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

Abstract

Background Maternal lipids during pregnancy and placental growth factors are associated with excess foetal 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 triglyceride (TG) and free fatty acids (FAs) during pregnancy, cord blood insulin-like growth factors (IGF) and LGA. 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 TG 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 FAs on placental IGF-1 secretion. Results We recruited 598 pregnant women–neonate pairs. Maternal plasma TG (180 (152.5–185.5) vs. 166 (133–206) mg/dL, p=0.04) and cord blood IGF-1 concentrations (72.7 ± 23.0 vs. 54.1 ± 22.8 ng/mL, p=0.0001) 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. Conclusions Certain FAs can induce placental IGF-1 secretion, which suggest a potential pathophysiology linking maternal plasma lipids and LGA.

Maternal lipid profile during early pregnancy and birth weight: A retrospective study

“…The influence of TG during pregnancy has gained some attention, and we found a stable association between TG with birth weight and adverse birth outcomes in all of the BMI groups in the current study. Our study is in line with several previous studies that reported a positive association between maternal TG concentrations in early pregnancy and higher birth weight and LGA ( 36 – 38 ). In a study proposed by Wang et al.…”

“…The influence of TG during pregnancy has gained some attention, and we found a stable association between TG with birth weight and adverse birth outcomes in all of the BMI groups in the current study. Our study is in line with several previous studies that reported a positive association between maternal TG concentrations in early pregnancy and higher birth weight and LGA (36)(37)(38). In a study proposed by Wang et al in 2016, maternal TG concentrations in early pregnancy were divided into quartiles, and they did not observe any association between the highest quartile and an increased prevalence of LGA, whereas in the current study, the highest TG quartile showed a significantly higher risk of LGA (39).…”

Sex-Dependent Regulation of Placental Oleic Acid and Palmitic Acid Metabolism by Maternal Glycemia and Associations with Birthweight

“…A previous study had found increased ceramide in placenta from normal-weight fetuses compared to those with intra-uterine growth restriction (IUGR), consistent with our current findings in females [ 64 ]. Ceramides likely affect fetal growth by acting as signaling molecules, decreasing the expression of nutrient transporters [ 65 , 66 , 67 ], and regulating placental inflammation, insulin signaling, AKT activation, and amino acid transport [ 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Negative associations of birthweight centile with OA-TGs in female cases, meanwhile, might indicate reduced sequestration of OA into TG storage, making it more available for transfer to the fetus, especially since cord plasma OA has previously been linked with increased birthweight [ 72 ].…”

Epigenetic and Transcriptomic Programming of HSC Quiescence Signaling in Large for Gestational Age Neonates

“…Alteration of growth signaling highlights the tight correlation between in utero environment and the epigenetic programming. Indeed, excessive fetal growth observed in LGA neonates results in part from gestational hyperglycemia, dyslipidemia, or over secretion of placental insulin-like growth factors [25][26][27]. Altogether, these results further illustrate how DNA methylation and chromatin accessibility are key co-epigenetics actors regulating TF activity.…”