Fetal Alcohol Spectrum Disorder (FASD) Accelerates Local Neuroinflammation in Hippocampus: A Preclinical Systematic Review and Meta-Analysis Study

Background — Prenatal alcohol exposure (PAE) causes fetal alcohol spectrum disorder (FASD). The hippocampus, an important part of the limbic system, is pathologically affected in FASD. The goal of this systematic review and meta-analysis was to evaluate biomarkers of neuroinflammation and neurogenesis in the hippocampus in FASD. Methods — All studies reporting the effects of PAE on the hippocampus were collected (as of June 12, 2025) in valid WoS, PubMed, Scopus, and ScienceDirect databases using MeSH keywords. After primary and secondary screening (PRISMA 2020 guidelines), the selected articles underwent study quality assessment (ARRIVE checklist). Data were extracted in two main areas: neuroinflammation (IL-1β, IL-6, and TNF-α cytokines) and neurogenesis (Ki67, DCX, and BrdU markers). Random and fixed effects models (comprehensive meta-analysis software: CMA version 2) were used for statistical analysis. Subgrouping and the I2 index were used to assess heterogeneity. Publication bias and sensitivity were also assessed. P-value of 0.05 or less was considered statistically significant, and a 95% confidence interval (95% CI) was calculated. Results — Of the 231 articles, 8 high-quality experiments were used for data extraction. The total effect of FASD on hippocampal neuroinflammation and neurogenesis was 1.323±0.125 (95% CI=1.078–1.568, p=0.000) and 0.288±0.482 (95% CI=-0.655–1.232, p=0.549), respectively. The results of subgroup analysis were as follows: IL-1β (0.972±0.222, 95% CI=0.537~1.407, p=0.000), IL-6 (1.954±0.204, 95% CI=1.555~2.354, p=0.000), TNF-α (0.916±0.224, 95% CI=0.476~1.356, p=0.000), BrdU+ cells (-1.468±1.109, 95% CI=-3.641~0.705, p=0.185), DCX+ cells (-0.234±1.191, 95% CI=-2.569~2.101, p=0.844), and Ki67+ cells (0.932±0.598, 95% CI=-0.241~2.104, p=0.119. Conclusion — FASD may lead to hippocampal neuroinflammation in neonates.