Early childhood blood pressure in relation to umbilical cord homocysteine and folate: insights from the ENVIRonmental influence ON AGEing birth cohort Study

BACKGROUND: High blood pressure (BP) tracks from childhood into adulthood, contributing to cardiovascular risk. How the prenatal one-carbon (1-C) metabolism, as reflected by umbilical cord homocysteine and folate, affects BP in early childhood is unknown. METHODS: The prospective population-based birth cohort ENVIRonmental influence ON earlyAGEing (ENVIRONAGE) comprised 500 mother-offspring pairs. Umbilical cord and maternal homocysteine and folate were measured by electrochemiluminescence immunoassay. The association of the offspring BP and risk of high BP was assessed by linear and logistic regression and by mediation analysis. Association sizes were expressed per doubling of the biomarkers and adjusted for the children's sex, age and weight and maternal age at delivery and parity. RESULTS: At 4.5 years (median), cord homocysteine was associated with higher diastolic and mean BP (MBP), but not SBP with association sizes of 1.67 mmHg [95% confidence interval (CI), 0.36-2.99] and 1.19 mmHg (0.01-2.38), respectively. The odds ratio for high childhood DBP with normotension as reference was 2.22 (1.34-3.68). Associations of BP with cord folate were not significant. Cord folate had only an indirect effect on DBP and MBP with effect sizes amounting to -3.04 (P = 0.027) and -2.30 (P = 0.061) mmHg. Maternal biomarkers were not associated with the offspring's BP. CONCLUSION: In this prospective birth cohort study, higher cord plasma homocysteine was associated with higher DBP in early childhood, whereas cord folate was only via homocysteine associated with the offspring's BP. The 1-C metabolism provides a mechanism for preventing high BP in childhood, which is a forerunner of hypertension in adolescence and adulthood.