Abstract

PURPOSE: The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes.

PARTICIPANTS: n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico.

FINDINGS TO DATE: Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling.

FUTURE PLANS: As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures.

Excerpts

ELEMENT 2015

Between 2015 and 2018, we followed-up children in ELEMENT 2011 through late adolescence and included additional similarly aged participants from the original cohorts. Goals of this study were similar in scope to ELEMENT 2011, but included new research foci: (1) characterising long-term consequences of early life exposure to fluoride; (2) exploring epigenetic and metabolomics mechanisms.

… In 2015, we rerecruited 224 of 250 ELEMENT 2011 participants. We also recruited 330 additional offsprings who were of similar age to ELEMENT 2011 participants, giving priority to those who had archived cord blood and urine samples and/or having been part of ELEMENT 2008. Additional data collected for 2015 included physical activity and sleep data from accelerometers; measures of fluoride exposure in food/beverages, water and plasma; and dental examinations for caries, enamel fluorosis and hypomineralisation…

Fluoride

Finally, a programme of research on the potential neurotoxicity of early life exposure to fluoride was recently started, with initial findings suggesting that prenatal fluoride exposure is associated with reduced measures of intelligence⁷⁶ as well as increased symptoms of ADHD in pre-school and elementary school age children.⁷⁷ Additionally, urinary fluoride concentrations were cross-sectionally associated with later pubic hair growth and genital development in boys aged 10–17 years, but not significantly related to pubertal development in girls.⁷⁸

References

77. Bashash M, Thomas D, Hu H, et al. Prenatal fluoride exposure and cognitive outcomes in children at 4 and 6-12 years of age in Mexico. Environ Health Perspect 2017; 125:097017.

77. Bashash M, Marchand M, Hu H, et al. Prenatal fluoride exposure and attention deficit hyperactivity disorder (ADHD) symptoms in children at 6-12years of age in Mexico City. Environ Int 2018; 121:658–66.

78. Liu Y, Téllez-Rojo M, Hu H, et al. Fluoride exposure and pubertal development in children living in Mexico City. Environmental Health 2019;18.

 

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