Prenatal exposure to pesticides and risk for holoprosencephaly: a case-control study
Prenatal exposure to pesticides and risk for holoprosencephaly: a case-control study
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DOI：
10.1186/s12940-020-00611-z
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发表时间：
2020-06-08
影响因子：
6
通讯作者：
Muenke, Maximilian
中科院分区：
文献类型：
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作者：
Addissie, Yonit A.;Kruszka, Paul;Muenke, Maximilian
背景在易感窗口期和特定剂量下接触农药与许多出生缺陷有关。早期的实验证据表明，杀虫剂中的活性成分与前脑无裂畸形（HPE）之间存在关联，HPE是人类前脑最常见的畸形（250个胚胎中有1个）。迄今为止，还没有人类研究检查过这种关联。本研究调查了多个暴露窗口期间的农药和HPE的胎儿风险。据推测，怀孕前和怀孕早期，即子宫内大脑发育的时间，是最关键的暴露窗口。方法采用回顾性病例对照研究设计问卷，评估家庭、职业和环境农药暴露情况。考虑了四个暴露窗口：孕前、妊娠早期、中期和晚期。病例是通过国家人类基因组研究所正在进行的HPE临床研究确定的。同样，对照组被确定为患有Williams-Beuren综合征的儿童，这是一种遗传综合征，也以先天性畸形为特征，但在病因学上与HPE无关。我们评估了病例和对照组之间暴露于农药的几率差异。结果91例病例和56例对照的研究结果显示，母亲在怀孕期间暴露于包括个人驱虫剂（校正比值比（aOR）2.89，置信区间（CI）：0.96-9.50）和宠物杀虫剂和杀螨剂（aOR 3.84，CI：1.04-16.32）在内的选定农药的HPE风险增加。在孕前或怀孕期间暴露于家庭害虫控制产品与HPE风险增加相关（aOR 2.60，OR：0.84-8.68）。虽然接触率很低，但没有发现怀孕期间职业接触农药的相关性（aOR：1.15，CI：0.11-11.42）。居住在农田附近的HPE可能性也更高（aOR 3.24，CI：0.94-12.31）。结论：观察结果与实验证据一致，表明妊娠期间暴露于个人、家庭和农业农药可能会增加HPE的风险。进一步研究基因与环境的相互作用是必要的。
Background Pesticide exposure during susceptible windows and at certain doses are linked to numerous birth defects. Early experimental evidence suggests an association between active ingredients in pesticides and holoprosencephaly (HPE), the most common malformation of the forebrain in humans (1 in 250 embryos). No human studies to date have examined the association. This study investigated pesticides during multiple windows of exposure and fetal risk for HPE. It is hypothesized that pre-conception and early pregnancy, the time of brain development in utero, are the most critical windows of exposure. Methods A questionnaire was developed for this retrospective case-control study to estimate household, occupational, and environmental pesticide exposures. Four windows of exposure were considered: preconception, early, mid and late pregnancy. Cases were identified through the National Human Genome Research Institute's ongoing clinical studies of HPE. Similarly, controls were identified as children with Williams-Beuren syndrome, a genetic syndrome also characterized by congenital malformations, but etiologically unrelated to HPE. We assessed for differences in odds of exposures to pesticides between cases and controls. Results Findings from 91 cases and 56 controls showed an increased risk for HPE with reports of maternal exposure during pregnancy to select pesticides including personal insect repellants (adjusted odds ratio (aOR) 2.89, confidence interval (CI): 0.96-9.50) and insecticides and acaricides for pets (aOR 3.84, CI:1.04-16.32). Exposure to household pest control products during the preconception period or during pregnancy was associated with increased risk for HPE (aOR 2.60, OR: 0.84-8.68). No associations were found for occupational exposures to pesticides during pregnancy (aOR: 1.15, CI: 0.11-11.42), although exposure rates were low. Higher likelihood for HPE was also observed with residency next to an agricultural field (aOR 3.24, CI: 0.94-12.31). Conclusions Observational findings are consistent with experimental evidence and suggest that exposure to personal, household, and agricultural pesticides during pregnancy may increase risk for HPE. Further investigations of gene by environment interactions are warranted.