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THE IMPACT OF MATERNAL DIABETES IN PREGNANCY ON THE DEVELOPING CARDIOVASCULAR SYSTEM OF THE CHILD

  • Author / Creator
    Boehme, Cleighton
  • Introduction
    There is increasing evidence that fetal exposures influence lifelong cardiovascular (CV) health. While gestational diabetes mellitus (GDM) is one such exposure, whether there are demonstrable changes in CV health in exposed children is unknown. Additionally, rodent models have suggested maternal diabetes during pregnancy is associated with increased risk of myocardial ischemia-reperfusion injury (IRI) in adult offspring; a finding not explored in humans. The objective of our primary study was to explore the CV health of children of mothers with GDM (CGDM) compared to children of healthy mothers, also examining the additive impact of other prenatal and postnatal exposures. The objective of our secondary study was to determine whether infants of mothers with diabetes (IDM) have worse outcomes associated with cardiopulmonary bypass for major congenital heart disease compared to infants of healthy mothers, and whether this relates to worse IRI.

    Methods
    Primary Study: This was a nested observational study, tied to the Alberta Pregnancy Outcomes and Nutrition Birth Cohort Study. Children of mothers with and without GDM but otherwise uncomplicated pregnancies were prospectively recruited. CV outcomes included: left ventricular (LV) mass z score, reactive hyperemia index score (lnRHI, EndoPAT), Doppler-based aortic and peripheral arterial pulse wave velocity (PWV), and carotid intima-media thickness. Maternal dietary intake and iron biomarkers in pregnancy and the child’s perinatal history were obtained, and the child’s current anthropometric parameters were measured. Children completed three 24-hour food recalls, and a Healthy Eating Index (HEI) score was calculated. Children’s physical activity was measured using an accelerometer, and daily time spent in moderate to vigorous physical activity (MVPA) was calculated. Associations between these factors and CV outcome measures were explored with univariate and multiple linear regression models.

    Secondary Study: IDM and infants of healthy mothers (controls) who underwent bypass surgery at <1 year at the Stollery Children’s Hospital were retrospectively identified. Risk Adjustment for Congenital Heart Surgery (RACHS) scale was used for surgical coding and pooled into Groups 1-3 (A) and 4-6 (B). Primary (postoperative intensive care and hospital lengths of stay, LOS) and secondary (Pediatric Risk of Mortality (PRISM) score, lowest mixed venous O2 saturation, highest lactate, glucose, urea and creatinine, and days intubated) outcomes were compared.

    Results
    Primary Study: We assessed 25 CGDM and 27 controls (mean age 10.9±0.7 years) with comparable birth/baseline characteristics. Aortic PWV was higher in CGDM vs controls (6.2±2.6 vs 4.8±1.6 m/s, p=0.03), and higher in CGDM of insulin vs diet controlled mothers (7.9±2.6 vs 5.5±2.2 m/s, p=0.03). No other primary CV health measures differed. Mothers with GDM, but not controls, demonstrated dietary improvement from the 2nd to 3rd trimester. The child’s HEI scores and daily MVPA did not differ between groups. Univariate regression models revealed associations of both the child’s percent body fat and HEI score with LV mass that persisted in a multiple regression model with inclusion of relevant covariates (B=-0.026, p=0.003 and B=0.020, p=0.008 respectively). Maternal serum ferritin in second (B=-0.0039, p=0.01) and third trimesters (B=-0.011, p=0.008) negatively correlated with the child’s lnRHI score in the univariate analyses, though the multiple regression models were inconclusive.

    Secondary Study: Eighty IDM (54 gestational, 26 pregestational) and 149 controls were included: 188 Group A, 41 Group B. Age at surgery, birth weight and male:female did not differ between IDM and controls; whereas, maternal age (IDM vs Controls: 33±6 vs 30±6 years, p<0.001), gestational age at birth (37±2 vs 38±2 weeks, p<0.001) and delivery mode (49% vs 34% C-section, p=0.03) were different. Within RACHS groupings, outcomes did not differ between all IDM and controls. However, IDM-gestational showed trends towards better outcomes after surgery (Group A intensive care LOS: 3±3 vs 4±3 days, p=0.02; Group B highest glucose: 13.4±2.0 vs 16.7±3.0 mmol/L, p=0.01), while IDM-pregestational exhibited worse outcomes in Group A (hospital LOS: 20±29 vs 10±7 days, p=0.046; highest urea: 11.0±4.4 vs 8.4±4.2 mmol/L, p=0.04) and similar trends in Group B (PRISM: 16±9 vs 10±5, P=0.11; highest glucose: 16.7±1.3 vs 14.3±2.7 mmol/L, p=0.06).

    Conclusions
    CGDM have increased aortic stiffness, highest in mothers requiring insulin. Elevated maternal iron status may impact the child’s endothelial function. Mechanisms and long-term implications of these findings require further investigation. Finally, the poorer outcomes associated with pregestational diabetes and better outcomes associated with GDM require further study.

  • Subjects / Keywords
  • Graduation date
    Fall 2022
  • Type of Item
    Thesis
  • Degree
    Master of Science
  • DOI
    https://doi.org/10.7939/r3-ps6h-7s95
  • License
    This thesis is made available by the University of Alberta Library with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.