Relationship between flame retardants and respiratory health- A systematic review and meta-analysis of observational studies.

Chronic respiratory diseases are a dealing cause of death and disability worldwide. Their prevalence is steadily increasing and the exposure to environmental contaminants, including Flame Retardants (FRs), is being considered as a possible risk factor. Despite the widespread and continuous exposure to FRs, the role of these contaminants in chronic respiratory diseases is yet not clear. This study aims to systematically review the association between the exposure to FRs and chronic respiratory diseases. Searches were performed using the Cochrane Library, MEDLINE, EMBASE, PUBMED, SCOPUS, ISI Web of Science (Science and Social Science Index), WHO Global Health Library and CINAHL EBSCO. Among the initial 353 articles found, only 9 fulfilled the inclusion criteria and were included. No statistically significant increase in the risk for chronic respiratory diseases with exposure to FRs was found and therefore there is not enough evidence to support that FRs pose a significantly higher risk for the development or worsening of respiratory diseases. However, a non-significant trend for potential hazard was found for asthma and rhinitis/rhinoconjunctivitis, particularly considering urinary organophosphate esters (OPEs) including TNBP, TPHP, TCEP and TCIPP congeners/compounds. Most studies showed a predominance of moderate risk of bias, therefore the global strength of the evidence is low. The limitations of the studies here reviewed, and the potential hazardous effects herein identified highlights the need for good quality large-scale cohort studies in which biomarkers of exposure should be quantified in biological samples.

Urinary concentrations and elimination half-lives of parabens, benzophenones, bisphenol and triclosan in Japanese young adults.

Environmental phenols are widely distributed in the environment and human samples, suggesting potential exposure to these chemicals. We designed an intervention trial with 30 participants over 6 days to assess the urinary concentrations and half-lives of environmental phenols in Japanese young people. The target environmental phenols include three parabens (methyl paraben, ethyl paraben, and propyl paraben), two benzophenones (benzophenone 1 and 3), two bisphenols (bisphenol F and bisphenol S), and triclosan. Throughout the intervention, the participants consumed the same food and drinks and used personal care products provided by the project. The target phenols were measured in urine from the participants using a liquid chromatography-tandem mass spectrometer. We compared the measured concentrations between the study periods to better understand the exposure tendency. Some statistically significant differences were observed. All target analytes were detected in more than 50% of samples collected on Day 0 (the day before the intervention). Methyl paraben was the dominant phenol detected in urine (1640 µg/g-creatinine), followed by ethyl paraben (119 µg/g-creatinine). Downward trends in creatinine-corrected concentrations were observed for all target analytes in some instances. Non-compartment analysis was performed to estimate urinary excretion parameters. The estimated half-lives ranged from 7.69 to 20.3 h. Use of paraben-free products during the intervention period reduced the body burden.

Urinary concentrations of environmental phenol among pregnant women in the Japan Environment and Children's Study.

Humans are exposed to various bisphenols, alkylphenols and nitrophenols through dietary intake, food packaging and container materials, indoor and outdoor air/dust. This study aimed to evaluate exposure of Japanese pregnant women to environmental phenols by measuring target compounds in urine samples. From a cohort of the Japan Environment and Children's Study, 4577 pregnant women were selected. Bisphenol A (BPA), bisphenol S (BPS), bisphenol F (BPF), bisphenol AF (BPAF), para-nitrophenol (PNP), 3-methyl-4-nitrophenol (PNMC), branched 4-nonylphenol (4-NP), linear 4-nonylphenol and 4-tert-octylphenol (4-t-OP) were analysed using a high-performance liquid chromatograph coupled to a triple-quadrupole mass spectrometer. The urinary metabolite data were combined with a questionnaire to examine the determinants of phenol exposure by machine learning. The estimated daily intake (EDI) and hazard quotient (HQ) of BPA were calculated. PNP (68.2%) and BPA (71.5%) had the highest detection frequencies, with median concentrations of 0.76 and 0.46 µg/g creatinine, respectively. PNMC, BPS, BPF and 4-NP were determined in 24.9%, 11.9%, 1.3% and 0.4% of samples, respectively, whereas BPAF (0.02%) and 4-t-OP (0.02%) were only determined in a few samples. The PNP concentrations measured in this study were comparable with those reported in previous studies, whereas the BPA concentrations were lower than those reported previously worldwide. The EDI of BPA was 0.014 µg/kg body weight/day. Compared with the tolerable daily intake set by the German Federal Institute for Risk Assessment, the median (95th percentile) HQ was 0.044 (0.2). This indicates that the observed levels of BPA exposure pose a negligible health risk to Japanese pregnant women. Determinants of bisphenol and nitrophenol exposure could not be identified by analysing the questionnaire solely, suggesting that biological measurement is necessary to assess exposure of pregnant women to bisphenols and nitrophenols. This is the first study to report environmental phenol exposure of Japanese pregnant women on a nationwide scale.

Evaluating the risk of phthalate and non-phthalate plasticizers in dust samples from 100 Japanese houses.

Phthalates are widely used as plasticizer and associated with various health issues. Recently, non-phthalate plasticizers are replacing phthalates; however, the exposure to these substances and the risk in Japan is unclear. In this study, we assessed the concentrations of phthalates, non-phthalate plasticizers, and phthalate degradation products in house dust and determined their respective exposure risks via oral and dermal routes. Twelve phthalates, seven non-phthalate plasticizers, and two degradation products were determined in the house dust obtained from 100 Japanese homes. The median concentration of di(2-ethylhexyl) phthalate (DEHP), accounting for 85 % of the total concentration of phthalates and non-phthalate plasticizers detected in this study, was 2.1 × 103 µg/g of dust. Apart from DEHP, diisononyl phthalate (DINP) and di(2-ethylhexyl) terephthalate (DEHT) were the most abundant in the house dust, accounting for 6.2 % (median: 1.7 × 102 µg/g of dust) and 6.1 % (median: 1.7 × 102 µg/g of dust) of the total concentrations, respectively. DEHP and DEHT concentrations in house dust were higher in apartment and small houses (floor area: ≤30 m2 or 31-60 m2 for DEHP and 31-60 m2 for DEHT) than in detached and large houses (floor area: ≥121 m2). Conversely, di-n-butyl phthalate (DnBP) concentrations were significantly higher in detached and large houses (floor area: ≥121 m2) than in apartment and small houses (floor area: ≤30 m2). The total hazard quotient (HQ), using the maximum concentration in house dust, revealed that oral and dermal exposure to house dust was 1.3 × 10-6-0.11 for adults (all substances) and 1.6 × 10-5-2.2 × 10-2 for preschool children (except for DnBP and DEHP), suggesting no risk. The HQs for DnBP and DEHP exposure via house dust for preschool children using the maximum values were 0.46 and 1.2, and 6.0 × 10-3 and 0.18 using the median values, indicating that risk of DEHP exposure should be exhaustively determined by considering other exposure routes that were not evaluated in this study, such as diet.

Association between maternal urinary neonicotinoid concentrations and child development in the Japan Environment and Children's Study.

BACKGROUND: Recent studies have reported the effect of neonicotinoid (NEO) exposures on development in human. However, information about the risk of childhood development delays due to NEO exposures is limited. OBJECTIVES: The study aimed to examine the association between NEO exposure and child development up to 4 years of age using data of the Japan Environment and Children's Study. METHODS: The study employed urinary NEO and metabolite concentrations in the first and second or third trimesters; the Japanese translation of the Ages and Stages Questionnaire (third edition; J-ASQ-3) scores on developmental delay in five domains, namely communication, gross motor skills, fine motor skills, problem solving, and personal-social characteristics from 6 months to 4 years of age; and self-reported questionnaire data. The associations between urinary NEO concentrations and J-ASQ-3 results were analysed using the treed distributed lag mixture model. A total of 8538 participants were included in statistical analyses. RESULTS: The determination rates of urinary acetamiprid-N-desmethyl (dm-ACE), clothianidin (CLO), dinotefuran (DIN) and thiamethoxam (THX) were greater than 50%. Median urinary dm-ACE, CLO, DIN and THX concentrations were 0.34, 0.14, 0.22 and 0.05 ng/ml, respectively, in samples collected during gestational weeks < 23, and 0.28, 0.12, 0.18 and 0.04 ng/ml, respectively, in those collected during gestational weeks ≥ 23. The binomial scores divided by the cut-off values of the J-ASQ were used in the treed distributed lag mixture model. The highest percentage for a domain with a value less than the cut-off value was 'problem solving' at 6 months of age among all the J-ASQ-3 scores (10.5%). There was no statistically significant association between maternal urinary dm-ACE, CLO, DIN and THX concentrations during pregnancy and the J-ASQ-3 results up to 4 years of age. Objective assessment of child development in different populations may be warranted to confirm our findings.

Corrigendum to ``A simultaneous, high-throughput and sensitive method for analysing 13 neonicotinoids and metabolites in urine using a liquid chromatography-tandem mass spectrometry'' [MethodsX 10 (2023) 102129].

[This corrects the article DOI: 10.1016/j.mex.2023.102129.].

A simultaneous, high-throughput and sensitive method for analysing 13 neonicotinoids and metabolites in urine using a liquid chromatography-tandem mass spectrometry.

A simultaneous, high-throughput and sensitive method for analysing nine neonicotinoid pesticides (NEOs) and four metabolites (NEOms) in urine using a liquid chromatography-tandem mass spectrometry (LC-MSMS) was developed. The method detection limit (MDL) and lowest concentration minimum reporting limit (LCMRL) of the nine NEOs were 0.0013-0.048 ng/ml and 0.0050-0.17 ng/ml, respectively. The MDL and LCMRL of the four NEOms were 0.0052-0.52 ng/ml and 0.011-1.6 ng/ml, respectively. Intermediate precision for the nine NEOs and four NEOms was 7.5-12.5% and 7.4-10.9%, respectively. Accuracy for the nine NEOs and four NEOms was 3.83-5.60% and 3.01-29.2%, respectively. The developed method was applied to analyse urine samples collected from participants of a large-scale birth cohort study, namely, the Japan Environment and Children's Study (JECS). •The NEO and NEOm concentrations in 100 µl urine samples were analysed using a highly sensitive LC-MSMS.•Automated solid phase extraction in a 96-well plate was utilised to achieve high-throughput analysis.•Intermediate precision and accuracy were less than 12.5% and 94.8-99.1%, respectively.

Pharmaceuticals and personal care products (PPCPs) in surface water and fish from three Asian countries: Species-specific bioaccumulation and potential ecological risks.

In Asian developing countries, undeveloped and ineffective sewer systems are causing surface water pollution by a lot of contaminants, especially pharmaceuticals and personal care products (PPCPs). Therefore, the risks for freshwater fauna need to be assessed. The present study aimed at: i) elucidating the contamination status; ii) evaluating the bioaccumulation; and iii) assessing the potential risks of PPCP residues in surface water and freshwater fish from three Asian countries. We measured 43 PPCPs in the plasma of several fish species as well as ambient water samples collected from India (Chennai and Bengaluru), Indonesia (Jakarta and Tangerang), and Vietnam (Hanoi and Hoa Binh). In addition, the validity of the existing fish blood-water partitioning model based solely on the lipophilicity of chemicals is assessed for ionizable and readily metabolizable PPCPs. When comparing bioaccumulation factors calculated from the PPCP concentrations measured in the fish and water (BAFmeasured) with bioconcentration factors predicted from their pH-dependent octanol-water partition coefficient (BCFpredicted), close values (within an order of magnitude) were observed for 58-91 % of the detected compounds. Nevertheless, up to 110 times higher plasma BAFmeasured than the BCFpredicted were found for the antihistamine chlorpheniramine in tilapia but not in other fish species. The plasma BAFmeasured values of the compound were significantly different in the three fish species (tilapia > carp > catfish), possibly due to species-specific differences in toxicokinetics (e.g., plasma protein binding and hepatic metabolism). Results of potential risk evaluation based on the PPCP concentrations measured in the fish plasma suggested that chlorpheniramine, triclosan, haloperidol, triclocarban, diclofenac, and diphenhydramine can pose potential adverse effects on wild fish. Results of potential risk evaluation based on the PPCP concentrations measured in the surface water indicated high ecological risks of carbamazepine, sulfamethoxazole, erythromycin, and triclosan on Asian freshwater ecosystems.

Health Risk Assessment Based on Exposure to Chemicals in Air.

Few studies have investigated personal exposure concentrations of not only some volatile organic compounds but also more types of chemicals including acidic gases and acrolein. We measured the personal exposure concentrations of 35 chemicals including these chemicals in indoor and outdoor air in Chiba-shi, Japan, for 7 days in summer and winter to assess the associated health risks in 22 people. The personal exposure concentrations of nitrogen dioxide were higher in winter than in summer, and those of formaldehyde, p-dichlorobenzene, and tetradecane were higher in summer than in winter. The personal exposure concentrations were mostly equal to or lower than the concentrations in indoor air, contrary to the results of a lot of previous studies. The high-risk chemicals based on personal exposure concentrations were identified as acrolein (max. 0.43 µg/m3), benzene (max. 3.1 µg/m3), and hexane (max. 220 µg/m3) in summer, and acrolein (max. 0.31 µg/m3), nitrogen dioxide (max. 320 µg/m3), benzene (max. 5.2 µg/m3), formic acid (max. 70 µg/m3), and hexane (max. 290 µg/m3) in winter. In addition, we estimated personal exposure concentrations according to the time spent at home and the chemical concentrations in indoor and outdoor air. We found that the estimated concentrations of some participants largely differed from the measured ones indicating that it is difficult to estimate personal exposure concentrations based on only these data.

Maternal Metals Exposure and Infant Weight Trajectory: The Japan Environment and Children's Study (JECS).

BACKGROUND: To our knowledge, the association of maternal exposure to metallic elements with weight trajectory pattern from the neonatal period has not been investigated. OBJECTIVES: The goals of this study were to identify infant growth trajectories in weight in the first 3 y of life and to determine the associations of maternal blood levels of lead, cadmium, mercury, selenium, and manganese with growth trajectory. METHODS: This longitudinal study, part of the Japan Environment and Children Study, enrolled 103,099 pregnant women at 15 Regional Centres across Japan between 2011 and 2014. Lead, cadmium, mercury, selenium, and manganese levels were measured in blood samples collected in the second (14-27 wk gestational age) or third trimester (≥28wk). Growth trajectory of 99,014 children was followed until age 3 y. Raw weight values were transformed to age- and sex-specific weight standard deviation (SD) scores, and latent-class group-based trajectory models were estimated to determine weight trajectories. Associations between maternal metallic element levels and weight trajectory were examined using multinomial logistic regression models after confounder adjustment. RESULTS: We identified 5 trajectory patterns based on weight SD score: 4.74% of infants were classified in Group I, very small to small; 31.26% in Group II, moderately small; 21.91% in Group III, moderately small to moderately large; 28.06% in Group IV, moderately large to normal; and 14.03% in Group V, moderately large to large. On multinomial logistic regression, higher maternal lead and selenium levels tended to be associated with increased odds ratios (ORs) of poor weight SD score trajectories (Groups I and II), in comparison with Group III. Higher levels of mercury were associated with decreased ORs, whereas higher levels of manganese were associated with increased ORs of "moderately large" trajectories (Groups IV and V). DISCUSSION: Maternal lead, mercury, selenium, and manganese blood levels affect infant growth trajectory pattern in the first 3 y of life. https://doi.org/10.1289/EHP10321.

Optimal method for determining the intraclass correlation coefficients of urinary biomarkers such as dialkylphosphates from imputed data.

Urinary biomarkers are commonly used in epidemiological studies as surrogates or indicators of exposure to chemical substances. Evaluating the reliability of a biomarker is highly important because use of an unreliable marker may lead to misclassification and attenuation bias, resulting in flawed interpretations and conclusions. Although intraclass correlation coefficient (ICC) is regarded as a typical index of test reliability, methods for determining the ICCs of urinary biomarkers have not been standardised, and different methods have been used. This study evaluated different imputation methods for left-censored data, i.e., four imputation or one substitution methods, before calculating ICCs, and at the same time mathematically assessed the impact of the left-censoring proportion on the estimated ICCs. Biomarkers of exposure to organophosphate pesticides, i.e., dialkylphosphates, were used as an example. The Gibbs sampler-based left-censored missing value imputation approach had the best performance for imputation of values below reporting limits, with lower values on Kolmogorov-Smirnov test statistics than other imputation/substitution methods, i.e., a univariate distribution fitting approach, multiple imputation by chained equation, a bootstrap expectation-maximisation algorithm approach, and a single value substitution. In all imputation methods, however, ICCs decreased as censoring rates increased. We propose a method to estimate true ICCs based on mathematical estimation.

Baseline Complete Blood Count and Chemistry Panel Profile from the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study of environmental factors affecting children's health and development. We summarize the complete blood count and chemistry panel statistical data from pregnant women enrolled in JECS. METHODS: Statistical data of up to 58,056 mother's sample in their first (gestational age ≤ 13 weeks) and second trimester (22-27 weeks) were calculated. RESULTS: Mean (SD) values in the first trimester were: white blood cell count, 7866 (1906)/µL; red blood cell count, 417 (33) 104/µL; hemoglobin, 12.4 (1.0) g/dL; hematocrit, 37.1 (2.6)%; mean corpuscular volume, 89.2 (4.7) fL; mean corpuscular hemoglobin, 29.8 (1.9) pg; mean corpuscular hemoglobin concentration, 33.3 (0.9)%; platelet count, 24.8 (5.2) 104/µL; HbA1c, 5.26 (0.26)%; total cholesterol, 181 (28) mg/dL; low density lipoprotein cholesterol, 95 (23) mg/dL; high density lipoprotein cholesterol, 73 (13) mg/dL; free cholesterol, 41 (7) mg/dL; triglycerides, 109 (47) mg/dL; total protein, 6.9 (0.4) g/dL; and albumin, 4.1 (0.2) g/dL. Mean values (SD) in the second trimester were: total cholesterol, 246 (38) mg/dL; free cholesterol, 61 (9) mg/dL; triglycerides, 183 (70) mg/dL; total protein, 6.5 (0.4) g/dL; and albumin, 3.6 (0.2) g/dL. CONCLUSIONS: These data will be useful for future JECS studies.

Study Design and Participants' Profile in the Sub-Cohort Study in the Japan Environment and Children's Study (JECS).

BACKGROUND: The Japan Environment and Children's Study (JECS) is a nationwide birth cohort study investigating environmental effects on children's health and development. A Sub-Cohort Study has begun, conducting extended exposure and outcome measurements by targeting a subgroup randomly selected from the JECS Main Study. We report the Sub-Cohort Study methodology and participants' baseline profiles. METHODS: Of 100,148 children in the JECS Main Study, children born after April 1, 2013 who met eligibility criteria ([1] all questionnaire and medical record data from children and their mothers collected from the first trimester to 6 months of age, [2] biospecimens [except umbilical cord blood] from children and their mothers collected at first to second/third trimester and delivery) were randomly selected for each Regional Centre at regular intervals. Face-to-face assessment of neuropsychiatric development, body measurement, paediatrician's examination, blood/urine collection for clinical testing and chemical analysis, and home visits (ambient and indoor air measurement and dust collection) are conducted. Participants are followed up at 1.5 and 3 years old for home visits, and 2, 4, 6, and 8 years old for developmental/medical examination. The details of protocols after age 10 are under discussion. RESULTS: Of 10,302 selected children, 5,017 participated. The profiles of the participating mothers, fathers and children did not substantially differ between the Main Study and Sub-Cohort Study. CONCLUSION: The JECS Sub-Cohort Study offers a platform for investigating associations between environmental exposure and outcomes.

Effects of Pesticide Intake on Gut Microbiota and Metabolites in Healthy Adults.

Animal experiments have indicated that pesticides may affect gut microbiota, which is responsible for the production of short-chain fatty acids (SCFAs) and polyamines. Here, we present a preliminary observation of the relationship between pesticide exposure and fecal SCFAs and polyamines in Japanese adults. In total, 38 healthy adults aged 69 ± 10 years (mean ± SD) were recruited and subjected to stool and spot urine tests. Urinary dialkylphosphates (DAP), 3-phenoxybenzoic acid, and glyphosate were assayed as pesticide exposure markers of organophosphorus insecticide (OP), a pyrethroid insecticide, and glyphosate, respectively. Significant negative correlations (p < 0.05, Spearman's rank correlation coefficient) were found between urinary DAP, fecal acetate (r = −0.345), and lactate (r = −0.391). Multiple regression analyses revealed that urinary DAP was a significant explanatory variable of fecal acetate concentration (p < 0.001, ß = −24.0, SE = 4.9, t = −4.9) with some vegetable intake (adjusted R-square = 0.751). These findings suggest that OP exposure is independently associated with lower fecal acetate levels, which may contribute to human health in middle-aged and older adult groups. Given that the human gut environment has long-term effects on the host, studies on wide-range age groups, including children, are necessary.

Spatial Variations of Indoor Air Chemicals in an Apartment Unit and Personal Exposure of Residents.

Indoor air quality (IAQ) can greatly affect health in people spending much time indoors. However, the influence of IAQ on personal exposure to chemical compounds in Japan remains poorly investigated. Hence, this study aimed to clarify this influence thoroughly within one apartment. We surveyed the concentrations of 61 chemical compounds in the air in nine different spaces within an apartment unit, as well as the personal exposure of two residents in Japan. Using three kinds of diffusive samplers, this study was conducted continuously for 7 days in summer and winter. Health risks were evaluated by calculating the margin of exposure (MOE) using the measured concentrations. Some chemical concentrations showed large spatial variations and the personal exposure concentrations of these compounds also differed among residents. According to the calculated MOE, the chemicals with the highest health risk were acrolein, p-dichlorobenzene, and acetaldehyde in summer and acrolein, nitrogen dioxide, formic acid, p-dichlorobenzene, and benzene in winter. The IAQ of the house could be divided in two, and the IAQ in the space where residents spent much time (i.e., bedroom) highly affected each of the residents' exposure. Investigating chemical concentrations in multiple spaces (including bedroom and living room) is necessary to understand the effect of IAQ on personal exposure.

Defining the Scope of Exposome Studies and Research Needs from a Multidisciplinary Perspective.

The concept of the exposome was introduced over 15 years ago to reflect the important role that the environment exerts on health and disease. While originally viewed as a call-to-arms to develop more comprehensive exposure assessment methods applicable at the individual level and throughout the life course, the scope of the exposome has now expanded to include the associated biological response. In order to explore these concepts, a workshop was hosted by the Gunma University Initiative for Advanced Research (GIAR, Japan) to discuss the scope of exposomics from an international and multidisciplinary perspective. This Global Perspective is a summary of the discussions with emphasis on (1) top-down, bottom-up, and functional approaches to exposomics, (2) the need for integration and standardization of LC- and GC-based high-resolution mass spectrometry methods for untargeted exposome analyses, (3) the design of an exposomics study, (4) the requirement for open science workflows including mass spectral libraries and public databases, (5) the necessity for large investments in mass spectrometry infrastructure in order to sequence the exposome, and (6) the role of the exposome in precision medicine and nutrition to create personalized environmental exposure profiles. Recommendations are made on key issues to encourage continued advancement and cooperation in exposomics.

Association between Haematological Parameters and Exposure to a Mixture of Organophosphate and Neonicotinoid Insecticides among Male Farmworkers in Northern Thailand.

Exposure to insecticides may result in various health problems. This study investigated the association between haematological parameters and exposure to a mixture of organophosphate (OP) and neonicotinoid (NEO) insecticides among male farmworkers in Fang district, Chiang Mai province, northern Thailand. Concentrations of urinary dialkylphosphates, non-specific metabolites of OPs, and NEOs and their metabolites and haematological parameters were measured in 143 male farmworkers. The Bayesian kernel machine regression model was employed to evaluate the associations. Exposure to a mixture of insecticides was significantly associated with the mean corpuscular haemoglobin concentration (MCHC) when the concentrations of all the compounds and their metabolites were at the 60th percentile or higher compared with the 50th percentile. Furthermore, exposure to clothianidin (CLO) showed a decreasing association with MCHC when all the other insecticides were at their mean concentrations. CLO was the most likely compound to reduce MCHC, and this was confirmed by sensitivity analysis. These findings suggest that exposure to NEO insecticides, especially CLO, affects the haematological status relating to haemoglobin parameters.

Association of prenatal exposure to cadmium with neurodevelopment in children at 2 years of age: The Japan Environment and Children's Study.

BACKGROUND: Prenatal cadmium exposure has been associated with adverse neurodevelopmental outcomes. However, previous findings are contradictory, and little is known about the potential modifiers of the cadmium-related neurodevelopmental risk. We investigated the associations between prenatal cadmium exposure and neurodevelopment in 2-year-old children and examined the influence of mother/child characteristics. METHODS: We recruited 3545 mother-child pairs from the Japan Environment and Children's Study. We collected maternal blood during mid/late pregnancy and cord blood at delivery, and measured cadmium concentrations using inductively coupled plasma mass spectrometry. Neurodevelopment was assessed using the Kyoto Scale of Psychological Development (KSPD), which includes cognitive-adaptive (C-A), language-social (L-S), postural-motor (P-M) and developmental quotient (DQ) domains. Associations between cadmium and KSPD scores were tested using multivariable models after controlling for confounders. RESULTS: Median levels (interquartile ranges) of cadmium in maternal and cord blood were 0.70 (0.52-0.95) and 0.04 (0.03-0.06) µg/L, respectively. Maternal blood cadmium concentrations were inversely associated with P-M scores in boys (ß = -1.4, 95% confidence interval (CI): -2.7, -0.038), DQ in children of mothers who smoked during pregnancy (ß = -2.9, 95% CI: -5.7, -0.12), P-M (ß = -5.4, 95% CI: -10, -0.67), C-A (ß = -6.1, 95% CI: -11, -1.8), L-S (ß = -9.0, 95% CI: -13, -4.8) and DQ scores (ß = -6.4, 95% CI: -9.6, -3.1) in children born to mothers with gestational diabetes. Cord blood cadmium concentrations were negatively associated with L-S scores (ß = -6.0., 95% CI: -11, -0.91) in children born to mothers with gestational diabetes. CONCLUSIONS: Prenatal cadmium exposure was negatively associated with neurodevelopment in boys, in children whose mothers smoked, and in children born to mothers with gestational diabetes. Further studies in other populations are needed to confirm our findings.