Cross-Sectional Associations between Prenatal Per- and Poly-Fluoroalkyl Substances and Bioactive Lipids in Three Environmental Influences on Child Health Outcomes (ECHO) Cohorts.

Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipids─metabolic and inflammation pathway indicators. We estimated associations between prenatal PFAS exposure and bioactive lipids, measuring 12 serum PFAS and 50 plasma bioactive lipids in 414 pregnant women (median 17.4 weeks' gestation) from three Environmental influences on Child Health Outcomes Program cohorts. Pairwise association estimates across cohorts were obtained through linear mixed models and meta-analysis, adjusting the former for false discovery rates. Associations between the PFAS mixture and bioactive lipids were estimated using quantile g-computation. Pairwise analyses revealed bioactive lipid levels associated with PFDeA, PFNA, PFOA, and PFUdA (p < 0.05) across three enzymatic pathways (cyclooxygenase, cytochrome p450, lipoxygenase) in at least one combined cohort analysis, and PFOA and PFUdA (q < 0.2) in one linear mixed model. The strongest signature revealed doubling in PFOA corresponding with PGD2 (cyclooxygenase pathway; +24.3%, 95% CI: 7.3-43.9%) in the combined cohort. Mixture analysis revealed nine positive associations across all pathways with the PFAS mixture, the strongest signature indicating a quartile increase in the PFAS mixture associated with PGD2 (+34%, 95% CI: 8-66%), primarily driven by PFOS. Bioactive lipids emerged as prenatal PFAS exposure biomarkers, deepening insights into PFAS' influence on pregnancy outcomes.

Metabolic Perturbations Associated with both PFAS Exposure and Perinatal/Antenatal Depression in Pregnant Individuals: A Meet-in-the-Middle Scoping Review.

PURPOSE OF REVIEW: Depression during the perinatal or antenatal period affects at least 1 in 10 women worldwide, with long term health implications for the mother and child. Concurrently, there is increasing evidence associating maternal exposure to per- and poly-fluoroalkyl substances (PFAS) to adverse pregnancy outcomes. We reviewed the body of evidence examining both the associations between PFAS exposure and perturbations in the maternal metabolome, and the associations between the maternal metabolome and perinatal/antenatal depression. Through this, we sought to explore existing evidence of the perinatal metabolome as a potential mediation pathway linking PFAS exposure and perinatal/antenatal depression. RECENT FINDINGS: There are few studies examining the metabolomics of PFAS exposure-specifically in pregnant women-and the metabolomics of perinatal/antenatal depression, let alone studies examining both simultaneously. Of the studies reviewed (N = 11), the majority were cross sectional, based outside of the US, and conducted on largely homogenous populations. Our review identified 23 metabolic pathways in the perinatal metabolome common to both PFAS exposure and perinatal/antenatal depression. Future studies may consider findings from our review to conduct literature-derived hypothesis testing focusing on fatty acid metabolism, alanine metabolism, glutamate metabolism, and tyrosine metabolism when exploring the biochemical mechanisms conferring the risk of perinatal/antenatal depression due to PFAS exposure. We recommend that researchers also utilize heterogenous populations, longitudinal study designs, and mediation approaches to elucidate key pathways linking PFAS exposures to perinatal/antenatal depression.

Miracle friends and miracle money in California: a mixed-methods experiment of social support and guaranteed income for people experiencing homelessness.

BACKGROUND: This paper describes the protocols for a randomized controlled trial using a parallel-group trial design that includes an intervention designed to address social isolation and loneliness among people experiencing homelessness known as Miracle Friends and an intervention that combines Miracles Friends with an economic poverty-reduction intervention known as Miracle Money. Miracle Friends pairs an unhoused person with a volunteer "phone buddy." Miracle Money provides guaranteed basic income of $750 per month for 1 year to Miracle Friends participants. The study will examine whether either intervention reduces social isolation or homelessness compared to a waitlist control group. METHODS: Unhoused individuals who expressed interest in the Miracle Friends program were randomized to either receive the intervention or be placed on a waitlist for Miracle Friends. Among those randomized to receive the Miracle Friends intervention, randomization also determined whether they would be offered Miracle Money. The possibility of receiving basic income was only disclosed to study participants if they were randomly selected and participated in the Miracle Friends program. All study participants, regardless of assignment, were surveyed every 3 months for 15 months. RESULTS: Of 760 unhoused individuals enrolled in the study, 256 were randomized to receive Miracle Friends, 267 were randomized to receive Miracle Money, and 237 were randomized to the waitlist control group. In the two intervention groups, 360 of 523 unhoused individuals were initially matched to a phone buddy. Of the 191 study participants in the Miracle Money group who had been initially matched to a volunteer phone buddy, 103 were deemed to be participating in the program and began receiving monthly income. DISCUSSION: This randomized controlled trial will determine whether innovative interventions involving volunteer phone support and basic income reduce social isolation and improve housing outcomes for people experiencing homelessness. Although we enrolled unhoused individuals who initially expressed interest in the Miracle Friends program, the study team could not reach approximately 30% of individuals referred to the study. This may reflect the general lack of stability in the lives of people who are unhoused or limitations in the appeal of such a program to some portion of the unhoused population. TRIAL REGISTRATION: ClinicalTrials.gov NCT05408884 (first submitted on May 26, 2022).