Placenta-to-organ Trajectories from Maternal Microplastics, Air Pollution, and Endocrine Disruptors to Fetal/Neonatal Dysfunction and Developmental Origins of Health and Disease: A Systematic Review and Evidence Map

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BSTRACT

Environmental toxicants such as microplastics, particulate air pollution, and endocrine-disrupting chemicals, including per- and polyfluoroalkyl substances (PFAS), phthalates, and bisphenols, represent urgent but incompletely quantified risks during pregnancy. The objective of this review was to systematically identify, appraise, and synthesize human and mechanistic evidence linking prenatal exposures to placental burden, fetal and neonatal organ dysfunction, and developmental origins of health and disease. A comprehensive search of PubMed and reference lists was conducted through February 2025, and studies were screened in duplicate according to predefined inclusion and exclusion criteria. Eligible studies included human observational cohorts, case series, meta-analyses, and mechanistic models reporting maternal exposure during pregnancy and subsequent placental, fetal, or neonatal outcomes. Risk of bias was independently assessed using the Newcastle–Ottawa Scale for cohort studies, risk of bias in nonrandomized studies of interventions for nonrandomized studies, risk of bias in systematic reviews for systematic reviews, and the A MeaSurement Tool to Assess Systematic Reviews, version 2 for meta-analyses. Of 1070 records identified, 968 abstracts were screened, 103 full texts were reviewed, and 33 studies were included, with 20 prioritized for detailed risk-of-bias analysis. Synthesis revealed consistent associations between maternal air pollution exposure and adverse neonatal brain, lung, and cardiac outcomes, with low-to-moderate risk of bias. PFAS were linked to lower birthweight, altered growth trajectories, metabolic and epigenetic remodeling, supported by longitudinal cohorts with high consistency. Phthalates were associated with impaired thyroid hormone signaling and neurodevelopmental delay, while bisphenols demonstrated modest but reproducible links to fetal growth and respiratory outcomes. Microplastics were detected in the human placenta with emerging evidence for growth restriction and potential fetal organ deposition, though data remain sparse. Overall, findings support the placenta as a mechanistic hub translating maternal exposures into multiorgan fetal vulnerability, with the strongest evidence for air pollution and PFAS, and substantial knowledge gaps for microplastics and bisphenols.