Dataset Information

Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.

ABSTRACT:

Background

Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to accurately assess OP exposure during pregnancy with single sampling. This study aimed to assess intra-individual variations of DAP concentrations and the reproducibility of the exposure dose categorization of OPs according to DAP concentration ranges in pregnant women in Japan.

Methods

Urine samples were collected from 62 non-smoking pregnant women (12-22?weeks of gestation) living in Aichi Prefecture, Japan. First morning void (FMV) and spot urine samples taken between lunch and dinner on the same day were collected on five different days during 2?weeks. The concentrations of DAP and creatinine in urine samples were measured using an ultra performance liquid chromatography with tandem mass spectrometry. Creatinine-adjusted and unadjusted concentrations were used for the intraclass correlation coefficient (ICC) calculations and surrogate category analyses.

Results

For all DAP metabolites, the creatinine-adjusted single ICCs exceeded 0.4, indicating moderate reliability. Overall, ICCs of spot urine samples taken in the afternoon were better than those taken as FMV. Surrogate category analyses showed that participants were categorized accurately into four exposure dose groups according to the quartile points.

Conclusion

This study indicated that a single urine sample taken in the afternoon may be useful in assessing OP exposure as long as the exposure is categorized into quartiles when conducting epidemiological studies in early to mid-pregnant women in Japan.

SUBMITTER: Hioki K

PROVIDER: S-EPMC6337762 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Publications

Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.

Hioki Keisuke K Ito Yuki Y Oya Naoko N Nakayama Shoji F SF Isobe Tomohiko T Ebara Takeshi T Shibata Kanemitsu K Nishikawa Naomi N Nakai Kunihiko K Kamida Tomota T Ueyama Jun J Sugiura-Ogasawara Mayumi M Kamijima Michihiro M

Environmental health and preventive medicine 20190117 1

<h4>Background</h4>Low-dose exposure to organophosphate (OP) insecticides during pregnancy may adversely affect neurodevelopment in children. To evaluate the OP exposure levels, single urine sampling is commonly adopted to measure the levels of dialkylphosphates (DAPs), common OP metabolites. However, the inter-day variations of urinary DAP concentrations within subjects are supposed to be large due to the short biological half-lives of the metabolites, and it is thus considered difficult to acc ...[more]

PMID: 30654738

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Project description:BackgroundPrenatal exposure to organophosphate (OP) pesticides has been associated with altered neuronal cell development and behavioral changes in animal offspring. However, the few studies investigating the association between prenatal OP pesticide exposure and neurodevelopmental outcomes such as Attention-Deficit Hyperactivity Disorder (ADHD) and autistic traits in children produced mixed findings.ObjectiveThe objective of the present study was to examine whether maternal urinary concentrations of OP pesticide metabolites are associated with ADHD and autistic traits in children participating in the Generation R Study, a population-based birth cohort from Rotterdam, the Netherlands.MethodMaternal concentrations of 6 dialkylphosphates (DAPs) were measured using gas chromatography coupled with tandem mass spectrometry in urine samples collected at <18 weeks, 18-25 weeks, and > 25 weeks of gestation in 784 mother-child pairs. DAP metabolite concentrations were expressed as molar concentrations divided by creatinine levels and log10 transformed. ADHD traits were measured at ages 3, 6, and 10 years using the Child Behavior Checklist (CBCL) (n = 781) and autistic traits were measured at age 6 years using the Social Responsiveness Scale (SRS) (n = 622). First, regression models were fit for the averaged prenatal exposure across pregnancy. Second, we investigated associations for each collection phase separately, and applied a mutually adjusted model in which the effect of prenatal DAP concentrations from each time period on ADHD and autistic traits were jointly estimated. All associations were adjusted for relevant confounders.ResultsMedian DAP metabolite concentration was 309 nmol/g creatinine at <18 weeks, 316 nmol/g creatinine at 18-25 weeks, and 308 nmol/g creatinine at >25 weeks of gestation. Overall, DAP metabolite concentrations were not associated with ADHD traits. For instance, a log10 increase in averaged total DAP concentrations across gestation was not associated with a lower ADHD score (-0.03 per SD 95 CI: -0.28 to 0.23). Similarly, no associations between maternal DAP concentrations and autistic traits were detected.ConclusionsIn this study of maternal urinary DAP metabolite concentrations during pregnancy, we did not observe associations with ADHD and autistic traits in children. These are important null observations because of the relatively high background DAP concentrations across pregnancy, the relatively large sample size, and the 10-year follow-up of the offspring. Given the measurement error inherent in our OP pesticide exposure biomarkers, future studies using more urine samples are needed to accurately measure OP pesticide exposure over pregnancy in relation to ADHD and autistic traits.

Project description:BackgroundSpot urine samples are often used to assess exposure to organophosphate (OP) pesticides in place of "gold standard" 24-hr samples, which are cumbersome to collect. Assessment of non-persistent chemicals using spot urine samples may result in exposure misclassification that could bias epidemiological analyses towards the null. Few studies have examined the validity of measurements of urinary metabolites in spot samples to estimate daily OP dose or the potential implications of reliance on spot samples for risk assessments.ObjectiveExamine the validity of using first morning void (FMV) and random non-FMV urine samples to estimate cumulative 24-hr OP pesticide dose among children living in an agricultural region.MethodsWe collected urine samples over 7 consecutive days, including two 24-hr samples, from 25 children living in an agricultural community. We used measurements of urinary dialkylphosphate (DAP) metabolites, data on nearby agricultural pesticide applications, and daily dietary intake data to estimate internal dose from exposure to a mixture of OP pesticides according to the U.S. Environmental Protection Agency Cumulative Risk Assessment guidelines. Dose estimates from volume- and creatinine-adjusted same-day FMV and non-FMV spot urine samples were compared to the "gold standard" estimates from 24-hr samples.ResultsNon-FMV samples had relatively weak ability to predict 24-hr dose (R2 = 0.09-0.38 for total DAPs) and tended to underestimate the percentage of samples exceeding regulatory guidelines. Models with FMV samples or the average of an FMV and non-FMV sample were similarly predictive of 24-hr estimates (R2 for DAPs = 0.40-0.68 and 0.40-0.80, respectively, depending on volume adjustment method).ConclusionReliance on non-FMV samples for risk assessments may underestimate daily OP dose and the percentage of children with dose estimates exceeding regulatory guidelines. If 24-hr urine sample collection is infeasible, we recommend future studies prioritize the collection of FMV samples to most accurately characterize OP dose in children.

Project description:BACKGROUND:In the Netherlands organophosphate (OP) pesticides are frequently used for pest control in agricultural settings. Despite concerns about the potential health impacts of low-level OP pesticides exposure, particularly in vulnerable populations, the primary sources of exposure remain unclear. The present study was designed to investigate the levels of DAP metabolites concentrations across pregnancy and to examine various determinants of DAP metabolite concentrations among an urban population of women in the Netherlands. METHOD:Urinary concentrations of six dialkyl phosphate (DAP) metabolites, the main urinary metabolites of OP pesticides, were determined at <18, 18-25, and >25 weeks of pregnancy in 784 pregnant women participating in the Generation R Study (between 2004 and 2006), a large population-based birth cohort in Rotterdam, the Netherlands. Questionnaires administered prenatally assessed demographic and lifestyle characteristics and maternal diet. Linear mixed models, with adjustment for relevant covariates, were used to estimate associations between the potential exposure determinants and DAP metabolite concentrations expressed as molar concentrations divided by creatinine levels. RESULTS:The median DAP metabolite concentration was 311 nmol/g creatinine for the first trimester, 317 nmol/g creatinine for the second trimester, and 310 nmol/g creatinine for the third trimester. Higher maternal age, married/living with a partner, underweight or normal weight (BMI of <18.5 and 18.5-<25), high education, high income, and non-smoking were associated with higher DAP metabolite concentrations, and DAP metabolite concentrations tended to be higher during the summer. Furthermore, fruit intake was associated with increased DAP metabolite concentrations. Each 100 g/d difference in fruit consumption was associated with a 7% higher total DAP metabolite concentration across pregnancy. Other food groups were not associated with higher DAP metabolite concentrations. CONCLUSIONS:The DAP metabolite concentrations measured in the urine of pregnant women in the Netherlands were higher than those in most other studies previously conducted. Fruit intake was the main dietary source of exposure to OP pesticides in young urban women in the Netherlands. The extent to which DAP metabolite concentrations reflect exposure to the active parent pesticide rather than to less toxic metabolites remains unclear. Further research will be undertaken to investigate the possible effects of this relatively high level OP pesticides exposure on offspring health.

Project description:BACKGROUND:Animal studies suggest that organophosphate (OP) pesticides exposure affects thyroid function, but evidence in humans remains sparse and inconclusive. Gestational exposure is of particular interest, since thyroid hormone is essential for fetal brain development. OP pesticides are able to cross the placental and blood-brain barrier and may interfere with fetal development processes regulated by thyroid hormone. OBJECTIVE:To investigate the association of gestational OP pesticides exposure during pregnancy with maternal and cord blood thyroid hormone concentrations. METHODS:This study was embedded within Generation R (Rotterdam, the Netherlands), a prospective population-based birth cohort. Mother-child pairs with OP pesticides assessment and maternal (N?=?715) or cord blood (N?=?482) thyroid hormone measurements were included. OP pesticides exposure was assessed at <18, 18-25, and >25?weeks gestation by measuring six urinary dialkylphosphate (DAP) metabolites. Thyroid stimulating hormone (TSH) and free thyroxine (FT4) were measured in maternal and cord blood. Maternal measures also included total thyroxine (TT4) and TPO antibodies (TPOAbs). To study the association of creatinine-adjusted DAP metabolite concentrations with thyroid function and TPO antibodies, multivariable linear regression models including relevant confounders were used. RESULTS:There was no association of DAP metabolites with maternal TSH, FT4, TT4 or TPOAb concentrations during pregnancy. Similarly, there was no association of DAP metabolites with cord blood TSH or FT4. Results did not change when DAP concentrations were analyzed at individual time points or as mean gestational exposure. CONCLUSION:Gestational OP pesticides exposure, as assessed by repeatedly measured urinary DAP metabolite concentrations in an urban population, was not associated with maternal or cord blood thyroid hormone concentrations. These findings do not support a mediating role for serum thyroid hormone availability in the relation of early life exposure to low levels of OP pesticides with child neurodevelopment. However, disruption of the thyroid system at tissue level cannot be excluded. In addition, this is one of the first studies on this subject and measurement error in DAP metabolites might have resulted in imprecise estimates. Future studies should use more urine samples to increase precision and should investigate specific OP pesticide metabolites.

Project description:OBJECTIVE:To evaluate whether urinary concentrations of organophosphate flame retardant (PFR) metabolites are associated with pregnancy loss among women conceiving with assisted reproductive technology (ART). DESIGN:Prospective preconception cohort of subfertile women. SETTING:Academic hospital fertility center in Boston, Massachusetts. PATIENT(S):A total of 155 women conceiving 179 pregnancies with ART. INTERVENTION(S):None. Mean exposure to each of five PFR metabolites was estimated by averaging the specific-gravity adjusted natural log concentrations from two urine samples collected during the ART cycle of conception. MAIN OUTCOME MEASURE(S):Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) for biochemical and total pregnancy loss (all losses <20 weeks' gestation) by quartiles of PFR metabolite concentrations were estimated using a repeated measures log-binomial model, accounting for multiple pregnancies per woman. RESULT(S):Of the 179 pregnancies, 31% ended in pregnancy loss (12% in biochemical loss). Among the three metabolites with high detection frequency [bis(1,3-dichloro-2-propyl) phosphate (BDCIPP), diphenyl phosphate (DPHP), and isopropylphenyl phenyl phosphate (ip-PPP)], an increased risk of biochemical loss was observed for women with DPHP concentrations in the fourth vs. first quartile (RR 1.64; 95% CI 0.61-4.39). Also found was an elevated risk of biochemical pregnancy loss among women in the highest quartile of the molar sum of urinary PFR metabolites compared with the lowest (RR 1.89; 95% CI 0.64-5.58). Urinary concentrations of ip-PPP and BDCIPP were not associated with either outcome. CONCLUSION(S):Among subfertile women, urinary DPHP metabolite concentrations measured during the ART cycle of conception may be associated with early pregnancy loss. Although this study is uniquely designed to investigate early markers of pregnancy success and maintenance, the small sample size likely contributed to imprecision. Given their increasing use as replacement chemicals for traditional flame retardants, exposure to PFRs may increase, and more studies will be needed to investigate their potential to impact pregnancy and reproduction.

Dataset Information

Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.

Background

Methods

Results

Conclusion

Publications

Intra-individual variations of organophosphate pesticide metabolite concentrations in repeatedly collected urine samples from pregnant women in Japan.

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