Pregnant women’s fluoride intake was associated with a reduction in their children’s IQ at ages 3 to 5 years, in an observational study published online today in JAMA Pediatrics.

… “Given there was limited evidence to support or refute fluoride safety, we weren’t really sure what to expect in the Canadian population, so we let the data tell the story,” lead author Christine Till, PhD, CPsych, an associate professor of psychology at York University in Toronto, Ontario, Canada, told Medscape Medical News.

“We’re certainly concerned about the size of the effect we’re seeing,” she said, but she acknowledged research in this field is in its early stages. “In terms of where we go from here, it will really depend on policymakers and public health scientists to weigh the benefits and risks of fluoridation, and our hope is that our results combined with other recent studies are going to inform this.” …

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… F. Perry Wilson, MD, MSCE, an associate professor of medicine and interim director of the Yale University School of Medicine’s Program of Applied Translational Research in New Haven, Connecticut, told Medscape Medical News that the biostatistical analysis looks solid. However, unmeasured confounders, such as maternal IQ, and other limitations remain, including the use of urine concentration instead of blood concentration, the latter being more precise for assessing potential fetal exposure, he said.

“In the end, it’s an interesting observational study which adds importantly to the existing literature in this space by examining the lower end of fluoride exposure,” said Wilson, who is writing a separate commentary about the study for Medscape Medical News. Past studies have mostly examined populations with extremely high fluoride exposure, he said, “but the subtle overall effect, isolated only to boys, and the presence of unmeasured confounding means we should be quite cautious about jumping to conclusions.”

But Scott Tomar, DMD, MPH, DrPH, a professor of dental public health at the University of Florida College of Medicine in Gainesville, was more skeptical of the findings. Tomar, a consultant to the US Food and Drug Administration (FDA) and American Dental Association, questioned why the only association seen in the urinary concentration analysis is in boys and how much the data supported the conclusions given that most participants consumed less than 1 mg/L of fluoride daily.

“I really don’t think this should have an effect on the policy of recommending water fluoridation in the United States or Canada,” Tomar told Medscape Medical News. “There’s nothing remotely resembling a linear relationship in the range at which the overwhelming majority of these subjects fell.” …

… “I think this is one of the most rigorous studies published in this whole field because they are using biological markers,” a substantial improvement over previous epidemiological studies that used only geographic or other indicators to determine fluoride exposure levels, said Howard Hu, MD, ScD, an affiliate professor in environmental and occupational health science at the University of Washington in Seattle. Hu was a coauthor, along with some authors from the current study, on the only previous study to use a biomarker in pregnant women, also urinary concentration, in Mexico City. He said that “urinary concentration tends to be more stable than blood concentration.”

“It would be hard to criticize this study as being subject to confounding or bias. The sensitivity analyses that were done strengthen the ability to conclude that the relationships they found were quite strong,” Hu said. However, he stopped short of making any recommendations based on the findings. “I’m committed to doing the science. What I can say is this study is really rigorous, but I’m going to leave the policy pronouncements to others.”

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In an accompanying editorial, David C. Bellinger, PhD, a professor of neurology and psychology at Harvard Medical School, Boston, Massachusetts, points out that past studies associating fluoride with reduced cognition — most often ecological ones — were “limited by their generally poor quality.” He notes that the authors of the current study “considered numerous potential threats to the validity of the findings,” resulting in apparently robust findings.”The hypothesis that fluoride is a neurodevelopmental toxicant must now be given serious consideration,” Bellinger writes, noting how long it took researchers to conclude no safe lower threshold of lead exposure exists. “Research on fluoride as a potential neurodevelopmental toxicant is still at an early stage, and a compelling weight of evidence from high-quality epidemiological studies has not yet developed.”…

Questions Remain Over Sex Differences and Effect Size

Several experts questioned why boys might show an effect when girls showed almost the opposite effect in the urinary analysis and why no sex differences showed up in the self-reported intake analysis. For the former, Till pointed out that the developmental neurotoxicity literature already shows males tend to be more sensitive to exposures, including lead and endocrine disruptors…

… But biostatistician Regina Nuzzo, PhD, a senior advisor for Statistics Communication and Media Innovation at the American Statistical Association, Washington, DC, points out that IQ study measures already include a degree of uncertainty, often with a margin of error of up to 5 points in either direction.

“So it’s very possible that the uncertainty in any precise IQ score is much higher than the effect of any kind of fluoridation in the water,” she told Medscape Medical News. “Overall, this looks like a classic case of statistical significance vs practical significance, plus a lot of uncertainty that might dwarf any actual effects.”

She also pointed out that urine collection only occurred three times during pregnancy, so otherwise mundane actions such as accidentally swallowing toothpaste that morning or having more black tea than usual on those days could affect the readings.

Hu also noted the possibility of measurement errors but suggested they would lead the other direction. Using just two or three measures of fluoride to estimate cumulative exposure during pregnancy may attenuate the effect, he said, so the “the real impact on IQ might be somewhere higher.”

Still, given the potential bias in self-reported intake, such as recall bias and social desirability bias, Nuzzo said a potentially substantial amount of uncertainty and error in the intake estimate could translate into “highly uncertain numbers coming out of the model.” …

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Concern About Effect of Findings

… The study authors did not call for any changes to water fluoridation policies, but some worry about what might result from these findings given the history of anti-fluoridation advocacy — despite broad public, health, and medical organizations’ support for water fluoridation, which the US Centers for Disease Control and Prevention has called one of the greatest “achievements in public health” of the 20th century. …

Other population-based studies that looked at fluoride exposure in children after birth, such as one in New Zealand, have not found an association with intelligence. Jonathan M. Broadbent, PhD, University of Otago Faculty of Dentistry in Dunedin, New Zealand, who led that study, said the topic certainly warrants further investigation given these findings…

*The original article is on 4 pages: 1st page, 2nd page, 3rd page, 4th page