LAUSR

Aims/hypothesis The aim of this work was to investigate the association of maternal HbA 1c during mid-pregnancy with biomarkers of glucose–insulin homeostasis during early childhood (4–7 years of age) and to assess whether and how offspring adiposity at birth and at age 4–7 years mediates this relationship among 345 mother–child pairs in the Healthy Start Study. Methods The exposure was maternal HbA 1c (mmol/mol) measured at 20–34 gestational weeks and categorised into tertiles. The outcomes were offspring fasting glucose, 1/insulin, HOMA2-IR, and HOMA2-B at age 4–7 years. The mediators were per cent fat mass (%FM) at birth, %FM at age 4–7 years, and the sum of the two as a metric of cumulative adiposity. Mediation analyses were conducted via a counterfactual-based approach. All models accounted for maternal race/ethnicity, offspring age and sex. Results There was a significant total effect of maternal HbA 1c on offspring glucose and 1/insulin. Specifically, we observed a positive trend across tertiles of HbA 1c and offspring glucose ( p trend <0.001), and an inverse trend across tertiles of HbA 1c and offspring 1/insulin ( p trend = 0.04). For instance, compared with offspring of women in the lowest tertile of HbA 1c , those whose mothers were in the second and third tertiles had 0.04 mmol/l (95% CI −0.05, 0.13) and 0.17 mmol/l (95% CI 0.08, 0.26) higher fasting glucose concentrations at age 4–7 years, respectively. Adjustment for pre-pregnancy BMI did not appreciably change the results. We found no evidence of mediation by offspring adiposity at any life stage. Conclusions/interpretation Offspring of women with higher HbA 1c during pregnancy had higher fasting glucose and lower insulin sensitivity by early childhood. These relationships were largely unaffected by the child’s own adiposity. Graphical abstract