Abstract

Background: Optimal gestational weight gain (GWG) is critical for fetal development and maternal health. Few studies have investigated metabolomic markers of GWG. Thus, we performed a metabolome-wide association study with GWG among pregnant women in the US. Methods: This longitudinal study included overweight or obese pregnant women (pre-pregnancy BMI ≥ 25) enrolled in the Health in Pregnancy and Postpartum study in early pregnancy (mean gestational week (GW) at baseline=12). Fasting plasma samples were collected both at baseline (N=39) and 32 GW (N=29). Untargeted metabolomic profiling was conducted using three different analytical platforms, including GC-TOF MS, HILIC-QTOF MS/MS, and CSH-QTOF MS/MS. Linear regressions were performed to identify metabolites at each time point and the change between two time points (i.e., metabolites 32 wk - metabolites baseline )/metabolites baseline ) that were individually associated with total GWG, a difference between delivery weight and pre-pregnancy weight. The least absolute shrinkage and selection operator (LASSO) regressions were conducted to select metabolites that were jointly associated with total GWG. Results: The mean (SD) age of 39 women enrolled was 30.4 (5.4) years and 38.5% were Blacks. A total of 769 known metabolites were profiled and annotated. Eight metabolites at 32 GW, including PC (34:4), LPC (22:5), isoleucine, arachidonic acid, TAG (52:6), TAG (58:7), and glyceric acid were positively whereas 3-Hydroxybutyrylcarnitine was negatively associated with GWG in both linear regressions (FDR < 0.1) and LASSO regressions (with no-zero coefficients) after adjusting for age, race, parity, and pre-pregnancy BMI (Figure 1). Metabolites at around 12 GW or changes between two time points were not associated with GWG (all FDRs ≥ 0.1). Conclusions: We identified eight metabolites at 32 GW that were significantly associated with total GWG in this longitudinal study of overweight and obese pregnant women. Future studies are warranted to replicate our findings.

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