title: Prenatal particulate air pollution and neurodevelopment in urban children: Examining sensitive windows and sex-specific associations.
abstract: BACKGROUND
  Brain growth and structural organization occurs in stages beginning prenatally. Toxicants may impact neurodevelopment differently dependent upon exposure timing and fetal sex.
  
  
  OBJECTIVE
  We implemented innovative methodology to identify sensitive windows for the associations between prenatal particulate matter with diameter ≤ 2.5 μm (PM2.5) and children's neurodevelopment.
  
  
  METHODS
  We assessed 267 full-term urban children's prenatal daily PM2.5 exposure using a validated satellite-based spatio-temporally resolved prediction model. Outcomes included IQ (WISC-IV), attention (omission errors [OEs], commission errors [CEs], hit reaction time [HRT], and HRT standard error [HRT-SE] on the Conners' CPT-II), and memory (general memory [GM] index and its components - verbal [VEM] and visual [VIM] memory, and attention-concentration [AC] indices on the WRAML-2) assessed at age 6.5±0.98 years. To identify the role of exposure timing, we used distributed lag models to examine associations between weekly prenatal PM2.5 exposure and neurodevelopment. Sex-specific associations were also examined.
  
  
  RESULTS
  Mothers were primarily minorities (60% Hispanic, 25% black); 69% had ≤12 years of education. Adjusting for maternal age, education, race, and smoking, we found associations between higher PM2.5 levels at 31-38 weeks with lower IQ, at 20-26 weeks gestation with increased OEs, at 32-36 weeks with slower HRT, and at 22-40 weeks with increased HRT-SE among boys, while significant associations were found in memory domains in girls (higher PM2.5 exposure at 18-26 weeks with reduced VIM, at 12-20 weeks with reduced GM).
  
  
  CONCLUSIONS
  Increased PM2.5 exposure in specific prenatal windows may be associated with poorer function across memory and attention domains with variable associations based on sex. Refined determination of time window- and sex-specific associations may enhance insight into underlying mechanisms and identification of vulnerable subgroups.
authors.affiliation: Kravis Children's Hospital, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Yueh-Hsiu Mathilda
authors.initials: YH
authors.lastname: Chiu
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Hsiao-Hsien Leon
authors.initials: HH
authors.lastname: Hsu
authors.affiliation: Department of Biostatistics, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Brent A
authors.initials: BA
authors.lastname: Coull
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Neurology Research, Children's Hospital Boston, Harvard Medical School, Boston, MA, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Bellinger
authors.affiliation: Department of Geography and Environmental Development, Ben-Gurion University of the Negev, Israel.
authors.forename: Itai
authors.initials: I
authors.lastname: Kloog
authors.affiliation: Department of Environmental Health, Harvard T.H. Chan School of Public Health, Boston, MA, USA; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA.
authors.forename: Joel
authors.initials: J
authors.lastname: Schwartz
authors.affiliation: Department of Preventive Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health & Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Robert O
authors.initials: RO
authors.lastname: Wright
authors.affiliation: Kravis Children's Hospital, Department of Pediatrics, Icahn School of Medicine at Mount Sinai, New York, NY, USA; The Mindich Child Health & Development Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. Electronic address: rosalind.wright@mssm.edu.
authors.forename: Rosalind J
authors.initials: RJ
authors.lastname: Wright
mesh_terms: D000393:Air Pollutants / Q000032:analysis / Q000633:toxicity*; D001288:Attention / Q000187:drug effects; D002648:Child; D002657:Child Development / Q000187:drug effects; D002675:Child, Preschool; D005260:Female; D005865:Gestational Age; D006801:Humans; D007360:Intelligence / Q000187:drug effects; D008297:Male; D018811:Maternal Exposure / Q000009:adverse effects*; D008568:Memory / Q000187:drug effects; D008962:Models, Theoretical; D065886:Neurodevelopmental Disorders / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D052638:Particulate Matter / Q000032:analysis / Q000633:toxicity*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000139:chemically induced* / Q000453:epidemiology / Q000503:physiopathology; D012737:Sex Factors; D012907:Smoking; D014481:United States; D014505:Urban Population
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter
keywords: Air pollution; Neurodevelopment; Particulate matter; Prenatal exposure; Sensitive windows; Sex-specific associations