Table 1
Details of the population, exposure, comparator, outcome (PECO) framework.
| COMPONENT | DESCRIPTION |
|---|---|
| Population | General population exposed through environment or poisoning. Occupational exposure to plastic-associated chemicals is included, except if the occupational exposure occurs through plastic manufacturing or fossil fuel extraction. Exposure through medical, surgical, or dental devices such as prostheses or implants was also excluded. Subgroup analyses focusing on population differences (e.g. age, gender) were included. |
| Exposure | Plastic-associated chemical exposure, considering comparisons of high vs. low exposure, any vs. none, and any linear or non-linear dose responses. Composite exposure to groups of chemicals (e.g. total phthalates, total polychlorinated biphenyls [PCBs]) and subgroup analyses of individual chemicals (e.g. specific phthalate diesters, specific PCB congeners) were included. Exposure measurements are required to be from human bio-samples. Indirect exposure measures (e.g. questionnaires, dust) were excluded. |
| Comparator | Comparisons within the general population, such as high vs. low exposure and any vs. none, without occupational, medical device-related, or indirect exposure measures. |
| Outcome | Health outcomes reported using statistical measures (e.g. relative risks [RR], odds ratios [OR], or regression coefficients). Meta-analyses needed to present separate analyses for different health outcomes and meet the primary or secondary analysis criteria of the reviewed articles. |
Table 2
Characteristics of included reviews.
| REVIEW DETAILS (AUTHOR AND YEAR AND NUMBER OF META-ANALYSES/EE) | OUTCOMES REPORTED | POPULATION (DESCRIPTION) | PLASTIC-ASSOCIATED CHEMICAL(S) INVESTIGATED | SUBGROUPS BY STUDY CHARACTERISTICS | BIOSPECIMEN AND EXPOSURE TIMING | AMSTAR SCORE (/11) |
|---|---|---|---|---|---|---|
| Birth outcomes (Fig 2) | ||||||
| Hu et al., 2018a [46] EE = 4 | Birth weight | Infants | BPA | Pregnancy stages | Urine, blood, or amniotic fluid; prenatal | 8 |
| Golestanzadeh et al., 2019 [54] EE = 10 | Birth weight | Infants | MMP, MEP, MnBP, MiBP, MBzP, ΣDEHP, MEHP, MEHHP, MEOHP, MECPP | Urine; prenatal | 5 | |
| *Govarts et al., 2012 [50] EE = 1 | Birth weight | Infants | PCB 153 | Cord plasma or serum; maternal serum or breast milk; prenatal | 3 | |
| Zou et al., 2019 [53] EE = 6 | Birth weight | Infants | Total PCBs | Pregnancy stages, samples analysed | Cord blood; maternal serum; prenatal | 4 |
| Negri et al., 2017 [47] EE = 26 | Birth weight | Infants | PFOA, PFOS | Transformed data, pregnancy stages, samples analysed | Cord serum; maternal serum or plasma or breast milk; prenatal | 8 |
| Steenland et al., 2018 [51] EE = 5 | Birth weight | Infants | PFOA | Pregnancy stages, samples analysed | Maternal or cord blood; prenatal | 4 |
| Zhong et al., 2020 [52] EE = 4 | Birth length, birth weight, head circumference, gestational age | Infants | BPA | Urine; prenatal | 5 | |
| Zhao et al., 2017 [45] EE = 10 | Birth length, birth weight, head circumference | Infants; with subgroup of girls and boys | Total PBDEs, BDE 47, BDE 99, BDE 100, BDE 153 | Serum; prenatal | 9 | |
| Johnson et al., 2014 [44] EE = 4 | Birth length, birth weight, head circumference, ponderal index | Infants | PFOA | Cord blood; maternal serum; prenatal | 10 | |
| Nieminen et al., 2013 [49] EE = 1 | Sex ratio | Infants | Total PCBs | Maternal blood or breast milk; paternal blood; cord blood; prenatal | 3 | |
| Zhang et al., 2020 [48] EE = 10 | Spontaneous pregnancy loss | Adult reproductive women | MMP, MEP, MnBP, MiBP, MBzP, ΣDEHP, MEHP, MEHHP, MEOHP, MECPP | Urine | 7 | |
| Child Reproductive outcomes (Fig 3) | ||||||
| Bigambo et al., 2020 [55] EE = 1 | Onset of puberty/early puberty | Girls | BPA | Urine; prenatal and postnatal | 5 | |
| Wen et al., 2015 [57] EE = 2 | Precocious puberty | Girls from 0.5 to 11.3 years of age | DnBP, DEHP | Samples analysed | Urine or serum; postnatal | 7 |
| Golestanzadeh et al., 2020 [56] EE = 27 | Abnormal timing of breast development (thelarche), abnormal timing of pubic hair development (pubarche) in girls and boys, abnormal age of menarche, testicular volume in boys | Adolescent boys and girls from 7 to 19 years of age | MMP, MEP, MnBP, MEHP, MEHHP, MEOHP | Urine; prenatal and postnatal | 6 | |
| Dorman et al., 2019 [58] EE = 1 | Anogenital distance | Male infants | ΣDEHP | Urine; prenatal | 8 | |
| Nelson et al., 2020 [59] EE = 2 | Anoclitoral and anofourchette distance | Female infants | BPA | Urine, cord serum or plasma; prenatal | 7 | |
| Adult reproductive outcomes (Fig 4) | ||||||
| Wen et al., 2019 [64] EE = 1 | Endometriosis | Women | BPA | Urine | 7 | |
| Cai et al., 2019 [60] EE = 5 | Endometriosis | Women | MEP, MBzP, MEHP, MEHHP, MEOHP | Urine or plasma | 7 | |
| Cano-Sancho et al., 2019 [61] EE = 5 | Endometriosis | Women | Total PCBs | Samples analysed, type of endometriosis | Serum or adipose tissue | 8 |
| Roy et al., 2015 [62] EE = 1 | Endometriosis | Women | Total PCBs | Serum | 3 | |
| Cai et al., 2015 [63] EE = 93 | Low sperm concentration, Low sperm morphology | Subfertile men | MMP, MEP, MnBP, MBzP, ΣDEHP, MEHP, MEOHP, MEHP + MEOHP (combined); with different concentration levels | Urine | 6 | |
| Low sperm motility | Subfertile men | MMP, MEP, MnBP, MBzP, DnBP, ΣDEHP, DEHP, MEHP, MEOHP; with different concentration levels | DnBP and DEHP in seminal fluid; phthalate metabolites in urine | 6 | ||
| Sperm motion (straight-line velocity, curvilinear velocity, linearity), sperm DNA (comet extent, %DNA in tail, tail distributed moment) | Subfertile men | MMP, MEP, MnBP, MBzP, MEHP; with different concentration levels | Urine | 6 | ||
| Low semen volume | Subfertile men; with subgroup of men in their reproductive age | MnBP | Urine | 6 | ||
| Endocrine outcomes (Fig 5) | ||||||
| Kim et al., 2019a [70] EE = 36 | Thyroid function (free thyroxine [ft4], total thyroxine [TT4], thyrotropin [TSH]) | Adults and children; with subgroups of children, adults, pregnant women | MEHP, MEHHP, MEOHP | Urine | 5 | |
| Zhao et al., 2015 [72] EE = 2 | Thyroid function (total thyroxine [TT4], thyrotropin [TSH]) | Adults and children | Total PBDEs | Serum (ng/g lipid) | 9 | |
| Kim et al., 2018 [71] EE = 66 | Thyroid function (free thyroxine [ft4], total thyroxine [TT4], thyrotropin [TSH], triiodothyronine [T3]) | Adults; with subgroups of pregnant and non-pregnant adults | PFOA, PFOS, PFHxS; with different concentration levels | Blood | 7 | |
| Hwang et al., 2018 [65] EE = 3 | Type 2 diabetes | Adults | BPA | Samples analysed | Serum or urine | 6 |
| Rancière et al., 2015[66] EE = 1 | Type 2 diabetes | Adults | BPA | Urine | 7 | |
| *Wu et al., 2013 [68] EE = 5 | Type 2 diabetes | Adults; majority women; one included study with PCB poisoning | Total PCBs, PCB 118, PCB 138, PCB 153, PCB 180 | Serum | 4 | |
| Song et al., 2016 [67] EE = 18 | Type 2 diabetes, insulin resistance, fasting insulin, fasting glucose, 2-hour glucose, 2-hour insulin | Adults; with subgroups of men and women | BPA, total phthalates, MEP, MiBP, total PCBs | Serum (total PCBs) or urine | 6 | |
| Shoshtari-Yeganeh et al., 2019 [69] EE = 10 | Insulin resistance | Adults and children | MMP, MEP, MiBP, MBzP, ΣDEHP, MEHP, MEHHP, MEOHP, MECPP, MCPP | Serum or urine | 4 | |
| Children’s neurodevelopmental outcomes (Fig 6) | ||||||
| Lam et al., 2017 [74] EE = 1 | Intelligence Quotient (IQ) using the Full Scale Intelligence Quotient (FSIQ) or McCarthy Scale | Children from 4 to 7 years of age | BDE-47 | Cord blood or maternal serum (ng/g lipid); prenatal | 11 | |
| Lee et al., 2018 [75] EE = 4 | Cognitive development or Intelligence Quotient (IQ) using Wechsler Intelligence Scale for Children (WISC), Bayley Scales of Infant Development (BSID) and subscale of BSID, Mental Development Index (MDI) and Full-scale intelligence quotient (FSIQ); psychomotor development using Psychomotor Development Index (PDI) | Children from 6 months to 12 years of age | DEHP metabolites (mDEHP) | Urine or plasma; prenatal and postnatal | 7 | |
| Radke et al., 2020 [76] EE = 30 | Cognitive development or Intelligence Quotient (IQ) using Bayley Scales of Infant Development, Mental Development Index (MDI), Bayley III Cognitive Development Scale and fine motor using Bayley III Fine Motor Scale | Children ≤ 4 years of age | MEP, MnBP, MiBP, MBzP, ΣDEHP | Girls and boys | Urine or plasma; prenatal and postnatal | 8 |
| *Forns et al., 2020 [77] EE = 30 | Attention Deficit Hyperactivity Disorder (ADHD) using Attention Syndrome Scale of the Child Behavior Checklist (CBCL-ADHD), Hyperactivity/Inattention Problems subscale of the Strengths and Difficulties Questionnaire (SDQ-Hyperactivity/Inattention) and ADHD Criteria of Diagnostic and Statistical Manual of Mental Disorders, 4th ed. | Children 4 to 11 years of age | PFOA, PFOS | Girls and boys; estimated PFAS levels from birth to 24 months | Maternal serum/plasma or breast milk; prenatal except for breast milk | 3 |
| Nutritional outcomes (Fig 7) | ||||||
| Ribeiro et al., 2019 [81] EE = 17 | BMI, BMI z-score, obesity, waist circumference | Adults and children | MEP, MnBP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP, MCPP | Urine; postnatal | 6 | |
| Rancière et al., 2015 [66] EE = 7 | Obesity, overweight (or generalised overweight), elevated waist circumference | Adults and children; with subgroup of adults and children | BPA | Urine; postnatal | 7 | |
| Ribeiro et al., 2020 [80] EE = 7 | Obesity, overweight (or generalised overweight), elevated waist circumference | Adults and children; with subgroup of adults and children | BPA | Urine; postnatal | 7 | |
| Kim et al., 2019b [78] EE = 4 | Obesity | Children; with subgroups of obese vs. normal-weight children | BPA; with subgroup of high exposure | Urine; postnatal | 6 | |
| Wu et al., 2020a [79] EE = 3 | Abdominal obesity, generalised obesity, overweight (or generalised overweight) | Adults and children | BPA | Urine; postnatal | 5 | |
| Liu et al., 2018 [82] EE = 6 | Obesity or overweight, BMI | Children | PFOA | Exposure timing, girls and boys | Maternal serum or plasma; cord blood; prenatal and postnatal | 7 |
| Golestanzadeh et al., 2019 [54] EE = 22 | BMI, BMI z-score, waist circumference | Children | MMP, MEP, MnBP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP, MnOP, MCPP | Urine; postnatal | 5 | |
| Circulatory outcomes (Fig 8) | ||||||
| *Dunder et al., 2019 [84] EE = 30 | Serum lipids (low-density cholesterol [LDL-C], high-density cholesterol [HDL-C], total cholesterol [TC], triglycerides [TG] and apolipoprotein B [ApoB]) | Adults and children | BPA | Adults (men and women) and children (girls and boys) | Urine; postnatal | 4 |
| Golestanzadeh et al., 2019 [54] EE = 24 | Systolic blood pressure, diastolic blood pressure, high-density cholesterol (HDL), triglycerides (TG) | Children | MMP, MBzP, ΣDEHP, MEHP, MEHHP, MEOHP, MCPP | Urine; postnatal | 5 | |
| Park et al., 2016 [85] EE = 4 | Hypertension | Adults | PCB 118, 153, dioxin-like PCBs, non-dioxin-like PCB | Serum (lipid) or adipose tissue | 7 | |
| Rancière et al., 2015 [66] EE = 1 | Hypertension | Adults | BPA | Urine | 7 | |
| Fu et al., 2020 [87] EE = 13 | Cardiovascular disease | Adults and children | BPA, MEP, MnBP, MiBP, MBzP, MEHP, MEHHP, MEOHP, MECPP, Total PCBs, PCB 138, 153, 180 | Urine, serum, plasma or adipose tissue; children, postnatal | 6 | |
| *Li et al., 2015 [83] EE = 7 | Cardiovascular disease, cerebrovascular disease and hypertension deaths | Adults; with subgroups of men and women with cerebrovascular disease and hypertension deaths | Special PCB exposure (poisoning) | Blood | 4 | |
| Respiratory outcomes (Fig 9) | ||||||
| Wu et al., 2020b [90] EE = 80 | Asthma | Adults and children | MEP, MnBP, MiBP, MBzP, DEHP or ΣDEHP, MEHP, MEHHP, MEOHP, MECPP, MCOP, MCNP, MCPP | Exposure timing prenatal and postnatal, adult men and women | Urine | 5 |
| Luo et al., 2020 [89] EE = 28 | Asthma, allergic rhinitis, wheeze | Children | PFOA, PFOS, PFHxS, PFNA | Exposure timing, prenatal and postnatal | Infant’s/children’s cord blood or plasma or serum; maternal serum or plasma | 7 |
| Li et al., 2017 [88] EE = 8 | Asthma | Children | MnBP, MiBP, MBzP, DEHP or ΣDEHP, MCOP | Exposure timing, prenatal and postnatal | Urine | 9 |
| *Gascon et al., 2014 [91] EE = 14 | Bronchitis, wheeze and bronchitis and/or wheeze | Infants/children | PCB 153 | Infants < 18 months and 18 to 49 months of age, prenatal and postnatal | Maternal blood or serum or breast milk; infant’s/children’s cord, plasma or serum; prenatal | 3 |
| Skin disorder outcomes (Fig 10) | ||||||
| Luo et al., 2020 [89] EE = 8 | Atopic dermatitis and eczema, with subgroups of skin disorder | Children | PFOA, PFOS, PFHxS, PFNA | Infant’s/children’s cord blood or plasma or serum; maternal serum or plasma; | 7 | |
| Cancer and cancer related mortality (Fig 11) | ||||||
| Roy et al., 2015 [62] EE = 1 | Breast cancer | Women | Total PCBs | Serum, plasma or adipose tissue | 3 | |
| Zhang et al., 2015 [93] EE = 1 | Breast cancer | Women | Total PCBs | Serum and adipose sample only | Serum, plasma or adipose tissue | 8 |
| Leng et al., 2016 [94] EE = 17 | Breast cancer | Women | PCB 187, 118, 138, 156, 170, 99, 153, 180, 183. Including analyses of two studies for only PCB 28, 52, 74, 77, 101, 105, 126, 167 | Serum, plasma or adipose tissue | 8 | |
| Zani et al., 2013 [92] EE = 6 | Breast cancer | Women | Total PCBs | Serum, plasma or adipose tissue | 2 | |
| Non-Hodgkin’s lymphoma | Adults and children | Total PCBs, PCB 118, PCB 138, PCB 153, PCB 180 | Blood, serum or adipose tissue | 2 | ||
| Catalani et al., 2019 [96] EE = 8 | Non-Hodgkin’s lymphoma (NHL), subtypes of NHL (chronic lymphocytic leukaemia, diffuse large B-cell lymphoma, follicular lymphoma | Adults and children | Total PCBs, PCB 118, PCB 138, PCB 153, PCB 180, PCB 170, | Blood, serum or adipose tissue | 7 | |
| Zani et al., 2017 [95] EE =3 | Non-Hodgkin’s lymphoma | Adults and children | Total PCBs | Blood, serum or adipose tissue | 5 | |
| Non-Hodgkin’s lymphoma mortality, melanoma mortality | Adults | Special PCB exposure (occupational) | Blood, serum or adipose tissue | 5 | ||
| *Li et al., 2015 [15] EE = 12 | All-cancer mortality and cancer-specific mortality (breast cancer, leukaemia, liver cancer, lung cancer, pancreatic cancer, rectal cancer, stomach cancer, uterine cancer) | Adults; with subgroups of men and women in some cancer types | Special PCB exposure (poisoning) | Blood | 4 | |
| Other outcomes (Fig 12) | ||||||
| *Li et al., 2015 [83] EE = 6 | Hepatic disease mortality, all-cause mortality | Adults; with subgroups of men and women | Special PCB exposure (poisoning) | Blood | 4 | |
| Case control studies (Supplementary Fig S1) | ||||||
| Wen et al., 2015 [57] EE = 7 | Precocious puberty | Girls from 0.5 to 11.3 years of age | MEP, DnBP, MnBP, MBzP, DEHP, MEHP | Samples analysed | Urine or serum; postnatal | 7 |
| Hu et al., 2018b [73] EE = 3 | Polycystic ovarian syndrome (PCOS) | Women; with subgroups with different age, method of measurement | BPA | Serum samples, age | Serum | 9 |
[i] Legend:
[ii] *pooled analysis.
[iii] EE: number of effect estimates (from main and subgroup analyses) included from the systematic review or pooled analysis.
[iv] Superscript number indicates the reference number in the harvest plot figures.
[v] Total phthalates: composite measure of phthalate metabolite exposure which is the total concentration of all phthalate metabolites measured.
[vi] ΣDEHP: sum of the DEHP metabolites (MEHP, MEHHP, MEOHP, MECPP, MCMHP).
[vii] Total PCBs: composite measure of PCB exposure which is the total concentration of all PCB congeners measured Total PBDEs: composite measure of PBDE exposure which is the total concentration of all PBDE congeners measured.
[viii] Bisphenol A (BPA), Di-n-butyl phthalate (DnBP), Di(2-ethylhexyl) phthalate (DEHP), Monomethyl phthalate (MMP), Monoethyl phthalate (MEP), Mono-n-butyl phthalate (MnBP), Monoisobutyl phthalate (MiBP), Monobenzyl phthalate (MBzP), Mono(2-ethylhexyl) phthalate (MEHP), Mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), Mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), Mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), Mono(2-carboxymethyl-5-hexyl) phthalate (MCMHP), Mono-n-octyl phthalate (MnOP), Mono(carboxyoctyl) phthalate (MCOP), Mono(carboxynonyl) phthalate (MCNP), Mono(3-carboxypropyl) phthalate (MCPP), Polychlorinated biphenyls (PCBs), Polybrominated diphenyl ethers (PBDEs) Perfluorooctanoic acid (PFOA), Perfluorooctanesulfonic acid (PFOS), Perfluorohexane sulfonate (PFHxS).
Figure 1
PRISMA flow diagram [35] presenting process of study identification, selection and final inclusion in the review project and the outcomes reported in this manuscript.
Figure 2
Harvest plot of exposure to plastic-associated chemicals and birth outcomes.
Plastic-associated chemicals included are bisphenol A (BPA) (pink); phthalate monoester metabolites (blue), encompassing monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and molar sum of the di(2-ethylhexyl) phthalate metabolites (∑DEHP); flame retardants (green) encompassing polychlorinated biphenyl (PCB), polybrominated diphenyl ethers (PBDEs), 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47), 2,2’,4,4’,5-pentabromodiphenyl ether (BDE-99), 2,2’,4,4’,6-pentabromodiphenyl ether (BDE-100), 2,2’,4,4’,5,5’-hexabromodiphenyl ether (BDE-153); and per- and polyfluoroalkyl substances (PFAS) (orange), encompassing perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS).
Outcomes are either dichotomous (†) or measured on a continuous scale (‡). Outcome measures include ‡birth weight, ‡birth length, ‡head circumference, ‡ponderal index, ‡gestational age, †secondary sex ratio and †spontaneous pregnancy loss.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4, moderate quality a score of 5–8 and high quality a score of 9–11. Dark filled bars represent the main analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no clear trend (–) (the estimate of relative risk was 1 or regression coefficient or mean difference was 0), or decrease (<) in the measure or risk estimate.
Figure 3
Harvest plot of exposure to plastic-associated chemicals and child reproductive outcome measures.
Plastic-associated chemicals included are bisphenol A (BPA) (pink); and phthalate diesters diethylhexyl phthalate (DEHP) and di-n-butyl phthalate (DnBP) and monoester metabolites (blue), including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and mono (3-carboxypropyl) phthalate (MCPP).
Outcomes are either dichotomous (†) or measured on a continuous scale (‡). Outcomes measured include †precocious puberty, ‡anogenital distance measured by anoclitoral and anofourchette distance in girls and anoscrotal and anopenile distance in boys, †abnormal timing/age of puberty/early puberty measured by pubarche, menarche, thelarche and testicular volume.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Moderate quality reflects a score of 5–8. Dark filled bars represent the main analyses of each review. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), or decrease (<) in the measure or risk estimate.
Figure 4
Harvest plot of exposure to plastic-associated chemicals and adult reproductive outcome measures.
Plastic-associated chemicals included are bisphenol A (BPA) (pink); phthalate monoester metabolites (blue), including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), molar sum of the di(2-ethylhexyl) phthalate metabolites (∑DEHP), and mono (3-carboxypropyl) phthalate (MCPP); and flame retardants (green) encompassing polychlorinated biphenyl (PCB).
Outcomes are either dichotomous (†) or measured on a continuous scale (‡). Outcomes measured include †endometriosis, †sperm concentration, ‡†sperm motility, †sperm morphology, †sperm volume, ‡sperm motion measured via straight line velocity, curvilinear velocity, linearity, and ‡sperm DNA damage measured via comet assay (comet extent), comet assay (percentage [%] DNA in tail) and comet assay (tail distributed moment).
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4 and moderate quality a score of 5–8. Dark filled bars represent the main analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no clear trend (–) (the estimate of relative risk was 1 or regression coefficient or mean difference was 0), or decrease (<) in the measure or risk estimate.
Figure 5
Harvest plot of exposure to plastic-associated chemicals and endocrine outcome measures.
Plastic-associated chemicals included are bisphenol A (BPA) (pink); phthalate monoester metabolites (blue), encompassing monomethyl phthalate (MMP), monoethyl phthalate (MEP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(3-carboxypropyl) phthalate (MCPP) and molar sum of the di(2-ethylhexyl) phthalate metabolites (∑DEHP); flame retardants (green) encompassing polychlorinated biphenyl (PCB), 2,3’,4,4’,5-pentachlorobiphenyl (PCB 118) group (gp) II, 2,2’,3,4,4’,5’-hexachlorobiphenyl (PCB 138) (gp II), 2,2’,4,4’,5,5’-hexachlorobiphenyl (PCB 153) (gp III), 2,2’,3,4,4’,5,5’-heptachlorobiphenyl PCB 180) (gp III), polybrominated diphenyl ethers (PBDEs); and per- and polyfluoroalkyl substances (PFAS) (orange), encompassing perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), and perfluorooctane sulfonate (PFOS).
Outcomes are either dichotomous (†) or measured on a continuous scale (‡). Outcomes measured include thyroid function measured by levels of ‡free thyroxine (fT4), ‡thyroxine (TT4), ‡thyroid-stimulating hormone (TSH), and ‡triiodothyronine (T3), †type 2 diabetes (T2D), ‡insulin resistance (HOMA-IR), ‡fasting insulin, ‡2-hour (hr) insulin, ‡fasting glucose and ‡2-hour glucose.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4, moderate quality a score of 5–8 and high quality a score of 9–11. Dark filled bars represent the main analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no clear trend (–) (the estimate of relative risk was 1 or regression coefficient or mean difference was 0), or decrease (<) in the measure or risk estimate.
Figure 6
Harvest plot of exposure to plastic-associated chemicals and children’s neurodevelopmental outcome measures.
Plastic-associated chemicals included are phthalates (blue) where exposure was determined based on monoester metabolites monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), molar sum of all di(2-ethylhexyl) phthalate metabolites measured (∑DEHP), and best single measure of metabolite(s) of di(2-ethylhexyl) phthalate (DEHP m.); flame retardants (green) including polybrominated diphenyl ethers (PBDEs) where exposure was determined based on a prevalent congener 2,2’,4,4’-tetrabromodiphenyl ether (BDE-47); and per- and polyfluoroalkyl substances (PFAS) (orange) including perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS).
Outcome measures are either dichotomous (†) or measured on a continuous scale (‡). Outcomes include ‡Cognitive Development and Intelligence Quotient (IQ) (measured on the Mental Development Index (MDI) of the Bayley Scales of Infant Development, 2nd ed. (BSID-II), Cognitive Development subscale of the Bayley Scales of Infant and Toddler Development, 3rd ed. (Bayley-III), General Cognitive Scale (GCS) of the McCarthy Scales of Children’s Abilities (MSCA), and Full Scale IQ (FSIQ) of the Wechsler Preschool & Primary Scale of Intelligence (WPPSI) or Wechsler Intelligence Scale for Children (WISC)); ‡Fine Motor/Psychomotor Development (measured on the Psychomotor Development Index (PDI) of BSID-II, and Fine Motor subscale of Bayley-III) and †Attention Deficit Hyperactive Disorder (ADHD) (measured with the Attention Problems Syndrome Scale of the Child Behaviour Checklist (CBCL), the Hyperactivity/Inattention subscale of the Strengths and Difficulties Questionnaire (SDQ) and the ADHD Diagnostic and Statistical Manual of Mental Disorder 4th ed (DSM-IV)).
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4, moderate (mod) quality a score of 5–8 and high quality a score of 9–11. Dark filled bars represent the primary analyses of each review; unfilled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no clear trend (–) (the estimate of relative risk was 1 or regression coefficient or mean difference was 0), or decrease (<) in the measure or risk estimate.
Figure 7
Harvest plot of exposure to plastic-associated chemicals and nutritional outcome measures.
Plastic-associated chemicals included are bisphenol A (BPA) (pink) and phthalate monoester metabolites (blue), including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono-n-octyl phthalate (MnOP) and mono (3-carboxypropyl) phthalate (MCPP).
Outcome measures are either dichotomous (†) or measured on a continuous scale (‡). Outcomes measured include †obesity including abdominal obesity and generalized obesity, †overweight including generalized overweight, ‡Body Mass Index (BMI) and ‡BMI z score, †elevated waist circumference and ‡waist circumference.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Moderate quality reflects a score of 5–8. Dark filled bars represent the primary analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no change (–) (the estimate of relative risk was 1 or regression coefficient or mean difference was 0), or decrease (<) in the measure or risk estimate.
Figure 8
Harvest plot of exposure to plastic-associated chemicals and circulatory outcome measures.
The plastic-associated chemicals included are bisphenol A (BPA) (pink); phthalate monoester metabolites (blue), including monomethyl phthalate (MMP), monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(3-carboxypropyl) phthalate (MCPP); mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), and the molar sum of the di(2-ethylhexyl) phthalate metabolites (∑DEHP); and flame retardants (green) including polychlorinated biphenyl (PCB).
Outcome measures are either dichotomous (†) or measured on a continuous scale (‡). Outcomes measured include serum lipids encompassing concentrations in low-density lipoprotein (LDL), high-density lipoprotein (HDL), total cholesterol (TC), triglycerides (TG) and apolipoprotein B (ApoB); child systolic blood pressure (SBP); child diastolic blood pressure (DBP); cardiovascular disease (CVD; for BPA and phthalates children also included with sampling frame [17]); CVD mortality; cerebrovascular disease mortality; hypertension and hypertension mortality.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4 and moderate (mod) quality a score of 5–8. Dark filled bars represent the primary analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no change (–) (the estimate of relative risk was 1 or regression coefficient or mean difference was 0), or decrease (<) in the measure or risk estimate.
Figure 9
Harvest plot of exposure to plastic-associated chemicals and respiratory outcomes.
Plastic-associated chemicals included are phthalate monoester metabolites (blue), encompassing monoethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), monoisobutyl phthalate (MiBP), monobenzyl phthalate (MBzP), mono(2-ethylhexyl) phthalate (MEHP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), mono(2-ethyl-5-oxohexyl) phthalate (MEOHP), mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), molar sum of the di(2-ethylhexyl) phthalate metabolites (∑DEHP), mono(carboxyisooctyl) phthalate (MCOP), monocarboxyisononyl phthalate (MCNP), and mono (3-carboxypropyl) phthalate (MCPP); flame retardants (green) including polychlorinated biphenyl (PCB); and per- and polyfluoroalkyl substances (PFAS) (orange) including perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA).
Outcomes are dichotomous (†) and include risk of asthma, bronchitis, wheeze and allergic rhinitis.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4, moderate (mod) quality a score of 5–8 and high quality a score of 9–11. Dark filled bars represent the primary analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no change (–) (the relative estimate was 1), or decrease (<) in the estimate.
Figure 10
Harvest plot of prenatal exposure to plastic-associated chemicals and skin-related outcomes in children.
Plastic-associated chemicals included are per- and polyfluoroalkyl substances (PFAS) (orange), encompassing perfluorohexane sulfonate (PFHxS), perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS) and perfluorononanoic acid (PFNA).
Outcomes are dichotomous(†) and include atopic dermatitis and eczema.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Moderate (mod) quality reflects a score of 5–8. Dark filled bars represent the primary analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>) or decrease (<) in the measure or risk estimate.
Figure 11
Harvest plot of exposure to plastic-associated chemicals and cancer outcomes.
Plastic-associated chemicals included are flame retardants (green), including polychlorinated biphenyl (PCB) further organised by group – gp I (44, 52, 101, 107, 187, 201), gp II (105, 118, 138, 156, 167, 170) and gp III (99, 153, 180, 183, 203) as well as PCB 28.
Outcomes are dichotomous (†) and include breast cancer, non-Hodgkin’s lymphoma (NHL), NHL subtypes—chronic lymphocytic leukemia (CLL), diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL)—and cancer-specific mortality: all cancer, breast cancer, leukaemia, liver cancer, lung cancer, melanoma, NHL, pancreatic cancer, rectal cancer, stomach cancer and uterine cancer. PCB poisoning refers to populations exposed to PCB-contaminated food and PCB occupational refers to populations occupationally exposed to PCBs.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4 and moderate (mod) quality a score of 5–8. Dark filled bars represent the primary analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>) or decrease (<) in the measure or risk estimate.
Figure 12
Harvest plot of exposure to plastic-associated chemicals and other outcomes.
Plastic-associated chemicals included are flame retardants (green), including polychlorinated biphenyls (PCB) in populations exposed to contaminated food.
All outcomes are dichotomous (†). Outcomes measured include mortality attributable to hepatic disease and all-cause mortality.
Each bar represents an individual effect estimate from the corresponding review, which is indicated by the number below each bar. The height of the bar represents the quality score of the review assessed using the AMSTAR tool. Low quality reflects a score of 1–4 and moderate quality a score of 5–8. Dark filled bars represent the primary analyses of each review; light filled bars represent sub-group analyses. Bars have been assigned as an increase or decrease (columns) in the measure where the change is statistically significant. Remaining bars appearing under ‘no change’ indicate direction of effect as an increase (>), no change (–) (the relative estimate was 1), or decrease (<) in the measure or risk estimate.