Associations between prenatal adversity and neonatal white matter microstructure on language outcomes at age 2 years

Background: Early life adversity is associated with microstructural alterations in white matter regions that subserve language. However, the mediating and moderating pathways between adversities experienced in utero and key neonatal white matter tracts including the corpus callosum (CC), superior longitudinal fasciculus (SLF), arcuate fasciculus (AF), inferior fronto-occipital fasciculus (IFOF), and uncinate on early language outcomes remains unknown. Methods: This longitudinal study includes 160 neonates, oversampled for prenatal exposure to adversity, who underwent diffusion MRI (dMRI) in the first weeks of life. dMRI parameters were obtained using probabilistic tractography in FSL. Maternal Social Disadvantage and Psychosocial Stress was assessed throughout pregnancy. At age 2 years, the Bayley Scales of Infant and Toddler Development-III evaluated language outcomes. Linear regression, mediation, and moderation assessed associations between prenatal adversities and neonatal white matter on language outcomes. Results: Prenatal exposure to Social Disadvantage (p<.001) and Maternal Psychosocial Stress (p<.001) were correlated with poorer language outcomes. When Social Disadvantage and maternal Psychosocial Stress were modeled simultaneously in relation to language outcomes, only Social Disadvantage was significant (p<.001). Independent of Social Disadvantage (p<.001), lower neonatal CC fractional anisotropy (FA) was related to poorer global (p=.02) and receptive (p=.02) language outcomes. CC FA did not mediate the association between Social Disadvantage and language outcomes (indirect effect 95% CIs -0.96-0.15), and there was no interaction between Social Disadvantage and CC FA on language outcomes (p>.05). Bilateral SLF/AF, IFOF, and uncinate were not significant (p>.05). Conclusions: Prenatal exposure to Social Disadvantage and neonatal CC FA were independently related to language problems by age 2, with no evidence of mediating or moderating associations with language outcomes. These findings elucidate the early neural underpinnings of language development and suggest that the prenatal period may be an important time to provide poverty-reducing support to expectant mothers to promote offspring neurodevelopmental outcomes.