Abstract
Background: Childhood wheeze may be related to pesticide exposure, and diet and genetics (Paroxonase; PON1) may modify the effects of exposure. Methods: We analyzed data from the HOME Study, a prospective pregnancy and birth cohort, to examine the association of gestational urinary organophosphate (OP) and pyrethroid (3PBA) metabolite concentrations with child wheeze, forced expiratory volume in one second (FEV1) at ages 4 and 5 years, and wheeze trajectory patterns through age 8 years. Results: Among 367 singletons, the frequency of wheeze ranged from 10.6% to 24.1% at each measurement age. OP and 3PBA metabolite concentrations were not associated with wheeze at 8 years or from birth to 8 years, but there were three significant interactions: (1) maternal daily fruit and vegetable consumption (less than daily consumption and increasing 3PBA was associated with wheeze at age 8 years, OR = 1.40), (2) maternal PON1-108 allele (CT/TT genotypes and high DE was associated with wheeze at age 8 years, OR = 2.13, 2.74) and (3) PON1192 alleles (QR/RR genotypes with higher diethylphosphate (DE) and dialkyl phosphate (DAP) were associated with wheeze at age 8 years, OR = 3.84). Pesticide metabolites were not consistently related to FEV1 or wheeze trajectory. Conclusions: Gestational OP and 3PBA metabolites were associated with child respiratory outcomes in participants with maternal dietary and genetic susceptibility.
Highlights
The prevalence of asthma in children has increased over the past four decades. in 2017, the lifetime prevalence among all children younger than 18 was 8.4%; the prevalence was higher amongAfrican American (12.6%), Hispanic (11.3%), and low-income children (11.0%) [1]
We considered variables which could be related to respiratory health and wheeze, such as serum cotinine measured in maternal samples collected at 16 weeks and 26 weeks gestation using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) [32,33]. the cotinine assay limit of detection (LOD) was 0.015 ng/mL, with a coefficient of variation (CV) ranging from 3 to 4% at high concentrations (1 ng/mL) to 10% at low concentrations (0.1 ng/mL) [34]
Waswheeze no interaction between maternal gestational 3-Phenoxybenzoic acid (3PBA) metabolites and PON1−108 alleles with child wheeze at age 8 years, but the associations between OP metabolites and child wheeze trended toward significance. the relationship of higher maternal diethyl phosphate (DE) and dialkyl phosphate (DAP) metabolite concentration with higher odds of wheezing for those with CC alleles versus those with TT alleles among white children was similar to what we found in the unstratified analysis
Summary
The prevalence of asthma in children has increased over the past four decades. in 2017, the lifetime prevalence among all children younger than 18 was 8.4%; the prevalence was higher amongAfrican American (12.6%), Hispanic (11.3%), and low-income children (11.0%) [1]. The prevalence of asthma in children has increased over the past four decades. Childhood wheeze may be related to pesticide exposure, and diet and genetics (Paroxonase; PON1) may modify the effects of exposure. OP and 3PBA metabolite concentrations were not associated with wheeze at 8 years or from birth to 8 years, but there were three significant interactions: (1) maternal daily fruit and vegetable consumption (less than daily consumption and increasing 3PBA was associated with wheeze at age 8 years, OR = 1.40), (2) maternal PON1-108 allele (CT/TT genotypes and high DE was associated with wheeze at age 8 years, OR = 2.13, 2.74) and (3) PON1192 alleles (QR/RR genotypes with higher diethylphosphate (DE) and dialkyl phosphate (DAP) were associated with wheeze at age. Pesticide metabolites were not consistently related to FEV1 or wheeze trajectory
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