Music Playlist Use in Clinical Trials of Psychedelic Assisted Psychotherapy: A Systematic Review.

Fluoride is a naturally occurring mineral that is widely recognized for its role in preventing dental caries []. In the United States, community water fluoridation (CWF) is a common practice, with nearly three-fourths of the population on public water systems receiving water adjusted to a federally recommended fluoride concentration []. While fluoride is beneficial for preventing dental caries, concerns over increasing systemic fluoride exposure and rising rates of enamel fluorosis led the U.S. Public Health Service to advocate for lowering the recommended fluoride concentration in drinking water from 0.7 to 1.2 mg/L to 0.7 mg/L in 2015 []. However, in some geographic areas [], groundwater wells or private unregulated wells may contain high levels of naturally occurring fluoride, posing a risk of excessive exposure []. The risk of excessive exposure is of particular concern during pregnancy, as fluoride readily crosses the placenta and reaches the fetal brain []. A growing body of research suggests fluoride is a developmental neurotoxicant [, ]. For instance, studies have associated higher maternal fluoride exposure during pregnancy with adverse neurodevelopmental outcomes in offspring, including lower intelligence quotient (IQ) scores [–] and increased symptoms of attention-deficit/hyperactivity disorder (ADHD) [, ]. Given the potential for fetal neurotoxicity, establishing valid and reliable biomarkers of prenatal exposure is essential []. Maternal urinary fluoride, a measure of recent fluoride exposure [], is the most commonly used biomarker in prior studies of developmental neurotoxicity of fluoride []. Weak to moderate positive correlations have been reported between maternal spot urinary fluoride concentrations (adjusted for dilution) and community water fluoride levels [, ]. In a Canadian study of 1,566 pregnant women, the correlation between water fluoride concentration and urinary fluoride averaged across three trimesters was 0.49 []. Similarly, a study of 965 pregnant women residing in Kansas, Missouri, Ohio, Kentucky, and Indiana [] reported a correlation of 0.30 between urinary fluoride measured in a single spot sample and water fluoride levels, while a smaller California study of 47 pregnant women found a correlation of 0.21 []. Despite these consistent positive correlations, spot urine samples have important limitations, as fluoride excretion can fluctuate in response to recent intake, hydration status, dietary influences [], and pregnancy-related factors [], thereby increasing within person variability in exposure estimation. Toenails are a more appropriate biomarker for estimating longer-term fluoride exposure compared to urine or plasma []. Toenails are preferred over fingernails due to their slower growth rate and lower potential for external contamination []. Fluoride is incorporated into toenails during their growth, reflecting cumulative fluoride systemic concentrations over a protracted period of approximately 3 to 4 months [, ]. Based on this exposure window, maternal toenail samples collected at 24–28 weeks’ gestation (approximately the second trimester) and at 6 weeks postpartum can provide cumulative measures of fluoride exposure during the early- and late-prenatal periods, respectively. Previous studies have demonstrated a positive association between fluoride content in toenails and fluoride in water, especially in communities with higher levels (e.g. exceeding 1.5 mg/L) [, ]. However, no studies to our knowledge have examined toenail fluoride from pregnant women and compared them directly with urinary and water fluoride levels, especially in communities with a high degree of variation of naturally occurring fluoride in water [].