Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort

Mikkel Vilmand; Iben Have Beck; Niels Bilenberg; Anna Maria Andersson; Anders Juul; Greet Schoeters; Henriette Boye; Hanne Frederiksen; Tina Kold Jensen

doi:10.1016/j.ntt.2023.107161

Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort

Mikkel Vilmand
, Iben Have Beck
, Niels Bilenberg
, Anna Maria Andersson
, Anders Juul
, Greet Schoeters
, Henriette Boye
, Hanne Frederiksen
, Tina Kold Jensen^*

^*Kontaktforfatter

Rigshospitalet
International Center for Research and Research Training in Endocrine Disruption of Male Reproduction and Child Health
Københavns Universitet
Flemish Institute of Technological Research
University of Antwerp

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › peer review

115 Downloads (Pure)

Abstract

Background: Phthalates are endocrine disrupters used in a variety of consumer products. Human studies suggest an association between phthalate exposure and cognitive development but adverse effects of the recently introduced phthalate substitutes have only been sparsely studied. Objectives: To investigate associations between prenatal and concurrent exposure to phthalates and IQ in 7-year-old children from the Odense Child Cohort. Methods: Pregnant women from the Odense Child Cohort had phthalate metabolites measured in urine samples during 3rd trimester in 2010 to 2012. In addition, phthalates were also measured in urine samples from their offspring at age 7 years. IQ was assessed at age 7 years using four subtests from Wechsler Intelligence Scale for Children. The total study population consisted of 585 mother-child pairs with available prenatal urinary phthalate metabolites concentrations and IQ data at age 7 years. A subset of those (N = 274) had urinary phthalate metabolites measured in child urine at age 7 years. Phthalate concentrations were grouped into tertiles and associations with IQ were investigated using multiple linear regression adjusting for sex, maternal education and maternal/child BMI. Results: Urinary phthalate metabolite concentrations both in pregnant women and children were generally lower compared to previous cohorts. Children with high prenatal urinary concentrations of MEP and metabolites of DEHP (∑DEHP_m)(3rd tertile) had −3.1 (95% CI: −5.5, −0.6) (MEP) and − 3.0 (−5.5, −0.6) (∑DEHP_m) IQ points at age 7 years compared to children with low concentrations (1st tertile). High concurrent urinary phthalate concentrations of MCPP, ∑DnHxP_m, ∑DiDP_m and ∑DiNP_m in the 3rd tertile was associated with −3.7 (−7.2, −0.2), −4.4 (−7.9, −0.9), −3.7 (−7.2, −0.2) and − 5.6 (−9.1, −2.2) IQ points, respectively, compared to those with the lowest concentrations (1st tertile). Conclusion: We found significant inverse associations between some prenatal and concurrent urinary phthalate concentrations and IQ at age 7 years in this low exposed population. This suggests that exposure to phthalates both prenatally and during early childhood could be hazardous to child neurodevelopment, however, large-scale prospective studies assessing phthalate exposure through multiple urine samples, and possibly investigating cocktail effects of the chemicals as well as long term follow-up are warranted.

Originalsprog	Engelsk
Artikelnummer	107161
Tidsskrift	Neurotoxicology and Teratology
Vol/bind	96
ISSN	0892-0362
DOI	https://doi.org/10.1016/j.ntt.2023.107161
Status	Udgivet - 1. mar. 2023

Bibliografisk note

Funding Information:
The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark, the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation.

Funding Information:
The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital , Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark , the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation , Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation .

Publisher Copyright:
© 2023 The Authors

Finansiering

The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark, the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation. The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital , Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark , the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation , Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation .

Dokumenter og links

10.1016/j.ntt.2023.107161Licens: CC BY

Open Access VersionForlagets udgivne version, 1,08 MBLicens: CC BY

SDU link

Tjek adgangen til materialet i Syddansk Universitetsbiblioteks søgemaskine

1 Afsluttet

Prenatal and early life PFAA exposure; impact on neuropsychological development in 1.5- to 7-year-old children in Odense Child Cohort
Jensen, T. K. (PI)
Novo Nordisk Fonden
01/01/2020 → 31/01/2024
Projekter: Projekt › Forskning

Citationsformater

@article{e77ba90338444992a3ffe2e5110ee7b0,

title = "Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort",

abstract = "Background: Phthalates are endocrine disrupters used in a variety of consumer products. Human studies suggest an association between phthalate exposure and cognitive development but adverse effects of the recently introduced phthalate substitutes have only been sparsely studied. Objectives: To investigate associations between prenatal and concurrent exposure to phthalates and IQ in 7-year-old children from the Odense Child Cohort. Methods: Pregnant women from the Odense Child Cohort had phthalate metabolites measured in urine samples during 3rd trimester in 2010 to 2012. In addition, phthalates were also measured in urine samples from their offspring at age 7 years. IQ was assessed at age 7 years using four subtests from Wechsler Intelligence Scale for Children. The total study population consisted of 585 mother-child pairs with available prenatal urinary phthalate metabolites concentrations and IQ data at age 7 years. A subset of those (N = 274) had urinary phthalate metabolites measured in child urine at age 7 years. Phthalate concentrations were grouped into tertiles and associations with IQ were investigated using multiple linear regression adjusting for sex, maternal education and maternal/child BMI. Results: Urinary phthalate metabolite concentrations both in pregnant women and children were generally lower compared to previous cohorts. Children with high prenatal urinary concentrations of MEP and metabolites of DEHP (∑DEHPm)(3rd tertile) had −3.1 (95\% CI: −5.5, −0.6) (MEP) and − 3.0 (−5.5, −0.6) (∑DEHPm) IQ points at age 7 years compared to children with low concentrations (1st tertile). High concurrent urinary phthalate concentrations of MCPP, ∑DnHxPm, ∑DiDPm and ∑DiNPm in the 3rd tertile was associated with −3.7 (−7.2, −0.2), −4.4 (−7.9, −0.9), −3.7 (−7.2, −0.2) and − 5.6 (−9.1, −2.2) IQ points, respectively, compared to those with the lowest concentrations (1st tertile). Conclusion: We found significant inverse associations between some prenatal and concurrent urinary phthalate concentrations and IQ at age 7 years in this low exposed population. This suggests that exposure to phthalates both prenatally and during early childhood could be hazardous to child neurodevelopment, however, large-scale prospective studies assessing phthalate exposure through multiple urine samples, and possibly investigating cocktail effects of the chemicals as well as long term follow-up are warranted.",

keywords = "Cognitive development, Cohort study, Endocrine disrupting chemicals, Neurotoxicology, Phthalates, Teratology",

author = "Mikkel Vilmand and Beck, \{Iben Have\} and Niels Bilenberg and Andersson, \{Anna Maria\} and Anders Juul and Greet Schoeters and Henriette Boye and Hanne Frederiksen and Jensen, \{Tina Kold\}",

note = "Funding Information: The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark, the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B\_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation. Funding Information: The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital , Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark , the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B\_FSS), Novo Nordisk Foundation , Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation . Publisher Copyright: {\textcopyright} 2023 The Authors",

year = "2023",

month = mar,

day = "1",

doi = "10.1016/j.ntt.2023.107161",

language = "English",

volume = "96",

journal = "Neurotoxicology and Teratology",

issn = "0892-0362",

publisher = "Elsevier",

}

TY - JOUR

T1 - Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort

AU - Vilmand, Mikkel

AU - Beck, Iben Have

AU - Bilenberg, Niels

AU - Andersson, Anna Maria

AU - Juul, Anders

AU - Schoeters, Greet

AU - Boye, Henriette

AU - Frederiksen, Hanne

AU - Jensen, Tina Kold

N1 - Funding Information: The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital, Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark, the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation, Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation. Funding Information: The participants in the Odense Child Cohort. The technicians at Hans Christian Andersen's Children's Hospital are acknowledged for their careful examination of the children. The lab technicians at Clinical Pharmacology, Pharmacy and Environmental Medicine, University of Southern Denmark and Department of Growth and Reproduction, Rigshospitalet are acknowledged for their thorough work in analyzing the blood and urine samples. This work was supported by Odense University Hospital , Denmark, the Region of Southern Denmark, The Municipality of Odense, Denmark, The University of Southern Denmark , the Mental Health Service of the Region of Southern Denmark, Odense Patient data Exploratory Network (OPEN), Denmark, The Danish Center for Hormone Disrupting Chemicals (MST-611-00012), The Danish Research Council (4004-00352B_FSS), Novo Nordisk Foundation , Denmark (grant no. NNF19OC0058266 and NNF17OC0029404), HBM4EU, EU Horizon 2020 (grant no. 733032), Sygeforsikring Danmark (journalnr. 2021-0173). The Collaborative foundation between Odense University Hospital and Rigshospitalet, Helsefonden, Beckettfonden, the Danish Mental Health Fund, Health Insurance Denmark. The LS-MS/MS equipment was financially supported by the Velux Foundation . Publisher Copyright: © 2023 The Authors

PY - 2023/3/1

Y1 - 2023/3/1

N2 - Background: Phthalates are endocrine disrupters used in a variety of consumer products. Human studies suggest an association between phthalate exposure and cognitive development but adverse effects of the recently introduced phthalate substitutes have only been sparsely studied. Objectives: To investigate associations between prenatal and concurrent exposure to phthalates and IQ in 7-year-old children from the Odense Child Cohort. Methods: Pregnant women from the Odense Child Cohort had phthalate metabolites measured in urine samples during 3rd trimester in 2010 to 2012. In addition, phthalates were also measured in urine samples from their offspring at age 7 years. IQ was assessed at age 7 years using four subtests from Wechsler Intelligence Scale for Children. The total study population consisted of 585 mother-child pairs with available prenatal urinary phthalate metabolites concentrations and IQ data at age 7 years. A subset of those (N = 274) had urinary phthalate metabolites measured in child urine at age 7 years. Phthalate concentrations were grouped into tertiles and associations with IQ were investigated using multiple linear regression adjusting for sex, maternal education and maternal/child BMI. Results: Urinary phthalate metabolite concentrations both in pregnant women and children were generally lower compared to previous cohorts. Children with high prenatal urinary concentrations of MEP and metabolites of DEHP (∑DEHPm)(3rd tertile) had −3.1 (95% CI: −5.5, −0.6) (MEP) and − 3.0 (−5.5, −0.6) (∑DEHPm) IQ points at age 7 years compared to children with low concentrations (1st tertile). High concurrent urinary phthalate concentrations of MCPP, ∑DnHxPm, ∑DiDPm and ∑DiNPm in the 3rd tertile was associated with −3.7 (−7.2, −0.2), −4.4 (−7.9, −0.9), −3.7 (−7.2, −0.2) and − 5.6 (−9.1, −2.2) IQ points, respectively, compared to those with the lowest concentrations (1st tertile). Conclusion: We found significant inverse associations between some prenatal and concurrent urinary phthalate concentrations and IQ at age 7 years in this low exposed population. This suggests that exposure to phthalates both prenatally and during early childhood could be hazardous to child neurodevelopment, however, large-scale prospective studies assessing phthalate exposure through multiple urine samples, and possibly investigating cocktail effects of the chemicals as well as long term follow-up are warranted.

AB - Background: Phthalates are endocrine disrupters used in a variety of consumer products. Human studies suggest an association between phthalate exposure and cognitive development but adverse effects of the recently introduced phthalate substitutes have only been sparsely studied. Objectives: To investigate associations between prenatal and concurrent exposure to phthalates and IQ in 7-year-old children from the Odense Child Cohort. Methods: Pregnant women from the Odense Child Cohort had phthalate metabolites measured in urine samples during 3rd trimester in 2010 to 2012. In addition, phthalates were also measured in urine samples from their offspring at age 7 years. IQ was assessed at age 7 years using four subtests from Wechsler Intelligence Scale for Children. The total study population consisted of 585 mother-child pairs with available prenatal urinary phthalate metabolites concentrations and IQ data at age 7 years. A subset of those (N = 274) had urinary phthalate metabolites measured in child urine at age 7 years. Phthalate concentrations were grouped into tertiles and associations with IQ were investigated using multiple linear regression adjusting for sex, maternal education and maternal/child BMI. Results: Urinary phthalate metabolite concentrations both in pregnant women and children were generally lower compared to previous cohorts. Children with high prenatal urinary concentrations of MEP and metabolites of DEHP (∑DEHPm)(3rd tertile) had −3.1 (95% CI: −5.5, −0.6) (MEP) and − 3.0 (−5.5, −0.6) (∑DEHPm) IQ points at age 7 years compared to children with low concentrations (1st tertile). High concurrent urinary phthalate concentrations of MCPP, ∑DnHxPm, ∑DiDPm and ∑DiNPm in the 3rd tertile was associated with −3.7 (−7.2, −0.2), −4.4 (−7.9, −0.9), −3.7 (−7.2, −0.2) and − 5.6 (−9.1, −2.2) IQ points, respectively, compared to those with the lowest concentrations (1st tertile). Conclusion: We found significant inverse associations between some prenatal and concurrent urinary phthalate concentrations and IQ at age 7 years in this low exposed population. This suggests that exposure to phthalates both prenatally and during early childhood could be hazardous to child neurodevelopment, however, large-scale prospective studies assessing phthalate exposure through multiple urine samples, and possibly investigating cocktail effects of the chemicals as well as long term follow-up are warranted.

KW - Cognitive development

KW - Cohort study

KW - Endocrine disrupting chemicals

KW - Neurotoxicology

KW - Phthalates

KW - Teratology

U2 - 10.1016/j.ntt.2023.107161

DO - 10.1016/j.ntt.2023.107161

M3 - Journal article

C2 - 36690047

AN - SCOPUS:85146839711

SN - 0892-0362

VL - 96

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

M1 - 107161

ER -

Prenatal and current phthalate exposure and cognitive development in 7-year-old children from the Odense child cohort

Abstract

Bibliografisk note

Finansiering

Dokumenter og links

SDU link

Fingeraftryk

Relaterede projekter

Prenatal and early life PFAA exposure; impact on neuropsychological development in 1.5- to 7-year-old children in Odense Child Cohort

Citationsformater