Collaboration between health care professionals and the pharmaceutical industry often drives medical progress and, thus, benefits patients. Clinical trials reflect this reality, as industry sources support about half of the investigations focused on drugs or devices, raising concerns about potential conflicts of interest (COIs).¹ Systematic reviews suggest an apparent bias of published studies that were more likely to report positive findings when the authors received support from industry.^2,3 While journal editors responded to these findings by mandating disclosures of potential COIs,^4-6 the possible extent of industry sponsorship came to light in the course of investigations by the Department of Justice, which led to a settlement between the United States and 5 companies owing to concerns about violations of federal anti-kickback regulations, as physicians had received consulting fees for using joint implants produced by these companies.⁷

The literature informing susceptible periods of exposure on children's neurodevelopment is limited. We evaluated the impacts of pre- and postnatal fine particulate matter (PM_2.5) exposure on children's cognitive and motor function among 1303 mother-child pairs in the Spanish INMA (Environment and Childhood) Study. Random forest models with temporal back extrapolation were used to estimate daily residential PM_2.5 exposures that we averaged across 1-week lags during the prenatal period and 4-week lags during the postnatal period. The McCarthy Scales of Children's Abilities (MSCA) were administered around 5 years to assess general cognitive index (GCI) and several subscales (verbal, perceptual-performance, memory, fine motor, gross motor). We applied distributed lag nonlinear models within the Bayesian hierarchical framework to explore periods of susceptibility to PM_2.5 on each MSCA outcome. Effect estimates were calculated per 5 μg/m³ increase in PM_2.5 and aggregated across adjacent statistically significant lags using cumulative β (β_cum) and 95% Credible Intervals (95%CrI). We evaluated interactions between PM_2.5 with fetal growth and child sex. We did not observe associations of PM_2.5 exposure with lower GCI scores. We found a period of susceptibility to PM_2.5 on fine motor scores in gestational weeks 1-9 (β_cum = -2.55, 95%CrI = -3.53,-1.56) and on gross motor scores in weeks 7-17 (β_cum = -2.27,95%CrI = -3.43,-1.11) though the individual lags for the latter were only borderline statistically significant. Exposure in gestational week 17 was weakly associated with verbal scores (β_cum = -0.17, 95%CrI = -0.26,-0.09). In the postnatal period (from age 0.5-1.2 years), we observed a window of susceptibility to PM_2.5 on lower perceptual-performance (β = -2.42, 95%CrI = -3.37,-1.46). Unexpected protective associations were observed for several outcomes with exposures in the later postnatal period. We observed no evidence of differences in susceptible periods by fetal growth or child sex. Preschool-aged children's motor function may be particularly susceptible to PM_2.5 exposures experienced in utero whereas the first year of life was identified as a period of susceptibility to PM_2.5 for children's perceptual-performance.

This study hypothesized that plasma folate and vitamin B₁₂ levels modified the association between blood lead and cadmium and total urinary arsenic levels and bone loss. A total of 447 study subjects who received a physical examination at the Wanfang Hospital Medical Center were recruited. Bone loss was defined as a calcaneus bone mineral density T-score less than −1. Blood cadmium and lead concentrations were measured by ICP-MS. Urinary arsenic species were determined using HPLC-HG-AAS. A SimulTRAC-SNB radioassay was used to measure plasma folate, vitamin B₁₂, and homocysteine levels. Total urinary arsenic and blood lead concentration were positively correlated with the odds ratio (OR) for bone loss in a dose–response manner. The OR and 95% confidence interval (CI) for bone loss in participants with blood lead concentrations > 56.14 versus ≤33.82 μg/dL were 1.82 and 1.10–3.01. No correlation between plasma folate and vitamin B₁₂ levels alone and bone loss was observed. However, this study is the first observational study to find that blood lead concentrations tend to increase the OR of bone loss in a low plasma folate and plasma vitamin B₁₂ group with multivariate ORs (95% CI) of 2.44 (0.85–6.96).

While prior studies report associations between fine particulate matter (PM_2.5) exposure and fetal growth, few have explored temporally refined susceptible windows of exposure. We included 2328 women from the Spanish INMA Project from 2003 to 2008. Longitudinal growth curves were constructed for each fetus using ultrasounds from 12, 20, and 34 gestational weeks. Z-scores representing growth trajectories of biparietal diameter, femur length, abdominal circumference (AC), and estimated fetal weight (EFW) during early (0-12 weeks), mid- (12-20 weeks), and late (20-34 weeks) pregnancy were calculated. A spatio-temporal random forest model with back-extrapolation provided weekly PM_2.5 exposure estimates for each woman during her pregnancy. Distributed lag non-linear models were implemented within the Bayesian hierarchical framework to identify susceptible windows of exposure for each outcome and cumulative effects [β_cum, 95% credible interval (CrI)] were aggregated across adjacent weeks. For comparison, general linear models evaluated associations between PM_2.5 averaged across multi-week periods (i.e., weeks 1-11, 12-19, and 20-33) and fetal growth, mutually adjusted for exposure during each period. Results are presented as %change in z-scores per 5 μg/m³ in PM_2.5, adjusted for covariates. Weeks 1-6 [β_cum = -0.77%, 95%CrI (-1.07%, -0.47%)] were identified as a susceptible window of exposure for reduced late pregnancy EFW while weeks 29-33 were positively associated with this outcome [β_cum = 0.42%, 95%CrI (0.20%, 0.64%)]. A similar pattern was observed for AC in late pregnancy. In linear regression models, PM_2.5 exposure averaged across weeks 1-11 was associated with reduced late pregnancy EFW and AC; but, positive associations between PM_2.5 and EFW or AC trajectories in late pregnancy were not observed. PM_2.5 exposures during specific weeks may affect fetal growth differentially across pregnancy and such associations may be missed by averaging exposure across multi-week periods, highlighting the importance of temporally refined exposure estimates when studying the associations of air pollution with fetal growth.