Mechanisms linking in utero stress to altered offspring behaviour

Development in utero is recognised as a determinant of health in later life, a concept known as early life ‘programming’. Several studies in humans have now shown a link between in utero stressors of maternal stress, anxiety and depression and adverse behavioural outcomes for the offspring including poorer cognitive function and behavioural and emotional problems. These behaviours are observed from the very early neonatal period and appear to persist through to adulthood. Underlying mechanisms are not known but overexposure of the developing foetus to glucocorticoids has been proposed. Dysregulation of the maternal and offspring hypothalamic–pituitary–adrenal (HPA) axis has been proposed as a mechanism linking in utero stress with offspring behavioural outcomes. Studies suggest that altered circulating levels of maternal cortisol during pregnancy and/or changes in placental gene expression or methylation, which result in increased glucocorticoid transfer to the developing foetus, are linked to changes in offspring behaviour and in activity of the offspring HPA axis. Further understanding of the underlying pathways and identification of any gestation of vulnerability are needed to help design interventions to reduce in utero stress and improve behavioural outcomes in the offspring.