Effects of Serum Insulin and Insulin-Like Growth Factor 1 Levels on the Association between Fetal Growth and Per- and Polyfluoroalkyl Substance Exposure Based on a Nested Case-Control Study

Abstract

Insulin and insulin-like growth factor 1 (IGF1) play key roles in fetal growth and development. However, their roles in the association between fetal growth and perfluoroalkyl and polyfluoroalkyl substance (PFAS) exposure remain unclear. In this study, the levels of 34 PFAS, IGF1, and insulin were measured in 258 paired mother-infant serum samples collected from a nested case-control study in Maoming city. Isomeric perfluorooctanesulfonate (PFOS) exposure significantly increased the preterm birth or low birth weight (PTB/LBW) risk, and the odds ratios for ∑2m, 3+4+5m, iso, and branched PFOS were 1.50, 1.72, 1.61, and 1.77, respectively. Cord IGF1 could explain 15.4, 13.4, 9.7, and 11.9% of these associations, respectively. Additionally, cord IGF1 mediated 12.3 to 44.6% of the associations between PFOS isomers, perfluorooctanoate acid (PFOA), and its alternative (perfluorobutanoic acid: PFBA) with a fetal growth index. For instance, cord IGF1 contributed 42.0% (95% Cl: 0.8, 140.0%), 42.7% (95% Cl: 13.0, 110.0%), and 43.0% (95% Cl: 8.4, 130.0%) to the associations between z-scores of birth weight and branched PFOS, PFOA, and PFBA, respectively. These findings suggest that cord IGF1 plays a mediating role in the associations between PFAS exposure and fetal growth.

Keywords: adverse outcomes; fetal growth index; insulin; insulin-like growth factor 1 (IGF1); mediation; per- and polyfluoroalkyl substances (PFAS).