Abstract
BackgroundPesticide 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.MethodsA 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.ResultsFindings 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).ConclusionsObservational 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.
Highlights
Pesticide exposure during susceptible windows and at certain doses are linked to numerous birth defects
Experimental evidence suggests that ingredients in pesticides may alter the HPE-associated Sonic Hedgehog (Shh) signaling pathway, possibly leading to an increased risk for holoprosencephaly [12]
In accordance with previous findings, among the HPE cases, 23.6% of tested probands had positive status for a mutation in one of the four most common genes associated with HPE, while maternal pregestational diabetes was found in 8 cases (9.2%) and 0 controls [10, 18]
Summary
Pesticide exposure during susceptible windows and at certain doses are linked to numerous birth defects. 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). This study investigated pesticides during multiple windows of exposure and fetal risk for HPE. As with other birth defects, the etiology of HPE is complex with genetic and environmental factors thought to interact and interfere with forebrain development [1]. While relatively common in utero, HPE often results in spontaneous abortions and has a birth rate of 1 in 10,000 [3,4,5], making epidemiologic studies identifying non-genetic risk factors more difficult. Experimental evidence suggests that ingredients in pesticides may alter the HPE-associated Sonic Hedgehog (Shh) signaling pathway, possibly leading to an increased risk for holoprosencephaly [12]
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