Prenatal Adversity and Neonatal White Matter Microstructure Independently Relate to Language Outcomes at Age 2 Years

Jacob Bjork; Jeanette K Kenley; Caleb Gardner; Aidan Latham; Tara A Smyser; J Philip Miller; Joshua S Shimony; Jeffrey J Neil; Barbara B Warner; Joan L Luby; Deanna M Barch; Cynthia E Rogers; Christopher D Smyser; Rachel E Lean

doi:10.1016/j.jpeds.2025.114676

Prenatal Adversity and Neonatal White Matter Microstructure Independently Relate to Language Outcomes at Age 2 Years

J Pediatr. 2025 May 30:285:114676. doi: 10.1016/j.jpeds.2025.114676. Online ahead of print.

Authors

Affiliations

¹ Psychiatry, Washington University School of Medicine, St. Louis, MO.
² Neurology, Washington University School of Medicine, St. Louis, MO.
³ Biostatistics and Medicine, Washington University School of Medicine, St. Louis, MO.
⁴ Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
⁵ Pediatrics, Washington University School of Medicine, St. Louis, MO.
⁶ Psychiatry, Washington University School of Medicine, St. Louis, MO; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO; Psychological and Brain Sciences, Washington University in St. Louis, St. Louis, MO.
⁷ Psychiatry, Washington University School of Medicine, St. Louis, MO; Biostatistics and Medicine, Washington University School of Medicine, St. Louis, MO.
⁸ Neurology, Washington University School of Medicine, St. Louis, MO; Biostatistics and Medicine, Washington University School of Medicine, St. Louis, MO; Mallinckrodt Institute of Radiology, Washington University School of Medicine, St. Louis, MO.
⁹ Psychiatry, Washington University School of Medicine, St. Louis, MO. Electronic address: rachel.lean@wustl.edu.

PMID: 40451571
DOI: 10.1016/j.jpeds.2025.114676

Abstract

Objective: To examine the mediating and moderating associations between prenatal exposure to adversity and neonatal white matter (WM) development on language outcomes at age 2 years.

Study design: This longitudinal study includes 160 infants (gestational ages 41 - 39 weeks, n = 83; 38 - 37 weeks, n = 62; 36 - 34 weeks, n = 15) with neonatal diffusion MRI and language assessments at age 2 years using the Bayley Scales of Infant and Toddler Development-III. Prenatal social disadvantage (PSD) and maternal psychosocial stress were assessed throughout the prenatal period. Multivariable and stepwise linear regression, mediation, and moderation analyses were used to investigate associations between prenatal adversities and neonatal WM on language outcomes. Maternal cognition and stimulation provided in the home were included as covariates.

Results: PSD and maternal psychosocial stress were associated with poorer language outcomes (P < .001). When PSD and maternal Psychosocial Stress were modeled simultaneously, only PSD was associated with language outcomes (P < .001). Independent of PSD (P < .001), lower neonatal fractional anisotropy (FA) in the corpus callosum (CC) was associated with poorer language outcomes (P = .02). CC FA did not mediate the association between PSD and language outcomes (indirect effect 95% CIs: -0.96 - 0.15), and there was no interaction between PSD and CC FA on language outcomes (P > .05).

Conclusions: PSD and neonatal CC FA were independently related to language outcomes, with no significant mediating or moderating pathways at this stage of development. These findings suggest the need for investigation of prenatal provision of poverty-reducing services and maternal psychosocial intervention services to promote offspring WM and language development.

Keywords: diffusion MRI; follow-up; in-utero; neurodevelopment; social disadvantage.