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



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.


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.


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.


Lower cord blood LEP methylation levels and certain maternal and fetal factors are associated with non-GDM macrosomia.

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We thank Xin-Yun Xu for assistance with collecting cord blood samples and Zi-Wei Liu for reviewing and providing advice on the preparation of the manuscript. This work was supported by the National Natural Science Foundation of China (to X.-J.Y., No. 81072378) and the Natural Science Funds of Zhejiang (to X.-J.Y., No. Y2101185).

Author information

H.-T.Y. and X.-J.Y. conceived and designed the study. Y.-H.W. was responsible for collecting the cord blood samples and data. Y.-C.W., Y.H. and Z.-F.L. conducted the statistical analyses. X.-X.X. and X.-J.Y. wrote the manuscript. All authors participated in discussions, made contributions to the manuscript, and approved the final version of the manuscript.

Competing interests

The authors declare no competing interests.

Correspondence to Xin-Jun Yang.

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