Associations of maternal o,p′-DDT and p,p′-DDE levels with birth outcomes in a Bolivian cohort
Introduction
Organochlorine pesticides (OCPs) have long been widely used as very effective pest control agents (UNEP, 1999). Many OCPs are lipophilic chemicals that are highly resistant to biodegradation, which facilitates their bioaccumulation in organisms and biomagnification up the food chain, especially in lipid-rich compartments (Olea et al., 2001, UNEP, 2012).
The pesticide dichlorodiphenyltrichloroethane (DDT) has been used worldwide in agriculture and for vector control since 1939 (Turusov et al., 2002). From the early 1970s, most countries have banned or severely restricted the production, handling, and disposal of many OCPs, including DDT, due to their high persistence in the environment and their proven or suspected clinical effects at doses earlier considered safe (UNEP, 2002, UNEP, 2003, UNEP, 2012). This has caused a substantial decline in levels of exposure in the countries where the prohibition was applied (Longnecker et al., 1997), although virtually all human populations still have detectable levels of OCPs in blood or adipose tissues (Porta et al., 2008). Furthermore, DDT is still used in several countries, either legally (e.g., in vector control campaigns) or illegally. Disease vector control campaigns alone involve the annual release of 4–5000 t of DDT worldwide (van den Berg, 2009). Thus, it has been reported that certain population groups are exposed to relatively high doses of this pesticide due to its recent utilization (Mercado et al., 2013, Rollin et al., 2009) or through their diet, especially fatty foods, considered the main source of exposure of OCPs in non-occupationally exposed populations (Dougherty et al., 2000).
Technical-grade DDT comprises a mixture of around 85% p,p′-DDT and 15% o,p′-DDT isomers (ATSDR, 2002). Once in the environment or living organisms, DDT is mainly metabolized to p,p´-dichlorodiphenyldichloroethylene (p,p′-DDE), which is even more persistent than its parent compound (UNEP, 1999). In fact, p,p′-DDE has been detected in most human populations, even those from regions in which DDT has long been banned or has never been used (CDC, 2009, Dewailly et al., 1999). p,p′-DDE levels are considered to indicate historic exposure to the parent compounds and/or direct exposure to this metabolite (Kezios et al., 2013), while p,p′- and o,p′-DDT are considered markers of recent exposure to the pesticide.
Agricultural activities accounted for 13.3% of the Gross Domestic Product in Bolivia in 2009 (INE, 2016), and 1.5 t OCPs were reported to be stored at disposal sites in 2004 (Ministerio de Desarrollo Sostenible, 2004). Although DDT was banned in the country in 1996, there is evidence of an illegal trade (UNEP, 2002), and a sample of Bolivian agricultural workers were found to have serum p,p´-DDE levels around 20-fold higher than those observed in a Bolivian urban population (Arrebola et al., 2012a, Arrebola et al., 2012b, Mercado et al., 2013).
It is known that both o,p′-DDT and p,p′-DDE can cross the placenta (Luzardo et al., 2009). Exposure during pregnancy can be particularly harmful for the mother (Arrebola et al., 2014) and for the developing fetus, which is especially sensitive to the action of certain environmental pollutants (Vizcaino et al., 2014). In fact, critical windows of development have been identified in which exposure to these chemicals might lead to fetal growth impairment (Windham and Fenster, 2008) and irreversible, pathological changes in adult life (Braw-Tal, 2010). Fetal growth is frequently assessed using surrogate measures at delivery, e.g. newborn weight, height and length of gestation, which are also risk factors for future morbidity during infancy and adulthood (Windham and Fenster, 2008). Potential mechanisms of action for fetal growth disruption might include the ability of these compounds to interfere with estrogen and androgen homeostasis (Li et al., 2008) and even thyroid function (Yaglova and Yaglov, 2015). In fact, neonatal TSH levels have been associated with both low birth weight (Korada et al., 2009) and maternal exposure to OCPs (Freire et al., 2013) and might therefore be a plausible mediator of the effect of these pollutants. Other potential mechanisms of DDT include the potential induction of epigenetic modifications in obesity-related genes, which can even be detected in the third generation of offspring (Skinner et al., 2013). However, the epidemiological evidence remains controversial (Fenster et al., 2006, Lenters et al., 2016, Longnecker et al., 2001, Lopez-Espinosa et al., 2011, Weisskopf et al., 2005), with discrepancies that might be related to different study designs, matrices for exposure assessment, biological endpoints, and/or population characteristics, including highly varied levels of exposure to DDT and its metabolites.
The aim of this study was to examine the potential association of cord blood serum levels of o,p′-DDT and p,p′-DDE with newborn anthropometric measurements, thyroid-stimulating hormone (TSH) levels, and length of gestation in a birth cohort from Santa Cruz de la Sierra, Bolivia. We also assessed the potential mediating effect of newborn TSH levels in associations with birth size and length of gestation. The study adds to the extensive literature on associations between OCPs and birth outcomes by investigating a high-level exposed population that exhibits indications of recent exposure to the DDT parent compounds, unlike in most previous studies.
Section snippets
Study area and population
Santa Cruz de la Sierra, the city with the largest population in Bolivia (1,500,000 inhabitants), is located in the eastern part of the country (Santa Cruz Region) at an altitude of 416 m above sea level. The economy of the city and its suburbs represents 35% of the Gross Domestic Product of Bolivia and is based on the hydrocarbon industry, logging, and agriculture. Around 80% of the total agricultural product of the country is grown in this tropical region, which has an average annual
Description of the study population and exposure levels
Table 1, Table 2 exhibit the main maternal and birth outcome characteristics, respectively, of the study population. Median maternal age at delivery was 23 yrs, and newborns had a median weight of 3390 g. There was a slightly higher proportion (55%) of female newborns, and mothers were predominantly non-smokers (96.5%), multiparous (62.5%), manual workers (86%), and living with an unmarried partner (72%). According to the WHO, a total of 59 (29.5%) mothers were classified as overweight/obese
Discussion
The majority of participants in this study of a Bolivian birth cohort had detectable serum levels of o,p′-DDT and p,p′-DDE. Our main findings were an association between prenatal exposure to p,p′-DDE and shorter gestational duration and a differential impact of o,p′-DDT and p,p′-DDE on fetal weight gain. To our best knowledge, this represents the first study of these characteristics in Bolivia and one of the very first in South America (Adetona et al., 2013, Benítez-Leite et al., 2007,
Conclusions
We contribute evidence on the potential impact of prenatal exposure to o,p′-DDT and p,p′-DDE on birth anthropometric measures and gestational length in a birth cohort recruited in Santa Cruz de la Sierra, Bolivia. These effects do not appear to be mediated by newborn TSH disruption.
Acknowledgments
The authors are indebted to all the participants and staff from Hospital de la Mujer Dr. Percy Boland, without whom this study would have been impossible. Authors are also grateful to Richard Davies for editorial assistance.
This study was partially supported by grants from the Andalusian Regional Government and European Regional Development Fund – FEDER (PI-0513-2012, EF-0708-2013, and BA15/00093). During this work, Dr JP Arrebola was first under a postdoctoral contract from the Junta de
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