# Identification of fetal alcohol-affected children: Alterations in imprinted gene expression and methylation as biomarkers of neurobehavioral and growth impairment.

> **NIH NIH R01** · COLUMBIA UNIVERSITY HEALTH SCIENCES · 2020 · $632,755

## Abstract

Abstract
Fetal alcohol spectrum disorders (FASD) are the most common preventable cause of neurodevelopmental
disabilities, with prevalence estimates of 3-10/1000 individuals in the US and up to 80/1000 in endemic
communities. The promise of an increasing number of interventions tailored to prenatal alcohol exposure
(PAE)-related neurobehavioral deficits is limited by diagnostic difficulties in clinical practice. Currently known
biomarkers of exposure are neither sensitive nor specific for neurobehavioral deficits, in part because not all
exposed children are affected. There is, therefore, a critical need for biomarkers of effect to identify
affected children who would benefit from early, tailored therapeutic interventions. A growing body of
literature has demonstrated alcohol-induced alterations in epigenetic programming as an important potential
mechanism in FASD, suggesting that such alterations may serve as biomarkers of effect. Imprinted genes
comprise a unique subset of epigenetically regulated genes that is sensitive to prenatal insults. There is
considerable overlap between the neurobehavioral domains affected by FASD and those seen in experimental
animal models of imprinted gene dysregulation, including learning, memory, and attachment. In a prenatally-
recruited, prospective longitudinal cohort, we recently found that PAE was associated with alterations in
placental level of expression of 11 of 93 expressed imprinted genes. Expression changes for five of these
genes statistically mediated effects of alcohol on postnatal growth, identifying these alterations as biomarkers
of fetal alcohol growth restriction. Given the remarkable overlap between the neurobehavioral domains affected
in FASD and those affected by alteration of imprinted gene expression in animal models, alcohol-induced
alterations in placental imprinted gene expression may also provide biomarkers for FASD neurocognitive
deficits. Although most epigenetic marks are specific to tissue-type and timing of exposure, genomic imprinting
maps and our pilot data indicate that markers of imprinted gene dysregulation identified in placental tissue may
be detected in blood samples obtained at older ages. The aims of this study are: (1) To characterize the
fetal alcohol-related imprintome signature in the placenta and in blood samples obtained at 6 yr; (2) To
identify alterations in imprinted gene level of expression and ICR methylation that can serve as
biomarkers of effect; (3) To validate findings in Aims 1 and 2 in blood samples from a 2nd, independent
cohort. The data for this study will come from two prospective longitudinal cohorts recruited from the Cape
Coloured community in Cape Town, South Africa, where the prevalence of FASD is among the highest in the
world. Results from this study will make it possible to identify affected children who would benefit from
early therapeutic interventions but would likely not be detected by current diagnostic tools.

## Key facts

- **NIH application ID:** 10023145
- **Project number:** 5R01AA027916-02
- **Recipient organization:** COLUMBIA UNIVERSITY HEALTH SCIENCES
- **Principal Investigator:** ROBERT COLIN CARTER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $632,755
- **Award type:** 5
- **Project period:** 2019-09-23 → 2023-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10023145

## Citation

> US National Institutes of Health, RePORTER application 10023145, Identification of fetal alcohol-affected children: Alterations in imprinted gene expression and methylation as biomarkers of neurobehavioral and growth impairment. (5R01AA027916-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10023145. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*