Exposure to Prenatal Social Disadvantage and Maternal Psychosocial Stress: Relationships to Neonatal White Matter Connectivity

Childhood exposure to poverty and related psychosocial stressors are associated with altered microstructure in fronto-limbic pathways evident at age 8-10 years. How early in neurodevelopment these associations can be detected remains unclear. In this longitudinal study, 399 mothers were oversampled for low income and completed social experience and background measures during pregnancy. Measures were analyzed with structural equation analysis resulting in two latent constructs: Social Disadvantage (education, insurance status, income-to-needs ratio [INR], neighborhood deprivation, nutrition) and Psychosocial Stress (depression, stress, life events, 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 risk in pregnancy and prenatal drug exposure. In moderation analysis, Psychosocial Stress was associated with lower MD in the left inferior CB among the lower-to-higher SES (INR ≥200%) group, but not the extremely low SES (INR <200%) group. Increasing access to social welfare programs that reduce the burden of poverty and related psychosocial stressors may be an important target to protect fetal brain development in fronto-limbic pathways. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the National Institute of Mental Health (R01 MH113883, K01 MH122735, T32 MH100019, F30 HD104313), March of Dimes Prematurity Research Center at Washington University, Washington University Intellectual and Developmental Disability Research Center (P50 HD103525), Children's Discovery Institute, McDonnell Center for Systems Neuroscience, and a NARSAD Young Investigator Grant (#28521) from the Brain and Behavior Research Foundation. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The IRB of Washington University School of Medicine gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes De-identified data is being deposited in the NIMH Data Archive and will be available after the conclusion of the eLABE 3-year wave.