Maternal Plasma Lipids During Pregnancy, Insulin-like Growth Factor-1, and Excess Fetal Growth

• Published in: The journal of clinical endocrinology and metabolism 2021-09, Vol.106 (9), p.e3461-e3472
• Main Authors: Chen, Kuan-Yu, Lin, Shin-Yu, Lee, Chien-Nan, Wu, Hung-Tsung, Kuo, Ching-Hua, Kuo, Han-Chun, Chuang, Chia-Chi, Kuo, Chun-Heng, Chen, Szu-Chi, Fan, Kang-Chih, Lin, Ming-Wei, Fang, Chi-Tai, Li, Hung-Yuan
• Format: Article
• Language: English
• Subjects: Analysis; Birth weight; Cord blood; Diabetes mellitus; Fetus; Fetuses; Growth; Growth factors; Hypertension; Instrument industry; Insulin; Insulin-like growth factor I; Insulin-like growth factors; Linoleic acid; Lipids; Monounsaturated fatty acids; Neonates; Oleic acid; Palmitic acid; Placenta; Plasma; Pregnancy; Pregnant women; Protein binding; Saturated fatty acids; Secretion; Stearic acid; Triglycerides
• ISSN: 0021-972X; 1945-7197
• DOI: 10.1210/clinem/dgab364

Abstract Context Maternal lipids during pregnancy and placental growth factors are associated with excess fetal growth. However, how these factors interact to increase the risk of delivering large-for-gestational-age (LGA) neonates remains unclear. In this study, we investigated the relationship between maternal plasma triglycerides (TGs) and free fatty acids (FFAs) during pregnancy, cord blood insulin-like growth factors (IGF), and LGA. Objective In a cell model, we studied the effect of different FAs on placental IGF-1 secretion. Methods This cohort study included pregnant women with term pregnancy and without diabetes or hypertensive disorders in pregnancy. Maternal fasting plasma TGs and FFAs were measured in the second trimester. Cord blood IGF-1, IGF-2, and IGF binding protein-1 and protein-3 were measured at the time of delivery. A human trophoblast cell line, 3A-sub-E, was used to evaluate the effect of different FFAs on placental IGF-1 secretion. Results We recruited 598 pregnant women–neonate pairs. Maternal plasma TG (180 mg/dL [152.5-185.5 mg/dL] vs 166 mg/dL [133-206 mg/dL], P = .04) and cord blood IGF-1 concentrations (72.7 ± 23.0 vs 54.1 ± 22.8 ng/mL, P < .001) were higher in the LGA group and were significantly associated with birth weight z score. Maternal plasma free palmitic acid (PA) and stearic acid (SA), but not oleic acid (OA) or linoleic acid (LA), were significantly associated with cord blood IGF-1 concentrations. In 3A-sub-E cells, treatment with PA, SA, and LA, but not OA, induced IGF-1 expression and secretion. Conclusion Certain FFAs can induce placental IGF-1 secretion, which suggests a potential pathophysiology linking maternal plasma lipids and LGA.