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In utero fluoride exposure at normal U.S. municipal ranges was associated with increased neurobehavioral problems in young kids, a prospective cohort study of 229 mother-child pairs in Los Angeles suggested.

Women in the 75th versus the 25th percentile for maternal urinary fluoride -- a difference of 0.68 mg/L -- during the third trimester of pregnancy had significantly higher risk of their child having overall behavioral scores in the borderline clinical or clinical range at age 36 months (OR 1.83, 95% CI 1.17-2.86), reported Ashley Malin, PhD, of the University of Florida in Gainesville, and colleagues.

About three-quarters of the U.S. population lives in areas with water fluoridation levels of 0.7 mg/L, which is recommended by the U.S. Public Health Service as optimal for dental health, they noted in .

"These findings suggest that there may be a need to establish recommendations for limiting exposure to fluoride from all sources during the prenatal period, a time when the developing brain is known to be especially vulnerable to injury from environmental insults," the researchers concluded.

Exposure to high fluoride levels is well established as adversely affecting neurodevelopment, Malin and colleagues wrote. These findings add to growing evidence that fluoride exposure at lower, U.S.-relevant levels may also be associated with poorer neurodevelopment.

"Specifically, higher prenatal fluoride exposure in Canada and/or Mexico has been associated with lower IQ among children and children , increased symptoms of attention-deficit/hyperactivity disorder (ADHD) among children , poorer executive function among children , and poorer performance on measures of global cognition among ," Malin's group noted.

"This is the first U.S.-based study to examine whether prenatal fluoride exposure is associated with child neurobehavioral outcomes," which helps address the question of generalizability, Malin told 番茄社区 in an email.

Malin and colleagues' study used urine samples archived from 2017 to 2020 and neurobehavioral data assessed from 2020 to 2023 from the Maternal and Developmental Risks from Environmental and Social Stressors pregnancy cohort, which primarily consisted of Hispanic women living in Los Angeles.

Although the U.S. cohort studied isn't nationally representative, it had "prenatal urinary fluoride concentrations that are typical of North American women," noted David Bellinger, PhD, MSc, of Harvard Medical School in Boston, who was not involved in the study.

"It cannot be interpreted as a replication of the key existing studies (e.g., MIREC [the Canadian cohort], ELEMENT [the Mexican cohort]) as it focused on a different outcome, children's behavior problems as reported by parents," Bellinger told 番茄社区 in an email. "However, it is generally consistent with the findings of those prior studies, insofar as it adds another well-conducted study to the overall body of evidence suggesting that at typical levels of exposures of pregnant women, fluoride might be associated with adverse child outcomes."

"As a result, it adds weight to the argument that regulatory agencies should at least consider potential adverse child health outcomes when establishing exposure standards for fluoride," Bellinger added. "Because sources of the fluoride exposure of the women were not evaluated in this study, however, the findings should not be interpreted as providing evidence either for or against water fluoridation."

In 2019, 番茄社区 reported on the MIREC cohort in JAMA Pediatrics that indicated higher fluoride intake during pregnancy was associated with lower IQ scores in boys, but not in girls. At the time, an editor's note was due to the contentious nature of the topic.

"This study is neither the first, nor will it be the last, to test the association between prenatal fluoride exposure and cognitive development," Dimitri Christakis, MD, MPH, of the University of Washington in Seattle and editor of JAMA Pediatrics, stated in the note. "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."

Malin's study examined outcomes for a prospective cohort of predominantly low-socioeconomic status women in the MADRES study who had maternal urinary fluoride measured during the third trimester of pregnancy and child scores on the Preschool Child Behavior Checklist (CBCL, for ages 1.5 to 5 years) at age 36 months.

Median specific gravity-adjusted maternal urinary fluoride at the third trimester was 0.76 mg/L. Mean maternal age of participants was 29 years. Slightly more than half of their offspring were female.

Overall, 14% of kids had a Total Problems T score in the borderline clinical or clinical range, 15.3% had an Internalizing Problems T score in this range, and 10% had an Externalizing Problems T score in this range.

Associations of specific gravity-adjusted maternal urinary fluoride with Externalizing Problems T scores or odds of having an Internalizing Problems T score in the borderline clinical or clinical range were positive but not statistically significant.

A 0.68 mg/L increase in maternal fluoride, which was the interquartile range, was associated with a 2.29-point increase in Internalizing Problems T scores (scale range 29-100, P=0.01 for difference) and a 2.14-point increase in Total Problems T scores (scale range 28-100, P=0.02).

Furthermore, the 75th versus 25th percentile for maternal urinary fluoride was associated with a 13.54% increase in raw scores for the Emotionally Reactive CBCL syndrome scale (P=0.02) and a 19.6% increase in raw scores for the Somatic Complaints CBCL syndrome scale (P=0.001).

The higher exposure group also had 11.29% higher scores on the Diagnostic and Statistical Manual of Mental Disorders Fifth Edition (DSM-5)-oriented Anxiety Problems scale of the CBCL (P=0.045) and an 18.53% increase in scores on the DSM-5–oriented Autism Spectrum Problems scale of the CBCL (P=0.009).

Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive, being incarcerated, and having a multiple gestation pregnancy.

Limitations included that the research team "measured fluoride in spot samples rather than 24-hour urine samples, which can be influenced by daily behaviors (eg, food and beverage consumption or use of fluoridated dental products), and therefore increase random error," Malin and colleagues wrote.

Additionally, there was a lack of data on tap water consumption habits, Malin and colleagues noted. Further limitations included that participants were excluded if they delivered their babies prior to 30 weeks' gestation, "which precluded examination of associations of [specific gravity-adjusted maternal urinary fluoride] with neurobehavior among children who were born very preterm."

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