Exposure to gestational diabetes is a stronger predictor of dysmetabolic traits in children than size at birth

Context and Objective: Being born small or large for gestational age and intrauterine exposure to gestational diabetes (GDM) increase the risk of type 2 diabetes (T2D) in the offspring, however, the potential combined deleterious effects of size at birth and GDM exposure remains unknown. We aimed to examine the independent effect of size at birth as well as the influence of GDM exposure in utero on cardio-metabolic traits, body composition, and puberty status in children.Design, Participants and Methods: This study is a longitudinal birth cohort study. We used clinical data from 490 offspring of mothers with GDM and 527 control offspring aged 9-16 years, born singleton at term from the Danish National Birth Cohort with available birth weight data.Results: We found no evidence of a U-shaped association between size at birth (expressed as birth weight, sex and gestational age adjusted z-score) and cardio-metabolic traits. Body size in childhood and adolescence reflected size at birth, but was not reflected in any metabolic outcome. No synergistic adverse effect of being born small or large for gestational age and being exposed to GDM was shown. However, GDM was associated with an adverse metabolic profile and earlier onset of female puberty in childhood and adolescence independently of size at birth.Conclusion: In childhood and adolescence, GDM is a stronger predictor of dysmetabolic traits than size at birth. The combination of being born small or large and being exposed to GDM does not exacerbate the metabolic profile in the offspring.