Placental micro- and nanoplastic contamination: A systematic review of eco-exposome pathways to preterm birth and neonatal outcomes

Abstract Objective: To systematically review emerging evidence on micro- and nanoplastic (MNP) contamination of the human placenta, explore molecular pathways underlying placental dysfunction, and evaluate associations with preterm birth and neonatal outcomes. Methods: Following PRISMA 2020 guidelines, literature searches (PubMed, Web of Science, Scopus) and grey sources were conducted through July 2025. Inclusion criteria comprised studies detecting MNPs in human placenta or fetal compartments, mechanistic experiments using human placental models, or reviews addressing pregnancy outcomes. Methodological quality was assessed using AMSTAR-2, ROBIS, or Newcastle–Ottawa Scale. Data were synthesized into three evidence domains: human biomonitoring, molecular pathways, and clinical implications. Results: Twenty studies met inclusion criteria (Table 1). MNPs were consistently detected in human placenta, amniotic fluid, cord blood, and meconium, with higher burdens in preterm versus term placentae. Mechanistic studies demonstrated oxidative stress, ferroptosis-mediated syncytiotrophoblast senescence, impaired trophoblast invasion, inflammatory responses (IL-6, TNF-α, NLRP3 activation), endocrine disruption (altered β-hCG and progesterone signaling), and epigenetic modifications (Table 2, Fig. 2). These pathways converge to impair nutrient and oxygen exchange and immune tolerance, increasing risks of preterm birth, fetal growth restriction, low birth weight, and neonatal respiratory and metabolic vulnerability (Table 3). Conclusion: Micro- and nanoplastic contamination of the human placenta is increasingly documented and biologically plausible as a contributor to preterm birth and neonatal morbidity. These findings support urgent investigation of exposure mitigation, standardized biomonitoring, and integration of eco-exposome risks into perinatal clinical practice and policy.