Epigenetics Embedding of Oral Feeding Skill Development in Preterm Infants - PROJECT SUMMARY/ABSTRACT Preterm infants admitted to the Neonatal Intensive Care Unit (NICU) endure a multitude of stressors. Early life stress may exceed their adaptive capacity and impede achievement of developmental milestones, such as oral feeding. Up to 70% of NICU preterm infants are challenged to feed orally, leading to failure to thrive, prolonged hospitalization, and high healthcare costs up to $200K per infant. There is considerable variation in the clinical progression of oral feeding skill development across preterm infants, with some infants having more difficulty than others. Robust evidence demonstrates that oral feeding skills require intact neurobehaviors. Early life stress disrupts neurobehavior development, which may compromise achievement of oral feeding skills. Yet, the extent to which early life stress impairs oral feeding skill development and the biomechanism whereby this occurs are unknown. Exposure to early life stress during sensitive periods of neuroplasticity results in epigenetic imprinting of stress response systems. Early life stress results in epigenetic modification of glucocorticoid-related genes, i.e., DNA methylation (DNAm) of NR3C1 and HSD11B2, which alters hypothalamic pituitary adrenocortical (HPA) regulation of cortisol levels and cortisol reactivity, disrupting neurobehaviors. Epigenetic modifications due to early life stress are durable and may affect infants’ health far beyond the neonatal period, increasing risk for life-long maladaptive feeding behaviors and poor health. The purpose of this study is to determine the extent to which early life stress, reflected by DNAm of NR3C1 and HSD11B2 gene promoters, compromises oral feeding skill development. In this prospective longitudinal study, we will enroll 60 clinically stable preterm infants (28-32 weeks gestational age). We will evaluate early life stress, DNAm of NR3C1 and HSD11B2 gene promoters, cortisol reactivity, neurobehaviors, and oral feeding skill development during NICU stay and at 2-weeks post-discharge. The following specific aims will be addressed. Aim 1. Determine the association among early life stress, cortisol reactivity, and oral feeding skill development. Aim 2. Determine the extent to which DNAm of NR3C1 and HSD11B2 is associated with cortisol reactivity and/or neurobehaviors. Aim 3. Determine the association among early life stress, DNAm of NR3C1 and HSD11B2, and oral feeding skill development. The proposed study will positively impact neonatal care by contributing novel knowledge that clarifies biobehavioral mechanisms whereby early life stress compromises progression of oral feeding skill development. The findings hold significant promise to identify modifiable processes that can be targeted to promote optimal oral feeding, better nutrition, and lower risk for life-long maladaptive eating behaviors.
