Prenatal exposure to maternal social disadvantage and psychosocial stress and neonatal white matter connectivity at birth

Significance

Childhood exposure to social disadvantage and related stressors is a major risk factor for altered brain development. The extent that these associations begin prenatally, when white matter is rapidly developing, remains unclear. In a sample of 289 neonates enriched for social disadvantage experienced prenatally, we use prospective data beginning early in gestation to show that prenatal exposure to social disadvantage is related to aberrant fronto-limbic white matter microstructure in the first weeks of life. The association between maternal psychosocial stress and cingulum bundle (CB) microstructure was observed in the setting of less-severe socioeconomic hardship. Associations between early life adversity and white matter development begins in utero, and fronto-limbic pathways are particularly vulnerable during this critical period of white matter development.

Abstract

Early life adversity (social disadvantage and psychosocial stressors) is associated with altered microstructure in fronto-limbic pathways important for socioemotional development. Understanding when these associations begin to emerge may inform the timing and design of preventative interventions. In this longitudinal study, 399 mothers were oversampled for low income and completed social background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent factors: social disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, and nutrition) and psychosocial stress (depression, stress, life events, and racial discrimination). At birth, 289 healthy term-born neonates underwent a diffusion MRI (dMRI) scan. Mean diffusivity (MD) and fractional anisotropy (FA) were measured for the dorsal and inferior cingulum bundle (CB), uncinate, and fornix using probabilistic tractography in FSL. Social disadvantage and psychosocial stress were fitted to dMRI parameters using regression models adjusted for infant postmenstrual age at scan and sex. Social disadvantage, but not psychosocial stress, was independently associated with lower MD in the bilateral inferior CB and left uncinate, right fornix, and lower MD and higher FA in the right dorsal CB. Results persisted after accounting for maternal medical morbidities and prenatal drug exposure. In moderation analysis, psychosocial stress was associated with lower MD in the left inferior CB among the lower-to-higher socioeconomic status (SES) (INR ≥ 200%) group, but not the extremely low SES (INR < 200%) group. Increasing access to social welfare programs that reduce the burden of social disadvantage and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways.