Cord Blood Leptin and Adiponectin as Predictors of Adiposity in Children at 3 Years of Age: A Prospective Cohort Study

The prevalence of adult and childhood obesity has been increasing to epidemic proportions over the past decade.1 In addition to nutrition and environmental factors early in development, accumulating evidence suggests that the development of obesity and its comorbidities may be influenced by intrauterine factors.2–4 Leptin and adiponectin are adipocyte-secreted hormones known to play critical roles in energy homeostasis in adults, but their fetal/neonatal effects are less well understood. Leptin, the product of the ob (obesity) gene, was discovered in 1994 and has since been shown to regulate energy homeostasis by relaying information about the body’s energy and nutrient stores from the periphery to the brain.5 Although secreted primarily from adipocytes, it is also found in other tissues, including placentas.6–8 High leptin levels in cord blood have been reported to correlate with fetal adiposity at birth.9,10 Adiponectin is another adipokine that is solely derived from adipose tissue, is reduced in obesity in adults, and, in many studies, is inversely related to leptin levels. 11,12 A large body of evidence supports the role of adiponectin in insulin sensitivity and lipid metabolism. Its role in neonatal and fetal growth remains poorly understood, with studies suggesting that, in contrast to adults, cord blood adiponectin is unrelated to birth weight13 or is positively associated with birth weight.14,15 The majority of studies examining the relationship between these adipocytokines and birth weight, as well as other childhood measures of adiposity, have been cross-sectional. Of the few prospective studies, 2 were moderately sized cohort studies (n = 185–197) examining only leptin in children ages 5 to 12 years with known risk factors for obesity (childhood obesity, parental obesity, Pima Indian). These studies found that leptin at these ages was positively correlated with weight, thus implying that these children had developed leptin resistance before they reached the 5- to 12-year age range.16,17 Two smaller cohort studies (n = 52–85) showed that adiponectin was inversely related to weight gain; however, these studies were limited not only by their small size but also by the fact that 1 study examined all of the infants with 1-month follow-up, whereas the other examined only small and average for gestational age infants for 2 years.18,19 Limited sample size and duration of follow-up, as well as exclusion of several subgroups and lack of adjustment for numerous potential confounders in previously published prospective studies, have precluded full elucidation of the physiologic role of leptin and adiponectin in early development. Thus, the relationship between cord blood levels of these hormones and ultimate outcomes at birth and beyond remains largely to be determined. We hypothesized that lower leptin levels at birth would activate hypothalamic appetite centers and neuroendocrine mechanisms that would result in increased weight at 6 months and 3 years of age. We also hypothesized that, similar to our recent findings in rodents, increasing adiponectin levels would be associated with increasing body weight and fat mass measures at 6 months and 3 years of life in children. We sought to clarify this question by analyzing longitudinal data from Project Viva, a larger cohort of pregnant women and their children. The objective of the study was to examine relationships of cord blood levels of adipokines with measures of childhood adiposity 3 years later.