Objective: The intrauterine environment is known to affect the offspring's long-term risk for obesity and diabetes. Previous data show that maternal metabolism and gestational weight gain (GWG) are associated with autonomic nervous system (ANS) function in fetuses in utero, which can be assessed with heart rate variability (HRV) . We have now examined whether this association is also present in 2-year-old children and addressed the impact of gestational diabetes (GDM) .
Research Design and Methods: We examined children of participants of the ongoing PREG study (NCT04270578) who had a 5-point 75g oral glucose tolerance test during pregnancy. To assess HRV, a 10-minute ECG was recorded in the offspring. We analyzed time domain (beats per minute (BPM) , Root Mean Square of successive differences (RMSSD)) , Standard Deviation of RR-Intervals (SDNN) and frequency domain parameters (low frequency (LF) , high frequency (HF) and LF/HF) of HRV.
Results: We examined 67 children (33 girls, 34 boys, age 25.3±1.6 months) . During pregnancy, 30 of their mothers had GDM, which was treated according to national guidelines. There were no differences between groups in birth weight, weight at age 2, and body fat. We observed statistically significant associations of GWG with heart rate, RMSSD, SDNN, HF power, and HF/LF, indicating a lower parasympathetic tone in children of mothers with low GWG. This association was attenuated in GDM-exposed children. ANS function correlated with body weight and body fat only in children from normoglycemic pregnancies (NGT) .
Conclusion: We found an impact of maternal GWG on offspring ANS function, which was missing in the presence of treated GDM. The balance of the ANS was related to offspring body composition only in children from NGT pregnancies. Our results point towards a critical impact of maternal weight gain during pregnancy on the developing ANS with longstanding consequences for body composition.
L.Fritsche: None. H.Preissl: None. M.Heni: Advisory Panel; Boehringer Ingelheim International GmbH, Research Support; Boehringer Ingelheim International GmbH, Sanofi, Speaker's Bureau; Amryt Pharma Plc, Boehringer Ingelheim International GmbH, Novo Nordisk. J.Hartkopf: None. J.Hummel: None. D.Löffler: None. H.Häring: None. A.Peter: None. A.L.Birkenfeld: None. R.Wagner: Advisory Panel; Akcea Therapeutics, Daiichi Sankyo, Sanofi-Aventis Deutschland GmbH, Speaker's Bureau; Lilly, Novo Nordisk, Sanofi-Aventis Deutschland GmbH. A.Fritsche: Advisory Panel; Boehringer Ingelheim International GmbH, Novo Nordisk, Sanofi-Aventis Deutschland GmbH.
The PREG study is supported in part by a grant from the Federal Ministry of Education and Research (BMBF) (01GI0925) to the German Center for Diabetes Research (DZD) and by grant from the Deutsche Diabetes Stiftung (380/02/16) to LF