Small-for-gestational-age and determinants of HOMA indices, leptin and adiponectin in infancy

Background: /Objective: Poor fetal growth “programs” an elevated risk of obesity and related metabolic dysfunctional disorders in adulthood. How this vulnerability was developed in early life remains unclear. We sought to assess whether small-for-gestational-age (SGA) - an indicator of poor fetal growth, is associated with altered metabolic health biomarkers in infancy and explore the determinants. Methods: This was a nested matched (1:2) study of 65 SGA (birth weight <10 th percentile) and 130 optimal-for-gestational-age (OGA, 25 th -75 th ) infants in the 3D birth cohort. The outcomes included homeostasis model assessment of insulin resistance (HOMA-IR) and beta-cell function (HOMA-β), circulating leptin and adiponectin concentrations at age 2 years. Results: HOMA-IR, HOMA-β, leptin and adiponectin concentrations were similar in SGA vs. OGA infants at age 2 years. Female sex and accelerated growth in length during mid-infancy (3-12 months) were associated with higher HOMA-IR. Caucasian ethnicity and decelerated growth in weight during late infancy (12-24 months) were associated with lower HOMA-IR. Decelerated growth in weight during mid-infancy was associated with lower HOMA-β. Circulating leptin was positively correlated with female sex and current BMI. Current BMI was positively correlated with circulating adiponectin in SGA infants only; each SD increase in BMI was associated with a 13.4% (4.0%-23.7%) increase in circulating adiponectin in SGA subjects. Conclusions: Insulin resistance and secretion, circulating leptin and adiponectin levels are normal in SGA subjects in infancy at age 2 years. The study is the first to report an SGA-specific positive correlation between current BMI and circulating adiponectin, suggesting dysfunctional adiposity-adiponectin negative feedback loop development during infancy in SGA subjects. This could be a mechanism in adverse metabolic programming in poor fetal growth.