The impact of stress and caregiver sensitivity on infant cellular aging in a population of under-resourced families: A randomized controlled trial.

Project Summary/ Abstract The aim of the proposed randomized controlled trial (RCT) is to test if an evidence-based home visiting model Promoting First Relationships® (PFR), that improves caregiver-sensitive and responsive care, delivered within a primary care setting (PFR-PC), will protect young infants from the effect of stress on accelerated cellular aging. During the first years of life, children are particularly vulnerable to adverse events, with lifelong consequences for physical- and mental-health outcomes. These adversities are disproportionately placed on minoritized populations and can lead to health disparities. One mechanism that has not yet received systematic exploration in young children, in the context of an RCT, is the study of telomere length and epigenetic age clocks, both are unique markers of cellular aging, including in pediatric samples. This RCT will focus on a sample of minoritized and under-resourced families receiving PFR through their primary care provider. The setting for this study is unique. We have partnered with WakeMed primary care in North Carolina, a busy pediatric practice that utilizes an integrated care model to serve a high-need patient population. We will recruit a low-income, community sample of 250 Spanish- and English-Speaking mothers and their infants receiving supportive primary care from WakeMed. Mothers will be randomized to Usual Care or to PFR-in Primary Care (PFR-PC) 10-week home visiting with follow-up PFR-PC content during well child visits. We will measure mothers’ telomere length at baseline and child telomere length and epigenetic age clocks at baseline and one- year post-intervention. Aim 1 will evaluate three under-studied heritability and intergenerational predictors of cellular aging in young children, namely maternal telomere length at baseline (i.e. heritability), and maternal Adverse Childhood Experiences, and paternal age at conception (i.e., intergenerational factors). Aim 2 will evaluate the impact of adversity on change in cellular aging. We will test if current maternal adversity (depression, discrimination, violence, difficult life events) predicts child cellular aging between baseline and 12-months post-intervention, controlling for heritability and intergenerational effects. Aim 3 will test whether PFR-PC reduces accelerated cellular aging, improves parenting sensitivity and child outcomes one-year post- intervention. Finally, an exploratory aim will evaluate PFR-PC implementation (dosage, quality, acceptability, satisfaction, and provider fidelity). The current proposal moves the integrated care model one step further and addresses families that need more than what is currently offered and targets prevention in an underserved population. Early interventions are key approaches to addressing the lasting consequences of early adversity, which represent a key public health crisis, especially when integrated into primary care settings that are low cost, disseminatable, and grounded in strong theoretical premises related to biological pathways through which early-life adversity is embedded within and across generations.