Birth Outcomes in Relation to Prenatal Exposure to Per- and Polyfluoroalkyl Substances and Stress in the Environmental Influences on Child Health Outcomes (ECHO) Program

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are persistent and ubiquitous chemicals associated with risk of adverse birth outcomes. Results of previous studies have been inconsistent. Associations between PFAS and birth outcomes may be affected by psychosocial stress. OBJECTIVES: We estimated risk of adverse birth outcomes in relation to prenatal PFAS concentrations and evaluate whether maternal stress modifies those relationships. METHODS: We included 3,339 participants from 11 prospective prenatal cohorts in the Environmental influences on the Child Health Outcomes (ECHO) program to estimate the associations of five PFAS and birth outcomes. We stratified by perceived stress scale scores to examine effect modification and used Bayesian Weighted Sums to estimate mixtures of PFAS. RESULTS: We observed reduced birth size with increased concentrations of all PFAS. For a 1-unit higher log-normalized exposure to perfluorooctanoic acid (PFOA), perfluorooctanesulfonic acid (PFOS), perfluorononanoic acid (PFNA), and perfluorohexane sulfonic acid (PFHxS), we observed lower birthweight-for-gestational-age z-scores of formula presented [95% confidence interval (CI): formula presented ], formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented ), formula presented (95% CI: formula presented , 0.06), and formula presented (95% CI: formula presented ), respectively. We observed a lower odds ratio (OR) for large-for-gestational-age: formula presented (95% CI: 0.38, 0.83), formula presented (95% CI: 0.35, 0.77). For a 1-unit increase in log-normalized concentration of summed PFAS, we observed a lower birthweight-for-gestational-age z-score [formula presented ; 95% highest posterior density (HPD): formula presented ] and decreased odds of large-for-gestational-age (formula presented ; 95% HPD: 0.29, 0.82). Perfluorodecanoic acid (PFDA) explained the highest percentage (40%) of the summed effect in both models. Associations were not modified by maternal perceived stress. DISCUSSION: Our large, multi-cohort study of PFAS and adverse birth outcomes found a negative association between prenatal PFAS and birthweight-for-gestational-age, and the associations were not different in groups with high vs. low perceived stress. This study can help inform policy to reduce exposures in the environment and humans. https://doi.org/10.1289/EHP10723

The effect of smear layer removal on marginal contraction gaps.

Journal of Oral Rehabilitation214411-41

An in vitro biofilm model of Staphylococcus aureus infection of bone

Chronic osteomyelitis is difficult to treat, with biofilm growth and the diffusion barrier to antibiotics presented by bone contributory factors. The aim of this study was to develop and evaluate an invitro model of osteomyelitis. A bioluminescent strain of Staphylococcus aureus was grown in bone blocks made from bovine femur. Light output was insufficient for detection of bacterial cells within bone by 24h and viable counting of crushed bone blocks was used to determine bacterial survival. Challenge of 72h biofilms with gentamicin and daptomycin for 24h demonstrated that only concentrations of 10 times the clinical peak serum target levels (100mgl−1 gentamicin and 1000mg l−1 daptomycin) resulted in significant reductions in cell viability compared to controls. Once daily dosing over 7days resulted in ≥3 log reductions in cell numbers by 48h. Thereafter no significant reduction was achieved, although emergence of resistance was suppressed. Determination of antibiotic concentration in bone blocks over 7days indicated that neither agent was able to consistently reach levels in bone of >10% of the original dose. The model was, therefore, able to demonstrate the challenges posed by biofilm growth on and within bone. Significance and Impact of the Study: The majority of studies of antibiotic efficacy in the treatment of chronic osteomyelitis are carried out in animals. We developed an invitro model of Staphylococcus aureus infection of bone to evaluate the ability of antibiotics to eradicate mature biofilms on surfaces analogous to necrotic bone. The results demonstrated the difficulties which occur in osteomyelitis treatment, with only very high concentrations of antibiotic able to penetrate the bone sufficiently to reduce bacterial survival whilst still failing to eradicate biofilms. This model could be of use in initial screening of novel compounds intended for use in the treatment of osteomyelitis