A mother’s exposure to fluoride during pregnancy could lower the intelligence of her children, researchers say.

Following a group of Mexican children from the time of their mother’s pregnancy to early adolescence, an international team of researchers found an association between high fluoride levels in the mothers’ urine and reduced scores on the children’s cognitive tests.

Contrary to the claims of fluoride activists, however, the study does not seal the case against fluoride, said first author Morteza Bashash, PhD, an assistant professor of public health at the University of Toronto in Canada.

“This is a piece of a puzzle,” he told Medscape Medical News. “We need to do more work to identify the nature of the effect. And we have a lot uncertainty in the results.”

Published September 19 in Environmental Health Perspectives, the study adds significantly to the body of data on fluoride’s effects because it followed a relatively large group for more than a decade, Dr Bashash said. “This kind of birth cohort study is considered a gold standard to determine what happened over time that eventually leads to some sort of outcome.”

Studies in rodents have shown that fluoride can alter their cognition and behavior, and researchers in China have found an association between human intelligence quotient (IQ) deficits and exposure to high levels of fluoride in water, as reported in a National Research Council review.

To probe this association further, Dr Bashash and colleagues examined data from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) project, a longitudinal study designed to explore the effects of toxins in Mexican children.

Two cohorts from the ELEMENT study comprised 997 mothers recruited from hospitals serving populations with low or moderate incomes from 1997 to 2001.

The women were all in at least their 14th week of gestation at the time of recruitment; planned to stay in the Mexico City area for at least 5 years; did not report a history of psychiatric disorders, high-risk pregnancies, or gestational diabetes or current use of daily alcohol, illegal drugs, or continuous prescription drugs; and were not diagnosed with preeclampsia, renal disease, circulatory diseases, hypertension, and seizures during the index pregnancy. For the current analysis, the researchers excluded mothers younger than 18 years, those without adequate urine samples, and those whose fluoride concentrations were extreme outliers.

When the children reached 4 years of age, they took the McCarthy Scales of Children’s Abilities test. Between ages 6 and 12 years, they took the Wechsler Abbreviated Scale of Intelligence test.

The researchers were able to obtain 287 mother–child pairs with data for the McCarthy test and 211 with data for the Wechsler test. On both tests, an average score is between 85 and 115, with a higher score indicating better performance.

The researchers found a significant correlation between General Cognitive Index (GCI), as measured by the McCarthy test, and IQ, as measured by the Wechsler test (Spearman r = 0.55; P < .01).

They found that for every increase of 0.5 mg/L in fluoride in the mother’s urine, the children’s GCIs changed by a mean score of ?3.76 (95% confidence interval [CI], ?6.32 to ?1.19).

Likewise, every increase of 0.5 mg/L in the mother’s urinary fluoride was associated with a change of ?2.37 in IQ (95% CI, ?4.45 to ?0.29).

The association remained after the researchers adjusted for child-related factors (gestational age and weight at birth, sex, being the first child, and age at outcome measurement) and maternal factors (smoking history, marital status, age at delivery, IQ, education, and cohort). The adjustments changed the decrease per 0.5 mg/L of maternal urinary fluoride in GCI to ?3.15 (95% CI, ?5:42 to ?0:87) and changed the decrease in IQ to ?2.50 (95% CI, ?4.12 to ?0:59).

For a subset of children with data available on socioeconomic status, maternal bone lead, and blood mercury, the researchers controlled for these variables as well and found that the association between maternal urinary fluoride and GCI and IQ did not change substantially.

The researchers found that GCI decreased with each increase in maternal urinary fluoride in a linear relationship. But the decrease in IQ only began at 0.8 mg fluoride per liter of maternal urine.

When they focused their analysis on fluoride in the children’s urine, they found no significant association with the prenatal concentration of fluoride in the mothers’ urine.

In addition, they found no statistically significant association between fluoride in the children’s urine and their IQ. (The authors did not report on a relationship of children’s urinary fluoride and GCI.)

The results justify further research, Dr Bashash said. He would like to follow the children to look for cognitive associations with fluoride as they get older, and he would like to look for other adverse events. Some colleagues are analyzing data on sexual maturation, he said.

However, whether enough evidence has accumulated to make policy recommendations, he could not say. “Decision making in medicine and public policy requires some sort of compromise and measurement of the risk and benefit,” he said. “There is a big argument. We know that fluoride has some beneficial effect in preventing caries. We show that there is a potential that it has some negative impact, too. Our piece of work gives the opportunity to help policymakers to make an informed decision.”

Others were less hesitant. In a press release, the antifluoride group the Fluoride Action Network wrote that the study “confirms” that fluoride is harmful to the fetal brain.

Philippe Grandjean, MD, PhD, adjunct professor of environmental health at Harvard University in Cambridge, Massachusetts, did not go quite that far, but said it adds to the evidence for rethinking fluoridation. “I think the study is a red flag,” he told Medscape Medical News. “And when you take it into consideration with the Chinese studies, I think the time is way overdue for a broad-scale reevaluation of fluoride exposure.”

Other methods of preventing dental caries might be more effective, making fluoridated water obsolete, he suggested.

The American Dental Association, in contrast, released a statement calling into question the applicability of the data to the United States. In both the United States and Mexico, naturally occurring levels of fluoride in water vary widely, but in the United States, many communities add fluoride to water, whereas in Mexico, fluoride is added to salt, the organization pointed out, so it is difficult to compare levels of exposure. The American Dental Association declined to respond to questions about its analysis.

Scott Tomar, DMD, MPH, DrPH, who has served as a consultant to the American Dental Association, challenged the study’s conclusions. “I think it’s more hypothesis-generating in my view than any definitive evidence of any association between fluoride content in either salt or water and either IQ or cognitive development,” he told Medscape Medical News.

The scatter plot of the data appears almost random for both IQ and GCI, said Dr Tomar, professor of community dentistry and behavioral science at the University of Florida in Gainesville. And the level at which the IQ data becomes significant is above the level at which fluoride in urine would be found in someone drinking fluoridated water in the United States, he said. (The recommended level of fluoridation in the United States varies between 0.7 and 1.2 mg/L, depending on a region’s mean temperature.)

The study was well designed, Dr Tomar said, but still it could not rule out other factors that might confound the results, such as toxins other than lead and mercury.

Furthermore, he said, children’s IQs in the United States have been increasing since the 1980s, even as more communities fluoridated their water.

“It’s not that I’m closing my mind to potential adverse effects,” he said. “But I’d say at a minimum we’d want to see a similar kind of observational study repeated in another environment, whether it’s in the United States or another country.”

This study was supported by the National Institutes of Health, the National Institute of Environmental Health Sciences/the US Environmental Protection Agency, and the National Institute of Public Health/Ministry of Health of Mexico. The authors, Dr Tomar, and Dr Grandjean have disclosed no relevant financial relationships.

*Original article online at http://www.medscape.com/viewarticle/886379#vp_1