Howard Hu

Evidence is accumulating linking prenatal fluoride exposure with adverse neurodevelopment. Maternal urinary fluoride (MUF) is a well-established biomarker of fluoride exposure. Because most fluoride is stored in calcified tissues, pregnancy-associated changes in bone metabolism may contribute to fetal fluoride exposure. We evaluated whether maternal bone resorption, indexed by urinary N-telopeptide of type I collagen (NTX), is associated with MUF across pregnancy. Participants were drawn from the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) birth cohorts. Each woman contributed one paired MUF–NTX measurement per trimester. Both biomarkers were creatinine-normalized to account for urine dilution. Trimester-specific generalized linear models with a Gamma distribution estimated associations between NTX and MUF, adjusting for maternal age, birth order, infant birthweight, and cohort. Across the trimesters, MUF was relatively stable (0.89 ± 0.37, 0.91 ± 0.41, and 0.83 ± 0.42 mg/L), whereas NTX increased with gestation (68.0 ± 33.5, 99.0 ± 50.3, and 132.4 ± 65.4 nmol BCE/mM creatinine). Higher NTX was consistently associated with higher MUF: β = 0.00315 (p < 0.0001) in Trimester 1, β = 0.00207 (p = 0.001) in Trimester 2, and β = 0.00253 (p < 0.0001) in Trimester 3, corresponding to 11%, 11%, and 18% higher MUF per 1-SD increase in NTX. Results were unchanged after adjustment for estimated fluoride intake, with no evidence of non-linearity. Maternal bone resorption was independently associated with MUF, consistent with a skeletal contribution to urinary fluoride. Research may be needed on measures that can blunt bone mobilization of fluoride during pregnancy.

Background: Lead exposure is estimated to cause approximately 3.5 million premature deaths a year, yet the key ongoing sources of lead exposure are unclear.Methods: We estimated the contribution of dietary lead intake to global blood lead levels (BLLs) for 7-year-old children and 22-year-old adults by applying the All-Ages Lead Model (AALM) to calculate blood lead levels (BLLs) based on 25 total diet studies (TDS) that quantify dietary lead intake across 46 countries.Results: For children, the population-weighted average dietary lead intake in low- and middle-income countries (LMICs) (32.0 μg/day) was found to be more than three times higher than in high-income countries (HICs) (9.3 μg/day), and more than 10 times higher than the FDA’s reference level for children (2.2 μg/day). The average impact on BLLs for children is estimated to be near 29 μg/L in LMICs and near 12 μg/L in HICs. Averaged across the TDS data, vegetables (27%) and cereals (24%) were found to contribute the most to dietary lead.Conclusions: While there are limitations associated with biokinetic modelling and the TDS data from LMICs, these results suggest that the contribution of dietary lead intake to global lead exposure is in the region of 40 to 50%, suggesting, in turn, that dietary lead intake is likely the largest current global driver of lead poisoning. Lead absorbed from the environment into food crops is expected to be the key driver of dietary lead. Current regulatory levels for maximum lead concentrations in foods (0.05-0.3 mg/kg) are out-of-date and may imply a dietary lead intake of 200 μg/day, far higher than the FDA reference level (2.2 μg/day). Collecting representative TDS data in high lead burden countries should be a priority. Further research is also recommended on upstream lead sources and pathways of lead uptake in plants, driving global food contamination.

Objectives: Equitable global health partnerships are recognized as critical for health equity; however, power imbalances and structural inequities continue to undermine these partnerships and ultimately their ability to achieve equitable health outcomes. As individuals within a US‑based academic institution engaged in global health partnerships during the current, complicated political moment, we recognize our responsibility to critically examine what it means for us to seek to engage equitably, both locally and globally. We therefore undertook an initiative to develop and adopt a set of principles to serve as internal guidance for how individuals within our institution engage in partnerships. We present our approach to promoting equity within our local and global research, education, and community partnerships, informed by existing literature, as an example of how academic institutions based in the Global North might seek to address power imbalances and to engage with others involved in similar efforts. Methods: We reviewed similar initiatives and existing principles. An internal, departmental committee coalesced around eight principles and drafted and iteratively refined their components. As part of ongoing, broader conversations with our partners, during this process, we engaged and sought the perspectives of our external partners, including from Brazil, India, and Kenya, to ensure the guidance was both informed by and resonated with their concerns about engaging with a US‑based institution. Findings: The principles of sustainability, mutual benefit and reciprocity, equitable governance, do no harm, locally identified priorities, compliance with ethical reviews and legal standards, information sharing, and accountability were elaborated and ultimately adopted by the full department faculty. Conclusions: Despite the best of intentions, we foresee challenges that may impact both implementation and outcomes. Continued reflection and dialogue with our partners and others engaged in similar initiatives is needed to address these challenges and the broader structural inequities embedded in global health.

Dental fluorosis indicates past fluoride intake. People living in Mexico City are exposed to fluoridated salt, which contributes significantly to fluoride intake. This study aimed to (1) estimate fluoride intake during early childhood and fluorosis prevalence in permanent teeth in adolescence and (2) identify intake windows associated with higher fluorosis scores in upper central incisors (UCIs). We included 432 participants from the ELEMENT project (Early-Life Exposures in Mexico to Environmental Toxicants), with data on fluoride intake at ages 1–5 and fluorosis (TFI) at adolescence. Median intakes ranged from 0.56 at age 1 to 1.14 mg/day at age 5, exceeding recommendations. All adolescents had some level of fluorosis, predominantly mild (62% with TFI 2). For every 0.1 mg of daily fluoride intake at age 1, the odds of higher TFI in UCIs were 1.08 [95% CI: 1.00–1.17]. At age 2, the odds were marginally significant [OR: 1.07; 95% CI: 1.00–1.16]. In conclusion, for participants of ELEMENT: (1) fluoride intake during early childhood exceeded recommendations and the prevalence of mild fluorosis in adolescence was high, and (2) fluorosis in UCIs was associated with dietary exposure during the first two years of life and may be used in future ELEMENT studies as exposure biomarkers.

Low-level lead poisoning in low- and middle-income countries has recently become a global priority, endorsed by the World Bank, UN agencies and others. Blood lead level (BLL) is a critical measure of individual lead exposure directly linked to adverse health outcomes. National BLL averages can be useful to target interventions but do not account for population size. We introduce the concept of the ‘cumulative population BLL’ (cpBLL), a metric combining average BLL with population size to estimate the overall lead burden in a country. Initial cpBLL estimates reveal that over 60% of the global lead burden is concentrated in just 12 countries, which highlights the need for targeted interventions in specific regions. The cpBLL tool, alternately called the ‘Lead Burden Index’, offers a way to help governments, donors and international organisations prioritise where the action is needed and can be used to measure the effectiveness of associated interventions.

Background/Objectives: Urinary fluoride (UF) is the most well-established biomarker for fluoride exposure, and understanding its distribution can inform risk assessment for potential adverse systemic health effects. To our knowledge, this study is the first to report distributions of UF among youth according to sociodemographic factors in a nationally representative United States (US) sample. Methods: The study included 1191 children aged 6-11 years and 1217 adolescents aged 12-19 years from the National Health and Nutrition Examination Survey (NHANES) 2015–2016. We examined UF according to sociodemographic variables as well as Spearman correlations between UF and plasma fluoride. Survey-weighted quantile regression examined associations between tap water fluoride and UF levels adjusted for covariates. Results: The average age of participants was 12.5 years. The median (IQR) UF and water fluoride concentrations were 0.52 (0.50) mg/L and 0.39 (0.54) mg/L, respectively. Children had higher UF levels than adolescents and males had higher UF levels than females. UF differed according to race/ethnicity among both children and adolescents. Specifically, non-Hispanic Black youth tended to have higher UF levels than all participants except for those classified as other race/multiracial. UF and plasma fluoride were moderately correlated for children and adolescents. Higher water fluoride levels were associated with higher UF levels, and the magnitudes of association were larger at higher quantiles of UF (β = 0.14, p < 0.001; β = 0.20, p< 0.001 at the 25th and 50th quantiles, respectively). The magnitude of association between water fluoride and UF was the largest for non-Hispanic Black participants (predictive margin = 0.3, p < 0.001). Conclusions: Non-Hispanic Black youth in the US may have greater fluoride exposure and receive more of their fluoride intake from tap water than youth of other races/ethnicities. Factors contributing to potential racial/ethnic disparities in fluoride exposure within the US warrant further investigation so that they can be mitigated to reduce the potential for harm.