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
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:BackgroundNitrate contamination is seen in drinking water worldwide. Nitrate may pass the placental barrier. Despite suggestive evidence of fetal harm, the potential association between nitrate exposure from drinking water and pregnancy loss remains to be studied. We aimed to investigate if nitrate in drinking water was associated with the risk of pregnancy loss.MethodsWe conducted a nationwide cohort study of 100,410 pregnancies (enrolled around gestational week 11) in the Danish National Birth Cohort (DNBC) during 1996-2002. Spontaneous pregnancy losses before gestational week 22 were ascertained from the Danish National Patient Registry and DNBC pregnancy interviews. Using the national drinking water quality-monitoring database Jupiter, we estimated the individual and time-specific nitrate exposure by linking geocoded maternal residential addresses with water supply areas. The nitrate exposure was analyzed in spline models using a log-transformed continuous level or classified into five categories. We used Cox proportional hazards models to estimate associations between nitrate and pregnancy loss and used gestational age (days) as the time scale, adjusting for demographic, health, and lifestyle variables.ResultsNo consistent associations were found when investigating the exposure as a categorical variable and null findings were also found in trimester specific analyses. In the spline model using the continuous exposure variable, a modestly increased hazard of pregnancy loss was observed for the first trimester at nitrate exposures between 1 and 10 mg/L, with the highest. adjusted hazard ratio at 5 mg/L of nitrate of 1.16 (95% CI: 1.01, 1.34). This trend was attenuated in the higher exposure ranges.ConclusionNo association was seen between drinking water nitrate and the risk of pregnancy loss when investigating the exposure as a categorical variable. When we modelled the exposure as a continuous variable, a dose-dependent association was found between drinking water nitrate exposure in the first trimester and the risk of pregnancy loss. Very early pregnancy losses were not considered in this study, and whether survival bias influenced the results should be further explored.
| S-EPMC9479399 | biostudies-literature
Project description:BackgroundThe loss of one or more pregnancies before viability (i.e. pregnancy loss or miscarriage), has been linked to an increased risk of diseases later in life such as myocardial infarction and stroke. Recurrent pregnancy loss (i.e. three consecutive pregnancy losses) and multiple sclerosis have both been linked to immunological traits, which could predispose to both occurrences. The objective of the current study was to investigate if pregnancy loss is associated with later autoimmune neurological disease.MethodsThis register-based cohort study, included the Danish female population age 12 or older between 1977-2017. Women were grouped hierarchically: 0, 1, 2, ≥3 pregnancy losses, primary recurrent pregnancy loss (i.e. not preceded by a delivery), and secondary recurrent pregnancy loss (i.e. preceded by a delivery). The main outcome was multiple sclerosis and additional outcomes were amyotrophic lateral sclerosis, Guillain-Barré syndrome, and myasthenia gravis. Bayesian Poisson regression estimated incidence rate ratios [IRR] and 95% credible intervals [CI] adjusted for year, age, live births, family history of an outcome, and education.ResultsAfter 40,380,194 years of follow-up, multiple sclerosis was diagnosed among 7,667 out of 1,513,544 included women (0.5%), median age at diagnosis 34.2 years (IQR 27.4-41.4 years), and median age at symptom onset 31.2 years (IQR 24.8-38.2). The adjusted IRR of multiple sclerosis after 1 pregnancy loss was: 1.03 (95% CI 0.95-1.11), 2 losses: 1.02 (95% CI 0.86-1.20), ≥3 non-consecutive losses: 0.81 (95% CI 0.51-1.24), primary recurrent pregnancy loss: 1.18 (95% CI 0.84-1.60), secondary recurrent pregnancy loss: 1.16 (95% CI 0.81-1.63), as compared to women with no pregnancy losses. Seven sensitivity analyses and analyses for additional outcomes did not show significantly elevated adjusted risk estimates.ConclusionsIn this nationwide study, pregnancy loss was not significantly associated with autoimmune neurological disorder.
| S-EPMC8970484 | 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:BackgroundThere is a growing body of evidence linking residential exposure to transportation noise with several nonauditory health outcomes. However, auditory outcomes, such as tinnitus, are virtually unexplored.ObjectivesWe aimed to investigate the association between residential transportation noise and risk of incident tinnitus.MethodsWe conducted a nationwide cohort study including all residents in Denmark age ≥30y, of whom 40,692 were diagnosed with tinnitus. We modeled road traffic and railway noise at the most (Ldenmax) and least (Ldenmin) exposed façades of all Danish addresses from 1990 until 2017. For all participants, we calculated 1-, 5-, and 10-y time-weighted mean noise exposure and retrieved detailed information on individual- and area-level socioeconomic covariates. We conducted analyses using Cox proportional hazards models.ResultsWe found positive associations between exposure to road traffic noise and risk of tinnitus, with hazard ratios of 1.06 [95% confidence interval (CI): 1.04, 1.08] and 1.02 (95% CI: 1.01, 1.03) per 10-dB increase in 10-y Ldenmin and Ldenmax, respectively. Highest risk estimates were found for women, people without a hearing loss, people with high education and income, and people who had never been in a blue-collar job. The association with road Ldenmin followed a positive, monotonic exposure-response relationship. We found no association between railway noise and tinnitus.DiscussionTo our knowledge, this is the first study to show that residential exposure to road traffic noise may increase risk of tinnitus, suggesting noise may negatively affect the auditory system. If confirmed, this finding adds to the growing evidence of road traffic noise as a harmful pollutant with a substantial health burden. https://doi.org/10.1289/EHP11248.
| S-EPMC9891135 | 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