Abstract
Abstract Objectives The roles of maternal lipidomic profile in fetal growth are rarely studied. This study aims to examine the association of lipidomic profiles over pregnancy with birth weight (BW), neonatal sum of skinfolds (SS) and length, and risks of large- and small-for-gestational-age (LGA, SGA). Methods Lipidome analyses were performed among 321 pregnant women from the NICHD Fetal Growth Study-Singletons in the plasma collected at gestational weeks 10–14, 15–26 (fasting), 23–31 and 33–39, using untargeted liquid chromatography-mass spectrometry (LC-MS). The associations of neonatal outcomes with 328 annotated lipid metabolites and 6–9 lipid networks constructed using weighted correlation network analysis were assessed using linear mixed-effects models adjusting for age, race, pre-pregnancy BMI, gestational age of blood collection, and infant sex. False discovery rate (FDR) <0.05 was considered significant. Results Both individual metabolites and networks were significantly related to neonatal outcomes. The relations varied by lipid molecular structure and timing in gestation. At weeks 10–14, two networks of medium-chain triglycerides (TG) were positively related to BW, neonatal SS and length. For instance, the beta for TG (50:5) abundance related to SS (1 mm) was 0.21 (FDR = 2.72E-11). In contrast, a network of lysophosphatidylcholines (LPC) and a network mainly of phospholipids (PC) and cholesteryl esters (CE) were inversely related to BW, whereas the network of LPC and a network of longer-chain TGs were inversely related to SS. For instance, the beta for LPC (18:3) abundance related to SS (1 mm) was −0.11 (FDR = 0.004). At weeks 15–26, a network mainly of medium-chain higher-saturation TGs was positively, whereas a network mainly of sphingomyelins (SM) and PCs was inversely related to BW, SS and length. Further, the network of LPC at weeks 15–26 was inversely related to LGA risk; the relative risk for each standard deviation of the eigenvalue was 0.52 (95% confidence interval: 0.34, 0.81, FDR = 0.02). Conclusions Generally, lipid networks of medium-chain TGs in the 1st and 2nd trimesters were positively whereas a network mainly of SMs and PCs in the 2nd trimester was inversely related to BW, SS, and length. Funding Sources National Institutes of Health.
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