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Higher fluoride intake during pregnancy was associated with lower IQ scores in boys, a Canadian study found.

Among 512 mother-child pairs, each 1-mg/L increase in maternal urinary fluoride concentration was associated with a decrease of 4.49 (95% CI -8.4 to -0.6) Full Scale IQ points for boys at 3 to 4 years after adjusting for demographic and quality-of-home variables, reported Christine Till, PhD, of York University in Toronto, and colleagues.

However, higher maternal fluoride levels were not associated with lower IQ scores for girls of the same age (+2.43 points per 1-mg/L, 95% CI -2.53 to 7.33), the researchers wrote in . Till and colleagues offered no explanation for the sex difference, saying only that "further investigation" is needed to determine "whether boys are potentially more vulnerable to neurocognitive effects associated with fluoride exposure."

Safety of water fluoridation has been debated for decades, Till told MedPage Today. "We realized there were major questions about the safety of fluoride even in 2015 when we started proposing this study, and especially for pregnant women and young children," she said. "We knew we needed data, regardless of whether it showed an effect or no effect, to address this major gap in knowledge."

U.S. cities have been to their water systems since the 1940s; by 2012, nearly three-quarters of the nation's water systems had fluoridated water. In 2015, the U.S. Public Health Service recommended an of 0.7 mg/L to balance the risk of dental fluorosis and benefit of protecting against dental caries.

A few studies testing whether maternal fluoride consumption had neurodevelopmental impacts on children have reinforced the safety concerns, wrote David Bellinger, PhD, MSc, of Harvard Medical School in Boston, in an .

One in 2013 found levels of fluoride comparable to the amount added to U.S. drinking water were not linked to IQ, but a mostly taking place in China did find negative neurodevelopmental impacts -- though at fluoride levels far greater than seen in the U.S.

Perhaps the strongest evidence supporting a neurotoxic effect was a conducted in Mexico, where the mean maternal urinary fluoride level (0.9 mg/L) was closer to U.S. norms, Bellinger noted. In this study, fluoride concentration in mothers' urine was inversely associated with cognitive scores in children. Unlike the present study by Till and her team, however, the Mexican study found no difference in neurodevelopment by sex.

"Research on fluoride as a potential neurodevelopmental toxicant is still at an early stage, and compelling weight of evidence from high-quality epidemiological studies has not yet developed," Bellinger cautioned.

However, considering fluoride exposure appears to be increasing, "the total cognitive loss at the population level that might be associated with children's prenatal exposure to fluoride could be substantial," he wrote. "If the hypothesis is true, the implications are worrisome."

Because of the topic's contentious nature, this study was subjected to additional scrutiny before its publication, noted JAMA Pediatrics Associate Editor Dimitri A. Christakis, MD, MPH, of the University of Washington in Seattle, in a .

"This study is neither the first, nor will it be the last, to test the association between prenatal fluoride exposure and cognitive development," Christakis said. "We hope that purveyors and consumers of these findings are mindful of that as the implications of this study are debated in the public arena."

Bellinger raised the possibility that IQ could be "just the tip of the iceberg" and questioned whether certain developmental domains may be more vulnerable to maternal fluoride exposure than others. It also remains unknown whether there is a certain threshold for maternal fluoride concentration and whether staying within this threshold could still be considered safe for in utero development, he noted.

Study details and other highlights

Women in this study were recruited from six Canadian cities as part of the (MIREC) cohort within the first 14 weeks of their pregnancy.

Their fluoride consumption was measured through urine spot samples at each trimester of pregnancy. Data from self-reported questionnaires administered in the first and third trimester that asked about drinking habits was also available for 400 mother-child pairs. As a third measure, researchers used standardized water treatment plant records to estimate how much fluoride was likely consumed per household based on postal codes.

About 90% of mothers were white. Upwards of two-thirds had completed at least a bachelor's degree and had household incomes of more than C$70,000.

The median maternal urinary fluoride concentration was 0.41 mg/L, with women living in areas with fluoridated drinking water having significantly higher mean concentrations than those who did not (0.69, SD 0.42, vs 0.40 mg/L, SD 0.27), the authors reported. Similarly, the median fluoride intake was higher for women in the former group than the latter.

Moreover, each overall 1-mg increase in estimated fluoride consumption by mothers during pregnancy was associated with a reduction of 3.7 points (95% CI −7.16 to −0.15, P=0.04) on IQ scores among boys and girls, Till and her team reported. There was no significant sex difference, however.

Findings did not substantially change after adjusting for concentrations of other metals including lead, mercury, and arsenic, nor did adjustment for creatinine levels in maternal urinary fluoride levels make a notable difference.

Among the study's limitations, Till and her team noted that urinary fluoride has a half-life of about 5 hours and that it could be affected by the consumption of other products, such as toothpaste or non-fluoridated bottled water. Also, maternal urinary fluoride concentrations are used as a proxy for in utero exposure, but the authors did not directly measure fetal intake. Finally, the authors did not have data on postnatal fluoride exposure, nor did their analyses adjust for maternal IQ or household income.