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.