Prenatal PM2.5 exposure and fetal neuroinflammation: A systematic review and meta-analysis of mechanistic pathways
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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.
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2. Rentschler J, Leonova N. Global air pollution exposure and poverty. Nat Commun 2023;14. https://doi.org/10.1038/s41467-023-39797-4.
3. Wasi’Ah NR, Iriana W, Ramadhina SQ. Comparison of Fine Particulate Matter (PM2.5) in Urban Areas Southeast Asia in Compliance with WHO Guidelines. IOP Conf. Ser. Earth Environ. Sci., vol. 1448, 2025. https://doi.org/10.1088/1755-1315/1448/1/012009.
4. Northeim K, Oppong JR. Mapping Health Fragility and Vulnerability in Air Pollution–Monitoring Networks in Dallas–Fort Worth. Int J Environ Res Public Health 2023;20. https://doi.org/10.3390/ijerph20031807.
5. Ernawati KK. Environmental Inequities and Global Health: Bridging the Gap in Vulnerable Communities. Innovation and Transformation of Public Health, 2025, p. 85–112. https://doi.org/10.4018/979-8-3373-1992-6.ch003.
6. Parikh G, Patel B. From exposure to outcomes: How air pollutants impact maternal and foetal health. Reproductive Toxicology 2025;138. https://doi.org/10.1016/j.reprotox.2025.109080.
7. Rahnemaei FA, Aghapour E, Asgharpoor H, Ardabili NS, Kashani ZA, Abdi F. Prenatal exposure to ambient air pollution and risk of fetal overgrowth: Systematic review of cohort studies. Ecotoxicol Environ Saf 2024;280. https://doi.org/10.1016/j.ecoenv.2024.116526.
8. Li L, Zhang X. The causal impact of fetal exposure to PM2.5 on birth outcomes: Evidence from rural China. Econ Hum Biol 2024;53. https://doi.org/10.1016/j.ehb.2024.101380.
9. Girardi P, Mastromatteo LY, Lanfranchi S, Scrimin S. Modeling the effects of prenatal PM2.5 exposure on development of school-aged children using functional regression. Environmental Pollution 2026;402. https://doi.org/10.1016/j.envpol.2026.128312.
10. Xu M-X, Zhu Y-F, Chang H-F, Liang Y. Nanoceria restrains PM2.5-induced metabolic disorder and hypothalamus inflammation by inhibition of astrocytes activation related NF-κB pathway in Nrf2 deficient mice. Free Radic Biol Med 2016;99:259–72. https://doi.org/10.1016/j.freeradbiomed.2016.08.021.
11. Shang Y, Wang H, Huang J, An J, Ren G, Wang Y, et al. Acetylcholine mediates nitro-PAHs induced inflammation and ameliorates the abnormalities in blood-brain barrier related proteins. Ecotoxicol Environ Saf 2025;305. https://doi.org/10.1016/j.ecoenv.2025.119173.
12. Ragusa A, Re A Lo, Segata M, Rinaldo D, la Motta G, De Vito M, et al. The Placenta and the Development of Human Health. Rare Diseases of the Immune System, vol. Part F1038, 2025, p. 57–75. https://doi.org/10.1007/978-3-032-02902-7_5.
13. Yong HEJ, Chan SY, Chakraborty A, Rajaraman G, Ricardo S, Benharouga M, et al. Significance of the placental barrier in antenatal viral infections. Biochim Biophys Acta Mol Basis Dis 2021;1867. https://doi.org/10.1016/j.bbadis.2021.166244.
14. Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Bmj 2021;372:n71. https://doi.org/10.1136/bmj.n71.
15. Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: Reporting guideline. The BMJ 2020;368:l6890. https://doi.org/10.1136/bmj.l6890.
16. Stroup DF. Meta-analysis of Observational Studies in Epidemiology. JAMA 2000;283:2008. https://doi.org/10.1001/jama.283.15.2008.
17. Hooijmans CR, Rovers MM, De Vries RBM, Leenaars M, Ritskes-Hoitinga M, Langendam MW. SYRCLE’s risk of bias tool for animal studies. BMC Med Res Methodol 2014;14:43. https://doi.org/10.1186/1471-2288-14-43.
18. Ouzzani M, Hammady H, Fedorowicz Z, Elmagarmid A. Rayyan-a web and mobile app for systematic reviews. Syst Rev 2016;5:210. https://doi.org/10.1186/s13643-016-0384-4.
19. Drevon D, Fursa SR, Malcolm AL. Intercoder Reliability and Validity of WebPlotDigitizer in Extracting Graphed Data. Behav Modif 2017;41:323–39. https://doi.org/10.1177/0145445516673998.
20. Sterne JA, Hernán MA, Reeves BC, Savović J, Berkman ND, Viswanathan M, et al. ROBINS-I: a tool for assessing risk of bias in non-randomised studies of interventions. BMJ 2016:i4919. https://doi.org/10.1136/bmj.i4919.
21. Schneider K, Schwarz M, Burkholder I, Kopp-Schneider A, Edler L, Kinsner-Ovaskainen A, et al. “ToxRTool”, a new tool to assess the reliability of toxicological data. Toxicol Lett 2009;189:138–44. https://doi.org/10.1016/j.toxlet.2009.05.013.
22. Veroniki AA, Jackson D, Viechtbauer W, Bender R, Bowden J, Knapp G, et al. Methods to estimate the between‐study variance and its uncertainty in meta‐analysis. Res Synth Methods 2016;7:55–79. https://doi.org/10.1002/jrsm.1164.
23. Borenstein M, Hedges L V, Higgins JPT, Rothstein HR. Introduction to Meta-Analysis. Wiley; 2021.
24. Egger M, Smith GD, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. Br Med J 1997;315:629–34. https://doi.org/10.1136/bmj.315.7109.629.
25. Duval S, Tweedie R. Trim and fill: A simple funnel-plot-based method of testing and adjusting for publication bias in meta-analysis. Biometrics 2000;56:455–63. https://doi.org/10.1111/j.0006-341X.2000.00455.x.
26. Viechtbauer W. Conducting meta-analyses in R with the metafor. J Stat Softw 2010;36:1–48. https://doi.org/10.18637/jss.v036.i03.
27. Morgan RL, Thayer KA, Santesso N, Holloway AC, Blain R, Eftim SE, et al. A risk of bias instrument for non-randomized studies of exposures: A users’ guide to its application in the context of GRADE. Environ Int 2019;122:168–84. https://doi.org/10.1016/j.envint.2018.11.004.
28. Mendoza-Ortega JA, Canul-Euan A, Perichart-Perera O, Solis-Paredes JM, Martínez-Medina S, Torres-Calapiz M, et al. Trimester-Specific Air Pollutant Exposure During Pregnancy and Infant Neurodevelopment at One Year: Insights into the Role of Inflammation and Oxidative Stress. Applied Sciences 2025;15:9753. https://doi.org/10.3390/app15179753.
29. Peterson BS, Bansal R, Sawardekar S, Nati C, Elgabalawy ER, Hoepner LA, et al. Prenatal exposure to air pollution is associated with altered brain structure, function, and metabolism in childhood. Journal of Child Psychology and Psychiatry 2022;63:1316–31. https://doi.org/10.1111/jcpp.13578.
30. Lin CH, Nicol CJB, Wan C, Chen SJ, Huang RN, Chiang MC. Exposure to PM2.5 induces neurotoxicity, mitochondrial dysfunction, oxidative stress and inflammation in human SH-SY5Y neuronal cells. Neurotoxicology 2022;88:25–35. https://doi.org/10.1016/j.neuro.2021.10.009.
31. Han Y, Yu Z, Chen Y, Guo X, Liu Y, Zhang H, et al. PM2.5 induces developmental neurotoxicity in cortical organoids. Environmental Pollution 2024;361:124913. https://doi.org/10.1016/j.envpol.2024.124913.
32. Zhang L, Xu F, Yang Y, Yang L, Wu Q, Sun H, et al. PM2.5 exposure upregulates pro-inflammatory protein expression in human microglial cells via oxidant stress and TLR4/NF-κB pathway. Ecotoxicol Environ Saf 2024;277:116386. https://doi.org/10.1016/j.ecoenv.2024.116386.
33. Liu Y, Li S, Liu B, Zhang J, Wang C, Feng L. Maternal urban particulate matter (SRM 1648a) exposure disrupted the cellular immune homeostasis during early life: The potential attribution of altered placental transcriptome profile. Science of the Total Environment 2024;912. https://doi.org/10.1016/j.scitotenv.2023.169432.
34. Li S, Li L, Zhang C, Fu H, Yu S, Zhou M, et al. PM2.5 leads to adverse pregnancy outcomes by inducing trophoblast oxidative stress and mitochondrial apoptosis via KLF9/CYP1A1 transcriptional axis. Elife 2023;12:1–35. https://doi.org/10.7554/eLife.85944.
35. Li J, Kong Y, Guo Z, Qu L, Zhang Z, Qu Z, et al. Maternal exposure to particulate matter from duck houses restricts fetal growth due to inflammatory damage and oxidative stress. Ecotoxicol Environ Saf 2024;273:116114. https://doi.org/10.1016/j.ecoenv.2024.116114.
36. Liang XT, Han CL, Lin BC, Shi Y, Xie XQ, Li K, et al. Effects of early life PM2.5 exposure on prefrontal cortex of offspring male rats. Zhongguo Ying Yong Sheng Li Xue Za Zhi 2022;38:1–5. https://doi.org/10.12047/j.cjap.6222.2022.001.
37. Yang Y, Yang T, Zhou J, Cao Z, Liao Z, Zhao Y, et al. Prenatal exposure to concentrated ambient PM2.5 results in spatial memory defects regulated by DNA methylation in male mice offspring. Environmental Science and Pollution Research 2022;30:35142–52. https://doi.org/10.1007/s11356-022-24663-5.
38. Zheng X, Wang X, Wang T, Zhang H, Wu H, Zhang C, et al. Gestational Exposure to Particulate Matter 2.5 (PM2.5) Leads to Spatial Memory Dysfunction and Neurodevelopmental Impairment in Hippocampus of Mice Offspring. Front Neurosci 2019;12. https://doi.org/10.3389/fnins.2018.01000.
39. Rahmatinia M, Mohseni-Bandpei A, Khodagholi F, Abdollahifar M-A, Amouei Torkmahalleh M, Hassani Moghaddam M, et al. Exposure to different PM2.5 extracts induces gliosis and changes behavior in male rats similar to autism spectrum disorders features. Environmental Pollution 2024;340:122804. https://doi.org/10.1016/j.envpol.2023.122804.
40. Berry A, Musillo C, Ajmone-Cat MA. Maternal stress disrupts placental proteome and fetal brain development in a sex-dependent manner. Res Sq 2024. https://doi.org/10.21203/rs.3.rs-5417536/v1.
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| Files | ||
| Issue | Vol 11 No 3 (2026): Summer 2026 | |
| Section | Review Article(s) | |
| Keywords | ||
| Particulate matter (PM2.5); Prenatal exposure; Neuroinflammation; Oxidative stress; Fetal neurodevelopment | ||
| Rights and permissions | |
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This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License. |
How to Cite
1.
Sofia N, Aprilea NA, As ZA. Prenatal PM2.5 exposure and fetal neuroinflammation: A systematic review and meta-analysis of mechanistic pathways. JAPH. 2026;11(3):411-434.
