Cord blood leptin DNA methylation levels are associated with macrosomia during normal pregnancy

Background We previously demonstrated an association between placental leptin (LEP) methylation levels and macrosomia without gestational diabetes mellitus (non-GDM). This study further explored the association between LEP methylation in cord blood and non-GDM macrosomia. Method We carried out a case–control study of 61 newborns with macrosomia (birth weight ≥4000 g) and 69 newborns with normal birth weight (2500–3999 g). Methylation in the LEP promoter region was mapped by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Results Average cord blood LEP methylation levels were lower in macrosomia newborns than in control newborns ( P < 0.001). Eleven CpG sites were associated with macrosomia. Multivariate logistic regression revealed that low LEP methylation levels [adjusted odds ratio (AOR) = 2.84, 95% confidence interval (CI): 1.72–4.17], high pre-pregnancy body mass index (AOR = 7.44, 95% CI: 1.99–27.75), long gestational age (AOR = 3.18, 95% CI: 1.74–5.79), high cord blood LEP concentration (AOR = 2.25, 95% CI: 1.34–3.77), and male newborn gender (AOR = 3.91, 95% CI: 1.31–11.69) significantly increased the risk of macrosomia. Conclusions Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.