Maternal Prenatal Stress in Relation to Child Neurodevelopmental Outcome in MARBLES: A High Familial Risk Cohort

Autism Spectrum Disorder (ASD) is a neurodevelopmental condition characterized by atypical development in social skills, language deficits, and restricted or repetitive interests and behaviors. In recent years, attention to ASD has increased due to the continual increase in prevalence. The CDC recently reported that 1 in 44 children in the United States was diagnosed with ASD in 2018, which is a nearly 23% increase since the reported estimate of 1 in 54 children just two years prior. It is unclear whether this increase is due to increasing awareness and improved detection or due to a true increase in the prevalence of this condition, as the etiology of ASD is still unknown.The prenatal period is a sensitive time when a mother’s behaviors and exposures can affect her child’s long-term health. Like genetic factors, many prenatal environmental factors can have lasting effects on the neurodevelopment of the child. Identifying prenatal exposures and understanding how they influence ASD risk is an area of research that is developing but warrants more inquiry. Maternal prenatal stress (MPS) is a complex exposure that depends on many factors, including the mother’s financial standing, family events and complications, and ability to provide her family with basic needs. Associations between maternal MPS and behavioral differences in her offspring have been reported in experimental animal models using rodents and non-human primates. In human epidemiologic studies, estimated associations of maternal prenatal stress with ASD have varied findings. Some investigations indicate prenatal exposure to stress as being associated with risk of neurodevelopmental disorders, including Attention Deficit Hyperactivity Disorder and ASD. Three studies found increased risk of ASD in mothers exposed to MPS, measured by death of a first-degree relative, family discord, or broad recall of any stressful events. However, a few studies found no association with ASD when measuring MPS through: exposure to specific rocket attacks, prospective collection of routine and major stressors, or experiencing death of a close relative. The discordant results might be explained by differing study designs. For example, the study examining death of a first-degree relative was retrospective, while the study examining death of a close relative was prospective. In addition, the studies’ stress measurements varied from recall of very specific events, like rocket attacks, to very broad recall, such as asking an open-ended question of whether or not the mothers experienced any stressful events during pregnancy.With inconsistent findings on the association between stressful life events and risk of ASD, this study measured stress in three ways and examined their respective associations with neurodevelopmental outcome (ASD, Typically developing (TD), or Non-typically developing (Non-TD)) in a high familial risk population, where pregnant women already had at least one other child with ASD so her subsequent children are at increased risk of developing ASD. In Chapter 1, the association between prenatal stressful life events and neurodevelopmental outcome was examined. In Chapter 2, the association of prenatal perceived stress and neurodevelopmental outcome was examined. In Chapter 3, the association of prenatal maternal urinary cortisol output and neurodevelopmental outcome was examined.Findings indicated that generally, stressful life events were not associated with ASD and Non-TD outcome, though more research is needed to understand the increased relative risk of Non-TD (compared to TD) when experiencing legal problems, including immigration issues. Compared to TD, increased perceived stress was associated with higher relative risk of Non-TD in the first trimester, and with higher relative risk of ASD in the second and third trimester. Lastly, prenatal cortisol was not associated with neurodevelopmental outcome. These findings support existing literature showing that stressful life events are not associated with neurodevelopmental outcomes. Additionally, the increased risks of ASD seen in Chapter 2 in the second and third trimesters are also supported by previous investigations. Overall, this study’s findings suggest that it may not be the stressful life events experienced during pregnancy or how the mother’s body biologically responds to these stressors, but instead how stressful the mothers perceive these events to be that may correlate with risk of ASD or Non-TD outcomes in the child. Stress reduction intervention could serve as preventative measures that help optimize the child’s long term neurodevelopmental health in high familial risk families