Research Article: Organophosphate exposures during pregnancy and child neurodevelopment: Recommendations for essential policy reforms

Date Published: October 24, 2018

Publisher: Public Library of Science

Author(s): Irva Hertz-Picciotto, Jennifer B. Sass, Stephanie Engel, Deborah H. Bennett, Asa Bradman, Brenda Eskenazi, Bruce Lanphear, Robin Whyatt

Abstract: In a Policy Forum, Irva Hertz-Picciotto and colleagues review the scientific evidence linking organophosphate pesticides to cognitive, behavioral, and neurological deficits in children and recommend actions to reduce exposures.

Partial Text: Organophosphate (OP) compounds were originally developed as human nerve gas agents during the 1930s–1940s, and some were later adapted as insecticides at lower doses [1]. High exposure to OP compounds leads to acute poisoning from the irreversible inhibition of the enzyme acetylcholinesterase (AChE), resulting in cholinergic syndrome (including narrowed pupils, excessive salivation, bronchoconstriction, mental confusion, convulsions or tremors, and in some cases, death). Additionally, delayed polyneuropathy has been described in association with high exposures [1].

Systematic reviews and multiple epidemiologic studies in the US and other countries, spanning diverse populations in both urban and agricultural settings, have linked OP exposures during fetal development with poorer cognitive, behavioral, and social development in children [7–11]. Generally, levels of exposure in these studies are too low to induce measurable depression of cholinesterase in adults. In one review, adverse effects of OP pesticide exposure on neurodevelopment were seen in all but one of the 27 studies evaluated; the strongest associations occurred following prenatal exposures [9]. Outcomes associated with OP pesticide exposure to the fetus include abnormal primitive reflexes in newborns; mental and motor delays among preschoolers; and decreases in working and visual memory, processing speed, verbal comprehension, perceptual reasoning, and IQ among elementary school–age children. Prenatal exposures also elevated risks for symptoms or diagnoses of attention-deficit/hyperactivity disorder (ADHD) and autism spectrum disorder (ASD).

Critical to understanding the influences on early child neurodevelopment is the distinction between acute effects after high-level exposures versus sequelae from chronic lower exposures. As noted above, by inhibiting the enzyme AChE, high-level OPs cause acute, in some cases fatal, effects in humans [2]. Indeed, internationally, pesticide poisonings take a heavy toll, estimated at 200,000 deaths per year [24], with approximately 99% occurring in developing countries [25]. About 110,000 pesticide self-poisoning deaths occur each year globally, which represents an average across the reporting countries of 13.7% of all suicides [26], with a wide range from 0.9% in low- and middle-income European countries to 48.3% for low- and middle-income countries of the Western Pacific region.

Pesticide regulations vary widely across the globe. As with pesticide usage, no database has consolidated this information for all countries. Table 1 shows available data on 47 OP insecticides [36] banned by one or more countries, as well as the level of health hazard and the number of countries that have banned each OP pesticide. The most comprehensive database available on current governmental regulation of pesticides provides data covering 39 of these 47 OP insecticides, obtained from 106 countries outside the US [37]. Included in this database are total bans, along with denials of approval, but not restrictions. Of the 106 countries, 81% have regulated one or more of the 39 OP insecticides [37]. The 28 countries of the European Union have taken action on the most OP pesticides (33). Additional countries that have banned more than 10 include the US (26), Cambodia (15), China (15), Saudi Arabia (15), Guinea (12), Korea (12), Mauritania (12), and Thailand (12). Notably, having regulations in place does not necessarily mean that they are enforced. Furthermore, some of the most toxic OP pesticides that are banned across dozens of countries are exported elsewhere, often to developing countries and sometimes in large quantities, for example, to Costa Rica and Guatemala [27]. In Mexico, at least a dozen OP pesticides that are classified as highly hazardous by the WHO Food and Agriculture Organization are used [38].

In 2014, the American Academy of Pediatrics called for pediatricians and governments to recognize and reduce pesticide exposures through education, pesticide labeling, public health surveillance, and regulatory action [47]. In 2016, an independent group of scientists and health professionals published the Project TENDR Consensus Statement as a national call to action to significantly reduce exposures to chemicals—including OP pesticides—that have been identified as putting children in the US, and likely throughout the world, at increased risk of neurodevelopmental disorders [48]. Project TENDR concluded that the evidence of significant risks to children’s neurodevelopment from OP pesticide exposure warrants strong regulatory action. In 2017, a United Nations report on the Right to Food called for changes to agricultural practices to ensure food that is safe, free from pesticides, and qualitatively adequate [24]. To achieve the goal of reducing exposures to OP insecticides, we therefore propose an action plan for governments, public health and medical institutions or organizations, and agricultural entities. Our recommendations are detailed in Box 1. These steps would markedly reduce prenatal and childhood exposures to OP pesticides.



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