title: Prenatal exposure to maternal bereavement and childbirths in the offspring: a population-based cohort study.
abstract: BACKGROUND
  The decline in birth rates is a concern in public health. Fertility is partly determined before birth by the intrauterine environment and prenatal exposure to maternal stress could, through hormonal disturbance, play a role. There has been such evidence from animal studies but not from humans. We aimed to examine the association between prenatal stress due to maternal bereavement following the death of a relative and childbirths in the offspring.
  
  
  METHODS
  This population-based cohort study included all subjects born in Denmark after 1968 and in Sweden after 1973 and follow-up started at the age of 12 years. Subjects were categorized as exposed if their mothers lost a close relative during pregnancy or the year before and unexposed otherwise. The main outcomes were age at first child and age-specific mean numbers of childbirths. Data was analyzed using Cox Proportional Hazards models stratified by gender and adjusted for several covariates. Subanalyses were performed considering the type of relative deceased and timing of bereavement.
  
  
  RESULTS
  A total of 4,121,596 subjects were followed-up until up to 41 years of age. Of these subjects, 93,635 (2.3%) were exposed and 981,989 (23.8%) had at least one child during follow-up time. Compared to unexposed, the hazard ratio (HR) [95% confidence interval] of having at least one child for exposed males and females were 0.98 [0.96-1.01] and 1.01 [0.98-1.03], respectively. We found a slightly reduced probability of having children in females born to mothers who lost a parent with HR = 0.97 [0.94-0.99] and increased probability in females born to mothers who lost another child (HR = 1.09 [1.04-1.14]), the spouse (HR = 1.29 [1.12-1.48]) or a sibling (HR = 1.13 [1.01-1.27]).
  
  
  CONCLUSIONS
  Our results suggested no overall association between prenatal exposure to maternal stress and having a child in early adulthood but a longer time of follow-up is necessary in order to reach a firmer conclusion.
authors: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors: Oleguer
authors: O
authors: Plana-Ripoll
authors: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark; Department of Epidemiology, Fielding School of Public Health, University of California Los Angeles, Los Angeles, California, United States of America.
authors: Jørn
authors: J
authors: Olsen
authors: Department of Biostatistics, University of Copenhagen, Copenhagen, Denmark.
authors: Per Kragh
authors: PK
authors: Andersen
authors: Departament d'Estadística i Investigació Operativa, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors: Guadalupe
authors: G
authors: Gómez
authors: Clinical Epidemiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors: Sven
authors: S
authors: Cnattingius
authors: Section for Epidemiology, Department of Public Health, Aarhus University, Aarhus, Denmark.
authors: Jiong
authors: J
authors: Li
mesh_terms: D000293:Adolescent; D000328:Adult; D001601:Bereavement; D015331:Cohort Studies; D003718:Denmark; D005260:Female; D006801:Humans; D008297:Male; D008423:Maternal Age; D033261:Maternal-Fetal Relations / Q000523:psychology*; D036801:Parturition / Q000523:psychology*; D011247:Pregnancy; D016016:Proportional Hazards Models; D018570:Risk Assessment / Q000379:methods / Q000706:statistics & numerical data; D012307:Risk Factors; D013315:Stress, Psychological / Q000523:psychology*; D013548:Sweden; D013997:Time Factors; D055815:Young Adult