662 - Preterm Risk Factors Modify the Association Between Epigenetic Age and Neurodevelopmental Outcomes

Publication Number: 2645.662

Rhandi Christensen, The Hospital for Sick Children, Toronto, ON, Canada; Chaini Konwar, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Beryl Zhuang, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Vann Chau, The Hospital for Sick Children, Toronto, ON, Canada; Mehmet Cizmeci, The Hospital for Sick Children, Toronto, ON, Canada; Ting Guo, The Hospital for Sick Children, Toronto, ON, Canada; Michael Kobor, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada; Julia L. MacIsaac, University of British Columbia, Vancouver, BC, Canada; Ruth Grunau, Unversity of British Columbia, Vancouver, BC, Canada; Steven P,.. Miller, University of British Columbia Faculty of Medicine, Vancouver, BC, Canada

Background: Studies examining biological predictors of neurodevelopment in the preterm population are limited. We previously demonstrated that epigenetic age acceleration is associated with better cognitive and motor outcomes in children born preterm. However, it remains unclear how epigenetic age interacts with established preterm risk factors to influence neurodevelopmental outcomes.

Objective: To determine whether the association between epigenetic age and neurodevelopmental outcomes at 3 years of age is modified by preterm risk factors including neonatal morbidity, severe brain injury, and socioeconomic status (SES).

Design/Methods: The study sample included a prospective cohort of children born between 24-32 weeks gestation, well-characterized with clinical data, brain imaging, and neurodevelopmental assessments at 3 years (Bayley-III cognitive and motor composites). Epigenetic age (in weeks) was determined using the Pediatric Buccal Epigenetic Clock and corrected for chronological age to give epigenetic age difference (EAD). Interaction effects between EAD and neonatal morbidity (infection, retinopathy of prematurity, bronchopulmonary dysplasia), severe brain injury (white matter injury grade ≥ 2, intraventricular hemorrhage grade 3, periventricular hemorrhagic infarction), and SES (measured by maternal education) on neurodevelopmental outcomes were examined using multivariable linear regression controlling for sex, gestational age and buccal cell proportion. Statistical significance was set as P < 0.05 for main effects, and P < 0.1 for interaction effects.

Results: A total of 102 participants (47% male) were included. Clinical details are presented in Table 1 and results of regression analyses are in Table 2. Severe brain injury modified the association between EAD and motor outcomes (P=0.04), with higher EAD being associated with better motor scores among children with severe brain injury (Figure 1). Maternal education modified the association between EAD and cognitive outcomes (P=0.05), with higher EAD being associated with higher cognitive scores among children from high SES backgrounds (Figure 2). No significant interaction effects were observed between EAD and neonatal morbidity.

Conclusion(s): Epigenetic differences contribute to the variability in neurodevelopmental outcomes in children born preterm. Epigenetic age acceleration was associated with better outcomes in children with severe brain injury and those from high SES environments. These findings indicate that biological factors interact with established preterm risk factors to influence neurodevelopment in children born preterm.

Tables


Figure 1
Higher epigenetic age difference was associated with better motor outcomes at 3 years in children with severe brain injury.

Figure 2
Higher epigenetic age difference was associated with better cognitive outcomes at 3 years in children from high SES backgrounds (high maternal education).