Vulnerability of the Neonatal Connectome following Postnatal Stress

Femke Lammertink*, Manon J.N.L. Benders, Erno J. Hermans, Maria L. Tataranno, Jeroen Dudink, Christiaan H. Vinkers, Martijn P. van den Heuvel

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)8948-8959
Number of pages12
JournalJournal of Neuroscience
Issue number48
Publication statusPublished - 30 Nov 2022


  • brain development
  • diffusion MRI
  • internalizing symptoms
  • postnatal stress
  • prematurity
  • resilience


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