280-OR: Metabolomic Signatures of Excess Fetal Growth in Pregnancies Complicated by Type 1 Diabetes (T1D)

Abstract

Background: In pregnancies complicated by T1D, glycemic control is only moderately associated with excess fetal growth, suggesting that nutrients other than glucose may be involved. Aims: We analyzed associations between metabolites in maternal and newborn plasma, and fetal growth patterns, in T1D pregnancies. Methods: We obtained maternal plasma samples in the 2nd and 3rd trimester and at delivery, and cord blood samples immediately after delivery, in 22 mother/infant dyads. We used an untargeted metabolomic platform (Broad Institute) and calculated correlation coefficients between individual metabolites and newborn growth percentiles adjusted for gestational age, sex, parity, and ethnicity (GROW percentile). We used a false discovery rate threshold of FDR<0.2. Large for gestational age (LGA) was defined as GROW percentile ≥90 and appropriate for gestational age (AGA) as between the 10th and 90th percentiles. Results: Forty-five percent of newborns were classified as LGA. Maternal age, BMI, diabetes duration, insulin dose and pump use did not differ between LGA vs. AGA. We identified stronger associations between GROW percentiles and metabolites in cord blood than with metabolites in maternal plasma during the 2nd or 3rd trimester. In cord blood, 29 metabolites were associated with GROW percentile (FDR<0.2). For 51 metabolites, the ratio between abundance in cord blood to abundance in maternal blood at delivery was associated with the GROW percentile (FDR <0.2). Many of the top-ranking metabolites positively associated with infant growth were long-chain glycerophosphocholines (e.g., LPC(20:3) β 0.035, p=0.0002, FDR 0.01; LPC(22:5) β 0.033, p=0.0008, FDR 0.03). Conclusion: Glycerophospholipids in cord blood were associated with excess fetal growth in T1D pregnancies, suggesting alterations in lipid metabolism. We also report associations between fetal growth and ratios of metabolites in cord blood to maternal blood, suggesting differences in placental transport. Disclosure E.M.Isganaitis: None. D.Wolfs: None. J.C.O'connell: None. G.A.Hansbury: None. S.Wolpowitz: None. C.B.Clish: None. T.James-todd: None. F.M.Brown: Other Relationship; Dexcom, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK036836, P30DK057521); Broad Institute