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Per-and polyfluoroalkyl substances (PFAS) are widespread pollutants that may impact youth adiposity patterns. We investigated cross-sectional associations between PFAS and body mass index (BMI) in teenagers/adolescents across nine European countries within the Human Biomonitoring for Europe (HBM4EU) initiative. We used data from 1957 teenagers (12-18 yrs) that were part of the HBM4EU aligned studies, consisting of nine HBM studies (NEBII, Norway; Riksmaten Adolescents 2016-17, Sweden; PCB cohort (follow-up), Slovakia; SLO CRP, Slovenia; CROME, Greece; BEA, Spain; ESTEBAN, France; FLEHS IV, Belgium; GerES V-sub, Germany). Twelve PFAS were measured in blood, whilst weight and height were measured by field nurse/physician or self-reported in ques-tionnaires. We assessed associations between PFAS and age-and sex-adjusted BMI z-scores using linear and logistic regression adjusted for potential confounders. Random-effects meta-analysis and mixed effects models were used to pool studies. We assessed mixture effects using molar sums of exposure biomarkers with toxicological/structural similarities and quantile g-computation. In all studies, the highest concentrations of PFAS were PFOS (medians ranging from 1.34 to 2.79 mu g/L). There was a tendency for negative associations with BMI z-scores for all PFAS (except for PFHxS and PFHpS), which was borderline significant for the molar sum of [PFOA and PFNA] and significant for single PFOA [beta-coefficient (95% CI) per interquartile range fold change =-0.06 (-0.17, 0.00) and-0.08 (-0.15,-0.01), respectively]. Mixture assessment indicated similar negative associations of the total mixture of [PFOA, PFNA, PFHxS and PFOS] with BMI z-score, but not all compounds showed associations in the same direction: whilst [PFOA, PFNA and PFOS] were negatively associated, [PFHxS] associated positively with BMI z-score. Our results indicated a tendency for associations of relatively low PFAS concentrations with lower BMI in European teenagers. More prospective research is needed to investigate this potential relationship and its implications for health later in life., European Commission 733032, Swedish Research Council European Commission 2017-00822

The prevalence of cryptorchidism has increased over the past decades, yet its origins remain poorly understood. Testis descent is dependent on androgens and likely affected by endocrine disrupting compounds (EDCs), targeting the androgen receptor (AR). We investigated the association between anti-androgenic activity, not derived from natural hormones, in maternal breast milk and impaired testis descent among boys. We performed a case-control study based on 199 breast milk samples from 94 mothers of cryptorchid boys and 105 random non-cryptorchid boys participating in the Norwegian HUMIS (Human Milk Study) cohort. For each participant, apolar, and polar fractions were extracted, and combined to reconstitute a mixture. Anti-androgenic activity was measured in all three fractions using the human cell-based in vitro anti-AR CALUX® assay and expressed in μg of flutamide equivalent, a well-known antiandrogen. Results from fraction analyses were compared among boys with cryptorchidism and controls using multiple logistic regression, controlling for appropriate confounders identified using a directed acyclic graph. Children's daily exposure to anti-androgenic EDCs through breastfeeding was estimated to 78 μg flutamide eq./kg of body weigh/day. The activity was higher in the polar fraction (1.48 ± 1.37 μg flutamide eq./g of milk) mainly representing non-persistent chemicals, in contrast to other fractions. However, the activity in the polar extracts was decreased when in mixtures with the apolar fraction, indicating synergistic interactions. No significant difference in the activity was observed according to cryptorchid status for polar, apolar or mixed breast milk fractions. The study showed anti-androgenic activity in nearly all human milk samples, and at levels higher than the advisory threshold. However, no significant association was observed between cryptorchidism and antiandrogenic activity measured in either polar, apolar, or mixture fractions derived from breast milk.

Triglyceride-bound fatty acids constitute the majority of lipids in human milk and may affect infant growth. We describe the composition of fatty acids in human milk, identify predictors, and investigate associations between fatty acids and infant growth using data from the Norwegian Human Milk Study birth cohort. In a subset of participants (n = 789, 30% of cohort), oversampled for overweight and obesity, we analyzed milk concentrations of detectable fatty acids. We modelled percent composition of fatty acids in relation to maternal body mass index, pregnancy weight gain, parity, smoking, delivery mode, gestational age, fish intake, and cod liver oil intake. We assessed the relation between fatty acids and infant growth from 0 to 6 months. Of the factors tested, excess pregnancy weight gain was positively associated with monounsaturated fatty acids and inversely associated with stearic acid. Multiparity was negatively associated with monounsaturated fatty acids and n-3 fatty acids while positively associated with stearic acid. Gestational age was inversely associated with myristic acid. Medium-chain saturated fatty acids were inversely associated with infant growth, and mono-unsaturated fatty acids, particularly oleic acid, were associated with an increased odds of rapid growth. Notably, excessive maternal weight gain was associated with cis-vaccenic acid, which was further associated with a threefold increased risk of rapid infant growth (OR = 2.9, 95% CI 1.2–6.6), suggesting that monounsaturated fatty acids in milk may play a role in the intergenerational transmission of obesity.