# Genetic and Epigenetic Effects on Childhood Cognitive Trajectories

> **NIH NIH R01** · UNIVERSITY OF MIAMI CORAL GABLES · 2023 · $312,468

## Abstract

PROJECT SUMMARY/ABSTRACT
Although survival rates for infants born extremely preterm (< 28 weeks’ gestation) have improved dramatically in
recent decades, cognitive impairment remains a major concern. Adequate cognition is foundational for high
quality of life and well-being. Compared to those born full term, extremely preterm children exhibit much higher
rates of cognitive function impairment from early childhood through adulthood; and this is associated with
neonatal inflammation. However, longitudinal research on cognitive function among extremely preterm children
is limited. Little is known about how genetic and epigenetic factors are associated with trajectories of cognitive
function, which can show longitudinal patterns such as downward/impaired, low-stable or upward-improvement.
This raises a key unanswered question: are there genetic-epigenetic links to neonatal inflammation that
predispose extremely preterm children to a particular trajectory of cognitive function? To address this question,
we propose these specific aims: 1) Identify perinatal and neonatal immune factors predicting trajectories of
cognitive function from ages 2 - 17 years among extremely preterm children; 2) Determine genetic variants and
gene-by-neonatal inflammation mediation that predict trajectories of cognitive function; and 3) Examine whether
DNA methylation modifies the effects of genetic variants and neonatal inflammation on trajectories of cognitive
function. Our central hypothesis is that genetic variants of immune-related genes interact with neonatal immune
factors to increase risk for a low-stable trajectory of cognitive function during childhood and adolescence.
Additionally, we hypothesize that DNA methylation can mediate the effects of genetic variants to protect against
the low-stable trajectory. These hypotheses are based on several preliminary findings from our team
demonstrating that neonatal inflammation, as well as genetic and epigenetic factors regulating immune
response, can influence cognitive function. This proposal leverages the Extremely Low Gestational Age Newborn
(ELGAN) study, a multi-center cohort of extremely preterm children currently followed to age 15 years (N = 810),
containing vast data on neurodevelopment and a unique biospecimen repository. Although ELGAN has DNA
methylation data from placentas on a subset of the sample, we propose to use banked umbilical cord specimens
for whole-genome genotyping and neonatal blood specimens for DNA methylation of the entire cohort. This
proposal aligns with the scheduled ELGAN follow-up at 17 years of age to collect cognitive function data. This
proposal has potential for significant impact on science and clinical practice related to cognitive function among
extremely preterm children and is among the first to study relationships among genetic, epigenetic, immune
factor and developmental trajectories of cognitive function. From this work, we can identify genes and
mechanisms that can be used for ri...

## Key facts

- **NIH application ID:** 10690686
- **Project number:** 5R01NR019245-04
- **Recipient organization:** UNIVERSITY OF MIAMI CORAL GABLES
- **Principal Investigator:** Hudson Santos
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2023
- **Award amount:** $312,468
- **Award type:** 5
- **Project period:** 2022-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10690686

## Citation

> US National Institutes of Health, RePORTER application 10690686, Genetic and Epigenetic Effects on Childhood Cognitive Trajectories (5R01NR019245-04). Retrieved via AI Analytics 2026-05-21 from https://api.ai-analytics.org/grant/nih/10690686. Licensed CC0.

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