated with similar reductions in risk as pregnancies ending in childbirth.
| S-EPMC6693051 | biostudies-literature
Project description:Osteoarthritis (OA) and dementia are prevalent causes of disability in geriatric patients. To date, information on the temporal correlation between these progressive diseases and the risk of dementia in patients with OA is limited. This retrospective population-based 4-year cohort study investigated the risk of dementia in patients with OA. We performed a case-control matched analysis by using the Taiwan Longitudinal Health Insurance Database 2005. Patients were selected on the basis of International Classification of Diseases, Ninth Revision, Clinical Modification codes for OA between January 1, 2004 and December 31, 2007. The prevalence and the adjusted hazard ratio (HR) of dementia in patients with and without OA were estimated. The OA cohort comprised 35,149 patients and the non-OA cohort (comparison cohort) comprised 70,298 patients (1:2). The incidence of dementia was 21.7 per 10,000 person-years in the OA cohort and 14.7 per 10,000 person-years in the non-OA cohort. The HR for dementia during the follow-up period was 1.33 (95% confidence interval [CI], 1.17-1.50, P < 0.001) for patients with OA. The adjusted HR for dementia was 1.25 (95% CI, 1.10-1.43, P < 0.001) for patients with OA. The results of this study indicated that OA is an independent risk factor for dementia.
| S-EPMC4434986 | biostudies-other
Project description:OBJECTIVES: Common genetic and environmental risk factors may explain the concurrent increase in the incidence of both inflammatory bowel disease (IBD) and asthma. We examined whether IBD in a parent is associated with an increased asthma risk in offspring. METHODS: This was a registry-based cohort study of all children born alive in Denmark in 1979-2009, followed through 2010. IBD and asthma were identified using hospital diagnoses; antiasthma medication was also used to identify asthma. We computed risk of asthma and estimated adjusted incidence rate ratios (aIRRs) with 95% confidence intervals (CIs) using Cox proportional-hazards regression. We evaluated asthma risk according to maternal and paternal IBD, Crohn's disease (CD), and ulcerative colitis (UC). Children without parental IBD were the comparison cohort for all comparisons. RESULTS: We identified 1,845,281 children, of whom 14,952 (0.8%) had a parent with IBD. The 10-year risk of asthma was 6.9% among offspring of parents with CD, 5.6% among offspring of parents with UC, and 5.0% among offspring of parents without IBD. The aIRR for asthma associated with parental IBD was 0.98 (95% CI: 0.91-1.04). The aIRR was 1.09 (95% CI: 0.98-1.22) for parental CD and 0.92 (95% CI: 0.84-1.00) for parental UC. Results were similar regardless of parent of origin or inclusion of antiasthma medication to define asthma. CONCLUSIONS: Our data do not provide evidence for an increased risk of asthma in offspring with a parental history of IBD.
| S-EPMC3759218 | biostudies-other
Project description:ObjectivesIt is unclear whether kidney disease is a risk factor for developing dementia. We examined the association between kidney disease and risk of future dementia.Design and settingNationwide historical registry-based cohort study in Denmark based on data from 1 January 1995 until 31 December 2016.ParticipantsAll patients diagnosed with kidney disease and matched general population cohort without kidney disease (matched 1:5 on age, sex and year of kidney disease diagnosis).Primary and secondary outcome measuresAll-cause dementia and its subtypes: Alzheimer's disease, vascular dementia and other specified or unspecified dementia. We computed 5-year cumulative incidences (risk) and hazard ratios (HRs) for outcomes using Cox regression analyses.ResultsThe study cohort comprised 82 690 patients with kidney disease and 413 405 individuals from the general population. Five-year and ten-year mortality rates were twice as high in patients with kidney disease compared with the general population. The 5-year risk for all-cause dementia was 2.90% (95% confidence interval: 2.78% to 3.08%) in patients with kidney disease and 2.98% (2.92% to 3.04%) in the general population. Compared with the general population, the adjusted HRs for all-cause dementia in patients with kidney disease were 1.06 (1.00 to 1.12) for the 5-year follow-up and 1.08 (1.03 to 1.12) for the entire study period. Risk estimates for dementia subtypes differed substantially and were lower for Alzheimer's disease and higher for vascular dementia.ConclusionsPatients diagnosed with kidney disease have a modestly increased rate of dementia, mainly driven by vascular dementia. Moreover, patients with kidney disease may be underdiagnosed with dementia due to high mortality and other comorbidities of higher priority.
| S-EPMC8543681 | biostudies-literature
Project description:BackgroundPrevious studies suggest that eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA), and alpha-linolenic acid (ALA), may decrease the risk of preeclampsia, but many suffer from important methodological limitations.MethodsWe prospectively examined the association between fat intake during pregnancy and preeclampsia and among 65,220 singleton pregnancies in the Danish National Birth Cohort (1996-2002). Women were asked to report their diet around gestation week 20 with a food frequency questionnaire. Preeclampsia diagnosis was obtained via linkage with the Danish National Patient Registry. We estimated relative risks (RR) and 95% confidence intervals (95% CI) of preeclampsia and severe preeclampsia according to fat intake using logistic regression models with generalized estimating equations to account for repeated pregnancies per woman while adjusting for potential confounders.ResultsWe documented 1302 cases of preeclampsia, including 301 cases of severe preeclampsia. Intake of long-chain omega-3 fatty acids was associated to preeclampsia. Women in the top quintile of DHA intake had a lower risk of preeclampsia (RR 0.67 (0.51-0.89)) and severe preeclampsia (RR 0.46 (0.25-0.83)) than women in the bottom quintile. Women who met daily recommended intake of EPA+DHA according to the Dietary Guidelines for Americans (≥250 mg/day), had a lower risk of severe preeclampsia (RR 0.77 (0.60-0.99)), but not of preeclampsia (RR 0.93 (0.82-1.05)). Conversely, ALA intake was associated with higher risk of severe preeclampsia (RR 1.71 (1.07-2.75)).ConclusionsHigher intake of DHA is inversely related to preeclampsia and severe preeclampsia, whereas ALA increases the risk of severe preeclampsia among Danish women.
| S-EPMC6405320 | biostudies-literature