title: Prenatal exposure to maternal stress following bereavement and cardiovascular disease: A nationwide population-based and sibling-matched cohort study.
abstract: Cardiovascular disease (CVD) is among the leading determinants of mortality and morbidity, and causation may begin in the early intrauterine environment. Prenatal exposures to glucocorticoids or stress are potential risk factors of CVD later in life, but empirical evidence from large population studies is lacking. We explored the association between prenatal stress due to maternal bereavement following the death of a relative and CVD in the exposed offspring.
  
  
  
  This population-based study included 2,607,851 children born in Denmark (1970-2008). Of these participants, 73,708 (2.8%) had a CVD event during follow-up (up to 40 years). A total of 50,940 (2.0%) subjects born to mothers who lost a relative during pregnancy or the year before were categorized as exposed. Cox Proportional Hazards models were used to analyse the data. The overall hazard ratio (HR) (95% confidence interval) of having a CVD was 1.13 (1.06-1.20); the estimate was 1.24 (1.11-1.38) for heart disease and 1.27 (1.01-1.60) for hypertension. Additional sibling-matched analyses showed an overall attenuated association (1.08 (0.94-1.24)).
  
  
  
  Our results suggested a modest association between prenatal stress and CVD, both in childhood and early adulthood, which could be of importance, especially at an older age when the individuals are followed over a long period.
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Denmark opr@ph.au.dk.
authors.forename: Oleguer
authors.initials: O
authors.lastname: Plana-Ripoll
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Denmark Department of Epidemiology and Social Science on Reproductive Health, Shanghai Institute of Planned Parenthood Research, WHO Collaborating Center for Research in Human Reproduction, National Population & Family Planning Key Laboratory of Contraceptive Drugs and Devices, China.
authors.forename: Xiaoqin
authors.initials: X
authors.lastname: Liu
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Denmark.
authors.forename: Natalie C
authors.initials: NC
authors.lastname: Momen
authors.affiliation: Section for Biostatistics, Department of Public Health, Aarhus University, Denmark.
authors.forename: Erik
authors.initials: E
authors.lastname: Parner
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Denmark Department of Epidemiology, Fielding School of Public Health, University of California, USA.
authors.forename: Jørn
authors.initials: J
authors.lastname: Olsen
authors.affiliation: Section for Epidemiology, Department of Public Health, Aarhus University, Denmark.
authors.forename: Jiong
authors.initials: J
authors.lastname: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D001601:Bereavement; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology* / Q000523:psychology; D002648:Child; D003718:Denmark / Q000453:epidemiology; D005260:Female; D005500:Follow-Up Studies; D005544:Forecasting; D006801:Humans; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008875:Middle Aged; D009017:Morbidity / Q000639:trends; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000453:epidemiology / Q000209:etiology* / Q000523:psychology; D012042:Registries; D012189:Retrospective Studies; D035781:Siblings; D013315:Stress, Psychological / Q000150:complications* / Q000453:epidemiology; D015996:Survival Rate / Q000639:trends; D055815:Young Adult
keywords: Cardiovascular disease; follow-up studies; pregnancy; registries; stress