母亲孕期拟除虫菊酯类农药暴露对1岁儿童淋巴细胞影响的队列研究OA

[Background]Pyrethroid pesticides(PYRs)can cross the placental barrier to cause intrauterine fetal exposure,which may lead to developmental immunotoxicity(DIT).However,the specific ef-fect of maternal PYR exposure during pregnancy on the cellular immune function of 1-year-old children remains unclear. [Objective]To explore the effect of PYRs exposure throughout the entire pregnancy on peripheral blood lymphocytes in 1-year-old children and potential sensitive window period of PYRs exposure. [Methods]A birth cohort was established by enrolling pregnant women in their first trimester and following them and their infants until one year of age.Ultra-high performance liquid chromatography-tandem mass spectrometry was used to detect the levels of PYRs metabolites,including 3-phenoxybenzoic acid(3PBA),4-fluoro-3-phenoxybenzoic acid(4F3PBA),and cis-3-(2,2-dichlorovinyl)-2,2-dimethylcyclopropane carboxylic acid(cis-DBCA),in the urine of pregnant women during the first trimester(gestational weeks 6-12),the second trimester(gestational weeks 21-24),and the third trimester(gestational weeks 33-36).Peripheral blood leukocyte and lymphocyte counts were measured in children at 12 months of age using the Coulter principle combined with flow cytometry.Exposure levels of PYRs metabolites in each trimester were divided into low,moderate,and high exposure groups based on the 25th(P25)and 75th(P75)per-centiles.Meanwhile,participants were classified as having repeated high or low exposure if their metabolite levels were>P75 or<P25 in at least two trimesters,respectively,while all others were categorized as having repeated moderate exposure.Generalized linear models were used to analyze the associations between trimester-specific and repeated PYRs metabolite exposure levels and the peripheral blood white blood cell(WBC)and lymphocyte counts in children aged 1 year. [Results]A total of 336 mother-child pairs were included in this study.For the pregnant women,the total detection rates of maternal urinary 3PBA,4F3PBA,and cis-DBCA across the three trimesters of pregnancy were 80.5％,100.0％,and 81.3％,respectively;and median creatinine-corrected concentrations were 0.24,0.36,and 0.42 μg·g-1,respectively.In children aged 1 year,the mean WBC and lymphocyte counts in peripheral blood were(8.9±2.0)×109·L-1 and(5.7±1.6)×109·L-1,respectively.The results of the generalized linear model analysis indicated that compared to the low exposure group,the high cis-DBCA exposure group during the third trimester of pregnancy had sig-nificantly lower peripheral blood WBC count(β=-0.87,95％CI:-1.51,-0.23)and lymphocyte count(β=-0.64,95％CI:-1.15,-0.13);and the repeated high-exposure group of cis-DBCA had significantly lower peripheral blood WBC count(β=-1.34,95％CI:-2.34,-0.34)and lymphocyte count(β=-0.80,95％CI:-1.60,-0.01)than the repeated low exposure group.Similarly,the repeated moderate-exposure group of cis-DBCA had a significantly lower peripheral blood WBC count(β=-0.83,95％CI:-1.59,-0.07)than the repeated low exposure group. [Conclusion]High maternal exposure to PYRs with cis-DBCA as the major metabolite exposure is associated with decreased peripheral leukocyte and lymphocyte counts in children aged 1 year,and repeated high-level exposure throughout gestation appears to exacerbate DIT in offspring.The third trimester of pregnancy maybe a sensitive window for children's DIT induced by exposure to PYRs during preg-nancy.