REVIEW ARTICLE

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

INyoman1

HariyasaSanjaya1

WikuAndonotopo

MD, PhD

2,12✉Emailwiku.andonotopo@gmail.com

MuhammadAdrianesBachnas3

JulianDewantiningrum1

MochammadBesari1

AdiPramono4

RyanSaktikaMulyana1

EvertSolomonPangkahila1

MuhammadIlham1

AldikaAkbar5

CutMeurahYeni6

DudyAldiansyah7

NuswilBernolian8

AnakAgung1

GedePutraWiradnyana1

AdhiPribadi9

SriSulistyowati1

MilanStanojevic10

AsimKurjak11

UniversitasUdayana1

Prof. dr.

I.G.N.G1

1Ngoerah General HospitalBaliIndonesia

2Maternal-Fetal Medicine Division, Women Health Center, Department of Obstetrics and GynecologyEkahospital BSD City, Tangerang, BantenSerpongIndonesia

314 Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Medical Faculty of Sebelas, Dr. Moewardi HospitalMaret UniversitySoloSurakartaIndonesia

4Maternal-Fetal Medicine Division, Department of Obstetrics and GynecologyMedical Faculty of Diponegoro UniversityDr. Kariadi HospitalSemarangIndonesia

5Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas AirlanggaDr. Soetomo General HospitalSurabayaIndonesia

6Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of MedicineUniversitas Syiah Kuala, Dr. Zainoel Abidin General HospitalAcehIndonesia

7Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of MedicineUniversitas Sumatera Utara, H. Adam Malik General HospitalMedanIndonesia

8Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas SriwijayaDr. Mohammad Hoesin General HospitalPalembangIndonesia

9Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of MedicineUniversitas Padjajaran, Hasan Sadikin General HospitalBandungIndonesia

Department of Neonatology and Rare DiseasesMedical University of WarsawPoland

11Department of Obstetrics and GynecologyMedical School University of ZagrebZagrebCroatia

12Fetomaternal Division, Women Health Center, Department of Obstetrics and GynecologyEkahospital BSD City, Tangerang, BantenSerpongIndonesia

I Nyoman Hariyasa Sanjaya¹, Wiku Andonotopo^2*, Muhammad Adrianes Bachnas³, Julian Dewantiningrum⁴, Mochammad Besari Adi Pramono⁵, Ryan Saktika Mulyana⁶, Evert Solomon Pangkahila⁷, Muhammad Ilham Aldika Akbar⁸, Cut Meurah Yeni⁹, Dudy Aldiansyah¹⁰, Nuswil Bernolian¹¹, Anak Agung Gede Putra Wiradnyana¹², Adhi Pribadi¹³, Sri Sulistyowati¹⁴, Milan Stanojevic¹⁵, and Asim Kurjak¹⁶

Authors:

^1,6,7,12 Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Udayana, Prof. dr. I.G.N.G Ngoerah General Hospital, Bali, Indonesia.

² Maternal-Fetal Medicine Division, Women Health Center, Department of Obstetrics and Gynecology, Ekahospital BSD City, Serpong, Tangerang, Banten, Indonesia.

^3,14 Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Medical Faculty of Sebelas Maret University, Dr. Moewardi Hospital, Solo, Surakarta, Indonesia.

^4,5 Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Medical Faculty of Diponegoro University, Dr. Kariadi Hospital, Semarang, Indonesia.

⁸ Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Airlangga, Dr. Soetomo General Hospital, Surabaya, Indonesia.

⁹ Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Syiah Kuala, Dr. Zainoel Abidin General Hospital, Aceh, Indonesia.

¹⁰ Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Sumatera Utara, H. Adam Malik General Hospital, Medan, Indonesia.

¹¹ Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine Universitas Sriwijaya, Dr. Mohammad Hoesin General Hospital, Palembang, Indonesia.

¹³ Maternal-Fetal Medicine Division, Department of Obstetrics and Gynecology, Faculty of Medicine, Universitas Padjajaran, Hasan Sadikin General Hospital, Bandung, Indonesia.

¹⁵ Medical University of Warsaw, Department of Neonatology and Rare Diseases, Poland.

¹⁶ Department of Obstetrics and Gynecology, Medical School University of Zagreb, Zagreb, Croatia

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.

Keywords:

Placenta

Microplastics

Nanoplastics

Preterm Birth

Eco-Exposome

Corresponding author:

Wiku Andonotopo MD, PhD, Fetomaternal Division, Women Health Center, Department of Obstetrics and Gynecology, Ekahospital BSD City, Serpong, Tangerang, Banten, Indonesia. https://orcid.org/0000-0001-9062-8501. Scopus Author ID: 6508217300

Email : wiku.andonotopo@gmail.com.

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.

Fig. 2

Conceptual Model Linking Micro- and Nanoplastic Exposure to Placental Molecular Disruption and Adverse Perinatal Outcomes. This 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.

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.
LIST OF FIGURES

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.

Fig. 1

PRISMA 2020 Flow Diagram of the Literature Screening and Selection Process. This 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.

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.

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.

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Yes