PRemature Infants, Moms, and the Social determinants of health - an Epigenetic Investigation (PRIMS-EI) - Preterm infants and their mothers are frequently exposed to toxic stress resulting from the neonatal intensive care unit (NICU) environment. Toxic stress develops when stress becomes excessive and causes prolonged activation of biologic stress responses, potentially disrupting brain circuitry and normal physiologic systems. Toxic stress increases the risk for alterations in stress responses and epigenetic alterations in both preterm infants and their mothers. Alterations in the glucocorticoid-related gene NR3C1 and the promoter region of the serotonin promoter gene SLC6A4 have been linked to toxic stress in both preterm infants and mothers during the perinatal period. Infant toxic stress from the NICU environment arises from repeated and aberrant exposures to excessive light, sound, and painful stimuli during a period of critical neurologic development. Maternal experiences of toxic stress result from an often-unexpected preterm birth, alterations in parental role attainment, infant illness, and the sights and sounds of the NICU. This toxic stress must be considered in the context of the maternal environmental influences as early life stress is directly linked to the environment of their mothers. Despite this, the mechanisms connecting infant toxic stress to maternal factors remain ill-defined. Importantly, the investigations accounting for a possible dyadic relationship between the preterm infant and mother are nonexistent. Although the relationship between environmental influences and epigenetic changes has been documented, there remains a critical need to identify the biomechanisms responsible for connecting the dyads’ environmental influences with toxic stress from the NICU environment and the resulting physiologic adaptations and disruptions. The purpose of this study is to delineate the impact of maternal environmental influences and toxic stress from the NICU environment for preterm infants and their mothers. In this descriptive, longitudinal study, we will enroll 80 preterm infants (< 32 weeks gestation) and their mothers. The primary aim is to evaluate how maternal environmental influences and toxic stress from the NICU environment are associated with alterations in methylation of NR3C1 and SLC6A4 in preterm infants and their mothers. The secondary aim is to evaluate whether toxic stress moderates the relationship between maternal environmental influences and methylation of NR3C1 and SLC6A4. Finally, we will explore preterm infant and maternal DNA methylation for concordance. Analyses will include descriptions of DNAm changes, Actor-Partner Interdependence Modeling, and general linear mixed model development. The results from this study will provide much needed information regarding the cumulative impact of toxic stress from the NICU environment and will guide future development and testing of target stress reducing interventions in this population. The proposed research is feasible and advance my training goals and help guarantee the success of my research career.
