Fetal macrosomia in a Hispanic/Latinx predominant cohort and altered expressions of genes related to placental lipid transport and metabolism

Fetal overgrowth, termed fetal macrosomia when birth weight is greater than 4000 grams, is the major concern in the treatment of gestational diabetes mellitus (GDM). However, to date, the underlying mechanisms of fetal macrosomia have not been understood completely. Placental lipid metabolism is emerging as a critical player in fetal growth. In this study, we hypothesized that fatty acid transport and metabolism in the placental tissue was impaired in GDM women, dependent on fetal sex. To test this hypothesis, we analyzed the incidence of GDM, fetal macrosomia, and obesity in a large cohort consisting of 17995 pregnant subjects and majority of subjects being Hispanic/Latinx, and investigated expression of genes related to lipid transport and metabolism in placenta from obese women with or without GDM, and with or without fetal macrosomia. The main findings include: 1) There is a higher incidence of GDM and obesity in Hispanic subjects compared to non-Hispanic subjects, but not fetal macrosomia; 2) Expressions of most of genes related to placental lipid transport and metabolism are not altered by the presence of GDM, fetal macrosomia, or fetal sex; 3) Expression of FABP4 is increased in obese women with GDM and fetal macrosomia, and this occurred in male placentas; 4) Expression of LPL is decreased in obese women with GDM despite fetal macrosomia, and this occurred in male placentas; 5) Expression of ANGPTL3 is decreased in obese women with GDM and fetal macrosomia, but is not altered when fetal sex is included in the analysis. This study indicates that there is race disparity in GDM with higher incidence of GDM in obese Hispanic women, although fetal macrosomia disparity is not present. Moreover, altered placental lipid transport may contribute to fetal overgrowth in obese women with GDM.