Metabolome-Wide Association Study of Cord Blood Metabolites With Blood Pressure in Childhood and Adolescence

Abstract

BACKGROUND: No studies have examined whether the cord blood metabolome—a reflection of in utero metabolism—influences blood pressure (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 children. METHODS: In the Boston Birth Cohort, we measured metabolites in cord blood plasma, and SBP and DBP at clinic visits between 3 and 18 years. We examined associations of cord metabolites with SBP and DBP percentiles using linear mixed models and with elevated BP using mixed-effects Poisson regression. RESULTS: Our study included 902 mother-child dyads (60% Black, 23% Hispanic, 45% female). Children were followed for a median of 9.2 (interquartile range, 6.7–11.7) years, and the median number of BP observations per child was 7 (interquartile range, 4–11). After false discovery rate correction, 3 metabolites were associated with SBP, 96 with DBP, and 24 with elevated BP; 2 metabolites (1-methylnicotinamide, dimethylguanidino valeric acid) were associated with all 3 outcomes, and 22 metabolites were associated with both DBP and elevated BP. After multivariable adjustment, 48 metabolites remained significantly associated with DBP. Metabolites that showed the strongest associations with SBP, DBP, and elevated BP included nucleotides (eg, xanthosine, hypoxanthine, xanthine) and acylcarnitines (eg, C6 and C7 carnitines), which represent fatty acid oxidation and purine metabolism pathways. CONCLUSIONS: In our urban and predominantly racial/ethnic minority cohort, we provide evidence that metabolomic alterations in utero, in particular, acylcarnitine- and purine-metabolism metabolites, may be involved in the early life origins of hypertension.

Cord Blood Insulin Concentration and Hypertension Among Children and Adolescents Enrolled in a US Racially Diverse Birth Cohort

“…Elevated insulin levels at birth persist into childhood, 13 which predisposes to increased BP in later life. 25 Fetal programming 14,26 and genetic susceptibility of hypertension 27 may also play important roles in this setting. In our study, the associations between cord blood insulin and BP outcomes, which were largely attenuated after adjustment for maternal OWO, diabetes, hypertensive disorders in pregnancy, preterm birth, and childhood BMI, remained significant, suggesting the involvement of fetal programming and genetic predisposition.…”

“…At each clinical visit, child's systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured by a clinical nurse on the right arm with the child in a sitting position using the automatic sphygmomanometer Masimo SET with an appropriately sized cuff, as described previously. 14 The age range of BP measurement was 3 to 18 years. BP percentiles were computed according to the national reference as a function of measured BP, age, sex, and height.…”

Purine degradation pathway metabolites at birth and the risk of lower respiratory tract infections in infancy

“…Cord blood samples were analysed using liquid chromatography–tandem mass spectrometry (LC–MS). We adhered to rigorous quality control protocols that have been previously described [ 10 ]. This analysis included 378 metabolites with a coefficient of variation <20%.…”

“…Non-detectable values were imputed as one-half of the minimal value of each metabolite. We used the natural logarithmic and rank-based inverse normal transformation methods to render the distributions approximately Gaussian and reduce the impact of outliers [ 10 ].…”

Neurodevelopment and Metabolism in the Maternal-Placental-Fetal Unit

“… 7 , 8 Umbilical cord blood has also been used to investigate fetal metabolism at birth. 9 However, we are not aware of any analysis of the associations among maternal, placental, and fetal metabolism. Therefore, we aimed to investigate the associations among metabolism in maternal serum, placental tissue, and umbilical cord serum using quantitative metabolomics and whether these measures were associated with neurodevelopmental outcomes in a prospective pregnancy cohort with high familial risk of ASD.…”