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

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posted on 2021-02-22, 19:44 authored by Jami L. Josefson, Denise M. Scholtens, Alan Kuang, Patrick M. Catalano, Lynn P. Lowe, Alan R. Dyer, Lucia C. Petito, William L. Lowe, Jr., Boyd E. Metzger, the HAPO Follow-up Study Cooperative Research Group
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 mid-pregnancy glucose and BMI with childhood adiposity.

RESEARCH DESIGN AND METHODS

Data on mother/offspring pairs (N=4832) 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 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), percent bodyfat(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%), percent bodyfat(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), percent bodyfat (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.

Funding

The HAPO Study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Diabetes and Digestive and Kidney Diseases (R01-HD-34242 and R01-HD-34243). The HAPO FUS was funded by grant 1U01-DK-094830 from the National Institute of Diabetes and Digestive and Kidney Diseases and the Eunice Kennedy Shriver National Institute of Child Health and Human Development. The HAPO Follow-up Study data were collected and managed using REDCap electronic data capture tools hosted at Northwestern University Feinberg School of Medicine. REDCap is supported at Feinberg School of Medicine by the Northwestern University Clinical and Translational Science Institute. The research reported in this article was supported, in part, by grant UL1TR001422 from the National Center for Advancing Translational Sciences, National Institutes of Health. Funding sources were not involved in the collection, analysis, or interpretation of any data, in the writing of the report, or in the decision to submit the article for publication.

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