ABSTRACT
Prenatal per- and poly-fluoroalkyl substances (PFAS) exposure may influence gestational outcomes through bioactive lipidsâmetabolic 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.
Subject(s)
Fluorocarbons , Lipids , Humans , Female , Pregnancy , Lipids/blood , Fluorocarbons/blood , Child Health , Cohort Studies , Cross-Sectional Studies , Adult , Environmental Pollutants/blood , Environmental Exposure , Maternal Exposure , ChildABSTRACT
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.
Subject(s)
Depression , Environmental Pollutants , Humans , Female , Pregnancy , Depression/chemically induced , Environmental Pollutants/toxicity , Fluorocarbons/toxicity , Maternal Exposure/adverse effects , Metabolome/drug effects , Pregnancy Complications/chemically induced , MetabolomicsABSTRACT
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).
Subject(s)
Ill-Housed Persons , Income , Loneliness , Social Isolation , Social Support , Humans , Ill-Housed Persons/psychology , California , Male , Female , Adult , Time Factors , Poverty , Randomized Controlled Trials as Topic , Friends , Middle Aged , Volunteers/psychologyABSTRACT
Research with administrative records involves the challenge of limited information in any single data source to answer policy-related questions. Record linkage provides researchers with a tool to supplement administrative datasets with other information about the same people when identified in separate sources as matched pairs. Several solutions are available for undertaking record linkage, producing linkage keys for merging data sources for positively matched pairs of records. In the current manuscript, we demonstrate a new application of the Python RecordLinkage package to family-based record linkages with machine learning algorithms for probability scoring, which we call probabilistic record linkage for families (PRLF). First, a simulation of administrative records identifies PRLF accuracy with variations in match and data degradation percentages. Accuracy is largely influenced by degradation (e.g., missing data fields, mismatched values) compared to the percentage of simulated matches. Second, an application of data linkage is presented to compare regression model estimate performance across three record linkage solutions (PRLF, ChoiceMaker, and Link Plus). Our findings indicate that all three solutions, when optimized, provide similar results for researchers. Strengths of our process, such as the use of ensemble methods, to improve match accuracy are discussed. We then identify caveats of record linkage in the context of administrative data.
Subject(s)
Algorithms , Medical Record Linkage , Humans , Medical Record Linkage/methods , Computer Simulation , Probability , Information Storage and RetrievalABSTRACT
Background: Per- and poly-fluoroalkyl substances (PFAS) exposure can occur through ingestion of contaminated food and water, and inhalation of indoor air contaminated with these chemicals from consumer and industrial products. Prenatal PFAS exposures may confer risk for pregnancy-related outcomes such as hypertensive and metabolic disorders, preterm birth, and impaired fetal development through intermediate metabolic and inflammation pathways. Objective: Estimate associations between maternal pregnancy PFAS exposure (individually and as a mixture) and bioactive lipids. Methods: Our study included pregnant women in the Environmental influences on Child Health Outcomes Program: Chemicals in our Bodies cohort (CiOB, n=73), Illinois Kids Developmental Study (IKIDS, n=287), and the ECHO-PROTECT cohort (n=54). We measured twelve PFAS in serum and 50 plasma bioactive lipids (parent fatty acids and eicosanoids derived from cytochrome p450, lipoxygenase, and cyclooxygenase) during pregnancy (median 17 gestational weeks). Pairwise associations across cohorts were estimated using linear mixed models and meta-analysis. Associations between the PFAS mixture and individual bioactive lipids were estimated using quantile g-computation. Results: PFDeA, PFOA, and PFUdA were associated (p<0.05) with changes in bioactive lipid levels in all three enzymatic pathways (cyclooxygenase [n=6 signatures]; cytochrome p450 [n=5 signatures]; lipoxygenase [n=7 signatures]) in at least one combined cohort analysis. The strongest signature indicated that a doubling in PFOA corresponded with a 24.3% increase (95% CI [7.3%, 43.9%]) in PGD2 (cyclooxygenase pathway) in the combined cohort. In the mixtures analysis, we observed nine positive signals across all pathways associated with the PFAS mixture. The strongest signature indicated that a quartile increase in the PFAS mixture was associated with a 34% increase in PGD2 (95% CI [8%, 66%]), with PFOS contributing most to the increase. Conclusions: Bioactive lipids were revealed as biomarkers of PFAS exposure and could provide mechanistic insights into PFAS' influence on pregnancy outcomes, informing more precise risk estimation and prevention strategies.
ABSTRACT
Living in a neighborhood with high levels of intergenerational mobility is associated with better childhood cognition and behavior as well as adult health. Nevertheless, it is unclear if such differences originate earlier, and thus if neighborhood intergenerational mobility is associated with health differences at birth. To address this question, we examined whether neighborhood intergenerational mobility, independent of neighborhood poverty, was associated with low birth weight (LBW) in a population-based cohort of singleton children born in California in 2017 (n = 426,873). Although increased neighborhood mobility was associated with a decreased likelihood of LBW, it was no longer associated with LBW (OR = 0.98, CI = 0.96, 1.00) after adjusting for neighborhood poverty. Meanwhile, neighborhood poverty was associated with LBW (OR = 1.04, CI = 1.02, 1.05) after accounting for mobility, with the odds of LBW 9.4% higher among children born where neighborhood poverty was in the 90th percentile compared with children born where neighborhood poverty was in the 10th percentile. Findings indicate that neighborhood poverty, but not intergenerational mobility, is a robust and independent correlate of increased LBW births, and thus early developmental health. These findings also suggest that the role of neighborhood intergenerational mobility in child and adult health outcomes may emerge later in development, independent of LBW, or that the role of neighborhood intergenerational mobility in LBW may be indirectly mediated through exposure to neighborhood poverty.
Subject(s)
Birth Cohort , Infant, Low Birth Weight , Adult , Child , Cohort Studies , Humans , Infant, Newborn , Poverty , Residence CharacteristicsABSTRACT
The Children's Data Network (CDN) is a data and research collaborative focused on the linkage and analysis of administrative records. In partnership with public agencies, philanthropic funders, affiliated researchers, and community stakeholders, we seek to generate knowledge and advance evidence-rich policies that improve the health, safety, and well-being of the children of California. Given our experience negotiating access to and working with existing administrative data (and importantly, data stewards), the CDN has demonstrated its ability to perform cost-effective and rigorous record linkage, answer time-sensitive policy- and program-related questions, and build the public sector's capacity to do the same. Owing to steadfast and generous infrastructure and project support, close collaboration with public partners, and strategic analyses and engagements, the CDN has promoted a person-level and longitudinal understanding of children and families in California and in so doing, informed policy and program development nationwide. We sincerely hope that our experience-and lessons learned-can advance and inform work in other fields and jurisdictions.