Introduction:
Normal placental angiogenesis is a crucial process that establishes
feto-maternal circulation. Inadequate placental angiogenesis, defined as
defective remodeling of the uteroplacental arteries, can lead to
placental complications such as early pregnancy loss, preeclampsia and
intra-uterine growth restriction (IUGR) 1.
The physiological vascular changes observed in pregnancy, including an
increase in cardiac output and reduction in peripheral resistance and
blood pressure, are largely governed by alteration in endothelial
function mediated via nitric oxide and vascular endothelial growth
factor 2,3. Moreover, normal pregnancy is associated
with a reduction in central blood pressure, arterial stiffness and wave
reflection 4. There is a large body of evidence
indicating that endothelial dysfunction is involved in the
pathophysiology of preeclampsia. Studies, which have investigated
endothelial function by measuring flow mediated dilatation (FMD),
demonstrated decreased vasodilatation response in preeclamptic women
compared to normal pregnant women 56. Moreover,
augmentation index, a measure of systemic arterial stiffness, is
elevated in pregnancies complicated with hypertensive disease and
particularly preeclampsia 78. In addition, maternal
vascular function might help in defining a subset of patients who will
develop severe preeclampsia characteristics 9. These
findings supports the perception that vascular dysfunction is the
underlying pathophysiology of preeclampsia. In line with this
hypothesis, several studies have shown that endothelial dysfunction is
more common in women with a history of preeclampsia many years after the
affected pregnancy, compared to women with previous normal pregnancy.
These findings might explain their increased risk of future
cardiovascular disease 10–12. Similar to
preeclampsia, isolated intra-uterine growth restriction (IUGR) is also
associated with future maternal increased risk of ischemic heart disease13. Moreover, endothelial function, measured by FMD,
was significantly reduced in women with previous isolated
placenta-mediated IUGR 6-24 months after delivery 14.
Nevertheless, maternal endothelial function has never been evaluated
during pregnancies complicated by isolated placenta-mediated IUGR.
There are several noninvasive methods for endothelial function
assessment, all of which are based on the change in diameter and flow in
arteries in response to post ischemic reactive hyperemia15. A widely used method for assessing endothelial
function is flow mediated dilation (FMD). Nonetheless, the clinical
application of FMD is limited due to its dependence on the operator’s
skills , its technical difficulties and problems with calibration
between laboratories, which may preclude its use in widespread clinical
practice 16. Therefore, new noninvasive techniques
have been developed in-order to make endothelial function assessment
more accessible in general medical practice. Reactive
hyperemia-peripheral artery tonometry (RH-PAT,
EndoPATTM-2000, Itamar Ltd., Caesarea, Israel) has
been recently developed as a simple and potentially more reproducible
method. Previous studies validated the use of
EndoPATTM and found a reliable correlation with
conventional FMD 1718.
Therefore, our aim was to compare endothelial function of healthy women
during pregnancy complicated with IUGR to those with normal pregnancies
using the EndoPATTM method.