Early life exposure to PFAS, phthalates, and BPA is associated with lower Bone Mineral Density, evaluated using REMS, during the first year of life

Background:This study (clinical trial: NCT06750523) evaluated bone status from intrauterine life and investigated factors affecting BMD in infants. We present data on early-life exposure to EDCs and BMD from birth to 12 months of age. Materials and methods:This prospective study analyzed urinary concentrations of EDCs in 88 healthy AGA infants at 1 month of age. EDCs were analyzed (4 bisphenols, 14 phthalates, 5 parabens and 29 PFAS) by UPLC-MS/MS. BMD was assessed using REMS. BMD z-scores were evaluated at 48 hours after birth (V0), at 1(V1), 3(V3), 6(V6), and 12 months of life (V12). Associations between urinary EDC concentrations and BMD z-scores were evaluated by correlation and principal component analyses (PCA). Results:At V0 BMD z-score was 1.31±0.87; -0.09±0.61at V1; -0.06±0.99 at V3; -0.03±0.97at V6, and - 0.04±1.01 at V12. At birth, BMD z-scores were higher in females compared to males(p:0.028), but this disappeared thereafter. In the infant’s urine, BPA was detected in 62.5% of samples, BPS in 19.3%; EtPB in 1.1%, MePB in 21.6%, PrPB in9.1%. Among PFAS, 6-2_FTS was detected in 73.9% of samples,PFBA in 70.5%,PFDA in 3.4%,PGHxS in 29.5%,PFNA in 15.9%,PFOA in 69.3%,PFOS in 76.1%, PFPHpA in 78.4%, PFPHxA in 63.6%. DBP was detected in 2.3%, MBP in 100%, MBzP in 22.7%, MEHHP in 62.5%, MEHP in 1.1%, MEOHP in 42.0% and MEP in 98.9%. BPA and PFDA were associated with BMD z-score at V0 (r: -0.31, p:0.025 and r:0.99, p:0.038). MePB was associated with BMD z-scores at V6 and V12(r:-0.52,p:0.044 and r:- 0.738,p:0.009). PFHxS, PFNA and PFOS presented associations with V6 BMD z-scores (r:-0.49, p:0.015; r:- 0.615, p:0.037, and r:-0.287,p:0.030). DEP was associated with BMD z-scores at V6 and V12(r:- 0.557,p:0.039 and r:-0.703, p:0.035). MBP, MBzP, and MEOHP were associated with BMD z-scores at V12 (r:-0.346, p:0.015; r:-0.654,p:0.040; r:-0.501, p:0.021, respectively). PCA found a cluster (19%) of BPA and phthalates (MBzP, MBP, MEOHP) with BMD z-score at V12, suggesting that higher exposure is associated with lower BMD at 1 year of age. Conclusions:Early-life exposure to EDCs may be associated with lower BMD during the first year of life. Infancy is a vulnerable window for environmental exposure and skeletal development, highlighting the need to reduce EDC exposure.