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

Abstract

OBJECTIVE: Normal pregnancy is characterized by significant changes in maternal hemodynamics that are associated with fetal growth. Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with large-for-gestational age and macrosomia, but the relationship between maternal hemodynamic parameters and birth weight (BW) among women with GDM has not been established. Our objective was to investigate the influence of maternal hemodynamics on neonatal BW in healthy pregnancies and in those complicated by GDM. METHODS: This was a prospective, cross-sectional case-control study of women aged ≥ 16 years with a singleton viable pregnancy, recruited between January 2016 and February 2021 at Leicester Royal Infirmary, Leicester, UK. GDM was defined as a fasting glucose level ≥ 5.3 mmol/L and/or serum glucose level ≥ 7.8 mmol/L, 2 h following a 75-g oral glucose load. We collected data on maternal characteristics and pregnancy outcome, including body mass index (BMI) at booking and BW centile adjusted for gestational age at delivery. Maternal hemodynamic parameters were assessed at 34-42 weeks' gestation using the Arteriograph® and bioreactance techniques. Graphical causal inference methodology was used to identify causal effects of the measured variables on neonatal BW centile. RESULTS: Included in the analysis were 141 women with GDM and 136 normotensive non-diabetic pregnant controls. 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), aortic pulse wave velocity (PWV) and BMI at booking. Among the controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal BW. Each SD increase in booking BMI produced an increase of 8.4 BW centiles (P = 0.002), in CO produced an increase of 9.4 BW centiles (P = 0.008) and in aortic PWV produced an increase of 7.1 BW centiles (P = 0.017). We found no significant relationship between MAP, TPR or aortic AIx and neonatal BW. Maternal hemodynamics influenced neonatal BW among the women with GDM in a similar manner to that in the control group, but only the relationship between maternal BMI and neonatal BW reached statistical significance, with a 1-SD increase in BMI producing an increase of 6.1 BW centiles (P = 0.019). CONCLUSIONS: Maternal BMI, CO and PWV were determinants of BW in our control group. The relationship between maternal hemodynamics and neonatal BW was similar between women with GDM and healthy controls. Our findings therefore suggest that fetal growth restriction in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.