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. 2022 Sep;212(Pt D):113555.
doi: 10.1016/j.envres.2022.113555. Epub 2022 May 22.

Prenatal organophosphorus pesticide exposure and executive function in preschool-aged children in the Norwegian Mother, Father and Child Cohort Study (MoBa)

Jake E Thistle  1 , Amanda Ramos  2 , Kyle R Roell  2 , Giehae Choi  3 , Cherrel K Manley  2 , Amber M Hall  2 , Gro D Villanger  4 , Enrique Cequier  5 , Amrit K Sakhi  5 , Cathrine Thomsen  5 , Pål Zeiner  6 , Ted Reichborn-Kjennerud  7 , Kristin R Øvergaard  6 , Amy Herring  8 , Heidi Aase  4 , Stephanie M Engel  2
Affiliations

Prenatal organophosphorus pesticide exposure and executive function in preschool-aged children in the Norwegian Mother, Father and Child Cohort Study (MoBa)

Jake E Thistle et al. Environ Res. 2022 Sep.

Abstract

Introduction: Prenatal exposure to organophosphorus pesticides (OPPs) has been associated with neurodevelopmental deficits in children, however evidence linking OPPs with specific cognitive mechanisms, such as executive function (EF), is limited.

Objective: This study aims to evaluate the association between prenatal exposure to OPPs with multiple measures of EF in preschool-aged children, while considering the role of variant alleles in OPP metabolism genes.

Methods: We included 262 children with preschool attention-deficit/hyperactivity disorder (ADHD), and 78 typically developing children, from the Preschool ADHD substudy of the Norwegian, Mother, Father, and Child Cohort Study. Participants who gave birth between 2004 and 2008 were invited to participate in an on-site clinical assessment when the child was approximately 3.5 years; measurements of EF included parent and teacher rating on Behavior Rating Inventory of Executive Function-Preschool (BRIEF-P), and three performance-based assessments. We measured OPP metabolites in maternal urines collected at ∼17 weeks' gestation to calculate total dimethyl- (ΣDMP) and diethyl phosphate (ΣDEP) metabolite concentrations. We estimated multivariable adjusted β's and 95% confidence intervals (CIs) corresponding to a change in z-score per unit increase in log-ΣDMP/DEP. We further characterized gene-OPP interactions for maternal variants in PON1 (Q192R, M55L), CYP1A2 (1548T > C), CYP1A1 (IntG > A) and CYP2A6 (-47A > C).

Results: Prenatal OPP metabolite concentrations were associated with worse parent and teacher ratings of emotional control, inhibition, and working memory. A one log-∑DMP increase was associated with poorer teacher ratings of EF on the BRIEF-P (e.g. emotional control domain: β = 0.55, 95% CI: 0.35, 0.74), when weighted to account for sampling procedures. We found less consistent associations with performance-based EF assessments. We found some evidence of modification for PON1 Q192R and CYP2A6 -47A > C. Association with other variants were inconsistent.

Conclusions: Biomarkers of prenatal OPP exposure were associated with more adverse teacher and parent ratings of EF in preschool-aged children.

Keywords: Executive function; MoBa; Organophosphorus pesticide; Prenatal exposure; Preschool ADHD.

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Figures

Figure 1.
Figure 1.. Association of log-∑DMP and log-∑DEP with preschool-aged measurements of executive function in regression analysis with weighting by sampling fractions
CI, confidence interval; DMP, dimethylphosphate, DEP, diethylphosphate, NEPSY, A Developmental NEuro-PSYchological Assessment a. Dimethyl- and diethyl phosphate metabolites concentrations were adjusted for specific gravity (SG) by standardizing to the geometric mean. Concentrations below the limit of detection were imputed from a log-normal distribution. Metabolites were summed by molar weight (∑DEP, ∑DMP), and log (natural) transformed. DEDTP was not included in ∑DEP as 99% of values were below the limit of detection. Samples were measured maternal spot urines collected at ~17 weeks’ gestation. b. β for change in z-score per unit increase in log-∑DMP/DEP standardized so higher scores correspond to worse executive function. Weighted to the population eligible for the ADHD substudy using sampling fractions. c. Adjusted for fruit consumption (servings/day), raw vegetable consumption (servings/day), age at childbirth, pre-pregnancy body mass index (kg/m2), maternal ADHD score, nulliparity, birth year, season of urine collection, and child sex.
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