Abstract
Key PointsQuestion Is prenatal fluoride exposure associated with child neurobehavior in a US-based sample?
Findings In this cohort study of 229 pregnant women and their children, a 0.68 mg/L (ie, 1 IQR) increase in specific gravity–adjusted maternal urinary fluoride during pregnancy was associated with nearly double the odds of T scores for total child neurobehavioral problems being in the borderline clinical or clinical range.
Meaning These findings suggest that prenatal fluoride exposure may increase risk of neurobehavioral problems among children living in an optimally fluoridated area in the US.
Importance Recent studies in Canadian and Mexican populations suggest an association of higher prenatal fluoride exposure with poorer neurobehavioral development, but whether this association holds for US-based populations is unknown.
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Objective To examine associations of third trimester maternal urinary fluoride (MUF) with child neurobehavior at age 3 years in the US.
Design, Setting, and Participants This prospective cohort study utilized 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 (MADRES) pregnancy cohort, which consisted of predominately Hispanic women residing in Los Angeles, California. Cohort eligibility criteria at recruitment included being 18 years of age or older, less than 30 weeks’ gestation, and a fluent English or Spanish speaker. Exclusion criteria included having a disability preventing participation or provision of informed consent, being HIV positive or incarcerated, and having a multiple gestation pregnancy. There were 263 mother-child pairs who completed the 3-year study visit. In this analysis, women who reported prenatal smoking were excluded. Data analysis was conducted from October 2022 to March 2024.
Exposure Specific gravity-adjusted MUF (MUFSG), a biomarker of prenatal fluoride exposure.
Main Outcomes and Measures Neurobehavior was quantified using the Preschool Child Behavior Checklist (CBCL), which included composite scores for Total Problems, Internalizing Problems, and Externalizing Problems. CBCL composite T scores range from 28 to 100. T scores from 60 to 63 are in the borderline clinical range, whereas scores above 63 are in the clinical range. Linear and logistic regression models adjusted for covariates were conducted.
Results A total of 229 mother-child pairs (mean [SD] maternal age, 29.45 [5.67] years; 116 female children [50.7%] and 113 male children [49.3%]) who had MUFSG measured were included in the study. Median (IQR) MUFSG was 0.76 (0.51-1.19) mg/L, and 32 participants (14.0%) had a Total Problems T score in the borderline clinical or clinical range. A 1-IQR (0.68 mg/L) increase in MUFSG was associated with nearly double the odds of the Total Problems T score being in the borderline clinical or clinical range (odds ratio, 1.83; 95% CI, 1.17-2.86; P = 008), as well as with a 2.29-point increase in T score for the Internalizing Problems composite (B = 2.29; 95% CI, 0.47-4.11; P = .01) and a 2.14-point increase in T score for the Total Problems composite (B = 2.14; 95% CI, 0.29-3.98; P = .02).
Conclusions and Relevance In this prospective cohort study of mother-child pairs in Los Angeles, California, prenatal fluoride exposure was associated with increased neurobehavioral problems. These findings suggest that there may be a need to establish recommendations for limiting fluoride exposure during the prenatal period.
Full-text study online at https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2818858
Excerpts:
Child neurobehavioral outcomes were assessed from 2020 to 2023 via the Preschool CBCL, a valid measure of neurobehavior.22–24 The Preschool CBCL is a parent-reported measure of 99 items that was administered in MADRES when the child was approximately 36 months old. Children were rated on the CBCL by their mothers. The CBCL is available in English and Spanish. CBCL scores comprise 7 syndrome scales (Emotionally Reactive, Anxious-Depressed, Somatic Complaints, Withdrawn, Sleep Problems, Attention Problems, and Aggressive Behavior) characterizing problems that tend to co-occur together. The CBCL also includes 5 DSM-5–oriented scales that are comprised of items determined to be consistent with DSM-5 diagnostic categories (Depressive Problems, Anxiety Problems, Oppositional Defiant Problems, Autism Spectrum Problems, and ADHD Problems). Scores on CBCL syndrome scales are grouped to produce an Internalizing Problems composite score and Externalizing Problems composite score. Scales that focus primarily on issues within the self comprise the Internalizing Problems composite. Conversely, scales that focus on other-directed problems and expectations for the child comprise the Externalizing Problems composite. Lastly, a Total Problems composite score is calculated by summing scores on all 99 items.24 Internalizing Problems, Externalizing Problems, and Total Problems composite T scores range from 28 to 100. T scores ranging from 60 to 63 are in the borderline clinical range, whereas those above 63 are in the clinical range.24 We calculated 2-category clinical index variables of normal vs borderline clinical or clinical for statistical analyses for each composite variable (see the eMethods in Supplement 1 for additional details about the CBCL scales).
This cohort study found that prenatal fluoride exposure was associated with increased risk for neurobehavioral problems among children residing in the US. 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.