# Cognitive and transcriptomic effects of Epigallocatechin gallate in fetal alcohol spectrum disorders

## TL;DR

This study explores whether EGCG, a natural antioxidant, can improve cognitive and behavioral issues in children with fetal alcohol spectrum disorders.

## Contribution

This is the first pilot study to investigate EGCG as a potential therapeutic for FASD-related cognitive and behavioral impairments.

## Key findings

- EGCG treatment led to significant improvements in perceptual reasoning and working memory after one year.
- Behavioral improvements were observed in aggressive behavior and face memory after EGCG treatment.
- EGCG modulated molecular pathways related to neuroinflammation, immune response, and neurogenesis.

## Abstract

Prenatal alcohol exposure impacts fetal development, leading to Fetal Alcohol Spectrum Disorders (FASD) characterized by cognitive, behavioral, and physical impairments. This pre-post, open-label, non-randomized pilot study explores Epigallocatechin-3-Gallate (EGCG), a potent antioxidant and neuronal plasticity modulator, as a therapeutic intervention for FASD improvement. In a 12-month pilot study, patients with 40 FASD (mean age 10 ± 3 years) received 9 mg/kg/day of EGCG, with outcomes assessed through RNA sequencing and neurocognitive evaluations (WISC-IV, CBCL 6–18, and NEPSY-II). Reduced levels of oxidative stress were observed after 6 and 12 months of treatment with EGCG. Significant neurocognitive improvements were shown after one year of treatment in Perceptual Reasoning Index (PRI) and Working Memory Index (WMI) using the WISC-IV test. CBCL test revealed an improvement in aggressive behavior scores after EGCG treatment. NEPSY-II assessment showed improvements in face memory and delayed face memory. Interestingly, no significant improvements were observed in intelligence quotient, attention, anxiety, or depression, which affect a proportion of individuals diagnosed with FASD. Additionally, EGCG modulates molecular pathways associated with neuroinflammation, immune response, and neurogenesis. This study highlights EGCG as a potential therapeutic candidate to ameliorate cognitive and behavioral deficits in children affected by FASD, revealing potential pathways and biomarkers that contribute to these improvements.

ClinicalTrials.gov identifier: NCT02558933 (registered 22 September 2015).

The online version contains supplementary material available at 10.1038/s41598-025-34576-1.