Associations of parental and perinatal factors with subsequent risk of stress-related disorders: a nationwide cohort study with sibling comparison

Yuchen Li, Arvid Sjölander, Huan Song, Sven Cnattingius, Fang Fang, Qian Yang, Lorena Fernández de la Cruz, David Mataix-Cols, Gustaf Brander, Jiong Li, Wei Zhang, Katja Fall, Brian M. D’Onofrio, Catarina Almqvist, Paul Lichtenstein, Unnur Anna Valdimarsdóttir, Donghao Lu*

*Corresponding author for this work

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Little is known about the contribution of pregnancy-related parental and perinatal factors to the development of stress-related disorders. We aimed to investigate whether parental/perinatal adversities entail higher risks of stress-related disorders in the offspring, later in life, by accounting for genetic and early environmental factors. Based on the nationwide Swedish registers, we conducted a population-based cohort study of 3,435,747 singleton births (of which 2,554,235 were full siblings), born 1973–2008 and survived through the age of 5 years. Using both population- and sibling designs, we employed Cox regression to assess the association between parental and perinatal factors with subsequent risk of stress-related disorders. We identified 55,511 individuals diagnosed with stress-related disorders in the population analysis and 37,433 in the sibling analysis. In the population-based analysis we observed increased risks of stress-related disorders among offspring of maternal/paternal age <25, single mothers, parity ≥4, mothers with BMI ≥ 25 or maternal smoking in early pregnancy, gestational diabetes, and offspring born moderately preterm (GA 32–36 weeks), or small-for-gestational-age. These associations were significantly attenuated toward null in the sibling analysis. Cesarean-section was weakly associated with offspring stress-related disorders in population [hazard ratio (HR) 1.09, 95% confidence interval (CI) 1.06–1.12] and sibling analyses (HR 1.10, 95% CI 1.02–1.20). Our findings suggest that most of the observed associations between parental and perinatal factors and risk of stress-related disorders in the population analysis are driven by shared familial environment or genetics, and underscore the importance of family designs in epidemiological studies on the etiology of psychiatric disorders.

Original languageEnglish
Pages (from-to)1712-1719
Number of pages8
JournalMolecular Psychiatry
Issue number3
Publication statusPublished - 1 Jan 2022

Bibliographical note

This study was supported by the China Scholarship Council (to Ms YL), Grant of Excellence, Icelandic Research Fund (grant number: 163362-051, to Dr. UAV), ERC Consolidator Grant (grant number: 726413, to Dr UAV), and Swedish Research Council (grant number: 2016-02234, to Dr UAV and 2020-01003 to Dr DL). We also acknowledge the financial support from the Swedish Research Council through the Swedish Initiative for Research on Microdata in the Social And Medical Sciences (SIMSAM) framework (grant number: 340-2013-5867).

© 2021. The Author(s).

Other keywords

  • Child, Preschool
  • Cohort Studies
  • Diabetes, Gestational
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Mental Disorders/epidemiology
  • Pregnancy
  • Proportional Hazards Models
  • Risk Factors
  • Siblings
  • Sweden/epidemiology
  • Geðraskanir


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