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

Abstract

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 to 2014 at the Boston Medical Center. Child SBP percentile was calculated according to US reference data and elevated SBP was defined as SBP⩾75th percentile.

Results: A U-shaped relationship between maternal Hcy and her child SBP was observed. The risk for child elevated SBP was higher among 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 among 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.

Conclusions: 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.

Figure 1

The association between maternal plasma homocysteine and child SBP percentile stratified by prepregnancy BMI category. The graph displays the crude association between maternal plasma homocysteine concentration and offspring SBP percentile stratified by maternal prepregnancy BMI category.

Figure 2

The combined effect of maternal plasma homocysteine and maternal prepregnancy obesity on SBP percentile and proportion of child elevated SBP (SBP≥75th) in the Boston Birth Cohort (BBC) A, The y-axis presents least square means and 95%CI of child SBP percentiles, as estimated using a generalized linear model with adjustment for maternal age, race/ethnicity, education, smoking, alcohol intake, parity, perceived stress during pregnancy, diabetes and hypertensive disorders. There was no significant interaction between maternal Hcy status and prepregnancy obesity (P > .05). B, The y-axis presents adjusted probabilities and 95%CI of child elevated SBP, as estimated using a logistic regression model with adjustment for the previously mentioned covariates. There was no significant interaction between maternal Hcy status and prepregnancy obesity (P > .05). Body mass index was calculated as weight in kilograms divided by height in meters squared. The Boston Birth Cohort (BBC) uses a rolling enrollment; the study sample consisted of children enrolled from 1998 to 2012 who have been followed up from birth up to the last visit recorded by electronic medical record. Maternal plasma homocysteine quartile (Q) range: Q1: 3.14 to 6.27umol/L; Q2: 6.28 to 7.54umol/L; Q3: 7.55 to 9.57umol/L; Q4: 9.58 to 22.59umol/L

Figure 2

The combined effect of maternal plasma homocysteine and maternal prepregnancy obesity on SBP percentile and proportion of child elevated SBP (SBP≥75th) in the Boston Birth Cohort (BBC) A, The y-axis presents least square means and 95%CI of child SBP percentiles, as estimated using a generalized linear model with adjustment for maternal age, race/ethnicity, education, smoking, alcohol intake, parity, perceived stress during pregnancy, diabetes and hypertensive disorders. There was no significant interaction between maternal Hcy status and prepregnancy obesity (P > .05). B, The y-axis presents adjusted probabilities and 95%CI of child elevated SBP, as estimated using a logistic regression model with adjustment for the previously mentioned covariates. There was no significant interaction between maternal Hcy status and prepregnancy obesity (P > .05). Body mass index was calculated as weight in kilograms divided by height in meters squared. The Boston Birth Cohort (BBC) uses a rolling enrollment; the study sample consisted of children enrolled from 1998 to 2012 who have been followed up from birth up to the last visit recorded by electronic medical record. Maternal plasma homocysteine quartile (Q) range: Q1: 3.14 to 6.27umol/L; Q2: 6.28 to 7.54umol/L; Q3: 7.55 to 9.57umol/L; Q4: 9.58 to 22.59umol/L