Placental Micro- and Nanoplastic Contamination: A Systematic Review of Eco-Exposome Pathways to Preterm Birth and Neonatal Outcomes

Placental Micro- and Nanoplastic Contamination: A Systematic Review of Eco-Exposome Pathways to Preterm Birth and Neonatal Outcomes | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Placental Micro- and Nanoplastic Contamination: A Systematic Review of Eco-Exposome Pathways to Preterm Birth and Neonatal Outcomes Wiku Andonotopo, MD, MSc, PhD, I Nyoman Hariyasa Sanjaya, Muhammad Adrianes Bachnas, and 2 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8193385/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version 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. Obstetrics & Gynecology Placenta Microplastics Nanoplastics Preterm Birth Eco-Exposome Figures Figure 1 Figure 2 Highlights First comprehensive synthesis of human and mechanistic evidence linking placental micro- and nanoplastic (MNP) contamination to preterm birth and neonatal outcomes. Quantitative human studies demonstrate higher placental MNP burdens in preterm versus term pregnancies. Molecular pathways identified include oxidative stress, ferroptosis-driven syncytiotrophoblast senescence, trophoblast invasion impairment, inflammatory signaling, endocrine disruption, and epigenetic modifications. Clinical and policy relevance : Findings support the need for standardized biomonitoring, maternal exposure mitigation, and integration of eco-exposome considerations into perinatal care. Introduction Global plastic production has exceeded 400 million metric tons annually, resulting in ubiquitous environmental contamination by microplastics and nanoplastics (MNPs). These particles are now detected in diverse eco-exposome pathways including drinking water, air, food chains, and consumer products, with evidence of human exposure at levels capable of systemic distribution¹⁷,¹⁸. Recently, MNPs have been identified within human placental tissues and fetal compartments, including amniotic fluid, cord blood, and meconium¹⁻³,⁶,¹², marking a potential paradigm shift in understanding perinatal environmental risks (Table 1 ). Table 1 Key Literature Summary of 20 Studies Author Country Sample Type Study Design Detection Method Polymers Detected Key Outcomes Relevance to Preterm/ Neonatal Quality Assessment Score Key Insight Halfar et al., 2023 ₁ Czech Republic Amniotic fluid & placenta Observational FTIR, Raman PE, PS, PVC First evidence of MPs in amniotic fluid & placenta Suggestive (direct evidence) NOS: ★★★☆ First human evidence of MPs in placenta & amniotic fluid SMFM, 2025 ₂ USA Human placenta Observational Py-GC/MS PE, PET, PVC, PC Higher microplastic burden in preterm vs term placenta Direct evidence NOS: ★★★☆ Higher MP burden in preterm vs term placenta (dose-response) Ragusa et al., 2021 ₃ Italy Human placenta Observational Raman PE, PS Microplastics confirmed in placenta (all samples) Suggestive NOS: ★★★☆ Plastics present in all placenta samples (universal exposure) Zurub et al., 2024 ₄ Canada Review Review Narrative synthesis N/A MPs linked to fertility & pregnancy risk Framework AMSTAR-2: Low Narrative link between MPs and reproductive health outcomes Shultz, 2024 ₅ USA News summary Media N/A N/A All human placentas positive for plastics Indirect N/A Media summary emphasizing ubiquity of plastic contamination Zhu et al., 2024 ₆ China Cord blood, placenta, meconium Pilot cohort Raman PE, PS, PET MPs in fetal compartments incl. meconium Direct evidence NOS: ★★☆☆ MNPs translocate to fetal compartments (cord blood, meconium) Carrington, 2024 ₇ UK News summary Media N/A N/A All tested placentas contain MPs Indirect N/A Media confirming ubiquity of MPs in placenta de Sousa et al., 2024 ₈ Brazil Placental explants Experimental Spectroscopy & biochemical assays PS Oxidative stress & metabolic disruption in placenta Mechanistic link ROBIS: Moderate Demonstrated oxidative stress & metabolic disruption in placenta Nacka-Aleksić et al., 2025 ₉ Serbia Trophoblast cells Experimental Fluorescence & invasion assay PS nanoparticles Nanoplastics impair trophoblast invasion Mechanistic link ROBIS: Moderate Showed invasion impairment by nanoplastics Balali et al., 2024 ₁₀ Iran Review Review Narrative synthesis Mixed Reproductive toxicity pathways of MPs Framework AMSTAR-2: Low Comprehensive review of reproductive toxicity mechanisms Poinsignon et al., 2025 ₁₁ France Placental cells Experimental Biochemical assays PS Nanoplastics cause inflammation & endocrine disruption Mechanistic link ROBIS: Moderate Inflammatory & endocrine disruption responses observed Jochum et al., 2025 ₁₂ USA Human placenta Observational Py-GC/MS Mixed Preterm placenta high MP/NP concentration Direct evidence NOS: ★★★☆ Independent correlation of high MNP burden with preterm birth Chen et al., 2025 ₁₃ China Syncytio- trophoblast Experimental Molecular assays PS nanoparticles Placental ferroptosis & aging pathway Mechanistic link ROBIS: Moderate Ferroptosis-induced syncytiotrophoblast aging mechanism Durkin et al., 2024 ₁₄ EU Cohort protocol Protocol N/A N/A Framework for exposure assessment in pregnancy Framework N/A Established pregnancy exposure assessment framework Yu et al., 2024 ₁₅ Taiwan Animal model Animal experimental Fluorescent tracing PS, PE Maternal exposure impacts offspring development Experimental fetal outcome link ROBIS: Moderate Showed maternal plastic exposure affects offspring development Anifowoshe et al., 2025 ₁₆ India Review Review Narrative synthesis Mixed MNP threat to fetoplacental unit Framework AMSTAR-2: Low Identified MPs/NPs as a threat to fetoplacental health Wikipedia, 2025 ₁₇ Global Overview Overview N/A Mixed Human health overview of microplastics Indirect N/A Summarized human health impacts of microplastics Wan et al., 2024 ₁₈ China Placental health assessment Risk assessment Targeted risk framework Mixed Risk assessment for placental impact Risk framework ROBIS: Moderate Developed targeted risk assessment strategy for placenta Zimmermann, 2023 ₁₉ Switzerland Gene expression News brief Transcriptomics N/A Nanoplastics alter placental gene expression Mechanistic N/A Reported NP-induced gene expression changes in placenta Medley et al., 2023 ₂₀ USA Systematic review Systematic review Mixed methods Mixed Systematic evidence of placental translocation Evidence synthesis AMSTAR-2: Moderate Synthesized evidence for placental translocation of MPs/NPs Legend: PE = polyethylene; PS = polystyrene; PET = polyethylene terephthalate; PVC = polyvinyl chloride; PC = polycarbonate; MPs = microplastics; NPs = nanoplastics; AMSTAR-2 = A MeaSurement Tool to Assess systematic Reviews, version 2; ROBIS = Risk Of Bias In Systematic reviews; NOS = Newcastle–Ottawa Scale. Existing evidence suggests that placental contamination by MNPs is more than a marker of exposure. Quantitative studies have demonstrated higher micro- and nanoplastic burdens in preterm compared with term placentae²,¹², while pilot data indicate MNP transfer across the placental barrier and into fetal circulation⁶. Parallel in vitro and ex vivo studies show molecular disruptions involving oxidative stress, mitochondrial injury, ferroptosis-driven syncytiotrophoblast senescence, impaired trophoblast invasion, endocrine disruption, inflammatory signaling, and epigenetic modifications⁸⁻¹¹,¹³,¹⁸,¹⁹ (Table 2 , Fig. 2 ). Despite these advances, no prior review has systematically synthesized human evidence, mechanistic data, and clinical outcomes of placental MNP exposure, nor integrated eco-exposome perspectives into perinatal medicine (Table 3 ). Table 2 Molecular Pathways Linking Micro/Nanoplastics to Preterm Birth & Neonatal Outcomes Pathway / Mechanism Experimental Model Plastic Exposure Type Key Molecular Findings Downstream Placental Effect Associated Pregnancy / Neonatal Outcome Oxidative Stress 8 , 11 , 18 Human placental explants Polystyrene MPs (10–50 µm) ↑ ROS, ↓ GPX4, mitochondrial dysfunction Placental aging, impaired nutrient transport Preterm birth, fetal growth restriction Ferroptosis & Placental Aging¹³ Syncytiotrophoblast cells (BeWo) PS-NPs (40–200 nm) GPX4 suppression, lipid peroxidation Syncytiotrophoblast senescence Preterm birth Impaired Trophoblast Invasion⁹ HTR-8/SVneo cell line PS-NPs (40 nm) ↓ MMP-2, ↓ invasion capacity Impaired spiral artery remodeling Preterm birth, impaired placental perfusion Immune Activation & Inflammation 10 , 16 Mouse pregnancy model Mixed environmental MPs ↑ IL-6, TNF-α, NLRP3 activation Placental inflammation Preterm labor, fetal growth effects Legend: MPs = microplastics; NPs = nanoplastics; ROS = reactive oxygen species; GPX4 = glutathione peroxidase 4; MMP-2 = matrix metalloproteinase-2; IL-6 = interleukin-6; TNF-α = tumor necrosis factor alpha; NLRP3 = nod-like receptor protein 3. Table 3 Clinical and Public Health Implications of Micro/Nanoplastic Exposure During Pregnancy Exposure Source Maternal-Fetal Compartment Impacted Potential Clinical Implications Research / Policy Gap Recommended Actions Drinking water & bottled water 17 , 18 Maternal blood, placenta Potentially higher risk of preterm birth due to chronic ingestion No routine biomonitoring; poor regulatory threshold Public awareness campaigns, safer water packaging policies Airborne environmental MPs 10 , 16 Maternal lung → systemic circulation → placenta May trigger inflammation & oxidative stress → preterm labor No standardized air monitoring; underestimated exposure Urban emission controls, air filtration strategies for pregnant women Food chain exposure (seafood, table salt) 49 Placental barrier, cord blood, fetal tissues MNP translocation into fetal compartment; potential metabolic programming effects No dietary risk labeling; lack of fetal outcome data Food-chain monitoring, targeted dietary guidelines for pregnant women Consumer products & plastics additives 15 , 17 Maternal circulation & placenta Potential endocrine disruption (altered β-hCG, progesterone) Chemical risk assessments often exclude pregnancy-specific endpoints Integrate plastics risk into reproductive toxicology policies Occupational exposure (industrial, healthcare)²³ Placental accumulation, maternal-fetal interface Higher exposure among specific working populations; unclear dose-response Limited occupational health studies in pregnancy Workplace exposure monitoring, protective equipment standards Legend: MPs = microplastics; NPs = nanoplastics; β-hCG = beta-human chorionic gonadotropin. References indicate supporting evidence from the systematic review database. Given increasing global attention to environmental pollution and maternal-fetal health, a clear conceptual framework linking placental MNP contamination to adverse pregnancy and neonatal outcomes is urgently needed. We hypothesize that MNP exposure activates multiple convergent molecular pathways within the placenta, resulting in impaired nutrient transport, disrupted endocrine and immune signaling, and heightened risk of preterm birth and related neonatal morbidities¹⁰,¹⁶. This review systematically evaluates published literature on MNP contamination of the human placenta (Fig. 1 ), integrates molecular pathway evidence (Fig. 2 ), and examines clinical implications for preterm birth and neonatal outcomes. Our aim is to advance translational understanding and inform future biomonitoring, clinical strategies, and policy development. Methodology Review Design This systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, as illustrated in Fig. 1 . A predefined review protocol established the eligibility criteria, data extraction strategy, and risk of bias assessment approach prior to literature searching and screening. Literature Search Strategy A comprehensive search of PubMed, Web of Science, and Scopus databases was performed, complemented by grey literature sources including preprints, conference proceedings, and institutional reports. The search strategy incorporated controlled vocabulary and free-text terms related to microplastics, nanoplastics, placenta, pregnancy, preterm birth, and neonatal outcomes. Search strings were adapted for each database and limited to studies published between January 2000 and July 2025 in the English language. Additional articles were identified by manual reference screening of all included papers to ensure capture of emerging evidence. Eligibility Criteria Eligible studies included those that detected micro- or nanoplastic particles in human placenta, amniotic fluid, cord blood, or meconium; mechanistic studies employing human placental tissues, trophoblast models, or relevant animal analogues exploring molecular pathways of placental dysfunction; and reviews or protocols addressing pregnancy-related micro- and nanoplastic exposure. Studies were excluded if they focused on non-pregnancy populations, lacked assessment of micro- or nanoplastics, or consisted solely of commentary or editorial content without primary data. Duplicate reports and studies lacking sufficient methodological details were also excluded. Study Selection Two reviewers independently screened titles and abstracts for relevance and subsequently assessed the full text of eligible articles. Disagreements were resolved through discussion until consensus was reached. The stepwise process of identification, screening, and inclusion of eligible studies is summarized in the PRISMA flow diagram (Fig. 1 ). Data Extraction Data from included studies were systematically extracted using a predefined matrix capturing author and year, study region, type of biological sample, detection techniques employed, identified polymer types, molecular pathways implicated, and pregnancy or neonatal outcomes reported. These findings were synthesized to generate a comprehensive summary of existing literature (Table 1 ), an integrated analysis of molecular pathways (Table 2 ), and a translation of findings into clinical and public health implications (Table 3 ). Quality Assessment The methodological quality and risk of bias of the included studies were assessed using internationally recognized tools appropriate to study design. Observational studies were evaluated using the Newcastle–Ottawa Scale, review-based publications were appraised with the Risk of Bias in Systematic Reviews (ROBIS) tool, and systematic reviews and protocols were assessed using AMSTAR-2. The results of these assessments are presented in Table 1 under the column Quality Assessment Score . Data Synthesis Given the heterogeneity in study designs, exposure assessment methods, and outcome measures, quantitative meta-analysis was not feasible. Instead, a narrative synthesis was undertaken, grouping evidence into three principal domains: human biomonitoring of micro- and nanoplastic contamination of pregnancy-related biological compartments, mechanistic pathways linking these exposures to placental dysfunction, and clinical or public health implications relevant to perinatal medicine. Molecular disruptions were mapped to conceptual pathways illustrated in Fig. 2 , providing an integrative framework connecting environmental exposure to adverse pregnancy and neonatal outcomes. Results and Findings Literature Screening and Study Characteristics The search strategy identified 336 records from electronic databases and 14 additional records through grey literature sources. After removal of duplicates, 270 unique records were screened by title and abstract, resulting in 70 full-text articles assessed for eligibility. Fifty articles were excluded for reasons including irrelevant population or outcomes, insufficient microplastic or nanoplastic assessment, or duplication of data sets. Twenty studies met all inclusion criteria and were included in the final qualitative synthesis (Fig. 1 ). Included studies comprised human biomonitoring investigations of placental and fetal compartments¹⁻³,⁶,¹², mechanistic studies involving human placental explants and trophoblast models⁸⁻¹¹,¹³,¹⁸,¹⁹, and integrative reviews and protocols addressing micro- and nanoplastic exposure during pregnancy⁴,¹⁰,¹⁴,¹⁶,²⁰. Biological matrices analyzed included human placenta¹⁻³,⁶,¹², amniotic fluid¹, cord blood and meconium⁶, and experimental trophoblast or syncytiotrophoblast cell lines⁸,⁹,¹¹,¹³. Detection methods varied, with Raman spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis–gas chromatography/mass spectrometry being the most commonly applied techniques (Table 1 ). Evidence of Micro- and Nanoplastic Contamination in Human Pregnancy Multiple studies demonstrated the presence of micro- and nanoplastics in human placenta across diverse populations¹⁻³,⁶,¹². Halfar et al.¹ provided the first combined evidence of microplastic particles in both amniotic fluid and placental tissue, while Ragusa et al.³ reported detection of plastic particles in all placenta samples analyzed. Zhu et al.⁶ extended these findings by identifying particles in fetal cord blood and meconium, confirming transplacental transfer. Quantitative assessments revealed higher micro- and nanoplastic burdens in preterm compared with term placentae²,¹², with identified polymer types including polyethylene (PE), polystyrene (PS), polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polycarbonate (PC). These findings establish widespread placental exposure and suggest a dose-response relationship with adverse pregnancy outcomes (Table 1 ). Molecular Pathways and Placental Dysfunction Mechanistic investigations provide strong biological plausibility linking micro- and nanoplastic exposure to placental dysfunction. Experimental studies using human placental explants and trophoblast cells revealed increased oxidative stress, characterized by reactive oxygen species (ROS) generation and mitochondrial dysfunction⁸,¹¹,¹⁸,¹⁹. Syncytiotrophoblast ferroptosis, associated with glutathione peroxidase 4 (GPX4) suppression and lipid peroxidation, was reported as a novel pathway promoting placental aging and senescence¹³. Endocrine disruption was evident from altered β-hCG and progesterone signaling pathways⁹,¹¹, while impaired trophoblast invasion and spiral artery remodeling were linked to downregulation of matrix metalloproteinase 2 (MMP-2) activity⁹. Inflammatory signaling, particularly interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and NLRP3 inflammasome activation, was frequently observed⁸,¹⁰,¹⁶. Additionally, epigenetic alterations, including changes in DNA methylation and microRNA expression, suggested a mechanism for persistent fetal programming¹⁹. Collectively, these pathways converge to impair nutrient and oxygen transport, disturb immune tolerance, and disrupt endocrine homeostasis. The mechanistic relationships are summarized in Table 2 and illustrated in the conceptual framework presented in Fig. 2 , demonstrating how multiple molecular insults can produce clinically significant placental dysfunction. Clinical and Neonatal Outcomes Several studies linked placental micro- and nanoplastic contamination with clinical outcomes, notably preterm birth²,¹² and low birth weight. Translational data suggested that exposure-driven placental dysfunction may contribute to neonatal respiratory distress and metabolic vulnerability, consistent with animal and in vitro evidence showing impaired trophoblast invasion, oxidative stress, and immune activation¹⁵,¹⁶. Table 3 integrates these findings into a framework of clinical and public health implications, highlighting potential exposure sources, risk compartments, and recommended policy responses. Evidence Gaps and Heterogeneity Despite converging evidence of placental exposure and mechanistic disruption, the included literature exhibited several limitations. Human studies were predominantly cross-sectional with small sample sizes, and detection methodologies varied in sensitivity and specificity, limiting comparability across studies¹⁻³,⁶,¹². Mechanistic investigations often relied on high-dose experimental models⁸⁻¹¹,¹³, which may not fully reflect real-world exposure levels. Furthermore, few studies incorporated longitudinal follow-up to capture delayed neonatal or childhood outcomes. Quality assessment using the Newcastle–Ottawa Scale, ROBIS, and AMSTAR-2 (Table 1 ) indicated moderate risk of bias across most studies, underscoring the need for standardized biomonitoring and harmonized outcome measures to strengthen future causal inference. Discussion Principal Findings This systematic review demonstrates that micro- and nanoplastic (MNP) particles are consistently detectable in human placental tissues, amniotic fluid, cord blood, and meconium¹⁻³,⁶,¹², indicating maternal–fetal exposure across diverse populations and environmental contexts (Table 1 , Fig. 1 ). Importantly, quantitative analyses show higher burdens of MNPs in preterm compared with term placentae²,¹², suggesting that plastic particle contamination may represent an underrecognized environmental risk factor for preterm birth. These findings are supported by experimental data showing that MNPs trigger multiple placental molecular disruptions—including oxidative stress, ferroptosis-driven syncytiotrophoblast senescence, impaired trophoblast invasion, endocrine disruption, inflammation, and epigenetic modifications⁸⁻¹¹,¹³,¹⁸,¹⁹—providing biologically plausible pathways by which MNP exposure could impair placental function and fetal development (Table 2 , Fig. 2 ). Translational studies further indicate that these disruptions may lead to adverse neonatal outcomes including growth restriction, respiratory distress, and metabolic vulnerability¹⁵,¹⁶, emphasizing the public health significance of these exposures (Table 3 ). Integration with Existing Knowledge The present synthesis adds to a rapidly expanding body of evidence linking environmental contamination with adverse perinatal outcomes. Early reports of microplastic presence in the human placenta³ sparked debate over the biological significance of these findings; subsequent studies have confirmed their widespread occurrence and demonstrated transfer into fetal compartments¹,⁶,¹². Our analysis highlights, for the first time in a systematic framework, the convergence of MNP detection data with mechanistic studies demonstrating tissue-level toxicity, endocrine and immune signaling perturbations, and epigenetic programming effects⁸⁻¹¹,¹³,¹⁸,¹⁹. These molecular events are consistent with known pathways leading to placental insufficiency and preterm labor. The integration of molecular toxicology with clinical outcome evidence (Tables 2 – 3 , Fig. 2 ) distinguishes this review from earlier narrative accounts⁴,¹⁰,¹⁶,²⁰ and positions environmental plastic contamination as an emergent determinant of maternal and neonatal health. Biological Plausibility and Mechanistic Insights The mechanisms by which MNPs may compromise placental function are increasingly well-characterized. Oxidative stress, a hallmark of environmental toxicant exposure, has been observed in human placental explants and trophoblast cell models following MNP exposure, resulting in mitochondrial dysfunction and lipid peroxidation⁸,¹¹,¹⁸,¹⁹. The discovery of ferroptosis—a regulated cell death pathway dependent on iron and lipid peroxidation—as a mediator of syncytiotrophoblast senescence adds a novel mechanistic dimension¹³. This pathway is particularly compelling given emerging links between ferroptosis and pregnancy complications such as preeclampsia and intrauterine growth restriction. Invasion and vascular remodeling defects, linked to reduced matrix metalloproteinase 2 activity, provide another plausible link between MNP exposure and impaired placental perfusion⁹. Furthermore, inflammatory activation via IL-6, TNF-α, and NLRP3 inflammasome signaling⁸,¹⁰,¹⁶, along with endocrine disruption affecting β-hCG and progesterone signaling⁹,¹¹, indicate broad dysregulation of immune and hormonal networks critical for fetal development. Epigenetic modifications, including altered DNA methylation and miRNA expression¹⁹, suggest potential for long-term developmental programming effects extending beyond birth. Clinical Implications These findings underscore the need to consider environmental plastic exposure as a potential modifiable risk factor in perinatal medicine. While clinical practice has historically focused on maternal comorbidities, infection, and genetics as drivers of preterm birth, the present synthesis (Tables 1 – 3 ) highlights the placenta as an exposure-sensitive organ, vulnerable to novel environmental contaminants. The detection of MNPs in fetal cord blood and meconium⁶ suggests that exposure occurs during critical developmental windows, potentially altering fetal immune and metabolic programming. Translational implications include the need for exposure risk assessment during pregnancy, incorporation of environmental history into prenatal care, and consideration of targeted counseling regarding dietary, occupational, and household sources of plastic exposure (Table 3 ). Public Health and Policy Implications At the population level, plastic contamination is a global and growing problem. The ubiquity of MNPs in air, water, and food chains¹⁷,¹⁸ raises urgent questions about regulatory oversight, product safety, and environmental mitigation strategies. Findings of placental MNP contamination add momentum to calls for integrated “eco-exposome” approaches to maternal and child health, bridging environmental science, toxicology, and perinatal care. Policy interventions could include improved monitoring of plastic additives, stricter product labeling, enhanced consumer awareness, and targeted research funding focused on early-life exposures and long-term health effects (Table 3 ). Strengths and Limitations of the Evidence Base The strength of this review lies in its comprehensive scope, integration of molecular mechanistic studies with human biomonitoring, and translation of findings into clinical and public health frameworks. Nevertheless, limitations of the primary literature temper conclusions. Human studies were predominantly cross-sectional and often limited to small sample sizes¹⁻³,⁶,¹², limiting causal inference. Detection methods lacked harmonization, with variable size cutoffs and polymer identification thresholds, precluding quantitative meta-analysis. Mechanistic studies, while informative, often employed high-dose exposures⁸⁻¹¹,¹³ that may exceed typical environmental levels, and few studies linked molecular endpoints directly to clinical outcomes. Quality assessment revealed moderate risk of bias in most observational studies and narrative reviews, reflecting the early stage of this research field (Table 1 ). Future Directions Future research should focus on longitudinal cohort designs to capture prenatal exposure, placental burden, and postnatal health trajectories, incorporating standardized analytical methods and validated biomarkers. Mechanistic studies should refine dose–response relationships and explore synergistic effects with other environmental pollutants. The integration of omics approaches, including epigenomics and metabolomics, may provide additional insights into how MNP exposure programs fetal development. Clinically, incorporating environmental exposure screening into prenatal visits and developing guidelines for risk mitigation could represent critical next steps. Policy responses should target upstream determinants, including plastic production, waste management, and consumer product design, to reduce population-level exposures and associated perinatal risks. This review provides convergent evidence that MNP contamination of the human placenta is real, mechanistically disruptive, and clinically relevant. By linking environmental exposure to molecular pathways of placental dysfunction and adverse neonatal outcomes (Tables 1 – 3 , Figs. 1 – 2 ), these findings expand the paradigm of perinatal risk factors to include the eco-exposome. Urgent, coordinated action is needed to close knowledge gaps, implement preventive strategies, and protect maternal and neonatal health in an increasingly plastic-contaminated world. Strengths, Limitations, and Future Directions Strengths This review integrates evidence across human exposure data, molecular pathway studies, and clinical implications within a unified conceptual framework. It applies a systematic approach to literature searching, screening, and quality appraisal while incorporating mechanistic and translational perspectives into perinatal medicine. The narrative synthesis highlights multiple biological pathways by which environmental contaminants may disrupt placental function and influence neonatal outcomes, providing clinicians, researchers, and policymakers with a clear overview of this emerging field. Limitations Despite the breadth of evidence, certain limitations restrict definitive conclusions. Most observational studies are cross-sectional and relatively small in scale, limiting causal inference. Detection methods for micro- and nanoplastics vary widely in particle size thresholds, analytical sensitivity, and reporting standards, hindering direct comparison across studies. Experimental studies often utilize exposure levels exceeding typical environmental concentrations, raising questions about real-world relevance. Furthermore, few investigations extend follow-up beyond delivery, limiting understanding of long-term neonatal and childhood health effects. The overall methodological rigor of the evidence base reflects the early stage of research in this area. Future Directions Future work should prioritize prospective cohort designs integrating maternal exposure assessment, placental contamination analysis, and neonatal outcome tracking over time. Standardized detection methodologies, including harmonized particle characterization and reporting frameworks, are essential to enable robust meta-analyses and global comparisons. Mechanistic research should refine dose–response relationships and explore interactions between plastic particles and other environmental contaminants. Incorporation of multi-omics platforms may reveal biomarkers of exposure and mechanisms of fetal programming. Clinically, routine prenatal care could evolve to include environmental exposure screening and counseling. From a public health perspective, strategies to mitigate exposure at the population level, including improved packaging, air quality control, and plastic waste management, represent critical preventive measures. Conclusion Placental contamination by micro- and nanoplastic particles is increasingly recognized as a biologically significant phenomenon. These particles have the potential to disrupt key placental functions, impair maternal-fetal exchange, and contribute to adverse pregnancy and neonatal outcomes. The emerging evidence base suggests a need to consider environmental plastic exposure as a modifiable determinant of perinatal health. Standardized biomonitoring, integrated clinical guidelines, and coordinated public health policies are required to address this evolving risk. Future studies with longitudinal design, refined exposure assessment, and mechanistic insight will be essential to define causality and inform prevention strategies aimed at safeguarding maternal and neonatal health in an era of pervasive environmental plastic contamination. Declarations DISCLOSURE Acknowledgments The authors appreciate the Indonesian Society of Obstetrics and Gynecology (POGI) and the Indonesian Society of Maternal-Fetal Medicine (HKFM) for encouraging and supporting the work of this review article. Conflict of Interest The authors declare that there is no conflict of interest regarding the publication of this manuscript. Funding This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Author Contributions All authors made substantial contributions to all aspects of this research. Contributions include conception and design of the study, development of the search strategy, literature screening and data extraction, quality assessment, interpretation of findings, drafting of the manuscript, critical revision for important intellectual content, and approval of the final version to be published. All authors agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. References Halfar J, Čabanová K, Vávra K, Delongová P, Motyka O, Špaček R, et al. Microplastics and additives in patients with preterm birth: The first evidence of their presence in both human amniotic fluid and placenta. Chemosphere. 2023;343:140301. https://doi.org/10.1016/j.chemosphere.2023.140301 Society for Maternal-Fetal Medicine. New study finds high concentrations of plastics in the placentae of infants born prematurely [Internet]. 2025 [cited 2025 Jul 30]. Available from: https://www.smfm.org/news/new-study-finds-high-concentrations-of-plastics-in-the-placentae-of-infants-born-prematurely Ragusa A, Svelato A, Santacroce C, Catalano P, Notarstefano V, Carnevali O, et al. Plasticenta: First evidence of microplastics in human placenta. Environ Int. 2021;146:106274. https://doi.org/10.1016/j.envint.2020.106274 Zurub RE, Cariaco Y, Wade MG, Bainbridge SA. Microplastics exposure: implications for human fertility, pregnancy and child health. Front Endocrinol (Lausanne). 2024;14:1330396. https://doi.org/10.3389/fendo.2023.1330396 Shultz CL. Plastics from bags and bottles found in every human placenta, new scientific study reveals [Internet]. People. 2024 [cited 2025 Jul 30]. Available from: https://people.com/plastics-found-in-every-human-placenta-8605681 Zhu M, Li X, Lin W, Zeng D, Yang P, Ni W, et al. Microplastic particles detected in fetal cord blood, placenta, and meconium: a pilot study of nine mother–infant pairs in South China. Toxics. 2024;12:850. https://doi.org/10.3390/toxics12120850 Carrington D. Microplastics found in every human placenta tested in study [Internet]. The Guardian. 2024 [cited 2025 Jul 30]. Available from: https://www.theguardian.com/environment/2024/feb/27/microplastics-found-every-human-placenta-tested-study-health-impact de Sousa AKA, Pires KSN, Cavalcante IH, Cavalcante ICL, Santos JD, Queiroz MIC, et al. Polystyrene microplastics exposition on human placental explants induces time-dependent cytotoxicity, oxidative stress and metabolic alterations. Front Endocrinol (Lausanne). 2024;15:1481014. https://doi.org/10.3389/fendo.2024.1481014 Nacka-Aleksić M, Vilotić A, Pirković A, Živanović M, Ljujić B, Jovanović Krivokuća M. Nano-scale dangers: Unravelling the impact of nanoplastics on human trophoblast invasion. Chem Biol Interact. 2025;405:111317. https://doi.org/10.1016/j.cbi.2024.111317 Balali H, Morabbi A, Karimian M. Concerning influences of micro/nano plastics on female reproductive health: focusing on cellular and molecular pathways from animal models to human studies. Reprod Biol Endocrinol. 2024;22:141. https://doi.org/10.1186/s12958-024-01314-7 Poinsignon L, Lefrère B, Ben Azzouz A, Chissey A, Colombel J, Djelidi R, et al. Exposure of the human placental primary cells to nanoplastics induces cytotoxic effects, an inflammatory response and endocrine disruption. J Hazard Mater. 2025;490:137713. https://doi.org/10.1016/j.jhazmat.2025.137713 Jochum M, Garcia M, Hammerquist A, Howell J, Stanford M, Liu R, et al. Elevated Micro- and Nanoplastics Detected in Preterm Human Placentae. Res Sq [Preprint]. 2025;rs.3.rs-5903715. https://doi.org/10.21203/rs.3.rs-5903715/v1 Chen Z, Zheng M, Wan T, Li J, Yuan X, Qin L, et al. Gestational exposure to nanoplastics disrupts fetal development by promoting the placental aging via ferroptosis of syncytiotrophoblast. Environ Int. 2025;197:109361. https://doi.org/10.1016/j.envint.2025.109361 Durkin AM, Zou R, Boucher JM, Boyles MS, van Boxel J, Bustamante M, et al. Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study. JMIR Res Protoc. 2024;13:e63176. https://doi.org/10.2196/63176 Yu HR, Sheen JM, Tiao MM. The impact of maternal nanoplastic and microplastic particle exposure on mammal’s offspring. Cells. 2024;13:1380. https://doi.org/10.3390/cells13161380 Anifowoshe AT, Akhtar MN, Majeed A, Singh AS, Ismail TF, Nongthomba U. Microplastics: A threat to Fetoplacental unit and Reproductive systems. Toxicol Rep. 2025;14:101938. https://doi.org/10.1016/j.toxrep.2025.101938 Wikipedia contributors. Microplastics and human health [Internet]. Wikipedia. 2025 [cited 2025 Jul 30]. Available from: https://en.wikipedia.org/wiki/Microplastics_and_human_health Wan D, Liu Y, Chang Q, Liu Z, Wang Q, Niu R, et al. Micro/Nanoplastic Exposure on Placental Health and Adverse Pregnancy Risks: Novel Assessment System Based upon Targeted Risk Assessment Environmental Chemicals Strategy. Toxics. 2024;12:553. https://doi.org/10.3390/toxics12080553 Zimmermann L. Nanoplastics affect gene expression in the placenta and reproductive health, scientists find [Internet]. Food Packaging Forum. 2023 [cited 2025 Jul 30]. Available from: https://foodpackagingforum.org/news/nanoplastics-affect-gene-expression-in-the-placenta-and-reproductive-health-scientists-find Medley EA, Spratlen MJ, Yan B, Herbstman JB, Deyssenroth MA. A Systematic Review of the Placental Translocation of Micro- and Nanoplastics. Curr Environ Health Rep. 2023;10:99-111. https://doi.org/10.1007/s40572-023-00391-x Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. We do this by developing innovative software and high quality services for the global research community. Our growing team is made up of researchers and industry professionals working together to solve the most critical problems facing scientific publishing. Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-8193385","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Systematic Review","associatedPublications":[],"authors":[{"id":549911484,"identity":"f16811b1-93e3-4d20-bd03-e2a488c83a10","order_by":0,"name":"Wiku Andonotopo, MD, MSc, PhD","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAA+ElEQVRIiWNgGAWjYDACZjYwxdgA5cuBiAMPiNQC1mYM1pKA1xo0LYlg6/BpMTjOlibBUHNHtl+6+fiDjzts0ueHHX4ItMVOTrcBh5bDbMckGI49M54551hi48wzabkbb6cZALUkG5sdwK7F7DB7mwQD2+HEDTdyDJt52w7nbpydANJyIHEbXi3/EFrSDWenfyCgBegwxjaElgR56Rz8ttgfZku2SOw7bDxzRlriTKBfDDdI5xQcSDDA7RfJ/mOGNz58OyzbL5F84AMwxOTlZ6dv/vChwk4OlxYwSIAxQDFjAFZpgEc5CgBpkW8gVvUoGAWjYBSMFAAAXSdnxYZZUWIAAAAASUVORK5CYII=","orcid":"https://orcid.org/0000-0001-9062-8501","institution":"Dept. of OBSGYN, Maternal Fetal Medicine Unit, Women Health Center, Eka Hospital, BSD Serpong, Tangerang, BANTEN, INDONESIA","correspondingAuthor":true,"prefix":"","firstName":"","middleName":"MSc MD Wiku","lastName":"Andonotopo","suffix":"MD"},{"id":549911485,"identity":"fc4ad85d-2429-4ebc-9cad-032b4dfca1e5","order_by":1,"name":"I Nyoman Hariyasa Sanjaya","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"I","middleName":"Nyoman Hariyasa","lastName":"Sanjaya","suffix":""},{"id":549911486,"identity":"7f56646e-c6e5-4236-ba58-d052725864d2","order_by":2,"name":"Muhammad Adrianes Bachnas","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Muhammad","middleName":"Adrianes","lastName":"Bachnas","suffix":""},{"id":549911487,"identity":"52f83664-5e8e-4d57-948b-691fe8813d1a","order_by":3,"name":"Mochammad Besari Adi Pramono","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Mochammad","middleName":"Besari Adi","lastName":"Pramono","suffix":""},{"id":549911488,"identity":"83b1a797-487c-4831-9393-8ee79bb0d366","order_by":4,"name":"Julian Dewantiningrum","email":"","orcid":"","institution":"","correspondingAuthor":false,"prefix":"","firstName":"Julian","middleName":"","lastName":"Dewantiningrum","suffix":""}],"badges":[],"createdAt":"2025-11-24 12:24:11","currentVersionCode":1,"declarations":{"humanSubjects":false,"vertebrateSubjects":false,"conflictsOfInterestStatement":false,"humanSubjectEthicalGuidelines":false,"humanSubjectConsent":false,"humanSubjectClinicalTrial":false,"humanSubjectCaseReport":false,"vertebrateSubjectEthicalGuidelines":false},"doi":"10.21203/rs.3.rs-8193385/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-8193385/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":97124179,"identity":"3bc330da-bb17-42ed-a462-bb5db272b755","added_by":"auto","created_at":"2025-12-01 08:09:45","extension":"docx","order_by":0,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":5051656,"visible":true,"origin":"","legend":"","description":"","filename":"REVIEWARTICLEPlacentalNanoplastic.docx","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/b53db4b4959261b029ef39e7.docx"},{"id":97124150,"identity":"04aa6b67-f814-4b8c-a1d6-9e10d033cc2f","added_by":"auto","created_at":"2025-12-01 08:09:42","extension":"json","order_by":1,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":342,"visible":true,"origin":"","legend":"","description":"","filename":"rs8193385.json","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/fd9742679329cb88c876f472.json"},{"id":97124164,"identity":"0c64028a-b5d4-4d37-8661-fad30947528e","added_by":"auto","created_at":"2025-12-01 08:09:44","extension":"xml","order_by":2,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":114283,"visible":true,"origin":"","legend":"","description":"","filename":"rs81933850enriched.xml","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/4fb02a28ba208a5c7d2c9c85.xml"},{"id":97124149,"identity":"4af900f6-5eae-43d1-8089-122a6b668068","added_by":"auto","created_at":"2025-12-01 08:09:42","extension":"jpeg","order_by":3,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":843928,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage1.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/c052a699e8cf0974fd93741b.jpeg"},{"id":97124142,"identity":"b9ce5e05-aacc-4af0-a448-781af730d715","added_by":"auto","created_at":"2025-12-01 08:09:42","extension":"jpeg","order_by":4,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":1532637,"visible":true,"origin":"","legend":"","description":"","filename":"floatimage2.jpeg","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/343daa68f55b5523e4a6e6d9.jpeg"},{"id":97124145,"identity":"4897de41-107a-47db-90f1-1004b222f37c","added_by":"auto","created_at":"2025-12-01 08:09:42","extension":"png","order_by":5,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":138286,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/7ab89834f7ce17f0c9825673.png"},{"id":97124143,"identity":"b0ff50c9-8adb-45c4-a30a-fca32117d43c","added_by":"auto","created_at":"2025-12-01 08:09:42","extension":"png","order_by":6,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":313337,"visible":true,"origin":"","legend":"","description":"","filename":"Onlinefloatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/f92775654b603281abaea711.png"},{"id":97124154,"identity":"aed8c8c3-d2c2-4092-a589-2f055fc68a9f","added_by":"auto","created_at":"2025-12-01 08:09:43","extension":"xml","order_by":7,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":111205,"visible":true,"origin":"","legend":"","description":"","filename":"rs81933850structuring.xml","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/b37304c6bbc091364882c4f1.xml"},{"id":97124159,"identity":"b1238cb1-c3eb-442b-b185-dbcd9b6e3eee","added_by":"auto","created_at":"2025-12-01 08:09:44","extension":"html","order_by":8,"title":"","display":"","copyAsset":false,"role":"acdc-reference","size":123164,"visible":true,"origin":"","legend":"","description":"","filename":"earlyproof.html","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/74722d4ca0111c68b60fab30.html"},{"id":97124110,"identity":"11724196-a509-430b-945e-7fc30b627508","added_by":"auto","created_at":"2025-12-01 08:09:36","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":595532,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003ePRISMA 2020 Flow Diagram of the Literature Screening and Selection Process. \u003c/strong\u003eThis figure illustrates the systematic literature selection process following the PRISMA 2020 guidelines. A total of 336 records were identified (322 from electronic databases and 14 from additional sources). After removing duplicates, 270 records remained for title and abstract screening. Of these, 70 full-text articles were reviewed for eligibility. Fifty were excluded (19 for inappropriate study design, 17 for insufficient data, and 14 for duplicate reporting). Finally, 20 studies met all inclusion criteria and were included in the qualitative synthesis. This rigorous selection process ensures transparency and methodological robustness in evaluating the evidence linking micro- and nanoplastic placental contamination to preterm birth and neonatal outcomes.\u003c/p\u003e","description":"","filename":"1.png","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/f95401071b95408627dcdaa1.png"},{"id":97124111,"identity":"746de22e-bfda-4a6a-94ca-000fd2a75ad0","added_by":"auto","created_at":"2025-12-01 08:09:36","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1083759,"visible":true,"origin":"","legend":"\u003cp\u003e\u003cstrong\u003eConceptual Model Linking Micro- and Nanoplastic Exposure to Placental Molecular Disruption and Adverse Perinatal Outcomes. \u003c/strong\u003eThis figure illustrates the integrated eco-exposome model of micro- and nanoplastic exposure pathways and their biological impact on pregnancy. Environmental sources—including airborne microplastics, contaminated food chains, consumer products, and associated additives and byproducts—enter the maternal body primarily via inhalation and ingestion. These particles accumulate in the placenta, where they trigger multiple molecular disruptions: oxidative stress (ROS generation, mitochondrial dysfunction), ferroptosis (GPX4 suppression, syncytiotrophoblast senescence, lipid peroxidation), inflammatory response (IL‑6, TNF‑α, NLRP3 inflammasome activation), epigenetic modifications, and endocrine disruption (altered β‑hCG and progesterone signaling). Collectively, these pathways impair placental function and are mechanistically linked to adverse outcomes including preterm birth, fetal growth restriction, low birth weight, neonatal respiratory distress, and long‑term metabolic vulnerability.\u003c/p\u003e","description":"","filename":"2.png","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/c016645394824172901ba711.png"},{"id":97140827,"identity":"75606f58-e0bb-4bac-a3c8-d36e6f4de980","added_by":"auto","created_at":"2025-12-01 10:05:50","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":3218531,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-8193385/v1/54be5472-50af-4fbd-85e9-8f24eb7ed92b.pdf"}],"financialInterests":"The authors declare no competing interests.","formattedTitle":"\u003cp\u003e\u003cstrong\u003ePlacental Micro- and Nanoplastic Contamination: A Systematic Review of Eco-Exposome Pathways to Preterm Birth and Neonatal Outcomes\u003c/strong\u003e\u003c/p\u003e","fulltext":[{"header":"Highlights","content":"\u003col start=\"1\" type=\"1\"\u003e\n \u003cli\u003e\u003cstrong\u003eFirst comprehensive synthesis\u003c/strong\u003e of human and mechanistic evidence linking placental micro- and nanoplastic (MNP) contamination to preterm birth and neonatal outcomes.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eQuantitative human studies\u003c/strong\u003e demonstrate higher placental MNP burdens in preterm versus term pregnancies.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eMolecular pathways\u003c/strong\u003e identified include oxidative stress, ferroptosis-driven syncytiotrophoblast senescence, trophoblast invasion impairment, inflammatory signaling, endocrine disruption, and epigenetic modifications.\u003c/li\u003e\n \u003cli\u003e\u003cstrong\u003eClinical and policy relevance\u003c/strong\u003e: Findings support the need for standardized biomonitoring, maternal exposure mitigation, and integration of eco-exposome considerations into perinatal care.\u003c/li\u003e\n\u003c/ol\u003e"},{"header":"Introduction","content":"\u003cp\u003eGlobal plastic production has exceeded 400 million metric tons annually, resulting in ubiquitous environmental contamination by microplastics and nanoplastics (MNPs). These particles are now detected in diverse eco-exposome pathways including drinking water, air, food chains, and consumer products, with evidence of human exposure at levels capable of systemic distribution\u0026sup1;⁷,\u0026sup1;⁸. Recently, MNPs have been identified within human placental tissues and fetal compartments, including amniotic fluid, cord blood, and meconium\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;, marking a potential paradigm shift in understanding perinatal environmental risks (Table \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab1\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eKey Literature Summary of 20 Studies\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAuthor\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eCountry\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eSample Type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eStudy Design\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDetection Method\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePolymers Detected\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eKey Outcomes\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRelevance to Preterm/\u003c/p\u003e\n \u003cp\u003eNeonatal\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eQuality Assessment Score\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eKey Insight\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHalfar et al., 2023 \u003csup\u003e₁\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCzech Republic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAmniotic fluid \u0026amp; placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFTIR, Raman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePE, PS, PVC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst evidence of MPs in amniotic fluid \u0026amp; placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSuggestive (direct evidence)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNOS: ★★★☆\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFirst human evidence of MPs in placenta \u0026amp; amniotic fluid\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSMFM, 2025 \u003csup\u003e₂\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuman placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePy-GC/MS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePE, PET, PVC, PC\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigher microplastic burden in preterm vs term placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDirect evidence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNOS: ★★★☆\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigher MP burden in preterm vs term placenta (dose-response)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRagusa et al., 2021 \u003csup\u003e₃\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eItaly\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuman placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRaman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePE, PS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMicroplastics confirmed in placenta (all samples)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSuggestive\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNOS: ★★★☆\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlastics present in all placenta samples (universal exposure)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZurub et al., 2024 \u003csup\u003e₄\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCanada\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNarrative synthesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMPs linked to fertility \u0026amp; pregnancy risk\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFramework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAMSTAR-2: Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNarrative link between MPs and reproductive health outcomes\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShultz, 2024 \u003csup\u003e₅\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNews summary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll human placentas positive for plastics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndirect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedia summary emphasizing ubiquity of plastic contamination\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZhu et al., 2024 \u003csup\u003e₆\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCord blood, placenta, meconium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePilot cohort\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRaman\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePE, PS, PET\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMPs in fetal compartments incl. meconium\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDirect evidence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNOS: ★★☆☆\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMNPs translocate to fetal compartments (cord blood, meconium)\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCarrington, 2024 \u003csup\u003e₇\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUK\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNews summary\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAll tested placentas contain MPs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndirect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedia confirming ubiquity of MPs in placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ede Sousa et al., 2024 \u003csup\u003e₈\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBrazil\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental explants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSpectroscopy \u0026amp; biochemical assays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOxidative stress \u0026amp; metabolic disruption in placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMechanistic link\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROBIS: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDemonstrated oxidative stress \u0026amp; metabolic disruption in placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNacka-Aleksić et al., 2025 \u003csup\u003e₉\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSerbia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTrophoblast cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFluorescence \u0026amp; invasion assay\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS nanoparticles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNanoplastics impair trophoblast invasion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMechanistic link\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROBIS: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShowed invasion impairment by nanoplastics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBalali et al., 2024 \u003csup\u003e₁₀\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIran\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNarrative synthesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReproductive toxicity pathways of MPs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFramework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAMSTAR-2: Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eComprehensive review of reproductive toxicity mechanisms\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePoinsignon et al., 2025 \u003csup\u003e₁₁\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFrance\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental cells\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eBiochemical assays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNanoplastics cause inflammation \u0026amp; endocrine disruption\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMechanistic link\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROBIS: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eInflammatory \u0026amp; endocrine disruption responses observed\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eJochum et al., 2025 \u003csup\u003e₁₂\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuman placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eObservational\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePy-GC/MS\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreterm placenta high MP/NP concentration\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDirect evidence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNOS: ★★★☆\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndependent correlation of high MNP burden with preterm birth\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChen et al., 2025 \u003csup\u003e₁₃\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSyncytio- trophoblast\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExperimental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMolecular assays\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS nanoparticles\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental ferroptosis \u0026amp; aging pathway\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMechanistic link\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROBIS: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerroptosis-induced syncytiotrophoblast aging mechanism\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDurkin et al., 2024 \u003csup\u003e₁₄\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEU\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eCohort protocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eProtocol\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFramework for exposure assessment in pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFramework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEstablished pregnancy exposure assessment framework\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eYu et al., 2024 \u003csup\u003e₁₅\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTaiwan\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnimal model\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnimal experimental\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFluorescent tracing\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS, PE\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal exposure impacts offspring development\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eExperimental fetal outcome link\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROBIS: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eShowed maternal plastic exposure affects offspring development\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAnifowoshe et al., 2025 \u003csup\u003e₁₆\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndia\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNarrative synthesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMNP threat to fetoplacental unit\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFramework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAMSTAR-2: Low\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIdentified MPs/NPs as a threat to fetoplacental health\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWikipedia, 2025 \u003csup\u003e₁₇\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGlobal\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOverview\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuman health overview of microplastics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIndirect\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSummarized human health impacts of microplastics\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWan et al., 2024 \u003csup\u003e₁₈\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChina\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental health assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRisk assessment\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTargeted risk framework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRisk assessment for placental impact\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eRisk framework\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eROBIS: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDeveloped targeted risk assessment strategy for placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eZimmermann, 2023 \u003csup\u003e₁₉\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSwitzerland\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGene expression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNews brief\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eTranscriptomics\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNanoplastics alter placental gene expression\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMechanistic\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eN/A\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eReported NP-induced gene expression changes in placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMedley et al., 2023 \u003csup\u003e₂₀\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUSA\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSystematic review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSystematic review\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed methods\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSystematic evidence of placental translocation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eEvidence synthesis\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAMSTAR-2: Moderate\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSynthesized evidence for placental translocation of MPs/NPs\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"10\"\u003eLegend: PE\u0026thinsp;=\u0026thinsp;polyethylene; PS\u0026thinsp;=\u0026thinsp;polystyrene; PET\u0026thinsp;=\u0026thinsp;polyethylene terephthalate; PVC\u0026thinsp;=\u0026thinsp;polyvinyl chloride; PC\u0026thinsp;=\u0026thinsp;polycarbonate; MPs\u0026thinsp;=\u0026thinsp;microplastics; NPs\u0026thinsp;=\u0026thinsp;nanoplastics; AMSTAR-2\u0026thinsp;=\u0026thinsp;A MeaSurement Tool to Assess systematic Reviews, version 2; ROBIS\u0026thinsp;=\u0026thinsp;Risk Of Bias In Systematic reviews; NOS\u0026thinsp;=\u0026thinsp;Newcastle\u0026ndash;Ottawa Scale.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eExisting evidence suggests that placental contamination by MNPs is more than a marker of exposure. Quantitative studies have demonstrated higher micro- and nanoplastic burdens in preterm compared with term placentae\u0026sup2;,\u0026sup1;\u0026sup2;, while pilot data indicate MNP transfer across the placental barrier and into fetal circulation⁶. Parallel in vitro and ex vivo studies show molecular disruptions involving oxidative stress, mitochondrial injury, ferroptosis-driven syncytiotrophoblast senescence, impaired trophoblast invasion, endocrine disruption, inflammatory signaling, and epigenetic modifications⁸⁻\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3;,\u0026sup1;⁸,\u0026sup1;⁹ (Table \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e). Despite these advances, no prior review has systematically synthesized human evidence, mechanistic data, and clinical outcomes of placental MNP exposure, nor integrated eco-exposome perspectives into perinatal medicine (Table \u003cspan class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003ctable id=\"Tab2\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eMolecular Pathways Linking Micro/Nanoplastics to Preterm Birth \u0026amp; Neonatal Outcomes\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePathway / Mechanism\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExperimental Model\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePlastic Exposure Type\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eKey Molecular Findings\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eDownstream Placental Effect\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eAssociated Pregnancy / Neonatal Outcome\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOxidative Stress \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e8\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e11\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHuman placental explants\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePolystyrene MPs (10\u0026ndash;50 \u0026micro;m)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026uarr; ROS, \u0026darr; GPX4, mitochondrial dysfunction\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental aging, impaired nutrient transport\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreterm birth, fetal growth restriction\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFerroptosis \u0026amp; Placental Aging\u0026sup1;\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSyncytiotrophoblast cells (BeWo)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS-NPs (40\u0026ndash;200 nm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eGPX4 suppression, lipid peroxidation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eSyncytiotrophoblast senescence\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreterm birth\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImpaired Trophoblast Invasion⁹\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHTR-8/SVneo cell line\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePS-NPs (40 nm)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026darr; MMP-2, \u0026darr; invasion capacity\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImpaired spiral artery remodeling\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreterm birth, impaired placental perfusion\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eImmune Activation \u0026amp; Inflammation \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMouse pregnancy model\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMixed environmental MPs\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003e\u0026uarr; IL-6, TNF-\u0026alpha;, NLRP3 activation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental inflammation\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePreterm labor, fetal growth effects\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"6\"\u003eLegend: MPs\u0026thinsp;=\u0026thinsp;microplastics; NPs\u0026thinsp;=\u0026thinsp;nanoplastics; ROS\u0026thinsp;=\u0026thinsp;reactive oxygen species; GPX4\u0026thinsp;=\u0026thinsp;glutathione peroxidase 4; MMP-2\u0026thinsp;=\u0026thinsp;matrix metalloproteinase-2; IL-6\u0026thinsp;=\u0026thinsp;interleukin-6; TNF-\u0026alpha;\u0026thinsp;=\u0026thinsp;tumor necrosis factor alpha; NLRP3\u0026thinsp;=\u0026thinsp;nod-like receptor protein 3.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cdiv class=\"gridtable\"\u003e\n \u003cdiv align=\"left\" class=\"colspec\"\u003e\u003cbr\u003e\u003c/div\u003e\n \u003ctable id=\"Tab3\" border=\"1\"\u003e\n \u003ccaption language=\"En\"\u003e\n \u003cdiv class=\"CaptionNumber\"\u003eTable 3\u003c/div\u003e\n \u003cdiv class=\"CaptionContent\"\u003e\n \u003cp\u003eClinical and Public Health Implications of Micro/Nanoplastic Exposure During Pregnancy\u003c/p\u003e\n \u003c/div\u003e\n \u003c/caption\u003e\n \u003cthead\u003e\n \u003ctr\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eExposure Source\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eMaternal-Fetal Compartment Impacted\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003ePotential Clinical Implications\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eResearch / Policy Gap\u003c/p\u003e\n \u003c/th\u003e\n \u003cth align=\"left\"\u003e\n \u003cp\u003eRecommended Actions\u003c/p\u003e\n \u003c/th\u003e\n \u003c/tr\u003e\n \u003c/thead\u003e\n \u003ctbody\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eDrinking water \u0026amp; bottled water \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal blood, placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePotentially higher risk of preterm birth due to chronic ingestion\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo routine biomonitoring; poor regulatory threshold\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePublic awareness campaigns, safer water packaging policies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eAirborne environmental MPs \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal lung \u0026rarr; systemic circulation \u0026rarr; placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMay trigger inflammation \u0026amp; oxidative stress \u0026rarr; preterm labor\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo standardized air monitoring; underestimated exposure\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eUrban emission controls, air filtration strategies for pregnant women\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFood chain exposure (seafood, table salt) \u003csup\u003e49\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental barrier, cord blood, fetal tissues\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMNP translocation into fetal compartment; potential metabolic programming effects\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eNo dietary risk labeling; lack of fetal outcome data\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eFood-chain monitoring, targeted dietary guidelines for pregnant women\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eConsumer products \u0026amp; plastics additives \u003csup\u003e\u003cspan class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan class=\"CitationRef\"\u003e17\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eMaternal circulation \u0026amp; placenta\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePotential endocrine disruption (altered \u0026beta;-hCG, progesterone)\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eChemical risk assessments often exclude pregnancy-specific endpoints\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eIntegrate plastics risk into reproductive toxicology policies\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003ctr\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eOccupational exposure (industrial, healthcare)\u0026sup2;\u0026sup3;\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003ePlacental accumulation, maternal-fetal interface\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eHigher exposure among specific working populations; unclear dose-response\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eLimited occupational health studies in pregnancy\u003c/p\u003e\n \u003c/td\u003e\n \u003ctd align=\"left\"\u003e\n \u003cp\u003eWorkplace exposure monitoring, protective equipment standards\u003c/p\u003e\n \u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tbody\u003e\n \u003ctfoot\u003e\n \u003ctr\u003e\n \u003ctd colspan=\"5\"\u003eLegend: MPs\u0026thinsp;=\u0026thinsp;microplastics; NPs\u0026thinsp;=\u0026thinsp;nanoplastics; \u0026beta;-hCG\u0026thinsp;=\u0026thinsp;beta-human chorionic gonadotropin. References indicate supporting evidence from the systematic review database.\u003c/td\u003e\n \u003c/tr\u003e\n \u003c/tfoot\u003e\n \u003c/table\u003e\n\u003c/div\u003e\n\u003cp\u003eGiven increasing global attention to environmental pollution and maternal-fetal health, a clear conceptual framework linking placental MNP contamination to adverse pregnancy and neonatal outcomes is urgently needed. We hypothesize that MNP exposure activates multiple convergent molecular pathways within the placenta, resulting in impaired nutrient transport, disrupted endocrine and immune signaling, and heightened risk of preterm birth and related neonatal morbidities\u0026sup1;⁰,\u0026sup1;⁶.\u003c/p\u003e\n\u003cp\u003eThis review systematically evaluates published literature on MNP contamination of the human placenta (Fig. \u003cspan class=\"InternalRef\"\u003e1\u003c/span\u003e), integrates molecular pathway evidence (Fig. \u003cspan class=\"InternalRef\"\u003e2\u003c/span\u003e), and examines clinical implications for preterm birth and neonatal outcomes. Our aim is to advance translational understanding and inform future biomonitoring, clinical strategies, and policy development.\u003c/p\u003e"},{"header":"Methodology","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eReview Design\u003c/h2\u003e\u003cp\u003eThis systematic review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines, as illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e. A predefined review protocol established the eligibility criteria, data extraction strategy, and risk of bias assessment approach prior to literature searching and screening.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eLiterature Search Strategy\u003c/h3\u003e\n\u003cp\u003eA comprehensive search of PubMed, Web of Science, and Scopus databases was performed, complemented by grey literature sources including preprints, conference proceedings, and institutional reports. The search strategy incorporated controlled vocabulary and free-text terms related to microplastics, nanoplastics, placenta, pregnancy, preterm birth, and neonatal outcomes. Search strings were adapted for each database and limited to studies published between January 2000 and July 2025 in the English language. Additional articles were identified by manual reference screening of all included papers to ensure capture of emerging evidence.\u003c/p\u003e\n\u003ch3\u003eEligibility Criteria\u003c/h3\u003e\n\u003cp\u003eEligible studies included those that detected micro- or nanoplastic particles in human placenta, amniotic fluid, cord blood, or meconium; mechanistic studies employing human placental tissues, trophoblast models, or relevant animal analogues exploring molecular pathways of placental dysfunction; and reviews or protocols addressing pregnancy-related micro- and nanoplastic exposure. Studies were excluded if they focused on non-pregnancy populations, lacked assessment of micro- or nanoplastics, or consisted solely of commentary or editorial content without primary data. Duplicate reports and studies lacking sufficient methodological details were also excluded.\u003c/p\u003e\n\u003ch3\u003eStudy Selection\u003c/h3\u003e\n\u003cp\u003eTwo reviewers independently screened titles and abstracts for relevance and subsequently assessed the full text of eligible articles. Disagreements were resolved through discussion until consensus was reached. The stepwise process of identification, screening, and inclusion of eligible studies is summarized in the PRISMA flow diagram (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\n\u003ch3\u003eData Extraction\u003c/h3\u003e\n\u003cp\u003eData from included studies were systematically extracted using a predefined matrix capturing author and year, study region, type of biological sample, detection techniques employed, identified polymer types, molecular pathways implicated, and pregnancy or neonatal outcomes reported. These findings were synthesized to generate a comprehensive summary of existing literature (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e), an integrated analysis of molecular pathways (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e), and a translation of findings into clinical and public health implications (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eQuality Assessment\u003c/h2\u003e\u003cp\u003eThe methodological quality and risk of bias of the included studies were assessed using internationally recognized tools appropriate to study design. Observational studies were evaluated using the Newcastle\u0026ndash;Ottawa Scale, review-based publications were appraised with the Risk of Bias in Systematic Reviews (ROBIS) tool, and systematic reviews and protocols were assessed using AMSTAR-2. The results of these assessments are presented in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e under the column \u003cem\u003eQuality Assessment Score\u003c/em\u003e.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eData Synthesis\u003c/h3\u003e\n\u003cp\u003eGiven the heterogeneity in study designs, exposure assessment methods, and outcome measures, quantitative meta-analysis was not feasible. Instead, a narrative synthesis was undertaken, grouping evidence into three principal domains: human biomonitoring of micro- and nanoplastic contamination of pregnancy-related biological compartments, mechanistic pathways linking these exposures to placental dysfunction, and clinical or public health implications relevant to perinatal medicine. Molecular disruptions were mapped to conceptual pathways illustrated in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e, providing an integrative framework connecting environmental exposure to adverse pregnancy and neonatal outcomes.\u003c/p\u003e"},{"header":"Results and Findings","content":"\u003cdiv id=\"Sec11\" class=\"Section2\"\u003e\u003ch2\u003eLiterature Screening and Study Characteristics\u003c/h2\u003e\u003cp\u003eThe search strategy identified 336 records from electronic databases and 14 additional records through grey literature sources. After removal of duplicates, 270 unique records were screened by title and abstract, resulting in 70 full-text articles assessed for eligibility. Fifty articles were excluded for reasons including irrelevant population or outcomes, insufficient microplastic or nanoplastic assessment, or duplication of data sets. Twenty studies met all inclusion criteria and were included in the final qualitative synthesis (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cp\u003eIncluded studies comprised human biomonitoring investigations of placental and fetal compartments\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;, mechanistic studies involving human placental explants and trophoblast models⁸⁻\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3;,\u0026sup1;⁸,\u0026sup1;⁹, and integrative reviews and protocols addressing micro- and nanoplastic exposure during pregnancy⁴,\u0026sup1;⁰,\u0026sup1;⁴,\u0026sup1;⁶,\u0026sup2;⁰. Biological matrices analyzed included human placenta\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;, amniotic fluid\u0026sup1;, cord blood and meconium⁶, and experimental trophoblast or syncytiotrophoblast cell lines⁸,⁹,\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3;. Detection methods varied, with Raman spectroscopy, Fourier transform infrared spectroscopy, and pyrolysis\u0026ndash;gas chromatography/mass spectrometry being the most commonly applied techniques (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec12\" class=\"Section2\"\u003e\u003ch2\u003eEvidence of Micro- and Nanoplastic Contamination in Human Pregnancy\u003c/h2\u003e\u003cp\u003eMultiple studies demonstrated the presence of micro- and nanoplastics in human placenta across diverse populations\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;. Halfar et al.\u0026sup1; provided the first combined evidence of microplastic particles in both amniotic fluid and placental tissue, while Ragusa et al.\u0026sup3; reported detection of plastic particles in all placenta samples analyzed. Zhu et al.⁶ extended these findings by identifying particles in fetal cord blood and meconium, confirming transplacental transfer. Quantitative assessments revealed higher micro- and nanoplastic burdens in preterm compared with term placentae\u0026sup2;,\u0026sup1;\u0026sup2;, with identified polymer types including polyethylene (PE), polystyrene (PS), polyethylene terephthalate (PET), polyvinyl chloride (PVC), and polycarbonate (PC). These findings establish widespread placental exposure and suggest a dose-response relationship with adverse pregnancy outcomes (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec13\" class=\"Section2\"\u003e\u003ch2\u003eMolecular Pathways and Placental Dysfunction\u003c/h2\u003e\u003cp\u003eMechanistic investigations provide strong biological plausibility linking micro- and nanoplastic exposure to placental dysfunction. Experimental studies using human placental explants and trophoblast cells revealed increased oxidative stress, characterized by reactive oxygen species (ROS) generation and mitochondrial dysfunction⁸,\u0026sup1;\u0026sup1;,\u0026sup1;⁸,\u0026sup1;⁹. Syncytiotrophoblast ferroptosis, associated with glutathione peroxidase 4 (GPX4) suppression and lipid peroxidation, was reported as a novel pathway promoting placental aging and senescence\u0026sup1;\u0026sup3;. Endocrine disruption was evident from altered β-hCG and progesterone signaling pathways⁹,\u0026sup1;\u0026sup1;, while impaired trophoblast invasion and spiral artery remodeling were linked to downregulation of matrix metalloproteinase 2 (MMP-2) activity⁹. Inflammatory signaling, particularly interleukin-6 (IL-6), tumor necrosis factor alpha (TNF-α), and NLRP3 inflammasome activation, was frequently observed⁸,\u0026sup1;⁰,\u0026sup1;⁶. Additionally, epigenetic alterations, including changes in DNA methylation and microRNA expression, suggested a mechanism for persistent fetal programming\u0026sup1;⁹.\u003c/p\u003e\u003cp\u003eCollectively, these pathways converge to impair nutrient and oxygen transport, disturb immune tolerance, and disrupt endocrine homeostasis. The mechanistic relationships are summarized in Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e and illustrated in the conceptual framework presented in Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e, demonstrating how multiple molecular insults can produce clinically significant placental dysfunction.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec14\" class=\"Section2\"\u003e\u003ch2\u003eClinical and Neonatal Outcomes\u003c/h2\u003e\u003cp\u003eSeveral studies linked placental micro- and nanoplastic contamination with clinical outcomes, notably preterm birth\u0026sup2;,\u0026sup1;\u0026sup2; and low birth weight. Translational data suggested that exposure-driven placental dysfunction may contribute to neonatal respiratory distress and metabolic vulnerability, consistent with animal and in vitro evidence showing impaired trophoblast invasion, oxidative stress, and immune activation\u0026sup1;⁵,\u0026sup1;⁶. Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e integrates these findings into a framework of clinical and public health implications, highlighting potential exposure sources, risk compartments, and recommended policy responses.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec15\" class=\"Section2\"\u003e\u003ch2\u003eEvidence Gaps and Heterogeneity\u003c/h2\u003e\u003cp\u003eDespite converging evidence of placental exposure and mechanistic disruption, the included literature exhibited several limitations. Human studies were predominantly cross-sectional with small sample sizes, and detection methodologies varied in sensitivity and specificity, limiting comparability across studies\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;. Mechanistic investigations often relied on high-dose experimental models⁸⁻\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3;, which may not fully reflect real-world exposure levels. Furthermore, few studies incorporated longitudinal follow-up to capture delayed neonatal or childhood outcomes. Quality assessment using the Newcastle\u0026ndash;Ottawa Scale, ROBIS, and AMSTAR-2 (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) indicated moderate risk of bias across most studies, underscoring the need for standardized biomonitoring and harmonized outcome measures to strengthen future causal inference.\u003c/p\u003e\u003c/div\u003e"},{"header":"Discussion","content":"\u003cdiv id=\"Sec17\" class=\"Section2\"\u003e\u003ch2\u003ePrincipal Findings\u003c/h2\u003e\u003cp\u003eThis systematic review demonstrates that micro- and nanoplastic (MNP) particles are consistently detectable in human placental tissues, amniotic fluid, cord blood, and meconium\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;, indicating maternal\u0026ndash;fetal exposure across diverse populations and environmental contexts (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e). Importantly, quantitative analyses show higher burdens of MNPs in preterm compared with term placentae\u0026sup2;,\u0026sup1;\u0026sup2;, suggesting that plastic particle contamination may represent an underrecognized environmental risk factor for preterm birth. These findings are supported by experimental data showing that MNPs trigger multiple placental molecular disruptions\u0026mdash;including oxidative stress, ferroptosis-driven syncytiotrophoblast senescence, impaired trophoblast invasion, endocrine disruption, inflammation, and epigenetic modifications⁸⁻\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3;,\u0026sup1;⁸,\u0026sup1;⁹\u0026mdash;providing biologically plausible pathways by which MNP exposure could impair placental function and fetal development (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e). Translational studies further indicate that these disruptions may lead to adverse neonatal outcomes including growth restriction, respiratory distress, and metabolic vulnerability\u0026sup1;⁵,\u0026sup1;⁶, emphasizing the public health significance of these exposures (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec18\" class=\"Section2\"\u003e\u003ch2\u003eIntegration with Existing Knowledge\u003c/h2\u003e\u003cp\u003eThe present synthesis adds to a rapidly expanding body of evidence linking environmental contamination with adverse perinatal outcomes. Early reports of microplastic presence in the human placenta\u0026sup3; sparked debate over the biological significance of these findings; subsequent studies have confirmed their widespread occurrence and demonstrated transfer into fetal compartments\u0026sup1;,⁶,\u0026sup1;\u0026sup2;. Our analysis highlights, for the first time in a systematic framework, the convergence of MNP detection data with mechanistic studies demonstrating tissue-level toxicity, endocrine and immune signaling perturbations, and epigenetic programming effects⁸⁻\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3;,\u0026sup1;⁸,\u0026sup1;⁹. These molecular events are consistent with known pathways leading to placental insufficiency and preterm labor. The integration of molecular toxicology with clinical outcome evidence (Tables\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e) distinguishes this review from earlier narrative accounts⁴,\u0026sup1;⁰,\u0026sup1;⁶,\u0026sup2;⁰ and positions environmental plastic contamination as an emergent determinant of maternal and neonatal health.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec19\" class=\"Section2\"\u003e\u003ch2\u003eBiological Plausibility and Mechanistic Insights\u003c/h2\u003e\u003cp\u003eThe mechanisms by which MNPs may compromise placental function are increasingly well-characterized. Oxidative stress, a hallmark of environmental toxicant exposure, has been observed in human placental explants and trophoblast cell models following MNP exposure, resulting in mitochondrial dysfunction and lipid peroxidation⁸,\u0026sup1;\u0026sup1;,\u0026sup1;⁸,\u0026sup1;⁹. The discovery of ferroptosis\u0026mdash;a regulated cell death pathway dependent on iron and lipid peroxidation\u0026mdash;as a mediator of syncytiotrophoblast senescence adds a novel mechanistic dimension\u0026sup1;\u0026sup3;. This pathway is particularly compelling given emerging links between ferroptosis and pregnancy complications such as preeclampsia and intrauterine growth restriction. Invasion and vascular remodeling defects, linked to reduced matrix metalloproteinase 2 activity, provide another plausible link between MNP exposure and impaired placental perfusion⁹. Furthermore, inflammatory activation via IL-6, TNF-α, and NLRP3 inflammasome signaling⁸,\u0026sup1;⁰,\u0026sup1;⁶, along with endocrine disruption affecting β-hCG and progesterone signaling⁹,\u0026sup1;\u0026sup1;, indicate broad dysregulation of immune and hormonal networks critical for fetal development. Epigenetic modifications, including altered DNA methylation and miRNA expression\u0026sup1;⁹, suggest potential for long-term developmental programming effects extending beyond birth.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec20\" class=\"Section2\"\u003e\u003ch2\u003eClinical Implications\u003c/h2\u003e\u003cp\u003eThese findings underscore the need to consider environmental plastic exposure as a potential modifiable risk factor in perinatal medicine. While clinical practice has historically focused on maternal comorbidities, infection, and genetics as drivers of preterm birth, the present synthesis (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) highlights the placenta as an exposure-sensitive organ, vulnerable to novel environmental contaminants. The detection of MNPs in fetal cord blood and meconium⁶ suggests that exposure occurs during critical developmental windows, potentially altering fetal immune and metabolic programming. Translational implications include the need for exposure risk assessment during pregnancy, incorporation of environmental history into prenatal care, and consideration of targeted counseling regarding dietary, occupational, and household sources of plastic exposure (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec21\" class=\"Section2\"\u003e\u003ch2\u003ePublic Health and Policy Implications\u003c/h2\u003e\u003cp\u003eAt the population level, plastic contamination is a global and growing problem. The ubiquity of MNPs in air, water, and food chains\u0026sup1;⁷,\u0026sup1;⁸ raises urgent questions about regulatory oversight, product safety, and environmental mitigation strategies. Findings of placental MNP contamination add momentum to calls for integrated \u0026ldquo;eco-exposome\u0026rdquo; approaches to maternal and child health, bridging environmental science, toxicology, and perinatal care. Policy interventions could include improved monitoring of plastic additives, stricter product labeling, enhanced consumer awareness, and targeted research funding focused on early-life exposures and long-term health effects (Table\u0026nbsp;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e).\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec22\" class=\"Section2\"\u003e\u003ch2\u003eStrengths and Limitations of the Evidence Base\u003c/h2\u003e\u003cp\u003eThe strength of this review lies in its comprehensive scope, integration of molecular mechanistic studies with human biomonitoring, and translation of findings into clinical and public health frameworks. Nevertheless, limitations of the primary literature temper conclusions. Human studies were predominantly cross-sectional and often limited to small sample sizes\u0026sup1;⁻\u0026sup3;,⁶,\u0026sup1;\u0026sup2;, limiting causal inference. Detection methods lacked harmonization, with variable size cutoffs and polymer identification thresholds, precluding quantitative meta-analysis. Mechanistic studies, while informative, often employed high-dose exposures⁸⁻\u0026sup1;\u0026sup1;,\u0026sup1;\u0026sup3; that may exceed typical environmental levels, and few studies linked molecular endpoints directly to clinical outcomes. Quality assessment revealed moderate risk of bias in most observational studies and narrative reviews, reflecting the early stage of this research field (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e).\u003c/p\u003e\u003cdiv id=\"Sec23\" class=\"Section3\"\u003e\u003ch2\u003eFuture Directions\u003c/h2\u003e\u003cp\u003eFuture research should focus on longitudinal cohort designs to capture prenatal exposure, placental burden, and postnatal health trajectories, incorporating standardized analytical methods and validated biomarkers. Mechanistic studies should refine dose\u0026ndash;response relationships and explore synergistic effects with other environmental pollutants. The integration of omics approaches, including epigenomics and metabolomics, may provide additional insights into how MNP exposure programs fetal development. Clinically, incorporating environmental exposure screening into prenatal visits and developing guidelines for risk mitigation could represent critical next steps. Policy responses should target upstream determinants, including plastic production, waste management, and consumer product design, to reduce population-level exposures and associated perinatal risks. This review provides convergent evidence that MNP contamination of the human placenta is real, mechanistically disruptive, and clinically relevant. By linking environmental exposure to molecular pathways of placental dysfunction and adverse neonatal outcomes (Tables\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Tab3\" class=\"InternalRef\"\u003e3\u003c/span\u003e, Figs.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e1\u003c/span\u003e\u0026ndash;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e2\u003c/span\u003e), these findings expand the paradigm of perinatal risk factors to include the eco-exposome. Urgent, coordinated action is needed to close knowledge gaps, implement preventive strategies, and protect maternal and neonatal health in an increasingly plastic-contaminated world.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e\u003cdiv id=\"Sec24\" class=\"Section2\"\u003e\u003ch2\u003eStrengths, Limitations, and Future Directions\u003c/h2\u003e\u003cdiv id=\"Sec25\" class=\"Section3\"\u003e\u003ch2\u003eStrengths\u003c/h2\u003e\u003cp\u003eThis review integrates evidence across human exposure data, molecular pathway studies, and clinical implications within a unified conceptual framework. It applies a systematic approach to literature searching, screening, and quality appraisal while incorporating mechanistic and translational perspectives into perinatal medicine. The narrative synthesis highlights multiple biological pathways by which environmental contaminants may disrupt placental function and influence neonatal outcomes, providing clinicians, researchers, and policymakers with a clear overview of this emerging field.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec26\" class=\"Section3\"\u003e\u003ch2\u003eLimitations\u003c/h2\u003e\u003cp\u003eDespite the breadth of evidence, certain limitations restrict definitive conclusions. Most observational studies are cross-sectional and relatively small in scale, limiting causal inference. Detection methods for micro- and nanoplastics vary widely in particle size thresholds, analytical sensitivity, and reporting standards, hindering direct comparison across studies. Experimental studies often utilize exposure levels exceeding typical environmental concentrations, raising questions about real-world relevance. Furthermore, few investigations extend follow-up beyond delivery, limiting understanding of long-term neonatal and childhood health effects. The overall methodological rigor of the evidence base reflects the early stage of research in this area.\u003c/p\u003e\u003c/div\u003e\u003cdiv id=\"Sec27\" class=\"Section3\"\u003e\u003ch2\u003eFuture Directions\u003c/h2\u003e\u003cp\u003eFuture work should prioritize prospective cohort designs integrating maternal exposure assessment, placental contamination analysis, and neonatal outcome tracking over time. Standardized detection methodologies, including harmonized particle characterization and reporting frameworks, are essential to enable robust meta-analyses and global comparisons. Mechanistic research should refine dose\u0026ndash;response relationships and explore interactions between plastic particles and other environmental contaminants. Incorporation of multi-omics platforms may reveal biomarkers of exposure and mechanisms of fetal programming. Clinically, routine prenatal care could evolve to include environmental exposure screening and counseling. From a public health perspective, strategies to mitigate exposure at the population level, including improved packaging, air quality control, and plastic waste management, represent critical preventive measures.\u003c/p\u003e\u003c/div\u003e\u003c/div\u003e"},{"header":"Conclusion","content":"\u003cp\u003ePlacental contamination by micro- and nanoplastic particles is increasingly recognized as a biologically significant phenomenon. These particles have the potential to disrupt key placental functions, impair maternal-fetal exchange, and contribute to adverse pregnancy and neonatal outcomes. The emerging evidence base suggests a need to consider environmental plastic exposure as a modifiable determinant of perinatal health. Standardized biomonitoring, integrated clinical guidelines, and coordinated public health policies are required to address this evolving risk. Future studies with longitudinal design, refined exposure assessment, and mechanistic insight will be essential to define causality and inform prevention strategies aimed at safeguarding maternal and neonatal health in an era of pervasive environmental plastic contamination.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eDISCLOSURE\u003c/strong\u003e\u003c/p\u003e\n\u003cp\u003eAcknowledgments\u003c/p\u003e\n\u003cp\u003eThe authors appreciate the Indonesian Society of Obstetrics and Gynecology (POGI) and the Indonesian Society of Maternal-Fetal Medicine (HKFM) for encouraging and supporting the work of this review article.\u003c/p\u003e\n\u003cp\u003eConflict of Interest\u003c/p\u003e\n\u003cp\u003eThe authors declare that there is no conflict of interest regarding the publication of this manuscript.\u003c/p\u003e\n\u003cp\u003eFunding\u003c/p\u003e\n\u003cp\u003eThis research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.\u003c/p\u003e\n\u003cp\u003eAuthor Contributions\u003c/p\u003e\n\u003cp\u003eAll authors made substantial contributions to all aspects of this research. Contributions include conception and design of the study, development of the search strategy, literature screening and data extraction, quality assessment, interpretation of findings, drafting of the manuscript, critical revision for important intellectual content, and approval of the final version to be published. All authors agree to be accountable for all aspects of the work, ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHalfar J, Čabanov\u0026aacute; K, V\u0026aacute;vra K, Delongov\u0026aacute; P, Motyka O, \u0026Scaron;paček R, et al. Microplastics and additives in patients with preterm birth: The first evidence of their presence in both human amniotic fluid and placenta. Chemosphere. 2023;343:140301. https://doi.org/10.1016/j.chemosphere.2023.140301\u003c/li\u003e\n \u003cli\u003eSociety for Maternal-Fetal Medicine. New study finds high concentrations of plastics in the placentae of infants born prematurely [Internet]. 2025 [cited 2025 Jul 30]. Available from: https://www.smfm.org/news/new-study-finds-high-concentrations-of-plastics-in-the-placentae-of-infants-born-prematurely\u003c/li\u003e\n \u003cli\u003eRagusa A, Svelato A, Santacroce C, Catalano P, Notarstefano V, Carnevali O, et al. Plasticenta: First evidence of microplastics in human placenta. Environ Int. 2021;146:106274. https://doi.org/10.1016/j.envint.2020.106274\u003c/li\u003e\n \u003cli\u003eZurub RE, Cariaco Y, Wade MG, Bainbridge SA. Microplastics exposure: implications for human fertility, pregnancy and child health. Front Endocrinol (Lausanne). 2024;14:1330396. https://doi.org/10.3389/fendo.2023.1330396\u003c/li\u003e\n \u003cli\u003eShultz CL. Plastics from bags and bottles found in every human placenta, new scientific study reveals [Internet]. People. 2024 [cited 2025 Jul 30]. Available from: https://people.com/plastics-found-in-every-human-placenta-8605681\u003c/li\u003e\n \u003cli\u003eZhu M, Li X, Lin W, Zeng D, Yang P, Ni W, et al. Microplastic particles detected in fetal cord blood, placenta, and meconium: a pilot study of nine mother\u0026ndash;infant pairs in South China. Toxics. 2024;12:850. https://doi.org/10.3390/toxics12120850\u003c/li\u003e\n \u003cli\u003eCarrington D. Microplastics found in every human placenta tested in study [Internet]. The Guardian. 2024 [cited 2025 Jul 30]. Available from: https://www.theguardian.com/environment/2024/feb/27/microplastics-found-every-human-placenta-tested-study-health-impact\u003c/li\u003e\n \u003cli\u003ede Sousa AKA, Pires KSN, Cavalcante IH, Cavalcante ICL, Santos JD, Queiroz MIC, et al. Polystyrene microplastics exposition on human placental explants induces time-dependent cytotoxicity, oxidative stress and metabolic alterations. Front Endocrinol (Lausanne). 2024;15:1481014. https://doi.org/10.3389/fendo.2024.1481014\u003c/li\u003e\n \u003cli\u003eNacka-Aleksić M, Vilotić A, Pirković A, Živanović M, Ljujić B, Jovanović Krivokuća M. Nano-scale dangers: Unravelling the impact of nanoplastics on human trophoblast invasion. Chem Biol Interact. 2025;405:111317. https://doi.org/10.1016/j.cbi.2024.111317\u003c/li\u003e\n \u003cli\u003eBalali H, Morabbi A, Karimian M. Concerning influences of micro/nano plastics on female reproductive health: focusing on cellular and molecular pathways from animal models to human studies. Reprod Biol Endocrinol. 2024;22:141. https://doi.org/10.1186/s12958-024-01314-7\u003c/li\u003e\n \u003cli\u003ePoinsignon L, Lefr\u0026egrave;re B, Ben Azzouz A, Chissey A, Colombel J, Djelidi R, et al. Exposure of the human placental primary cells to nanoplastics induces cytotoxic effects, an inflammatory response and endocrine disruption. J Hazard Mater. 2025;490:137713. https://doi.org/10.1016/j.jhazmat.2025.137713\u003c/li\u003e\n \u003cli\u003eJochum M, Garcia M, Hammerquist A, Howell J, Stanford M, Liu R, et al. Elevated Micro- and Nanoplastics Detected in Preterm Human Placentae. Res Sq [Preprint]. 2025;rs.3.rs-5903715. https://doi.org/10.21203/rs.3.rs-5903715/v1\u003c/li\u003e\n \u003cli\u003eChen Z, Zheng M, Wan T, Li J, Yuan X, Qin L, et al. Gestational exposure to nanoplastics disrupts fetal development by promoting the placental aging via ferroptosis of syncytiotrophoblast. Environ Int. 2025;197:109361. https://doi.org/10.1016/j.envint.2025.109361\u003c/li\u003e\n \u003cli\u003eDurkin AM, Zou R, Boucher JM, Boyles MS, van Boxel J, Bustamante M, et al. Investigating Exposure and Hazards of Micro- and Nanoplastics During Pregnancy and Early Life (AURORA Project): Protocol for an Interdisciplinary Study. JMIR Res Protoc. 2024;13:e63176. https://doi.org/10.2196/63176\u003c/li\u003e\n \u003cli\u003eYu HR, Sheen JM, Tiao MM. The impact of maternal nanoplastic and microplastic particle exposure on mammal\u0026rsquo;s offspring. Cells. 2024;13:1380. https://doi.org/10.3390/cells13161380\u003c/li\u003e\n \u003cli\u003eAnifowoshe AT, Akhtar MN, Majeed A, Singh AS, Ismail TF, Nongthomba U. Microplastics: A threat to Fetoplacental unit and Reproductive systems. Toxicol Rep. 2025;14:101938. https://doi.org/10.1016/j.toxrep.2025.101938\u003c/li\u003e\n \u003cli\u003eWikipedia contributors. Microplastics and human health [Internet]. Wikipedia. 2025 [cited 2025 Jul 30]. Available from: https://en.wikipedia.org/wiki/Microplastics_and_human_health\u003c/li\u003e\n \u003cli\u003eWan D, Liu Y, Chang Q, Liu Z, Wang Q, Niu R, et al. Micro/Nanoplastic Exposure on Placental Health and Adverse Pregnancy Risks: Novel Assessment System Based upon Targeted Risk Assessment Environmental Chemicals Strategy. Toxics. 2024;12:553. https://doi.org/10.3390/toxics12080553\u003c/li\u003e\n \u003cli\u003eZimmermann L. Nanoplastics affect gene expression in the placenta and reproductive health, scientists find [Internet]. Food Packaging Forum. 2023 [cited 2025 Jul 30]. Available from: https://foodpackagingforum.org/news/nanoplastics-affect-gene-expression-in-the-placenta-and-reproductive-health-scientists-find\u003c/li\u003e\n \u003cli\u003eMedley EA, Spratlen MJ, Yan B, Herbstman JB, Deyssenroth MA. A Systematic Review of the Placental Translocation of Micro- and Nanoplastics. Curr Environ Health Rep. 2023;10:99-111. https://doi.org/10.1007/s40572-023-00391-x\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Placenta, Microplastics, Nanoplastics, Preterm Birth, Eco-Exposome","lastPublishedDoi":"10.21203/rs.3.rs-8193385/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8193385/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eObjective:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTo 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.\u003c/p\u003e\u003cp\u003e\u003cb\u003eMethods:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eFollowing 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\u0026ndash;Ottawa Scale. Data were synthesized into three evidence domains: human biomonitoring, molecular pathways, and clinical implications.\u003c/p\u003e\u003cp\u003e\u003cb\u003eResults:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTwenty studies met inclusion criteria (Table\u0026nbsp;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\u0026nbsp;2, Fig.\u0026nbsp;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\u0026nbsp;3).\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusion:\u003c/b\u003e\u003c/p\u003e\u003cp\u003eMicro- 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.\u003c/p\u003e","manuscriptTitle":"Placental Micro- and Nanoplastic Contamination: A Systematic Review of Eco-Exposome Pathways to Preterm Birth and Neonatal Outcomes","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-12-01 08:08:59","doi":"10.21203/rs.3.rs-8193385/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"423e4212-790a-4cb0-8efc-555d8ebf29c4","owner":[],"postedDate":"December 1st, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":58508288,"name":"Obstetrics \u0026 Gynecology"}],"tags":[],"updatedAt":"2025-12-01T08:08:59+00:00","versionOfRecord":[],"versionCreatedAt":"2025-12-01 08:08:59","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8193385","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8193385","identity":"rs-8193385","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}