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Maternal per- and polyfluoroalkyl substances exposure, cord blood lipidomics and infant anthropometry: A mediation
Lan Yang1, Likang Li1, Honglei Ji1
1Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Public Health, Fudan University, Shanghai, 200237, China.
Insights
Maternal exposure to per- and polyfluoroalkyl substances (PFAS) is linked to infant adiposity. Specific lipid metabolites in cord blood partially explain how PFAS exposure affects infant skinfold thickness, revealing key biological mechanisms.
Area of Science:
- Environmental Health
- Metabolomics
- Developmental Toxicology
Background:
- Maternal exposure to per- and polyfluoroalkyl substances (PFAS) is a growing concern.
- Previous studies suggest a link between PFAS exposure and offspring adiposity.
- The specific biological mechanisms driving this association remain largely unknown.
Purpose of the Study:
- To investigate the relationship between maternal PFAS exposure and cord blood lipid metabolites.
- To explore the mediating role of lipid metabolites in the association between PFAS and infant adiposity.
- To elucidate the underlying mechanisms of PFAS effects on infant growth.
Main Methods:
- Quantified 11 PFAS in maternal plasma from 525 mother-infant pairs.
- Analyzed 104 lipid metabolites in cord blood.
- Utilized principal component analysis for PFAS mixture assessment.
- Assessed infant anthropometry at birth, 6, and 12 months.
- Employed multiple linear regression and mediation analysis.
Main Results:
- Maternal PFAS exposure was associated with altered cord blood lipid profiles, including increased glycerophospholipids and decreased fatty acyls and bile acids.
- Specific glycerophospholipids, fatty acyls, and bile acids partially mediated the positive association between PFAS exposure and infant skinfold thickness.
- Mediation proportions ranged from 15.24% to 33.39% for identified lipid metabolites.
Conclusions:
- Novel insights into the mechanisms linking maternal PFAS exposure to infant adiposity are provided.
- Specific lipid metabolic pathways are implicated in mediating the effects of PFAS on infant growth.
- Findings highlight the importance of considering metabolic disruption in understanding PFAS-related health outcomes.
Abstract:
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.
