Maternal hemodynamics and neonatal birth weight in pregnancies complicated by gestational diabetes: new insights from novel causal inference analysis modeling

Abstract

Objectives: Normal pregnancy is characterised by significant changes in maternal hemodynamics which correlate with fetal growth. Pregnancies complicated by gestational diabetes (GDM) are associated with large for gestational age (LGA) and macrosomia, but the relationship between maternal hemodynamic parameters and birthweight among women with GDM is yet to be established. Our objective was to investigate the influence of maternal hemodynamics on neonatal birthweight in healthy pregnancies and those complicated by GDM. Methods: We conducted a prospective cross-sectional case controlled study. GDM was defined as a fasting glucose ≥5.3mmol/L, and/or serum glucose of ≥7.8mmol/L 2 hours following a 75g oral glucose load. Data were collected on maternal characteristics and pregnancy outcomes, including body mass index (BMI) and birth weight centile, adjusted for gestation at delivery. Maternal hemodynamics were assessed using the Arteriograph® and bioreactance techniques at 34-42 weeks gestation. Graphical causal inference methodology was used to identify causational effects of the measured variables on neonatal birthweight centile. Results: 141 women with GDM and 136 normotensive non-diabetic controls were included in the analysis. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), pulse wave velocity (PWV) and BMI. Among controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal birthweight. Each standard deviation increase in BMI, CO and PWV produced an increase of 8.4 (p=0.002), 9.4 (p=0.008) and 7.1 (p=0.017) birth weight centiles, respectively. We found no significant relationship between MAP, TPR or aortic AIx and neonatal birthweight. Among the women with GDM, maternal hemodynamics influenced neonatal birth weight in a similar manner to the control group. Only the relationship between maternal BMI and neonatal birthweight reached statistical significance, with a 1 standard deviation increase in BMI producing a 6.1 centile increase in the birthweight (p=0.019). Conclusions: Maternal BMI, CO and PWV were determinants of birthweight in our control group. The relationship between maternal hemodynamics and neonatal birthweight is similar between women with GDM and healthy controls. Our findings demonstrate that FGR in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. The differences between our findings and that of previous work could be reconciled by a non-linear relationship between MAP and neonatal birthweight, which warrants further investigation. This article is protected by copyright. All rights reserved.