A systematic review of neurodevelopmental effects of prenatal and postnatal organophosphate pesticide exposure
Introduction
Earlier restrictions on the use of some persistent pesticides have led to the use of non-persistent alternatives such as organophosphates (OPs), carbamates and pyrethroids, which are very useful for controlling pests in both agricultural and residential settings. Intensive use of these compounds is posing a significant risk to public health because of their potential adverse effects. Exposure to pesticides does not only affect those who use them occupationally, as the general population is also exposed to low concentrations through foodstuffs and the environment throughout their lifetime. There is scientific evidence of the carcinogenic, neurological, reproductive, immunological and genotoxic effects associated with exposure to non-persistent pesticides in adults (Koureas et al., 2012). However, little information is available about the effects in children, although researchers have observed a higher risk of adverse reproductive effects (Eskenazi et al., 2004, Lacasaña et al., 2006, Rauch et al., 2012) and changes in the nervous system and in neurobehavioural development (Bouchard et al., 2010, Engel et al., 2011, Eskenazi et al., 2007, Marks et al., 2010, Rauh et al., 2012). This means that the neurotoxic effects of these compounds on children's central nervous systems could be causing a series of subclinical neurodevelopmental disorders. This has been termed a ‘silent pandemic’ and could have major health, economic and social impact (Grandjean and Landrigan, 2006).
Toxicological studies in animals have provided information about the neurotoxicity mechanisms and adverse effects of non-persistent pesticides. For example, Maurissen (2000) and Rice and Barone (2000) observed changes in the nervous system development and sensory, motor and cognitive cerebral function of rodents associated with prenatal and early postnatal exposure to chlorpyrifos. Prenatal exposure even to low concentrations of chlorpyrifos also affects rodents’ organogenesis (Tian et al., 2005) and leads to behavioural changes such as hyperactivity and working and reference memory deficit.
Factors such as age, sex, nutritional status, lifestyle and genetic variability can modify the effects of non-persistent pesticides in children, who are particularly susceptible to these compounds. The health risks derived from exposure to toxic agents are strongly influenced by genetics as a result of the variability of the genes that code for metabolising enzymes (Costa et al., 2003, Eaton et al., 1998, Furlong, 2007). The different possible combinations of these polymorphisms can determine favourable or unfavourable metabolic configurations, either facilitating the breakdown of some neurotoxic compounds, or bioactivating initially inactive compounds or delaying the metabolic breakdown of active compounds (Costa et al., 2005a, Costa et al., 2005b, Guo et al., 2012). Recent studies have analysed the effect of different paraoxonase-1 (PON1) polymorphisms on neurodevelopment in children. Certain genotypes (PON1–108TT, PON1192QR and PON1192RR) may be associated with reduced mental and motor development in children exposed to OP pesticides (Engel et al., 2011, Eskenazi et al., 2010).
The limited number of epidemiological studies available and the huge variability of the methodologies used to assess exposure to OP pesticides and its effects on neurodevelopment in children make it difficult to compare their results. The aim of this review is to carry out a detailed analysis of the evidence gathered in the studies performed to date, taking into account some of the factors that can modify the effects of these pesticides, such as sex and gender differences, genetic variability and epigenetic factors. This will provide a better overview of the relationship between exposure to OP pesticides and neurodevelopment and behaviour in children.
Section snippets
Search strategy
A systematic review of articles in the PubMed, Scopus, Embase and Lilacs databases was carried out using the following key words or text word combinations: “organophosphates” OR “organophosphorus”, “child” OR “infant”, “neurodevelopment”, “neurobehavioral” OR “neurobehavioural” (for more details see Supplemental Material, annex I).
Inclusion and exclusion criteria
The articles selected for the review met the following inclusion criteria: (a) original articles; (b) published before or during December 2012; (c) written in
Results
134 articles were identified using the search strategy described above. Twenty of those met the inclusion criteria, 7 of which analysed prenatal exposure to OP pesticides, 8 analysed postnatal exposure, and 5 analysed both pre- and postnatal exposure. Cohort studies were the most frequent design (n = 10), followed by cross-sectional (n = 9) and case-control (n = 1) studies. The methodological quality of studies on prenatal exposure was high (n = 9) or moderate (n = 3), while that of studies on postnatal
Effects potentially associated with prenatal and postnatal exposure to OPs
The results of the aforementioned studies suggest that prenatal exposure to OP pesticides may affect neurodevelopment and behaviour in infancy and childhood as well as children's cognitive and motor function.
The average maternal urinary DAPs in the studies reviewed ranged from 81.3 nmol/L (Engel et al., 2007) to 132 nmol/L (Young et al., 2005). These levels are slightly higher than those found in the pregnant women who took part in the National Health and Nutrition Survey 1999–2000 (NHANES),
Conclusions
The studies included in this review used a wide variety of different designs and methods to evaluate the effects of OP pesticide exposure on neurodevelopment and behaviour in children, and this makes it difficult to compare their results. The studies reviewed suggest that exposure during pregnancy may have a negative effect on the child's mental and motor development and behaviour during the first stages of childhood. The effects associated with postnatal exposure are less consistent, although
Conflict of interest
The authors declare that there are no conflicts of interest.
Acknowledgements
This study was partially supported by grants from the Council of Innovation of the Andalusian Government (reference number P08-CTS-04313, FEDER funds), the Institute of Health Carlos III (reference numbers PI10/01101 and FIS-FEDER 11/02038) and the European Union (EU FP7-ENV-2011 DENAMIC 2cod 28957).
The content of this article is part of the PhD thesis of Beatriz Gonzalez-Alzaga which was conducted at the University of Granada under the doctoral programme “Clinical Medicine and Public Health”.
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