Newborn Adiposity and Cord Blood C-Peptide as Mediators of the Maternal Metabolic Environment and Childhood Adiposity
Authors: Josefson Jami L. , Scholtens Denise M. , Kuang Alan , Catalano Patrick M. , Lowe Lynn P. , Dyer Alan R. , Petito Lucia C. , Lowe William L. , Metzger Boyd E. ,   HAPO Follow-up Study Cooperative Research Group, Deerochanawong Chaicharn , Tanaphonpoonsuk Thadchanan , Chotigeat Sukeeta Binratkaew Uraiwan , Manyam Wanee , Forde Martinette , Greenidge Andre , Neblett Kathleen , Lashley Paula Michele , Walcott Desiree , Corry Katie , Francis Loraine , Irwin Jo-anne , Langan Anne , McCance David R. , Mousavi Maureen , Young Ian , Gutierrez Jennifer , Jimenez Jennifer , Lawrence Jean M. , Sacks David A. , Takhar Harpreet S. , Tanton Elizabeth , Brickman Wendy J. , Howard Jennifer , Josefson Jami L. , Miller Lauren , Bjaloncik Jacqui , Catalano Patrick M. , Davis Ajuah , Koontz Michaela , Presley Larraine , Smith Shoi , Tyhulski Amanda , Li Albert Martin , Ma Ronald C. , Ozaki Risa , Tam Wing Hung , Wong Michelle , Yuen Cindy Siu Man , Clayton Peter E. , Khan Aysha , Vyas Avni , Maresh Michael , Benzaquen Hadasse , Glickman Naama , Hamou Alona , Hermon Orna , Horesh Orit , Keren Yael , Lebenthal Yael , Shalitin Shlomit , Cordeiro Kristina , Hamilton Jill , Nguyen Hahn Y. , Steele Shawna , Chen Fei , Dyer Alan R. , Huang Wenyu , Kuang Alan , Jimenez Maria , Lowe Lynn P. , Lowe William L. , Metzger Boyd E. , Nodzenski Michael , Reisetter Anna , Scholtens Denise , Talbot Octavious , Yim Paul , Dunger David , Thomas Alicia , Horlick Mary , Linder Barbara , Unalp-Arida Aynur , Grave Gilman 
Published: February 2021

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, &lt;0.001), BMI z-score (0.072, 0.033–0.11, &lt;0.001), fat mass (kg) (0.51, 0.26–0.76, &lt;0.001), percentage of body fat (0.61, 0.27–0.95, &lt;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.