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

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).