Abstract 10153: Cord Blood Metabolite Signatures for Elevated Blood Pressure in Childhood and Adolescence

Abstract

Background: Risk factors for high blood pressure (BP) in children start in utero . Cord blood metabolites reflect exposures of the developing fetus to the in utero environment. No studies have examined whether cord blood metabolites are associated with BP in children. Objectives: To examine prospective associations of cord blood metabolites with systolic BP (SBP), diastolic BP (DBP), and risk of elevated BP in childhood and adolescence. Methods: We used data from the Boston Birth Cohort. Metabolites were measured in cord blood plasma samples collected at birth. SBP and DBP were measured at clinic visits between 3 to 18 years. We calculated BP percentiles per the 2017 American Academy of Pediatrics Clinical Practice Guideline. We examined associations of cord metabolites with SBP and DBP percentiles using linear mixed models and with elevated BP using mixed-effects Poisson regression. We used the False Discovery Rate (FDR) method to adjust for multiple comparisons. Results: Our study included 902 mother-child dyads (60% Black, 23% Hispanic, 45% female). Children were followed for a median of 9.2 (IQR: 6.7-11.7) years, and the median number of BP observations per child was 7 (IQR: 4-11). After FDR adjustment, 3, 94, and 22 metabolites were respectively associated with SBP, DBP, and risk of elevated BP; 2 metabolites (1-methylnicotinamide, dimethylguanidino valeric acid) were associated with all three outcomes, and 22 metabolites were associated with both DBP and risk of elevated BP. After multivariable adjustment, 48 metabolites remained significantly associated with DBP. Metabolites that showed the strongest associations with SBP, DBP, and risk of elevated BP included nucleotides (e.g., xanthosine, hypoxanthine, xanthine) and acylcarnitines (e.g., C6 and C7 carnitines), which represent fatty acid oxidation and purine metabolism pathways. Conclusions: In this predominantly urban, low-income, minority cohort, cord blood metabolites were prospectively associated with BP and risk of elevated BP from childhood to adolescence. Acylcarnitines and purine metabolism may be involved in the early life origins of hypertension. Cord metabolites may explain the intergenerational effects of in utero environments on BP in childhood and adolescence.