Examining the multivariate interactions between prenatal health and nutrition and inflammation during pregnancy with implications for offspring neurodevelopment.

• In Event: Prenatal Programming: Physiological and Neurodevelopmental Consequences

Abstract

Preconceptional and prenatal psychological stress, demographics, trauma, health, and nutrition all have potential to alter offspring neurodevelopmental outcomes. These aspects of the prenatal environment are hypothesized to influence fetal neurodevelopment via stress-sensitive aspects of maternal-placental-fetal biology (MPF), such as immune and endocrine functioning. A growing body of literature has established an important role for inflammation as a common pathway through which multiple aspects of the preconceptional and prenatal environment have the potential to alter the developing fetal brain and increase subsequent risk for poor neurodevelopmental outcomes and psychiatric disorders. Elevated maternal inflammation during pregnancy is associated with neonatal brain alterations that have been linked to poorer neurodevelopment in early childhood, including poorer executive functioning, increased negative affect, and delayed cognitive development. Several studies have also identified certain cytokines that mediate the pathway between maternal health during pregnancy and offspring neurobehavioral development in early childhood. However, the majority of research in this area has utilized univariate analyses that do not account for the highly interactive, multidimensional nature of the maternal inflammatory milieu and prenatal factors with potential to alter fetal brain development during pregnancy. Further, studies in this area of research utilizing longitudinal, clinical datasets often struggle to replicate their findings in independent datasets. We seek to add to this research by utilizing innovating multivariate analyses to examine potential inflammatory pathways by which the prenatal environment influences offspring neurodevelopment, replicated across two independent datasets. Biological samples were collected at 2 timepoints during pregnancy to derive the average across pregnancy of 34 stress-sensitive biological markers. Features of maternal life history, demographics, and lifestyle were surveyed throughout pregnancy. We first employed a canonical correlation analysis (CCA) to examine the relationship between 1) maternal preconceptional and prenatal health factors and 2) multiple biomarkers of stress and inflammation during pregnancy, using two independent datasets (n = 138, n = 326) to validate results. Preliminary results from these analyses showed that multiple factors in the maternal psychosocial environment, including childhood physical neglect and income, as well as several health factors, including pre-pregnancy BMI and arm circumference during pregnancy, were associated with a latent factor that showed positive loadings for multiple pro-inflammatory cytokines. This work has promising implications for improving reproducibility and using multivariate approaches to better understand multiple, interacting prenatal influences and candidate biological pathways through which the prenatal environment can influence offspring neurodevelopment.

Authors

• Madeleine Allen, Oregon Health & Science University (OHSU)
  Presenting Author

• Amber Kautz, University of Rochester Medical Center

• Eric Feczko, University of Minnesota

• Jerod M. Rasmussen, University of California, Irvine

• Karen L Lindsay, University of California Irvine

• Nora K. Moog, Charité - Universitätsmedizin Berlin

• Sonja Entringer, Charité University of Medicine Berlin

• Pathik D. Wadhwa, University of California, Irvine

• Claudia Buss, Charité University of Medicine Berlin

• Thomas G O'Connor, University of Rochester Medical Center

• Alice M. Graham, Oregon Health and Science University