Differential Effects of First and Third Trimester HbA1c Levels on Neonatal Weight and Placental Mediation in Type 1 Diabetes

Abstract

Context: In women with type 1 diabetes (T1D), the effects of glycaemic control on neonatal weight and the role of the placenta are not fully understood. Objective: This study explores the relationship between glycaemic control, neonatal weight, and placental weight. Design: A retrospective observational longitudinal study of pregnant women with T1DM. Setting: The study included 265 women with T1D. The target for the first A1c was set at ≤ 7.0%, while the target for the last A1c was ≤ 6.5%. The cohort was divided into four groups based on whether they achieved their target A1c (T) or had levels higher than the target (H) at each end. These groups were classified as Target-Target (T-T), Target-High (T-H), High-Target (H-T), and High-High (H-H). For the secondary objective, we included 154 women for whom placental weight data were available. Main outcome: We assessed the association between firstA1c, lastA1c, and neonatal weight, examining the mediation effect of the placenta. Results: The mean age of the participants was 29.4 years (SD 4.6), and the mean T1DM duration was 14.1 years (SD 7.1). The median neonatal weight was highest in the T-H group (3.56 kg) and lowest in the H-T group (3.20 kg) (p=0.009). FirstA1c was negatively correlated with neonatal weight (β-coefficient -150.9, p < 0.01), whereas lastA1c positively correlated (β-coefficient 162.5, p < 0.01). The association with firstA1c disappeared when correcting for placental weight, while lastA1c remained significant. The placenta mediates 65% of the impact of firstA1c on neonatal weight Conclusions: Poor glycaemic control early in pregnancy is linked to lower neonatal birth weight, while poor control in the third trimester is associated with higher birth weight. These findings emphasize the importance of maintaining adequate glycaemic control before and during early pregnancy for better health outcomes.