Background

Animal studies suggest that organophosphorus pesticides (OPs) may be environmental obesogens. While prenatal OP exposures have been associated with altered infant glucose metabolism, associations with pediatric adiposity remain unknown.

Methods

We summed concentrations of three dimethylphosphate (∑DMP) and three diethylphosphate (∑DEP) metabolites of OPs measured in third trimester spot urine samples collected from pregnant women enrolled in New York City, 1998–2002. We measured percent fat mass using bio-electrical impedance analysis and calculated age- and sex-standardized body mass index (BMI) z-scores from anthropometric measurements collected at approximately 4, 6, and 7–9 years of age (166 children, 333 observations). We assessed covariate-adjusted associations of OPs with repeated adiposity measures using linear mixed models and evaluated effect measure modification (EMM) by sex and paroxonase (PON) 1 –108C/T and Q192R polymorphisms measured in maternal peripheral blood samples.

Results

The geometric mean urinary concentration of ∑DMP metabolites (29.9 nmol/L, IQR: 105.2 nmol/L) was higher than ∑DEP metabolites (8.8 nmol/L, IQR: 31.2 nmol/L). Adjusted associations were null, with differences in fat mass per 10-fold increase in prenatal ∑DMP and ∑DEP concentrations of 0.7% (95% CI: −0.6, 2.0) and 0.8% (95% CI: −0.4, 2.0), respectively. Maternal PON1-108C/T polymorphisms modified relationships of prenatal ∑DMP with percent fat mass (EMM p-value = 0.18) and ∑DEP with BMI z-scores (EMM p-value = 0.12). For example, ∑DMP was modestly associated with increased percent fat mass among children of mothers with the at-risk CT or TT genotype (β = 1.2%, 95% CI: −0.6, 3.0) but not among those whose mothers had the CC genotype (β = −0.4%, 95% CI: −2.4, 1.5). Associations were not modified by sex or maternal PON1 Q192R polymorphisms.

Conclusions

We observed little evidence of a relationship between prenatal OP exposures and child adiposity, although there was some suggestion of increased risk among offspring of mothers who were slow OP metabolizers. Larger studies are warranted to further evaluate possible associations of prenatal OP exposures with child adiposity and differences by maternal PON1 genotype, which regulates OP metabolism and may increase susceptibility to exposure.

中文翻译：

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西奈山儿童环境健康研究中的产前母体有机磷农药暴露、对氧磷酶 1 和儿童肥胖。

背景

动物研究表明，有机磷农药 (OP) 可能是环境致癌物。虽然产前 OP 暴露与婴儿葡萄糖代谢改变有关，但与儿童肥胖的关联仍然未知。

方法

我们总结了从 1998-2002 年在纽约市登记的孕妇收集的妊娠晚期尿液样本中测得的 OP 的三种磷酸二甲酯 (∑DMP) 和三种磷酸二乙酯 (∑DEP) 代谢物的浓度。我们使用生物电阻抗分析测量脂肪量百分比，并根据在大约 4、6 和 7-9 岁（166 名儿童、333观察）。我们使用线性混合模型评估了 OP 与重复肥胖测量的协变量调整关联，并评估了性别和帕罗氧磷酶 ( PON) 1 –108C/T和Q192R多态性在母体外周血样本中测量的效应测量修正 (EMM)。

结果

∑DMP 代谢物的几何平均尿液浓度（29.9 nmol/L，IQR：105.2 nmol/L）高于 ∑DEP 代谢物（8.8 nmol/L，IQR：31.2 nmol/L）。调整后的关联无效，产前 ∑DMP 和 ∑DEP 浓度每增加 10 倍，脂肪量的差异分别为 0.7%（95% CI：-0.6、2.0）和 0.8%（95% CI：-0.4、2.0），分别。母体PON1 -108C /T多态性改变了产前 ∑DMP 与脂肪量百分比（EMM p 值 = 0.18）和 ∑DEP 与 BMI z 分数（EMM p 值 = 0.12）的关系。例如，∑DMP 与具有高危 CT 或 TT 基因型（β = 1.2%，95% CI：-0.6, 3.0）的母亲所生子女的脂肪量百分比增加适度相关，但与母亲患有 CC 的子女无关基因型 (β = −0.4%, 95% CI: −2.4, 1.5)。关联未因性别或母体PON1 Q192R 多态性而改变。

结论

我们几乎没有观察到产前 OP 暴露与儿童肥胖之间关系的证据，尽管有一些迹象表明 OP 代谢缓慢的母亲的后代风险增加。需要更大规模的研究来进一步评估产前 OP 暴露与儿童肥胖的可能关联以及母体PON1基因型的差异，PON1 基因型调节 OP 代谢并可能增加暴露的易感性。