Maternal per- and polyfluoroalkyl substances exposure, cord blood lipidomics and infant anthropometry: A mediation analysis

Maternal exposure to per- and polyfluoroalkyl substances (PFAS) has been associated with offspring adiposity; however, underlying mechanisms remain unclear. In this study, we quantified 11 PFAS in maternal plasma collected between 12 and 16 gestational weeks and 104 lipid metabolites in the cord blood of 525 mother-infant pairs. Principal components of multiple PFAS compounds, extracted by principal component analysis, were employed to investigate the effect of the PFAS mixture. Infant anthropometric indicators included weight, length, waist/arm circumference, and abdominal/triceps/subscapular skinfold thickness at birth and 6 and 12 months old. Multiple linear regression showed that maternal PFAS exposure was primarily associated with increased glycerophospholipids and decreased fatty acyls and bile acids in cord blood. Four glycerophospholipids (16:0 PI, 16:0–18:1 PI, 18:0–20:4 PI, and 18:0–18:1 PS), fatty acyls (5(S)-HETE, 15(S)-HETE, 13-HDoHE, and dhkPGF2), and bile acids (GCA, TCA, TCDA, and TDCA) partially mediated the positive associations of the first principle component of PFAS compounds (with positive loadings for all PFAS compounds), PFNA, and PFUdA with infant skinfold thickness with mediating proportions ranging from 15.24% to 33.39%. Our findings provide novel insights into mechanisms underlying the effects of maternal PFAS exposure on infant growth.