PROJECT SUMMARY
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 the developing fetal brain via stress-sensitive aspects of maternal-placental-fetal biology (MPF),
such as immune and endocrine functioning. However, previous research has centered around univariate
analyses that do not consider the wide array of preconceptional and prenatal factors with potential to influence
MPF biology and the developing fetal brain. Given the highly complex and interactive nature of these
relationships, multivariate analyses are well-suited to identify canonical patterns in high-dimensionality analyses
that may shed light on potential inflammatory mechanisms by which the preconceptional and prenatal
environment may influence offspring brain development. Inflammation may be best characterized by considering
multiple cytokines at once, as they appear to act co-dependently—cytokines that frequently work together to
communicate form cytokine networks. The use of cytokine networks has become an increasingly popular method
of conceptualizing and analyzing inflammation, given that specific cytokine networks are associated with certain
psychopathologies or heterogenous presentations of mental disorders. Further, specific cytokine networks
during pregnancy have been associated with altered offspring neurodevelopmental outcomes. Furthermore,
little to none of these studies have been reproduced in independent datasets. Given the increasing awareness
of limited reproducibility in neuroscience research, there has been an urgent push, spearheaded by the NIH,
towards rigorously designed experiments and increased reproducibility. The overall goal of the proposed
study is to examine how multiple preconceptional and prenatal factors affect maternal systemic
inflammation during pregnancy and associated alterations in offspring neurodevelopment, while
meeting the need for greater rigor and reproducibility in an innovative study design which will replicate
complex multivariate analyses across three high-dimensionality datasets. The specific aims of this
proposal are: 1) Identify maternal psychosocial contributors to the maternal inflammatory milieu during
pregnancy at a multivariate level; 2) Identify potent health indicators of the maternal inflammatory milieu during
pregnancy at a multivariate level; 3) Identify subgroups of participants with distinct patterns of maternal systemic
inflammation and examine potentially relevant interactions between health and psychosocial factors, as well as
neurodevelopmental outcomes associated with each cluster. This proposal intends to innovatively analyze
cytokine network activity as a potential pathway by which aspects of the preconceptional and prenatal
environment alter offspring neurodevelopment using multivariate statistical techniques. Additionally, given
frequent challenges with reproducibility in science, results from the analyses will be cross validated across three
independent datasets.
