Metabolomic Analysis of Prenatal Maternal Stress Effects on Offspring as a Result of the 2011 Queensland Flood
INTRODUCTION: It is widely acknowledged that the health outcomes of offspring are directly linked to the health of their mother during pregnancy. The impacts of pre-natal maternal stress (PNMS) can cascade as development of the offspring continues, and are linked to negative health outcomes.
OBJECTIVE: Our goal was to determine the metabolomic differences in offspring who were exposed in utero to the 2011 Queensland Flood in relation to the mother’s level of subjective distress and objective hardship.
METHODS: Ninety urine samples were obtained from 51 male and 39 female 4-year-old offspring. Metabolomic profiles were acquired using a 700 MHz Bruker Avance III HD NMR spectrometer and subsequently binned. Partial Least Squares-Discriminant Analysis (PLS-DA) was used to identify differences in high vs. low composite subjective distress and high vs. low objective hardship in metabolic profiles, in both male and female groups. Metabolites leading to significant group separation were identified using both Variable Importance Analysis based on random Variable Combination (VIAVC) and a Mann-Whitney U test. Metabolanalyst software was used for metabolite sets enrichment analysis of altered metabolites, and to identify potential biochemical pathways and disease pathologies in the offspring.
RESULTS: Group separation was observed between high and low levels of both objective hardship and composite subjective distress groups, in both males and females. Several metabolites were detected as being either up- or down-regulated, thus contributing to the observed separation, including creatinine and formate.
CONCLUSIONS: The metabolites identified as significantly altered have been associated with several negative health outcomes. Creatinine down- regulation has been associated with dysfunction in Krebs cycle thus potentially disturbing energy metabolism and contributing to psychiatric illness. Formate up-regulation has been linked to oxidative stress and correlated to metabolic dysfunction in genes relating to neurodegenerative diseases. Understanding the biological pathways affected by exposure to PNMS allows for an improved approach to patient treatment.