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Published on: June 13, 2021
Vulnerability of the Neonatal Connectome following Postnatal Stress
Femke Lammertink1, Manon J N L Benders2, Erno J Hermans3
1Department of Neonatology, University Medical Center Utrecht, Utrecht University, 3584 EA Utrecht, The Netherlands femke.lammertink@gmail.com.
Insights
High stress in preterm infants slows brain connectivity growth, particularly in regions like the amygdala and hippocampus. Preserved connectivity in these areas may protect against behavioral issues later in life.
Area of Science:
- Neuroscience
- Developmental Psychology
- Medical Imaging
Background:
- The preterm brain is vulnerable to stress, which can impact early development and later behavior.
- Understanding the effects of postnatal stress on neonatal brain networks is crucial for identifying resilience factors.
Purpose of the Study:
- To investigate how early life stress affects structural brain development in preterm infants.
- To determine if changes in brain connectivity architecture correlate with behavioral vulnerability in early childhood.
Main Methods:
- Longitudinal diffusion-weighted imaging (DWI) and tractography were used to assess structural brain connectivity in preterm infants.
- Postnatal stress was quantified by the number of invasive procedures during hospitalization.
- Brain connectivity was analyzed in relation to behavioral outcomes (internalizing symptoms) at 2-5 years of age.
Main Results:
- Higher levels of postnatal stress were associated with impaired growth of structural connectivity in a specific brain subnetwork (p = 0.003).
- This affected network included critical regions such as the amygdala, insula, hippocampus, and posterior cingulate cortex.
- Infants with more internalizing symptoms showed lower hippocampal and amygdala connectivity compared to resilient infants (p < 0.001).
Conclusions:
- Increased stress exposure during hospital stays in preterm infants is linked to slower development of structural brain connectivity.
- The hippocampus and amygdala may serve as key areas for resilience, potentially buffering against the negative effects of early stress.
- Findings offer insights into stress-induced brain reorganization and its role in resilient functioning.
Abstract:
Stress following preterm birth can disrupt the emerging foundation of the neonatal brain. The current study examined how structural brain development is affected by a stressful early 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 determined based on the number of invasive procedures during hospitalization (e.g., heel lance). Higher stress levels impaired structural connectivity growth in a subnetwork of 48 connections (p = 0.003), including the amygdala, insula, hippocampus, and posterior cingulate cortex. Findings were replicated in an independent validation sample (N = 123, 39.8% female, n = 91 with follow-up). Classifying infants into vulnerable and resilient based on having more or less internalizing symptoms at two to five years of age (n = 71) revealed lower connectivity in the hippocampus and amygdala for vulnerable relative to resilient infants (p < 0.001). Our findings suggest that higher stress exposure during hospital admission is associated with slower growth of structural connectivity. The preservation of global connectivity of the amygdala and hippocampus might reflect a stress-buffering or resilience-enhancing factor against a stressful early environment and early-childhood internalizing symptoms.SIGNIFICANCE STATEMENT The preterm brain is exposed to various external stimuli following birth. The effects of early chronic stress on neonatal brain networks and the remarkable degree of resilience are not well understood. The current study aims to provide an increased understanding of the impact of postnatal stress on third-trimester brain development and describe the topological architecture of a resilient brain. We observed a sparser neonatal brain network in infants exposed to higher postnatal stress. Limbic regulatory regions, including the hippocampus and amygdala, may play a key role as crucial convergence sites of protective factors. Understanding how stress-induced alterations in early brain development might lead to brain (re)organization may provide essential insights into resilient functioning.
