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Maternal Prenatal Stress Is Associated With Altered Uncinate Fasciculus Microstructure in Premature Neonates

  • Lautarescu, Alexandra1, 2
  • Pecheva, Diliana1
  • Nosarti, Chiara1
  • Nihouarn, Julie1
  • Zhang, Hui3
  • Victor, Suresh1
  • Craig, Michael2, 4
  • Edwards, A. David1
  • Counsell, Serena J.1
  • 1 Department of Perinatal Imaging and Health, Centre for Developing Brain, School of Biomedical Engineering and Imaging Sciences, King’s College London, London, United Kingdom
  • 2 Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology and Neuroscience, King’s College London, London, United Kingdom
  • 3 Department of Computer Science and Centre for Medical Image Computing, University College London, London, United Kingdom
  • 4 National Female Hormone Clinic, South London and Maudsley National Health Service Foundation Trust, London, United Kingdom
Published Article
Publication Date
Mar 15, 2020
DOI: 10.1016/j.biopsych.2019.08.010
PMID: 31604519
PMCID: PMC7016501
PubMed Central


Background Maternal prenatal stress exposure (PNSE) increases risk for adverse psychiatric and behavioral outcomes in offspring. The biological basis for this elevated risk is poorly understood but may involve alterations to the neurodevelopmental trajectory of white matter tracts within the limbic system, particularly the uncinate fasciculus. Additionally, preterm birth is associated with both impaired white matter development and adverse developmental outcomes. In this study we hypothesized that higher maternal PNSE was associated with altered uncinate fasciculus microstructure in offspring. Methods In this study, 251 preterm infants (132 male, 119 female) (median gestational age = 30.29 weeks [range, 23.57–32.86 weeks]) underwent brain magnetic resonance imaging including diffusion-weighted imaging around term-equivalent age (median = 42.43 weeks [range, 37.86–45.71 weeks]). Measures of white matter microstructure were calculated for the uncinate fasciculus and the inferior longitudinal fasciculus, a control tract that we hypothesized was not associated with maternal PNSE. Multiple regressions were used to investigate the relationship among maternal trait anxiety scores, stressful life events, and white matter microstructure indices in the neonatal brain. Results Adjusting for gestational age at birth, postmenstrual age at scan, maternal age, socioeconomic status, sex, and number of days on parenteral nutrition, higher stressful life events scores were associated with higher axial diffusivity (β = .177, q  = .007), radial diffusivity (β = .133, q  = .026), and mean diffusivity (β = .149, q  = .012) in the left uncinate fasciculus, and higher axial diffusivity (β = .142, q  = .026) in the right uncinate fasciculus. Conclusions These findings suggest that PNSE is associated with altered development of specific frontolimbic pathways in preterm neonates as early as term-equivalent age.

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