Newborn Adiposity and Cord Blood C-Peptide as Mediators of the Maternal Metabolic Environment and Childhood Adiposity

Abstract

Objective: Excessive childhood adiposity is a risk factor for adverse metabolic health. The objective was to investigate associations of newborn body composition and cord C-peptide with childhood anthropometrics and explore whether these newborn measures mediate associations of maternal midpregnancy glucose and BMI with childhood adiposity.

Research design and methods: Data on mother/offspring pairs (N = 4,832) from the epidemiological Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study and HAPO Follow-up Study (HAPO FUS) were analyzed. Linear regression was used to study associations between newborn and childhood anthropometrics. Structural equation modeling was used to explore newborn anthropometric measures as potential mediators of the associations of maternal BMI and glucose during pregnancy with childhood anthropometric outcomes.

Results: In models including maternal glucose and BMI adjustments, newborn adiposity as measured by the sum of skinfolds was associated with child outcomes (adjusted mean difference, 95% CI, P value) BMI (0.26, 0.12-0.39, <0.001), BMI z-score (0.072, 0.033-0.11, <0.001), fat mass (kg) (0.51, 0.26-0.76, <0.001), percentage of body fat (0.61, 0.27-0.95, <0.001), and sum of skinfolds (mm) (1.14, 0.43-1.86, 0.0017). Structural equation models demonstrated significant mediation by newborn sum of skinfolds and cord C-peptide of maternal BMI effects on childhood BMI (proportion of total effect 2.5% and 1%, respectively), fat mass (3.1%, 1.2%), percentage of body fat (3.6%, 1.8%), and sum of skinfolds (2.9%, 1.8%), and significant mediation by newborn sum of skinfolds and cord C-peptide of maternal glucose effects on child fat mass (proportion of total association 22.0% and 21.0%, respectively), percentage of body fat (15.0%, 18.0%), and sum of skinfolds (15.0%, 20.0%).

Conclusions: Newborn adiposity is independently associated with childhood adiposity and, along with fetal hyperinsulinemia, mediates, in part, associations of maternal glucose and BMI with childhood adiposity.

Figure 1

Mediation model of maternal glucose and BMI with childhood adiposity with newborn adiposity as the mediator. Diagram of a mediation analysis displaying maternal predictors glucose sum of z-scores and BMI (measured at mean 27.7 weeks gestation), childhood sum of skinfolds outcome (measured at mean 11.4 years of age), and newborn sum of skinfolds (measured at delivery) as the mediator. Regression coefficients and 95% CIs are reported for total effects of maternal glucose and BMI on childhood sum of skinfolds (c₁ and c₂) and indirect effects of maternal glucose and BMI on the newborn sum of skinfolds mediator (a₁ and a₂). The proportion of the total effect of maternal glucose sum of z-scores on childhood sum of skinfolds mediated by newborn sum of skinfolds is 15.0%. The proportion of the total effect of maternal BMI on childhood sum of skinfolds mediated by newborn sum of skinfolds is 2.9%.