Joint effect of maternal plasma homocysteine and prepregnancy obesity on child blood pressure: A prospective birth cohort study

BACKGROUND/OBJECTIVES: Elevated homocysteine (Hcy) is a known cardiovascular risk factor. However, its role in intergenerational cardiometabolic risk is unknown. We hypothesized that maternal elevated Hcy can act alone or in combination with maternal prepregnancy obesity to increase child systolic blood pressure (SBP). METHODS: This study included 1279 mother-child pairs who were enrolled at birth and followed prospectively up to age 9 years from 2003-2014 at the Boston Medical Center. Child SBP percentile was calculated according to U.S. reference data and elevated SBP was defined as SBP≥75(th) percentile. RESULTS: A U-shaped relationship between maternal Hcy and her child SBP was observed. The risk for child elevated SBP was higher amongst those in the lowest quartile (Q1, odds ratio (OR): 1.27; 95% confidence interval (CI): 0.94 - 1.72), and highest quartile (Q4, OR: 1.34; 95% CI: 1.00 -1.81) as compared with those in quartiles 2 and 3. The highest risk of child elevated SBP was found amongst children born to obese mothers with Hcy in Q4 (OR: 2.22; 95%CI: 1.35 - 3.64), compared with children of non-obese mothers with Hcy in Q2-Q3. This association was independent from maternal folate and vitamin B12 status, and was not mediated by gestational age or size at birth. CONCLUSION: In this prospective birth cohort, we observed a U- shaped association between maternal Hcy levels and child elevated SBP. Maternal high Hcy (Q4) and prepregnancy obesity jointly increased the risk of child elevated SBP by more than two fold.