Review Article

Cardiovascular Disease Risk in the Offspring of Diabetic Women: The Impact of the Intrauterine Environment

Table 1

Assessment of cardiovascular health in prepubescent offspring of diabetic women.

ModalityAgeMethodLimitationsEvidence in children of diabetics

Blood pressureFrom birth, but difficult
to perform reliably in infants
Oscillometric (most common) or auscultatory measurement of blood pressure with sphygmomanometer.  
Subjects need to be completely relaxed,
in a uniform position (e.g., sitting) and uniform site of measurement (e.g., right arm).  
Cuff needs to be correctly sized.
Minimum of two measurements.
May be difficult to obtain “resting” blood pressure in young children—as the cuffs can be uncomfortable and cause distress.Large cohort study of school children looked at subgroup of offspring of diabetic women and found no difference in systolic or diastolic blood pressure [67].  
Other studies have demonstrated higher systolic and mean blood pressures in offspring of diabetic women than controls [15].

Electrocardiography (ECG)All ages—can be performed in utero Leads are placed on chest wall in
standard locations. Electrical impulses are transmitted to ECG machine and ECG tracing is produced.
ECG most accurate if patient remains still during reading—can be difficult for young children. 
Requires the subject to be at a comparable level of exertion (e.g., at rest).
Infants of diabetic women demonstrate leftward axis deviation when compared to controls [68]. Fetuses of diabetic women demonstrate significantly more ST depression on fetal ECG during labour than infants of control women [69].

Vessel structure

Carotid artery intima-media thickness (cIMT)From 5 years of ageHigh-resolution B-mode ultrasonography. Measure thickness of intima-media of posterior wall of carotid.  
In adults correlates to atherosclerosis at autopsy [39] and coronary angiography [40] as well as predictor of future cardiovascular events [41].
Need to be able to access the neck over the carotid area [50].  
Has been used in children >5 years old [70], technically difficult in younger children.  
 Skilled operator required.
Although cIMT has been used to follow up mothers with gestational diabetes [71, 72], currently no studies in offspring of diabetic women.

Aortic intima-media thickness (aIMT)From birth/in utero High-resolution B-mode ultrasonography. Measure thickness of intima-media of posterior wall of abdominal aorta.  
Good correlation with cIMT [55].
Most easily performed on the settled infant/child.  
Yet to be correlated with long-term disease risk.
Increased aIMT found in offspring of diabetic women (additive effect with maternal obesity) [10].

Retinal vessel imagingFrom birth (pupillary dilatation required)
and from school age without dilatation
45° digital retinal photography
following pupil dilatation [62].  
Method has been used to evaluate retinopathy of prematurity in neonates.
Requires pupil dilation.   
May be uncomfortable for infants [63].
No current studies in offspring of diabetic women.  
Two large unselected cohort studies in children underway in Australia and Singapore.

Endothelial function

Pulse wave velocity (PWV)From 5 years of agePeripheral pulse wave form measured at the radial artery, carotid and femoral artery in order to calculate central aortic pressure as well as carotid-femoral pulse wave velocity.Would be limited by cooperation and physical access in younger children.One study looking at offspring of diabetic women at ~15 years found positive correlation between GDM (umbilical cord c-peptide, insulin) and arterial stiffness [73].

Brachial artery dilatationOlder children (~10 years and above)B-mode ultrasound—assessing dilator response of brachial artery to endothelial dependent and nondependent factors.  
First stage—pneumatic cuff suprasystolic for 5 minutes then deflates and measures brachial dilatation.   
Second stage—GTN given orally and measures brachial dilatation.
Poorly tolerated by children (both time taken and cuff discomfort).  
Invasive (administering GTN orally).  
Need to be fasting.
Studies in women with GDM—one study found no change [74].  
No studies in offspring of diabetic women.

EndopatOlder children (~10 years and above)Similar to brachial artery dilatation. Endopat apparatus on finger—measuring pulse wave. Measured at rest, then with pneumatic cuff inflated to 60 mmHg or 200 mmHg for one minute, then measured following deflation [75].Takes 15 minutes.  
Need to be fasting.  
May be difficult to tolerate in children (especially pneumatic cuff over systolic BP).  
Expensive.
No data in either diabetic women or their offspring.

Cardiac function

EchocardiographyFrom birth/in utero 2-dimensional, M mode and Doppler ultrasonography of the heart.Requires specialist paediatric echocardiographer/ sonographer with experience in interpreting paediatric findings.Increased risk of HCM in offspring of diabetic women [64].  
Resolution of changes by first year of life [65].  
No studies following offspring of diabetic women into adulthood.