New research
Stressful Life Events During Pregnancy and Offspring Depression: Evidence From a Prospective Cohort Study

https://doi.org/10.1016/j.jaac.2016.05.014Get rights and content

Objective

The fetal programming hypothesis posits that in utero exposure to stress can alter prenatal brain development and lifelong stress response. However, human studies linking objective prenatal stressors to offspring mental illness, especially depression, are rare. The purpose of this study was to examine the association between mothers’ exposure to prenatal stressful life events (SLEs) and offspring depression.

Method

The sample comprised 10,569 members of a prospective population-based cohort, the Avon Longitudinal Study of Parents and Children (ALSPAC). Mothers reported on the occurrence and impact of 42 prenatal SLEs. Offspring depressive symptoms were assessed using a computerized version of the Clinical Interview Schedule−Revised (CIS-R) at age 17 to 18, as well as 13 self-report statements from the Short Mood and Feelings Questionnaire (SMFQ) at 6 time points from ages 10 to 11 to 18 to 19. Latent class growth analysis (LCGA) was used to identify trajectories of depressive symptoms across adolescence.

Results

After adjusting for potential confounders, a 1-unit increase in maternal SLE scores (range, 0–168) during gestation was associated with increased offspring depressive symptoms (β = 0.07, p < .01) and major depression (odds ratio [OR] = 1.03, 95% CI 1.01, 1.06) at age 17 to 18. LCGA revealed 4 trajectories of depressive symptoms. High maternal SLEs (fourth quartile) were associated with membership in the trajectory characterized by stable, high levels of depression from age 10 to 11 to 18 to 19 years (OR = 1.72, 95% CI = 1.09, 2.71).

Conclusion

These results provide support for the fetal programming hypothesis, demonstrating that prenatal exposure to acute stress is associated with offspring depression in adolescence. Stress management may be of benefit for expectant mothers.

Section snippets

Sample

The sample was drawn from the Avon Longitudinal Study of Parents and Children (ALSPAC), an ongoing population-based study of the determinants of child health and development. The initial cohort consisted of 14,062 pregnant women with estimated delivery dates between April 1, 1991, and December 31, 1992. All participants provided informed consent, the study was approved by the ALSPAC Ethics and Law committee, and these analyses were approved by the Ottawa Health Science Network Research Ethics

Results

The prevalence of depression at age 17 to 18 years was 7.7% (Table 1). SLE scores ranged from 0 to 61, with a median of 6. The most commonly reported individual life events were prenatal tests for abnormality (53.4%), arguments with a partner (50.2%), and income reductions (20.8%). The events rated as most severe were death of a child (average severity rating among mothers who experienced the event: 3.38 on a 4-point scale), attempted abortion (3.28), and miscarriage scare (3.22).

Discussion

In this prospective study of 10,569 parents and offspring, we demonstrate that offspring of mothers exposed to stressful events during early pregnancy may be at increased risk for depression and elevated depressive symptoms at age 17 to 18 years, even after maternal depression, anxiety, and other known prenatal and early life risk factors were taken into account. This increased risk persisted after adjusting for stress in the late prenatal/early postnatal period, suggesting that exposure to

References (47)

  • S. Maccari et al.

    Prenatal stress and long-term consequences: implications of glucocorticoid hormones

    Neurosci Biobehav Rev

    (2003)
  • K.J. O’Donnell et al.

    Maternal prenatal anxiety and downregulation of placental 11beta-HSD2

    Psychoneuroendocrinology

    (2012)
  • E.P. Davis et al.

    Prenatal exposure to maternal depression and cortisol influences infant temperament

    J Am Acad Child Adolesc Psychiatry

    (2007)
  • I. Colman et al.

    A longitudinal typology of symptoms of depression and anxiety over the life course

    Biol Psychiatry

    (2007)
  • M.J. Essex et al.

    Maternal stress beginning in infancy may sensitize children to later stress exposure: effects on cortisol and behavior

    Biol Psychiatry

    (2002)
  • M.P. Austin et al.

    Prenatal stress, the hypothalamic-pituitary-adrenal axis, and fetal and infant neurobehaviour

    Early Hum Dev

    (2005)
  • D.I. Phillips et al.

    Fetal programming of autonomic and HPA function: do people who were small babies have enhanced stress responses?

    J Physiol

    (2006)
  • I. Colman et al.

    Birth weight, stress, and symptoms of depression in adolescence: evidence of fetal programming in a national Canadian cohort

    Can J Psychiatry

    (2012)
  • W. Wojcik et al.

    Foetal origins of depression? A systematic review and meta-analysis of low birth weight and later depression

    Psychol Med

    (2013)
  • T.G. O’Connor et al.

    Maternal antenatal anxiety and behavioural/emotional problems in children: a test of a programming hypothesis

    J Child Psychol Psychiatry Allied Discip

    (2003)
  • T.G. O’Connor et al.

    Maternal antenatal anxiety and children’s behavioural/emotional problems at 4 years. Report from the Avon Longitudinal Study of Parents and Children

    Br J Psychiatry

    (2002)
  • B.M. Gutteling et al.

    The effects of prenatal stress on temperament and problem behavior of 27-month-old toddlers

    Eur Child Adolesc Psychiatry

    (2005)
  • B.R.H. Van den Bergh et al.

    High antenatal maternal anxiety is related to ADHD symptoms, externalizing problems, and anxiety in 8-and 9-year-olds

    Child Dev

    (2004)
  • Cited by (47)

    • DNA methylation as a mediator in the association between prenatal maternal stress and child mental health outcomes: Current state of knowledge

      2022, Journal of Affective Disorders
      Citation Excerpt :

      In the Raine Study, results indicated that children of mothers who experienced five or more SLEs, regardless of timing (i.e., second or third trimester) and type of stressor (i.e., within or outside of participants' control), had over twice greater odds of experiencing clinically-significant internalizing symptoms by age 14 years (Robinson et al., 2011). Similarly, researchers from the ALSPAC cohort found that prenatal SLEs predicted depression symptoms and diagnoses in the offspring at age 17–18 years (Kingsbury et al., 2016). The children of mothers who were in the highest quartile of prenatal SLEs had nearly twice greater odds of experiencing consistently high depressive symptoms from early to late adolescence (Kingsbury et al., 2016).

    • Prenatal stress and offspring depression in adulthood: The mediating role of childhood trauma

      2022, Journal of Affective Disorders
      Citation Excerpt :

      There is strong evidence that prenatal maternal depression is associated with offspring depression in adulthood (Rogers et al., 2020; Tirumalaraju et al., 2020). Prenatal family adversity such as financial or relationship difficulties have also been associated with offspring depression even after accounting for maternal mental health (Kingsbury et al., 2016; Najman et al., 2017). Both sources of prenatal stress have also been associated with alterations to the hypothalamic-pituitary-adrenal (HPA) axis (Osborne et al., 2018; Van den Bergh et al., 2008), increased inflammation (Plant et al., 2016), and hyperresponsivity in the amygdala in the offspring (Knaap et al., 2018), offering support for a programming effect of prenatal stress on offspring depression through biologically mediated mechanisms (Hantsoo et al., 2019; Kim et al., 2015).

    View all citing articles on Scopus

    This article is discussed in an editorial by Dr. André Sourander on page 645.

    The UK Medical Research Council and the Wellcome Trust (Grant ref: 102215/2/13/2) and the University of Bristol provide core support for ALSPAC. This research was undertaken, in part, thanks to funding from the Canada Research Chairs program for IC. This research was additionally funded by the SickKids Foundation and the Canadian Institutes of Health Research (grant SKF 116328).

    Drs. Kingsbury and Weeks served as the statistical experts for this research.

    Disclosure: Drs. Kingsbury, Weeks, Evans, Mahedy, Colman, and Mss. MacKinnon and Dykxhoorn report no biomedical financial interests or potential conflicts of interest.

    View full text