Maternal pre-pregnancy BMI downregulates neonatal cord blood LEP methylation.

BACKGROUND: Neonatal adiposity has many determinants and may be a risk factor for future obesity. Epigenetic regulation of metabolically important genes is a potential contributor. OBJECTIVES: The objective of the study is to determine whether methylation changes in the LEP gene in cord blood DNA are impacted by the maternal environment or affect neonatal adiposity measures. METHODS: A cross-sectional study of 114 full-term neonates born to healthy mothers with normal glucose tolerance was performed. Cord blood was assayed for leptin and genome-wide DNA methylation profiles via the Illumina 450K platform. Neonatal body composition was measured by air displacement plethysmography. Multivariate linear regression models and semi-partial correlation coefficients were used to analyze associations. False discovery rate was estimated to account for multiple comparisons. RESULTS: Maternal pre-pregnancy BMI was associated with decreased methylation at five CpG sites near the LEP transcription start site in an adjusted model (false discovery rate <0.022 for each site). The association between maternal BMI and cord blood leptin approached significance (r = 0.18, p = 0.054). Cord blood leptin was positively correlated with neonatal adiposity measures including birth weight (r = 0.45, p < 0.001), fat mass (r = 0.47, p < 0.001) and percent body fat (r = 0.44, p < 0.001). CONCLUSIONS: Maternal pre-pregnancy BMI is strongly associated with decreased cord blood LEP gene methylation and may mediate the well-known association between maternal pre-pregnancy BMI and neonatal adiposity.

Excessive gestational weight gain in the first trimester among women with normal glucose tolerance and resulting neonatal adiposity.

OBJECTIVE: To assess whether weight gain above or below Institute of Medicine (IOM) recommended amounts in an ethnically diverse obstetric population with normal glucose tolerance is associated with differences in neonatal adiposity. STUDY DESIGN: In this prospective cohort study, healthy women with normal glucose tolerance based on the International Association of Diabetes and Pregnancy Study Groups guidelines were enrolled. Gestational weight at multiple time points were collected. Neonatal adiposity was measured by air displacement plethysmography at 24 to 72 h of life. Analyses included Fisher's exact test, analysis of variance and a trajectory analysis using a group-based weight gain trajectory model with a censored normal distribution. RESULTS: Overweight and obese women were more likely to exceed IOM weight gain guidelines. Regardless, there was no significant difference in %body fat of neonates born to mothers who either met or exceeded gestational weight gain (GWG) guidelines. GWG timing influenced neonatal anthropometrics: women who gained excessively by the first prenatal visit had neonates with significantly higher birth weight (3.91 vs 3.45 kg, P<0.001) and %body fat (13.7 vs 10.9%, P=0.0001) compared with women who had steady and moderate GWG. CONCLUSION: Avoidance of excessive GWG in the first trimester may prevent high amounts of neonatal adiposity.

Excessive weight gain in women with a normal pre-pregnancy BMI is associated with increased neonatal adiposity.

BACKGROUND: More than 40% of women with a normal pre-pregnancy body mass index (BMI) exceed the 2009 Institute of Medicine (IOM) guidelines' recommended weight gain of 25-35 lb. Excessive gestational weight gain is one modifiable factor that may be contributing to childhood overweight and obesity. OBJECTIVE: The objective of this study was to evaluate differences in adiposity from neonates born to mothers with a normal pre-pregnancy BMI who either gained within or above IOM guidelines. METHODS: Neonatal adiposity was measured within 72 h of birth by the method of air displacement plethysmography. RESULTS: Compared with mothers who gained within IOM guidelines (N = 27), mothers with excessive gestational weight gain (N = 11) (mean 29.0 vs. 45.2 lb) had neonates with 50% more fat mass (348 vs. 525 g) and 3% greater body fat (10.7 vs. 13.9%). CONCLUSIONS: Increased adiposity at birth may predispose these children to increased risk of obesity and highlight the importance that women avoid gaining excessive weight in pregnancy.