title: Maternal stress modifies the effect of exposure to lead during pregnancy and 24-month old children's neurodevelopment.
abstract: Lead and psychosocial stress disrupt similar but not completely overlapping mechanisms. Exposure during the prenatal period to each of these insults singularly has been found to alter normal neurodevelopment; however, longitudinal associations with stress modifying the effect of lead have not been sufficiently analyzed in epidemiologic studies.
  
  
  
  To evaluate prenatal stress as an effect modifier of gestational lead neurotoxicity.
  
  
  
  We used a structural equations modeling approach with a trivariate response to evaluate cognitive, language and motor scores of the Bayley Scales of Infant Development-III in 24month-old children (n=360). Maternal blood lead levels were measured at the 2nd and 3rd trimester and psychosocial stress during pregnancy was assessed using a negative life events (NLE) scale derived from the CRYSIS questionnaire.
  
  
  
  3rd trimester lead (mean 3.9±3.0 SDμg/dL) and stress (median=3 NLE) were negatively associated with Bayley III scores. Using the model's results we generated profiles for 0, 2, 4 and 6 NLE across lead levels (up to 10μg/dL) and observed a dose-response for the developmental scores when lead levels were below 2μg/dL. Each NLE curve had a different shape across increasing lead levels. Higher stress (NLE=6) resulted in lower cognitive scores for both sexes, in lower language scores in girls but not boys. In the absence of stress we saw a negative association with lead for all scores, however for language and motor scores, higher stress seemed to mask this association.
  
  
  
  Our work examined and confirmed prenatal stress exposure as a modifier of the well-known neurotoxic effects of prenatal lead. It adds to the existing evidence pointing at the importance of studying the co-exposure of chemical and non-chemical exposures, specifically of considering the emotional environment of children at early developmental stages of life.
authors.affiliation: National Council of Science and Technology, Avenida Insurgentes Sur 1582, Benito Juárez, Crédito Constructor, 03940 Ciudad de México, D.F., México. Electronic address: mtamayo@hsph.harvard.edu.
authors.forename: Marcela
authors.initials: M
authors.lastname: Tamayo Y Ortiz
authors.affiliation: National Institute of Public Health, Universidad No. 655 Colonia Santa María, Ahuacatitlán, Cerrada Los Pinos y Caminera, C.P. 62100, Cuernavaca, Morelos, México. Electronic address: mmtellez@insp.mx.
authors.forename: Martha María
authors.initials: MM
authors.lastname: Téllez-Rojo
authors.affiliation: National Institute of Public Health, Universidad No. 655 Colonia Santa María, Ahuacatitlán, Cerrada Los Pinos y Caminera, C.P. 62100, Cuernavaca, Morelos, México. Electronic address: bvaldivia@insp.mx.
authors.forename: Belem
authors.initials: B
authors.lastname: Trejo-Valdivia
authors.affiliation: National Institute of Perinatology, Calle Montes Urales #800, Miguel Hidalgo, Lomas Virreyes, 11000 Ciudad de México, D.F., México. Electronic address: lschnaas@hotmail.com.
authors.forename: Lourdes
authors.initials: L
authors.lastname: Schnaas
authors.affiliation: National Institute of Perinatology, Calle Montes Urales #800, Miguel Hidalgo, Lomas Virreyes, 11000 Ciudad de México, D.F., México. Electronic address: erikaosorio4@hotmail.com.
authors.forename: Erika
authors.initials: E
authors.lastname: Osorio-Valencia
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, United States. Electronic address: bcoull@hsph.harvard.edu.
authors.forename: Brent
authors.initials: B
authors.lastname: Coull
authors.affiliation: Department Environmental Health, Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Boston, MA 02115, United States. Electronic address: david.bellinger@childrens.harvard.edu.
authors.forename: David
authors.initials: D
authors.lastname: Bellinger
authors.affiliation: Department of Pediatrics, Icahn School of Medicine at Mount Sinai, 1428 Madison Ave, New York, NY 10029, United States. Electronic address: rosalind.wright@mssm.edu.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Wright
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, 1428 Madison Ave, New York, NY 10029, United States. Electronic address: robert.wright@mssm.edu.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
mesh_terms: D000328:Adult; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D003071:Cognition; D005260:Female; D006801:Humans; D007804:Language Development; D007854:Lead / Q000009:adverse effects* / Q000097:blood; D008297:Male; D018811:Maternal Exposure; D009048:Motor Skills; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects; D013315:Stress, Psychological; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D007854:Lead
keywords: Effect modification; Lead; Neurodevelopment; Prenatal; Stress