The impact of legacy per- and polyfluoroalkyl substances (PFAS) on fetal growth has been well studied, but assessments of next-generation PFAS and PFAS mixtures are sparse and the potential role of fetoplacental hemodynamics has not been studied. We aimed to evaluate associations between prenatal PFAS exposure and fetal growth and fetoplacental hemodynamics. We included 747 pregnant women from the BiSC birth cohort (Barcelona, Spain (2018-2021)). Twenty-three PFAS were measured at 32 weeks of pregnancy in maternal plasma, of which 13 were present above detectable levels. Fetal growth was measured by ultrasound, as estimated fetal weight at 32 and 37 weeks of gestation, and weight at birth. Doppler ultrasound measurements for uterine (UtA), umbilical (UmA), and middle cerebral artery (MCA) pulsatility indices (PI), as well as the cerebroplacental ratio (CPR - ratio MCA to UmA), were obtained at 32 weeks to assess fetoplacental hemodynamics. We applied linear mixed effects models to assess the association between singular PFAS and longitudinal fetal growth and PI, and Bayesian Weighted Quantile Sum models to evaluate associations between the PFAS mixture and the aforementioned outcomes, controlled for the relevant covariates. Single PFAS and the mixture tended to be associated with reduced fetal growth and CPR PI, but few associations reached statistical significance. Legacy PFAS PFOS, PFHpA, and PFDoDa were associated with statistically significant decreases in fetal weight z-score of 0.13 (95%CI (-0.22, -0.04), 0.06 (-0.10, 0.01), and 0.05 (-0.10, 0.00), respectively, per doubling of concentration. The PFAS mixture was associated with a non-statistically significant 0.09 decrease in birth weight z-score (95%CI -0.22, 0.04) per quartile increase. This study suggests that legacy PFAS may be associated with reduced fetal growth, but associations for next generation PFAS and for the PFAS mixture were less conclusive. Associations between PFAS and fetoplacental hemodynamics warrant further investigation.

The mpox 2022 outbreak was declared a public health emergency in July 2022. In August 2022, the MVA–BN vaccine received emergency use authorization in the United States (US) to target at-risk groups. This study (EUPAS104386) used HealthVerity’s administrative US healthcare data to generate real-world evidence for MVA–BN vaccine effectiveness and safety to prevent mpox disease in men who have sex with men (MSM) and transgender women, the most affected population during the 2022 mpox outbreak. Fully vaccinated subjects (two doses ≥ 28 days apart) were initially matched with five unvaccinated subjects on calendar date, age, US region, and insurance type. Subjects were followed from index date (14 days after the second dose) until death or data end to ascertain mpox occurrence. After propensity score adjustment, the MVA–BN vaccine effectiveness against mpox disease was 89% (95% CI: 12%, 99%) among those fully vaccinated; attenuated to 64% (95% CI: 40%, 78%) among those with any dose and 70% (95% CI: 44%, 84%) for those with only a single dose. One pericarditis adverse event of special interest was observed when the risk window was extended to 28 days. These results contribute to the totality of evidence supporting the favorable benefit/risk profile of the MVA–BN vaccine.

Exposure to endocrine-disrupting chemicals (EDCs) during pregnancy may influence the placenta and fetal growth; however, evidence is scarce regarding EDC mixtures, newer chemicals, and the role of angiogenic biomarkers and fetoplacental hemodynamics. We aimed to examine the associations between nonpersistent EDC mixtures and fetal growth, fetoplacental hemodynamics, and angiogenic biomarkers. We included 734 pregnant participants from the Barcelona Life Study Cohort (BiSC), Spain (2018-2021). Metabolites of phthalates, DINCH, insecticides, polycyclic aromatic hydrocarbons, pesticides, flame retardants, and parent compounds of phenols and parabens were measured in pools of week-long maternal urine samples at 18 and 34 weeks' gestation. Penalized LASSO-type multigroup Bayesian Weighted Quantile Sum Regression estimated associations with fetal growth, fetoplacental hemodynamics, and angiogenic biomarkers. Birthweight z-score decreased with low-molecular-weight phthalate (LMWP) (β = -0.119; CrI -0.224, -0.008) mixtures and increased with organophosphate mixtures (β = 0.143; CrI 0.042, 0.245). LMWP exposure was also associated with altered hemodynamics and angiogenic biomarkers; angiogenic biomarkers mediated the relationship with birthweight z-score (ACME = -0.032; 95% CI -0.062, -0.009; p = 0.002). This comprehensive study suggests that mixtures of low-molecular-weight phthalates and organophosphate compounds may alter fetal growth and that angiogenic biomarkers may play a role as mediator.

Phthalates and DINCH are non-persistent chemicals widely used in consumer products. In utero exposure to these compounds has been linked to adverse reproductive and long-term health outcomes, potentially through epigenetic changes in the placenta. This study investigated associations between maternal phthalate and DINCH metabolite levels and placental DNA methylation in 469 mother-child pairs from the Barcelona Life Study Cohort (BiSC). Fifteen phthalate and two DINCH metabolites were measured in pooled maternal urine samples collected at 19 and 35 weeks of gestation using liquid chromatography-tandem mass spectrometry (LC-MS/MS. Placental DNA methylation was assessed using the Illumina EPIC array. We applied robust linear regression models to test associations between single exposures at 19 weeks, 35 weeks, and whole pregnancy (average of the two time points), with each CpG site. In secondary analyses, quantile g-computation was used to test associations between exposure mixtures and suggestive CpGs (p-value < 1E-05). We identified 38 Bonferroni significant associations in the single exposure models (p-value < 1E-07)- 24 at 19 weeks, 8 at 35 weeks and 6 for the whole pregnancy period. Suggestive CpGs (p-value < 1E-05) were annotated to genes involved in metabolic, immune and vascular pathways, steroid biosynthesis, and sex hormone signaling. Sex-stratified analyses revealed 49 female-specific and 42 male-specific associations, most of which were identified at a single time point. Mixture analyses revealed 20 significant associations, all consistent in direction with the single-metabolite models. These results suggest that prenatal exposure to phthalates and DINCH may contribute to placental epigenetic alterations supporting a role for endocrine disruption, metabolism, and vascular and immune modulation in mediating their effects.