title: Early onset of coronary artery disease after prenatal exposure to the Dutch famine.
abstract: BACKGROUND
  Limited evidence suggests that maternal undernutrition at the time of conception is associated with increased cardiovascular disease risk in adult offspring.
  
  
  OBJECTIVE
  We investigated whether persons conceived during the Dutch famine of World War II had an early onset of coronary artery disease (CAD).
  
  
  METHODS
  We compared the age at onset and cumulative incidence of CAD between persons born as term singletons who were exposed to the 1944-1945 Dutch famine during late (n = 160), mid- (n = 138), or early (n = 87) gestation and 590 unexposed subjects at age 50 or 58 y. Age at CAD onset was defined as the age at which angina pectoris was identified (according to the Rose questionnaire), Q waves were observed on an electrocardiogram (Minnesota codes 1-1 or 1-2), or coronary revascularization was performed (by angioplasty or bypass surgery).
  
  
  RESULTS
  Of the 83 CAD cases identified, persons conceived during the famine were 3 y younger than the unexposed persons at the time of CAD diagnosis (47 y compared with 50 y) and had a higher cumulative incidence of CAD [13%; hazard ratio (HR) adjusted for sex: 1.9; 95% CI: 1.0, 3.8] than did the unexposed persons. The HR changed little after adjustment for smoking (HR: 1.8), social class (HR: 2.0), or size at birth (HR: 2.0).
  
  
  CONCLUSIONS
  We found an earlier onset of CAD among persons conceived during the famine, which suggests that maternal nutrition in early gestation may play a role in the onset of CAD. This finding agrees with evidence from animal experiments that identify periconceptional maternal diet as important in the offspring's adult health.
authors.affiliation: Department of Clinical Epidemiology and Biostatistics and the Developmental Origins of Adult Disease Centre, University of Southampton, Southampton, United Kingdom. r.c.painter@amc.uva.nl
authors.forename: Rebecca C
authors.initials: RC
authors.lastname: Painter
authors.forename: Susanne R
authors.initials: SR
authors.lastname: de Rooij
authors.forename: Patrick M
authors.initials: PM
authors.lastname: Bossuyt
authors.forename: Timothy A
authors.initials: TA
authors.lastname: Simmers
authors.forename: Clive
authors.initials: C
authors.lastname: Osmond
authors.forename: David J
authors.initials: DJ
authors.lastname: Barker
authors.forename: Otto P
authors.initials: OP
authors.lastname: Bleker
authors.forename: Tessa J
authors.initials: TJ
authors.lastname: Roseboom
mesh_terms: D017668:Age of Onset; D000375:Aging; D015331:Cohort Studies; D003324:Coronary Artery Disease / Q000453:epidemiology* / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D009426:Netherlands / Q000453:epidemiology; D009752:Nutritional Status; D011247:Pregnancy; D011248:Pregnancy Complications / Q000503:physiopathology; D011297:Prenatal Exposure Delayed Effects; D039401:Prenatal Nutritional Physiological Phenomena / Q000502:physiology; D012307:Risk Factors; D013217:Starvation / Q000503:physiopathology*