Abstract
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.
Highlights
Most people are exposed to some stressful life events or trauma throughout the life span [1]
The observed increased risks of stress-related disorders by adverse parental factors in the population analysis were largely attenuated to null in the sibling analysis, suggesting strong confounding by familial factors shared by siblings
The associations of very preterm birth and low 5 min Apgar score with stress-related disorders were attenuated by 40–60% in the sibling analysis, indicating that the association observed in the population analysis is largely driven by shared familial factors
Summary
Most people are exposed to some stressful life events or trauma throughout the life span [1] Such events raise the risk of severe psychiatric reactions, including posttraumatic stress disorder (PTSD) and acute stress reaction (ASR), adjustment disorder, and other stress reactions [1, 2]. These stress-related disorders are associated with a number of adverse health consequences, including cardiovascular [3] and metabolic diseases [4], autoimmune diseases [5], dementia [6], suicide [7], and premature mortality [8]. Except for childhood traumatic experiences [13], little is known about potential risk factors occurring before or shortly after birth [14]
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