Elsevier

NeuroToxicology

Volume 59, March 2017, Pages 65-70
NeuroToxicology

Full Length Article
In utero exposure to fluoride and cognitive development delay in infants

https://doi.org/10.1016/j.neuro.2016.12.011Get rights and content

Highlights

  • Enrolled 65 mother-baby pairs in an endemic hydrofluorosis area in Mexico.

  • Pregnant women from endemic hydrofluorosis areas had high levels of fluoride in urine.

  • Maternal exposure to Fluoride was negatively associated with cognitive functions in infants.

Abstract

The objective of this study was to evaluate the association between in utero exposure to fluoride (F) and Mental and Psychomotor Development (MDI and PDI) evaluated through the Bayley Scale of Infant Development II (BSDI-II) in infants. The sample included 65 mother-infant pairs. Environmental exposure to F was quantified in tap and bottled water samples and F in maternal urine was the biological exposure indicator; samples were collected during the 1st, 2nd and 3rd trimester of pregnancy. The mean values of F in tap water for the 1st, 2nd and 3rd trimester were 2.6 ± 1.1 mg/l, 3.1 ± 1.1 mg/l and 3.7 ± 1.0 mg/l respectively; above to 80% of the samples exceeded the reference value of 1.5 mg/l (NOM-127-SSA1-1994). Regarding F in maternal urine, mean values were 1.9 ± 1.0 mg/l, 2.0 ± 1.1 mg/l and 2.7 ± 1.1 mg/l for the 1st, 2nd and 3rd trimester respectively. The infants with MDI and PDI scores less than 85 points were 38.5% and 20.9% respectively. After adjusting for potential confounding factors (gestational age, age of child, marginalization index and type of water for consumption), the MDI showed an inverse association with F levels in maternal urine for the first (β = −19.05, p = 0.04) and second trimester (β = −19.34, p = 0.01). Our data suggests that cognitive alterations in children born from exposed mothers to F could start in early prenatal stages of life.

Introduction

Fluorides are naturally-occurring components in rocks and soil and are also found in air, water, plants, and animals. The general population is exposed to fluoride (F) through the consumption of drinking water, foodstuff, and dental products. Populations living in areas with naturally high F levels in water and soil may be exposed to high levels of F in water, especially if drinking water is provided from wells (ATSDR, 2003, Vineet Dhar1, 2009). In the central and north areas of Mexico there are groundwater with elevated levels of F (Ortega-Guerrero, 2009). In this areas, almost 90% of the population has the practice of use tap water for food preparation and direct consumption as drinking water (Jarquín-Yañez et al., 2015). The bioavailability of F through ingestion 80–100% (ATSDR, 2003).

Epidemiological research conducted in school age children living in endemic hydrofluorosis areas have evaluated the influence of exposure of F on cognitive development assessed as intelligence quotient scores (IQ). Different intelligence tests have been used (RAVEN-Chinese version, Wechsler Intelligence Scales, Stanford-Binet Intelligence Scale) and have reported lower IQ points associated with F exposure at concentrations of 2.20–3.94 mg/l compared with residents from control areas (concentrations of F in water <0.41 mg/l). The lack of biomarkers of exposure and control of potential confounders is an issue that has to be considered in these studies (Karimzade et al., 2014, Trivedi et al., 2012). Other well conducted research papers also reported that F decreases IQ scores (Ding et al., 2011, Rocha-Amador et al., 2007).

Cognitive development alterations associated with F exposure could start in early prenatal stages of life and come up later at school age; and likely continue into adulthood. Few studies have explored this hypothesis and the evidence is inconclusive. For example, Chinese newborns; scored lower in the Standard Neonatal Behavioral Neurological Assessment (NBNA) test in the high exposure group (F in urine 3.58 ± 1.47) compared with the control group (1.74 ± 0.96 mg/l); 36.48 ± 1.09 vs 38.28 ± 1.10, p < 0.05, respectively (Li et al., 2008). Another study in aborted fetuses of mothers living in an endemic hydrofluorosis area (4.3 ± 2.9 mg/l of F in urine) reported changes in neurotransmitters compared with levels of aborted fetuses of mothers living in non-endemic areas (F in urine 1.67 ± 0.8 mg/l) (Yu et al., 2008). Regarding experimental studies, data shows that F accumulates in the brain, specifically in the hippocampus; a region associated with memory, attention and learning (Shivarajashankara et al., 2001, Bhatnagar et al., 2006, Basha et al., 2011). About gestational exposure, some experimental studies, indicated that F alters learning and memory (Mullenix et al., 1995, Bera et al., 2007, Basha et al., 2011).

In endemic hydrofluorosis areas millions of people consume contaminated water daily, including pregnant women and there is evidence that support the F capacity to cross the placental and the blood-brain barriers and accumulate in critical areas of the brain related to cognitive development. The objective of this research was to evaluate the influence of in utero exposure to F in Mexicans infants born from mothers living in endemic hydrofluorosis areas on the Mental and Psychomotor Development (MDI and PDI) through the Bayley Scale of Infant Development II (BSDI-II).

Section snippets

Participants and recruitment

Authorizations from the authorities of the Ministry of Health (SSA) of the selected municipalities included for the study were obtained. The project protocol was conducted in accordance with the Declaration of Helsinki and was approved by the bioethics committees of the SSA from the municipalities. Follow up was conducted in pregnant women recruited from 2013 to 2014 who received prenatal care in health centers located in Durango City and Lagos de Moreno, Jalisco, Mexico. Both are endemic

Results

Table 1 shows the comparison of general characteristics of the pregnant women between participants in the biological monitoring and the women who agreed to their child’s cognitive evaluation. The average age of the participants was 22.4 ± 4.0, in education 41.5% of the participants had completed high school. Regarding marital status, 69.7% of the participants were married, 70.7% of the participants reported being housewives, and for 44.6% of the participants it was their first birth. About

Discussion

The objective of this research was to evaluate the influence of in utero exposure to F on Mental and Psychomotor Development evaluated through the BSDI II in Mexican children born from mothers living in endemic hydrofluorosis areas. The proportion of children with values of MDI less than minus one standard deviation (SD) was 38.5%; scores under 85 points are considered as an indicator of possible developmental delay. This test evaluates psychological processes such as attention, memory, sensory

Conclusion

Due the importance of cognitive development in children and the amount of people (millions) exposed daily; more studies need to be conducted to support the in utero exposure of F and effects in young children. Considering previous data supporting the potential neurotoxicity of F in school-age children, preventive measures in affected communities should be implemented (communication programs, treatments water methods and a continuous monitoring to guarantee water quality) to decrease the F

Conflict of interest

None.

Acknowledgements

The authors acknowledge the financial support of this research by CONACYT with number 181577, FONSEC 2012 and the University of Guanajuato through DAIP support with number FO-DAI-05, 2013. The present work was carried out during the first period of the first author postdoctoral training (fellowship number 239404).

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