The role of preterm birth and postnatal stress in neonatal structural brain development

Abstract

Preterm birth disrupts the emerging foundations of the brains architecture, and the continuum of early-life stress-provoked alterations reaches from a healthy adaptation with resilience to severe vulnerability and maladjustment with psychopathology. The current study examined how structural brain development is affected by a stressful extra-uterine environment and whether changes in topological architecture at term-equivalent age could explain the increased vulnerability for behavioral symptoms during early childhood. Longitudinal changes in structural brain connectivity were quantified using diffusion-weighted imaging (DWI) and tractography in preterm born infants (gestational age <28 weeks), imaged at 30 and/or 40 weeks of gestation (N=145, 43.5% female). A global index of postnatal stress was based on invasive procedures during hospitalization (e.g., heel lance). Infants were classified as vulnerable and resilient based on having more or less internalizing symptoms at 2-5 years of age (n=71). Findings were replicated in an independent validation sample (N=123, 39.8% female, n=91 with follow-up). Higher stress levels impaired structural connectivity growth in the amygdala, insula, hippocampus, and posterior cingulate cortex. The hippocampus, amygdala, and subthalamic nucleus showed lower global connectivity in vulnerable relative to resilient individuals. The distinct characteristics of the resilient brain allowed for a good predictive accuracy of group membership using local network measures (80%, p<10-5, {kappa}=0.61). These findings emphasize the detrimental impact of postnatal stress and, more importantly, the relative plasticity of the preterm brain. Resilience following postnatal stress appertains to a potential compensatory or innate ability to propagate global information flow. Significance StatementThe underdeveloped preterm brain is exposed to various external stimuli following birth. Although the importance of early adversity has been widely recognized, the essential understanding of the effects of early chronic stress on neonatal brain networks as well as the remarkable degree of resilience is not well understood. We aim to provide an increased understanding of the impact of postnatal stress on brain development between 30 and 40 weeks of gestation and describe the topological architecture of a resilient brain. We observed global alteration in neonatal brain networks following postnatal stress and identified key contributive regions conferring resilience to the development of future internalizing symptoms.