Pregnancy and early life represent crucial windows of susceptibility to environmental exposures and stress, increasing the risk of the offspring for behavioral disorders in childhood, including an increased susceptibility to anxiety. Epigenomic, metagenomic and metabolomic changes are likely key molecular mediators of these increased risks. Our team has spent the past decade identifying and describing these molecular mediators which are associated with an adverse in utero environment, including the use of large scale multi?omics data sets to relate them to behavior in early childhood and adolescence. We have found that composite maternal and neonatal morbidities were increased after Harvey landfall (?Hurricane Harvey exposed?) compared with individuals who delivered before Harvey (?Harvey unexposed). These adverse events were more common in pregnant women who answered positively to being directly affected by the hurricane, but did not vary by perceived stress. Thus, measures of stress and resilience following hurricane exposure, and how this potentially affects neurobehavioral outcomes and resilience in the children of these pregnant women, had not yet been studied and is the goal of this current proposal. We are very excited about our capacity and readiness to conduct this study on an aggressive 1 year timeline as outlined by our aims. We will leverage our existing and highly-characterized cohort of subjects who were pregnant at the time of Hurricane Harvey. From these subjects we have already sequenced maternal samples (placental, vaginal, oral, stool, and breastmilk) and infant specimens (stool and oral) for metagenomics analyses. We propose to follow-up on the children of this cohort, to continue the metagenomic, metabolomic and epigenomic studies afforded by the collection of these samples before, during and after Harvey. We propose to collect oral swabs and stool from these children, and perform behavioral and neuroimaging assessments at 4 years of age to determine the biologic signature of in utero exposure to Hurricane Harvey and resultant neurobehavior with this exposure. By integrating exposure measures from our existing, placental, neonatal and infant samples with accompanying robust clinical metadata, longitudinal metagenomic, epigenomic and metabolomic data, then integrating behavioral and neurostructural imaging data, we will be able inform and predict attributable risk. Having spent over a decade identifying both exposure risks and molecular mechanisms underlying the developmental origins of disease, we are uniquely poised to rapidly expand and integrate this data in our post-Harvey setting in an ongoing cohort with studies which are scientifically rigorous, feasible, justifiable, and of likely long-term significance and high translational impact. Follow-up of this existing cohort will provide an invaluable resource to the scientific community by making available large scale data sets on 200 subjects which include metagenomics, metabolomics, and epigenomics and neurobehavioral data related to Hurricane Harvey.
While the impact of the environmental exposures and increased levels of stress imparted by Hurricane Harvey is still being evaluated, we have found that composite maternal and neonatal morbidities were increased after Harvey landfall compared with individuals who delivered before Harvey. In this current proposal we will perform follow-up studies on the children of women who were pregnant at the time of Hurricane Harvey, investigating changes in the microbiome, metabolome and epigenome, as well as performing repeat behavioral and neuroimaging studies at approximately 4 years of age (and 12 months later). The net result of these studies will be to identify which neurobehavioral outcomes are directly attributable to in utero exposure to Hurricane Harvey and the increased maternal prenatal stress versus resilience associated with this exposure.
