An observational study finds that mothers with higher urinary fluoride levels have kids with slightly lower IQs, but the results might not hold water.

Usually, as studies come across my desk, I say “oh that one is interesting” and dig in to see if it’s worth spending a few minutes of your time on.  This week, I saw this study, appearing in JAMA Pediatrics and just thought “Oh no”. 

This is one of those studies that I just knew would blow up, and probably for the wrong reasons.

Despite very robust evidence that fluoridation of water reduces the incidence of cavities in kids, it has long been a bugaboo of conspiracy buffs ranging from General Jack D. Ripper to Alex Jones.

No one ever seems to complain about chlorinating water, but whatever.

In any case, the argument that fluoridation is a secret communist plot has never – ahem – held water, but several prior medical studies have documented a link, however small, between fluoride exposure and lower IQ in children. But all of those prior studies were flawed in one way or another, most often because the exposure was orders of magnitude higher than what is seen in the fluoridated water supply.

Enter JAMA Pediatrics, with what is really the best study to date of the effect of fluoride on IQ. 512 mother-child pairs from Canada were recruited during pregnancy and followed until the kids were around 3-4 years of age. At three points during pregnancy, the moms had their urinary fluoride concentrations measured. These measurements were averaged, and the researchers report, moms with higher levels had kids with lower IQs. 

Well, for boys at least. No effect was seen in girls. But as you can see from the scatter plot, the effect was really small – about 1.5 IQ points for moving between the 25th and 75th percentiles of urinary fluoride.

This held up even after adjusting for city, maternal education, race, child sex, and a score which measures the quality of the home environment.

Yikes, right? Is fluoridation causing a process of dumbening?  Is dumbening even a word?

Hold up. It’s caveat time.

First, this was not a randomized trial – no one was giving these moms fluoride or regulating what they drank, so confounders could be a major issue. I’m particularly worried about socioeconomic factors that may be linked to fluoridated water consumption and also children’s IQ.

But there’s potentially a bigger problem. The plausible mechanism for neurotoxicity of fluoride in utero is that blood fluoride crosses the placenta and gets into the fetus’ developing brain. Like this.

But blood fluoride wasn’t measured. Urine fluoride was. Now, as a nephrologist, this piques my interest because urine fluoride is NOT a perfect proxy for blood fluoride.

The authors know this. They realize, for example, that more dilute urine will have a lower fluoride concentration, and “correct” this problem by dividing urinary fluoride by urine specific gravity.

This introduces a new variable though. Assuming fluoride has no effect on child’s IQ, you could get results that look like this if moms with more dilute urine tend to have kids with lower IQs.

But wait, there’s more. Fluoride is freely filtered at the glomerulus, but it is reabsorbed in the renal tubules.

This is a pH dependent process, with more reabsorption occurring when the pH is lower. That means that women with higher urinary pH (due to a more vegetarian diet, or just prolonged fasting) will, on average, have higher urinary fluoride levels.  Another confounder, this one unaccounted for.

Does the presence of possible confounders invalidate the study? Of course not, but these factors remind us to interpret results like this really carefully – especially when the documented benefits of fluoridation rest on much firmer scientific footing than the possible harms.

 This commentary first appeared on medscape.com.