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      Maternal urinary concentrations of organophosphate ester metabolites: associations with gestational weight gain, early life anthropometry, and infant eating behaviors among mothers-infant pairs in Rhode Island

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          Abstract

          Background

          Organophosphate esters (OPEs)—used as flame retardants and plasticizers—are associated with adverse pregnancy outcomes such as reduced fecundity and live births and increased preterm delivery. OPEs may interfere with growth and metabolism via endocrine-disruption, but few studies have investigated endocrine-related outcomes. The objective of this pilot study ( n = 56 mother-infant pairs) was to evaluate associations of OPEs with gestational weight gain (GWG), gestational age at delivery, infant anthropometry, and infant feeding behaviors.

          Methods

          We quantified OPE metabolites (bis-2-chloroethyl phosphate [BCEP], bis (1,3-dichloro-2-propyl) phosphate [BDCPP], diphenyl phosphate [DPHP]) in pooled maternal spot urine collected throughout pregnancy (~ 12, 28, and 35 weeks’ gestation). We obtained maternal sociodemographic characteristics from questionnaires administered at enrollment and perinatal characteristics from medical record abstraction. Trained research assistants measured infant weight, length, head and abdominal circumferences, and skinfold thicknesses at birth and 6 weeks postpartum. Mothers reported infant feeding behavior via the Baby Eating Behavior Questionnaire (BEBQ). Using multiple linear regression, we assessed associations of log 2-transformed maternal urinary OPE metabolites with GWG, gestational age at delivery, infant anthropometry at birth, weekly growth rate, and BEBQ scores at 6 weeks postpartum. We used linear mixed effects (LME) models to analyze overall infant anthropometry during the first 6 weeks of life. Additionally, we considered effect modification by infant sex.

          Results

          We observed weak positive associations between all OPE metabolites and GWG. In LME models, BDCPP was associated with increased infant length (β = 0.44 cm, 95%CI = 0.01, 0.87) and weight in males (β = 0.14 kg, 95%CI = 0.03, 0.24). BDCPP was also associated with increased food responsiveness (β = 0.23, 95%CI = 0.06, 0.40). DPHP was inversely associated with infant abdominal circumference (β = − 0.50 cm, 95%CI = − 0.86, − 0.14) and female weight (β = − 0.19 kg, 95%CI = − 0.36, − 0.02), but positively associated with weekly growth in iliac skinfold thickness (β = 0.10 mm/wk., 95%CI = 0.02, 0.19). Further, DPHP was weakly associated with increased feeding speed. BCEP was associated with greater infant thigh skinfold thickness (β = 0.34 mm, 95%CI = 0.16, 0.52) and subscapular skinfold thickness in males (β = 0.14 mm, 95%CI = 0.002, 0.28).

          Conclusions

          Collectively, these findings suggest that select OPEs may affect infant anthropometry and feeding behavior, with the most compelling evidence for BDCPP and DPHP.

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          Most cited references59

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          Estimation of Average Concentration in the Presence of Nondetectable Values

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            Fetal origins of coronary heart disease.

            The fetal origins hypothesis states that fetal undernutrition in middle to late gestation, which leads to disproportionate fetal growth, programmes later coronary heart disease. Animal studies have shown that undernutrition before birth programmes persisting changes in a range of metabolic, physiological, and structural parameters. Studies in humans have shown that men and women whose birth weights were at the lower end of the normal range, who were thin or short at birth, or who were small in relation to placental size have increased rates of coronary heart disease. We are beginning to understand something of the mechanisms underlying these associations. The programming of blood pressure, insulin responses to glucose, cholesterol metabolism, blood coagulation, and hormonal settings are all areas of active research.
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              Phosphorus flame retardants: properties, production, environmental occurrence, toxicity and analysis.

              Since the ban on some brominated flame retardants (BFRs), phosphorus flame retardants (PFRs), which were responsible for 20% of the flame retardant (FR) consumption in 2006 in Europe, are often proposed as alternatives for BFRs. PFRs can be divided in three main groups, inorganic, organic and halogen containing PFRs. Most of the PFRs have a mechanism of action in the solid phase of burning materials (char formation), but some may also be active in the gas phase. Some PFRs are reactive FRs, which means they are chemically bound to a polymer, whereas others are additive and mixed into the polymer. The focus of this report is limited to the PFRs mentioned in the literature as potential substitutes for BFRs. The physico-chemical properties, applications and production volumes of PFRs are given. Non-halogenated PFRs are often used as plasticisers as well. Limited information is available on the occurrence of PFRs in the environment. For triphenyl phosphate (TPhP), tricresylphosphate (TCP), tris(2-chloroethyl)phosphate (TCEP), tris(chloropropyl)phosphate (TCPP), tris(1,3-dichloro-2-propyl)phosphate (TDCPP), and tetrekis(2-chlorethyl)dichloroisopentyldiphosphate (V6) a number of studies have been performed on their occurrence in air, water and sediment, but limited data were found on their occurrence in biota. Concentrations found for these PFRs in air were up to 47 μg m(-3), in sediment levels up to 24 mg kg(-1) were found, and in surface water concentrations up to 379 ng L(-1). In all these matrices TCPP was dominant. Concentrations found in dust were up to 67 mg kg(-1), with TDCPP being the dominant PFR. PFR concentrations reported were often higher than polybrominated diphenylether (PBDE) concentrations, and the human exposure due to PFR concentrations in indoor air appears to be higher than exposure due to PBDE concentrations in indoor air. Only the Cl-containing PFRs are carcinogenic. Other negative human health effects were found for Cl-containing PFRs as well as for TCP, which suggest that those PFRs would not be suitable alternatives for BFRs. TPhP, diphenylcresylphosphate (DCP) and TCP would not be suitable alternatives either, because they are considered to be toxic to (aquatic) organisms. Diethylphosphinic acid is, just like TCEP, considered to be very persistent. From an environmental perspective, resorcinol-bis(diphenylphosphate) (RDP), bisphenol-A diphenyl phosphate (BADP) and melamine polyphosphate, may be suitable good substitutes for BFRs. Information on PFR analysis in air, water and sediment is limited to TCEP, TCPP, TPhP, TCP and some other organophosphate esters. For air sampling passive samplers have been used as well as solid phase extraction (SPE) membranes, SPE cartridges, and solid phase micro-extraction (SPME). For extraction of PFRs from water SPE is recommended, because this method gives good recoveries (67-105%) and acceptable relative standard deviations (RSDs) (<20%), and offers the option of on-line coupling with a detection system. For the extraction of PFRs from sediment microwave-assisted extraction (MAE) is recommended. The recoveries (78-105%) and RSDs (3-8%) are good and the method is faster and requires less solvent compared to other methods. For the final instrumental analysis of PFRs, gas chromatography-flame photometric detection (GC-FPD), GC-nitrogen-phosphorus detection (NPD), GC-atomic emission detection (AED), GC-mass spectrometry (MS) as well as liquid chromatography (LC)-MS/MS and GC-Inductively-coupled plasma-MS (ICP-MS) are used. GC-ICP-MS is a promising method, because it provides much less complex chromatograms while offering the same recoveries and limits of detection (LOD) (instrumental LOD is 5-10 ng mL(-1)) compared to GC-NPD and GC-MS, which are frequently used methods for PFR analysis. GC-MS offers a higher selectivity than GC-NPD and the possibility of using isotopically labeled compounds for quantification. Copyright © 2012 Elsevier Ltd. All rights reserved.
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                Author and article information

                Contributors
                kcrawford@middlebury.edu
                nicola.hawley@yale.edu
                aic7@cdc.gov
                goh3@cdc.gov
                froehlichr@mail.magee.edu
                PHas@wihri.org
                lisa.gallagher@dartmouth.edu
                david_savitz@brown.edu
                joseph_braun_1@brown.edu
                EWerner@KentRI.org
                megan.e.romano@dartmouth.edu
                Journal
                Environ Health
                Environ Health
                Environmental Health
                BioMed Central (London )
                1476-069X
                11 September 2020
                11 September 2020
                2020
                : 19
                : 97
                Affiliations
                [1 ]GRID grid.254880.3, ISNI 0000 0001 2179 2404, Department of Epidemiology, , Geisel School of Medicine at Dartmouth, ; Lebanon, NH USA
                [2 ]GRID grid.260002.6, ISNI 0000 0000 9743 9925, Current Address: Program in Environmental Studies, , Middlebury College, ; Middlebury, VT USA
                [3 ]GRID grid.47100.32, ISNI 0000000419368710, Department of Epidemiology, , Yale University School of Public Health, ; New Haven, CT USA
                [4 ]GRID grid.416778.b, ISNI 0000 0004 0517 0244, Division of Laboratory Sciences, , National Center for Environmental Health, Centers for Disease Control and Prevention, ; Atlanta, GA USA
                [5 ]GRID grid.21925.3d, ISNI 0000 0004 1936 9000, Department of Obstetrics, Gynecology, and Reproductive Sciences, , University of Pittsburgh, ; Pittsburgh, PA USA
                [6 ]GRID grid.241223.4, Division of Maternal-Fetal Medicine, , Women & Infants Hospital of Rhode Island, ; Providence, RI USA
                [7 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Department of Epidemiology, , Brown University School of Public Health, ; Providence, RI USA
                [8 ]GRID grid.40263.33, ISNI 0000 0004 1936 9094, Department of Obstetrics and Gynecology, , Warren Alpert Medical School of Brown University, ; Providence, RI, USA
                Author information
                http://orcid.org/0000-0002-8945-808X
                Article
                648
                10.1186/s12940-020-00648-0
                7488675
                32917231
                1c22e552-d18d-4852-bbe6-c59bcd224345
                © The Author(s) 2020

                Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

                History
                : 3 April 2020
                : 21 August 2020
                Funding
                Funded by: FundRef http://dx.doi.org/10.13039/100000066, National Institute of Environmental Health Sciences;
                Award ID: R01-ES024381
                Award ID: R00-ES020346
                Award Recipient :
                Funded by: National Institute of General Medical Sciences (US)
                Award ID: P20-GM104416
                Funded by: FundRef http://dx.doi.org/10.13039/100000054, National Cancer Institute;
                Award ID: 5R25CA134286-10
                Funded by: FundRef http://dx.doi.org/10.13039/100006418, Brown University;
                Award ID: Research Seed Funding
                Award Recipient :
                Categories
                Research
                Custom metadata
                © The Author(s) 2020

                Public health
                organophosphate ester (ope),triphenyl phosphate (tphp),tri-2-chloroethyl phosphate [tcep],tri (1,3-dichloro-2-propyl) phosphate [tdcpp],pregnancy,infant anthropometry,gestational weight gain (gwg),baby eating behavior questionnaire (bebq)

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