Date of Award

5-20-2022

Degree Type

Thesis

Degree Name

PhD in Health Sciences

First Advisor

Dr Mushtaq Ahmed

Second Advisor

Dr Satwat Hashmi

Third Advisor

Dr Nuruddin Mohammed

Department

Community Health Sciences

Abstract

Objectives: Adverse intra uterine environment may lead to reprogramming of fetal growth and development thus predisposing them to risk for chronic diseases such as cardiovascular disease (CVD). The objective of this work was to assess CVD changes by assessing cardiac structure and function (using conventional and deformation analysis) as well as macro-vascular function measured by blood pressure, carotid intima media thickness (cIMT) and pulse wave velocity (PWV) in children exposed to diabetes or preeclampsia in-utero as compared to non-exposed group.
Methods: This was a retrospective cohort study which included children born to mothers with exposure to hyperglycemia (n=68 in each group) or preeclampsia in-utero (n= 80 in each group) and non-exposed group with the exposure status being identified from maternal records. Children with any chromosomal or congenital abnormality or born to mothers with co-morbids besides the exposure of interest were also excluded. Myocardial morphology and function using echocardiogram and cIMT and PWV was performed to evaluate cardiac function as well as macrovascular remodeling in these children. Data is presented as mean +/- standard deviation, median and interquartile range and frequencies and percentages as appropriate. Z scores were also calculated for echocardiographic data using the Boston z score calculator. Multivariable linear regression was used to compare the effect of the exposure on the cardiac and vascular outcomes in the exposed and non-exposed groups controlling for confounders such as maternal age, maternal BMI and child BMI. Subgroup analysis to assess differences between controlled vs uncontrolled hyperglycemia and early vs late onset preeclampsia in the groups was also performed.
Results: There was no significant difference in cardiac morphology, myocardial systolic and diastolic function, and macro-vascular assessment between the children exposed to maternal yperglycemia as compared to non-exposed children. Subgroup analysis demonstrated a significantly decreased mitral E/A ratio in children whose mothers were on medications as compared to those on dietary control (1.7+/- 0.3 as compared to 1.6+/-0.2 respectively, p = 0.01), and a higher cIMT in children whose mothers were on medication (0.48 +/- 0.1) as compared to controls (0.46 +/- 0.1) respectively (p value =0.03). Forty one percent (n=33) mothers had early onset preeclampsia. Children in the exposed group had significantly higher prevalence of Stage 1 systolic and diastolic hypertension (22%, n=18 and 35%, n=28 respectively) as compared to the non-exposed group (9%, n=7 and 19% n =15 respectively, p=0.01). Children in the exposed group also had higher pulse wave velocity as compared to non-exposed group (0.42 +/- 0.1 vs 0.39 +/- 0.1, p=0.03). Subgroup analysis revealed that blood pressure and pulse wave velocity changes were primarily determined by early onset preeclampsia.
Conclusion: In-utero exposure to maternal hyperglycemia was not associated with cardiovascular structural and function changes in children. However, exposure to preeclampsia was associated with blood pressure and vascular changes in young children. Future work requires long term follow up of exposure to preeclampsia from fetal to adult life to assess these changes over the life course and may justify routine blood pressure screening for exposed children.

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Last Page

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