ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study was based on the HAPO prospective birth cohort, which has previously generated several publications on maternal gestational diabetes in relation to neonatal anthropometry and childhood glucose metabolism^1,2. It examined if cord blood leptin was positively associated with peripubertal obesity and adiposity, and if this relationship was dependent on maternal BMI, hyperglycemia and/or other maternal factors.

This is an important question, because animal models have shown that interfering with perinatal leptin exposure can impact on adiposity outcomes in older offspring³ suggesting it could be a biomarker for both risk identification and prevention.

This secondary analysis included a highly diverse subgroup of 986 pregnant mothers, chosen from the initial 23,316 participants, recruited in 15 centers from 9 countries between 2000 and 2006. Offspring were examined within 3 days of birth and again at 10-14 y old (mean 11.5±1.1 y). Mothers were of different ethnicities (44% White, 25% Black, 16% Asian, 14% Hispanic), and 15% had gestational diabetes. Mean gestational age at delivery was 39.9±1.9 w, mean birthweight was 3402.7±466.6, and half were females. At childhood follow-up, 28% were overweight or obese, and 11% obese. Cord blood leptin (log-transformed) and multiple measures of adiposity were also recorded at birth and again at follow-up, along with pubertal status.

Linear regression was performed, adjusting for several maternal covariates. As expected, cord blood leptin was positively associated with neonatal adiposity, and also with peripubertal leptin. Positive associations between cord blood leptin and childhood obesity were partially attenuated by adjustments for maternal BMI and glucose. They remained significant for childhood % body fat, body fat mass, sum of skinfolds, and log-transformed serum leptin. The odds ratio (OR) for overweight or obesity was 1.21 (95% CI=1.03-1.42), for obesity (OR=1.31, 95% Cl=1.04-1.66) and for % body fat >85th percentile (OR=1.38, 95% Cl=1.12-1.73).

The robust and consistently positive relationships observed here contrast with previously reported inconsistent results. The authors hypothesize this may be due to their larger sample size, the high proportion of overweight and obese children, and older age at follow-up, as the peripubertal period appears to be a metabolic turning point. The mechanism by which neonatal leptin impacts future adiposity remains to be determined.

References: 1. Lowe WL Jr, Scholtens DM, Lowe LP, Kuang A, Nodzenski M, Talbot O, Catalano PM, Linder B, Brickman WJ, Clayton P, Deerochanawong C, Hamilton J, Josefson JL, Lashley M, Lawrence JM, Lebenthal Y, Ma R, Maresh M, McCance D, Tam WH, Sacks DA, Dyer AR, Metzger BE. Hyperglycemia and adverse pregnancy outcome follow-up study (HAPO FUS): maternal gestational diabetes mellitus and childhood glucose metabolism. Diabetes Care. 2019;42(3):372-380. doi: 10.2337/dc18-1646.2. Group HSCR. Hyperglycemia and Adverse Pregnancy Outcome (HAPO) Study: associations with neonatal anthropometrics. Diabetes. 2009;58(2):453-459. doi: 10.2337/db08-11123. Stocker CJ, Cawthorne MA. The influence of leptin on early life proùgramming of obesity. Trends Biotechnol. 2008;26(10):545-551. doi: 10.1016/j.tibtech.2008.06.004.