title: In utero exposure to mixtures of xenoestrogens and child neuropsychological development.
abstract: BACKGROUND
  To date, no epidemiological studies have explored the impact and persistence of in utero exposure to mixtures of xenoestrogens on the developing brain. We aimed to assess whether the cumulative effect of xenoestrogens in the placenta is associated with altered infant neuropsychological functioning at two and at four years of age, and if associations differ among boys and girls.
  
  
  METHODS
  Cumulative prenatal exposure to xenoestrogens was quantified in the placenta using the biomarker Total Effective Xenoestrogen Burden (TEXB-alpha) in 489 participants from the INMA (Childhood and the Environment) Project. TEXB-alpha was split in tertiles to test its association with the mental and psychomotor scores of the Bayley Scales of Infant Development (BSID) at 1-2 years of age, and with the McCarthy Scales of Children׳s Abilities (MSCA) general cognitive index and motor scale assessed at 4-5 years of age. Interactions with sex were investigated.
  
  
  RESULTS
  After adjustment for potential confounders, no association was observed between TEXB-alpha and mental scores at 1-2 years of age. We found a significant interactions with sex for the association between TEXB-alpha and infant psychomotor development (interaction p-value=0.029). Boys in the third tertile of exposure scored on average 5.2 points less than those in the first tertile on tests of motor development at 1-2 years of age (p-value=0.052), while no associations were observed in girls. However, this association disappeared in children at 4-5 years of age and no association between TEXB-alpha and children׳s cognition was found.
  
  
  CONCLUSIONS
  Our results suggest that boys' early motor development might be more vulnerable to prenatal exposure to mixtures of xenoestrogens, but associations do not persist in preschool children.
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), C/ Doctor Aiguader, 83. 08003 Barcelona, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), Barcelona, Spain. Electronic address: nvilahur@creal.cat.
authors.forename: Nadia
authors.initials: N
authors.lastname: Vilahur
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Department of Radiology, Centro de Investigación Biomédica, University of Granada, Granada, Spain; Instituto de Investigación Biosanitaria de Granada, Hospital Universitario San Cecilio, Granada, Spain.
authors.forename: Mariana F
authors.initials: MF
authors.lastname: Fernández
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), C/ Doctor Aiguader, 83. 08003 Barcelona, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Genomics and Disease Group, Bioinformatics and Genomics Program, Centre for Genomic Regulation (CRG), Barcelona, Spain.
authors.forename: Mariona
authors.initials: M
authors.lastname: Bustamante
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Department of Radiology, Centro de Investigación Biomédica, University of Granada, Granada, Spain.
authors.forename: Rosa
authors.initials: R
authors.lastname: Ramos
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), C/ Doctor Aiguader, 83. 08003 Barcelona, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain; Department of Genes and Environment, Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway.
authors.forename: Joan
authors.initials: J
authors.lastname: Forns
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Centre for Public Health Research (CSISP-FISABIO), Valencia, Spain; University of Valencia, Valencia, Spain.
authors.forename: Ferran
authors.initials: F
authors.lastname: Ballester
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Centre for Public Health Research (CSISP-FISABIO), Valencia, Spain.
authors.forename: Mario
authors.initials: M
authors.lastname: Murcia
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; University of Oviedo, Asturias, Oviedo, Spain.
authors.forename: Isolina
authors.initials: I
authors.lastname: Riaño
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Biodonostia, Health Research Institute, San Sebastián, Spain; Sub-Directorate for Public Health of Gipuzkoa, Department of Health, Government of the Basque Country, San Sebastian, Spain.
authors.forename: Jesús
authors.initials: J
authors.lastname: Ibarluzea
authors.affiliation: CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Department of Radiology, Centro de Investigación Biomédica, University of Granada, Granada, Spain.
authors.forename: Nicolás
authors.initials: N
authors.lastname: Olea
authors.affiliation: Center for Research in Environmental Epidemiology (CREAL), C/ Doctor Aiguader, 83. 08003 Barcelona, Spain; Hospital del Mar Research Institute (IMIM), Barcelona, Spain; CIBER Epidemiología y Salud Pública (CIBERESP), Spain; Department of Health and Life Sciences, University Pompeu Fabra (UPF), Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Sunyer
mesh_terms: D002675:Child, Preschool; D004967:Estrogens / Q000633:toxicity*; D005260:Female; D006801:Humans; D009483:Neuropsychological Tests; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D015262:Xenobiotics / Q000633:toxicity*
chemical_list: D004967:Estrogens; D015262:Xenobiotics
keywords: Mixtures; Neuropsychological development; Placenta; Sex; TEXB; Xenoestrogens