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

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.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.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%).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.