Gestational organophosphate ester exposure and preschool attention-deficit/hyperactivity disorder in the Norwegian Mother, Father, and Child cohort study

Amber M Hall; Amanda M Ramos; Samantha Sm Drover; Giehae Choi; Alexander P Keil; David B Richardson; Chantel L Martin; Andrew F Olshan; Gro D Villanger; Ted Reichborn-Kjennerud; Pål Zeiner; Kristin R Øvergaard; Amrit K Sakhi; Cathrine Thomsen; Heidi Aase; Stephanie M Engel

doi:10.1016/j.ijheh.2022.114078

Gestational organophosphate ester exposure and preschool attention-deficit/hyperactivity disorder in the Norwegian Mother, Father, and Child cohort study

Int J Hyg Environ Health. 2023 Mar:248:114078. doi: 10.1016/j.ijheh.2022.114078. Epub 2022 Nov 28.

Authors

Amber M Hall¹, Amanda M Ramos², Samantha Sm Drover³, Giehae Choi⁴, Alexander P Keil², David B Richardson², Chantel L Martin², Andrew F Olshan², Gro D Villanger⁵, Ted Reichborn-Kjennerud⁶, Pål Zeiner⁷, Kristin R Øvergaard⁸, Amrit K Sakhi⁹, Cathrine Thomsen⁹, Heidi Aase⁵, Stephanie M Engel²

Affiliations

¹ Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA. Electronic address: amber_hall@brown.edu.
² Department of Epidemiology, Gillings School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
³ Department of Public Health Sciences, School of Medicine, Queen's University, Kingston, Ontario, Canada.
⁴ Department of Environmental Health and Engineering, Johns Hopkins University, Baltimore, MD, USA.
⁵ Department of Child Health and Development, Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
⁶ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Department of Mental Disorders, Division of Mental and Physical Health, Norwegian Institute of Public Health, Oslo, Norway.
⁷ Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁸ Institute of Clinical Medicine, University of Oslo, Oslo, Norway; Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway.
⁹ Department of Food Safety, Division of Climate and Environmental Health, Norwegian Institute of Public Health, Oslo, Norway.

Abstract

Background: Attention-deficit/hyperactivity-disorder (ADHD) is a leading neurodevelopmental disorder in children worldwide; however, few modifiable risk factors have been identified. Organophosphate esters (OPEs) are ubiquitous chemical compounds that are increasingly prevalent as a replacement for other regulated chemicals. Current research has linked OPEs to neurodevelopmental deficits. The purpose of this study was to assess gestational OPE exposure on clinically-assessed ADHD in children at age 3 years.

Methods: In this nested case-control study within the Norwegian Mother, Father, and Child Cohort study, we evaluated the impact of OPE exposure at 17 weeks' gestation on preschool-age ADHD. Between 2007 and 2011, 260 ADHD cases were identified using the Preschool Age Psychiatric Assessment and compared to a birth-year-stratified control group of 549 children. We categorized bis(2-butoxyethyl) phosphate (BBOEP) and bis(1,3-dichloro-2-propyl) phosphate (BDCIPP) as values < limit of detection (LOD) (BBOEP N = 386, BDCIPP N = 632), ≥LOD but < limit of quantification (LOQ) (BBOEP N = 413; BDCIPP N = 75), or above LOQ (BBOEP N = 70; BDCIPP N = 102). Diphenyl phosphate (DPhP) and di-n-butyl phosphate (DnBP) were categorized as quartiles and also modeled with a log10 linear term. We estimated multivariable adjusted odds ratios (ORs) using logistic regression and examined modification by sex using an augmented product term approach.

Results: Mothers in the 3rd DnBP quartile had 1.71 times the odds of having a child with ADHD compared to the 1st quartile (95%CI: 1.13, 2.58); a similar trend was observed for log10 DnBP and ADHD. Mothers with BDCIPP ≥ LOD but < LOQ had 1.39 times the odds of having a child with ADHD compared to those with BDCIPP < LOD (95%CI: 0.83, 2.31). Girls had lower odds of ADHD with increasing BBOEP exposure (log10 OR: 0.55 (95%CI: 0.37, 0.93), however boys had a weakly increased odds (log10 OR: 1.25 (95%CI: 0.74, 2.11) p-interaction = 0.01].

Conclusions: We found modest increased odds of preschool ADHD with higher DnBP and BDCIPP exposure.

Keywords: ADHD; Flame retardant; MoBa; Neurodevelopment; Organophosphate ester; Preschool.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, N.I.H., Intramural

MeSH terms

Attention Deficit Disorder with Hyperactivity* / epidemiology
Case-Control Studies
Child
Child, Preschool
Cohort Studies
Esters
Fathers
Female
Flame Retardants*
Humans
Male
Mothers
Norway / epidemiology
Organophosphates
Phosphates

Substances

bis(2-butoxyethyl)phosphate
dinoseb
Flame Retardants
Organophosphates
Phosphates
Esters

Abstract

Publication types

MeSH terms

Substances

Grants and funding