Relation of clinical and metabolic characteristics to neonatal adiposity among obese pregnant women.

摘要

Background: Amongst overweight and obese women metabolic dysfunction is evident in early pregnancy, and increased fetal growth precedes the clinical diagnosis of gestational diabetes at 20 weeks' gestation, followed by excessive fetal adipose tissue accretion. However, in obese women it is currently unknown which early pregnancy maternal exposures, including dietary, metabolic and demographic factors, contribute to the development of fetal adiposity. Our primary aim was to examine the relationship of early (15-18 weeks' gestation) pregnancy maternal clinical and biochemical variables with neonatal adiposity as assessed by skin fold thicknesses (SFT). As a secondary aim, we assessed pathways between early pregnancy maternal characteristics and neonatal adiposity, and explored the potential mediating role of the maternal late second trimester metabolic profile using casual mediation analysis. Method: We used data from the UK Pregnancies Better Eating and Activity Trial (UPBEAT), a randomised controlled trial of 1555 obese pregnant women (mean BMI 36.3 kg/m ) which assessed an antenatal intervention promoting a low glycaemic diet and increased physical activity. Maternal and neonatal adiposity were assessed by skinfold thicknesses (SFT). Maternal baseline socio-demographic, medical and family characteristics were recorded at 15-18 weeks' gestation. The mother's biochemical profile was evaluated at 15-18 and 24-29 weeks' gestation by measurement of targeted candidate biomarkers and metabolomics profile using nuclear mass spectrometry (NMR). Detailed neonatal anthropometry was collected in a subgroup. To examine associations with infant adiposity, multivariable linear regression was undertaken with adjustment for potential confounders. To assess potential pathways between early and late 2~nd trimester variables and neonatal adiposity, mediation analysis using parametric regression was undertaken. Results: Neonatal (n = 502) SSFT (sum of triceps and sub-scapular skin fold thicknesses) was greater in multiparous vs. nulliparous mothers (β= 1.06 mm, 95%CI 0.58 to 1.53), and was linearly associated with higher maternal birthweight (β = 0.55 mm/kg; 0.001 to 0.01). Neonatal SSFT was also positively associated with maternal 15-18 week triceps SFT (β = 0.04 mm/mm, 0.013 to 0.079), and inversely related to maternal 15-18 week suprailiac SFT (β = -0.035 mm/mm, -0.057 to -0.013). Neonatal SSFT was not related to any biochemical variables measured in early (15-18 weeks) pregnancy but was associated with maternal fasting concentrations of glucose, serum insulin, C-peptide and glycoprotein acetyls at 26-28 weeks' gestation. Associations of parity (4.5%), early pregnancy triceps (12.5%) and suprailiac SFT (13.9%) with neonatal SSFT were partially mediated by fasting glucose at 26-28 weeks' gestation. Conclusions: This extensive study has identified some novel and potentially modifiable maternal characteristics in early pregnancy that are associated with neonatal adiposity. The mediating role of second trimester glycaemia emphasises the need for optimal glucose control in obese women before conventional 28 week screening for gestational diabetes.