Prenatal PM2.5 exposure and fetal neuroinflammation: A systematic review and meta-analysis of mechanistic pathways

Abstract

Prenatal exposure to fine Particulate Matter (PM2.5) has been associated with adverse neurodevelopmental outcomes in offspring. However, the biological mechanisms underlying these effects remain incompletely understood. This study aimed to systematically review and synthesize current evidence regarding inflammatory and oxidative stress pathways involved in PM2.5- induced fetal neurodevelopmental toxicity. A systematic review and meta-analysis were conducted following PRISMA 2020 guidelines and prospectively registered in PROSPERO (CRD420261386294). Six electronic databases (Scopus, PubMed, Web of Science, Embase, ScienceDirect, and PsycINFO) were searched up to April 2026. Human, animal, and in vitro studies evaluating prenatal PM2.5 exposure and neuroinflammatory or oxidative stress outcomes were included. Risk of bias was assessed using ROBINS-I, SYRCLE, and ToxRTool. A total of 43 primary studies (12 human, 22 animal, 9 in vitro) were included. Meta-analysis showed significant increases in inflammatory markers (IL- 6: SMD = 1.47; 95% CI 1.02–1.92; I² = 64%) and oxidative stress markers (SMD = 1.21; 95% CI 0.78–1.64). Effects were stronger in male offspring and during late gestation. Most studies consistently reported PM2.5-induced neuroinflammation and oxidative damage. Prenatal PM2.5 exposure is associated with substantial neuroinflammatory and oxidative stress responses in fetal brain development, supporting a mechanistic role of the maternal–placental–fetal axis. These findings highlight the importance of environmental pollution control and preventive strategies to protect maternal and fetal health.