Understand the problems in IUGR pregnancy & explore novel techniques to better detect and treat IUGR
Intrauterine growth restriction is a pregnancy complication in which the fetus is not growing at a normal rate due to placenta insufficiency. The prevalence of this disease is 3% in developed country and up to 10-15% in developing country. IUGR babies suffer 5-10x higher mortality and life-long morbidity risk and unfortunately, there is no treatment for IUGR.
It has been reported that the umbilical and placenta vascular size in IUGR was significant smaller as compared to that of in normal cases. The reduction of vascular size in IUGR increases the placenta flow resistance significantly as the flow resistance is inversely proportional to the 4th power of the diameter, thus restricting the blood flow to fetus.
Wall shear stress has been know to affect the growth and remodeling of the vessels, whereby endothelial cells will response to the shear stress and maintain the shear stress at physiological level. For example, increased shear stress will cause vasodilation while decreased shear stress will cause vasoconstriction.
In my research, I focus on understanding the growth and remodeling of the vascular vessels. I keen to investigate whether the IUGR vascular vessels response to shear stress. Does the reduction of vascular size in IUGR caused by abnormal shear stress level or caused by other factors.
One of the ways to study the flow during the pregnancy is to acquire ultrasound images and perform simulation based on the ultrasound measurements. This allows us to study the in vivo patient-specific flow hemodynamics.
I hope, with my research findings, we can understand more on this idiopathic disease and novel strategies can be derived to treat IUGR.
Abstract: The foundation for adult health is laid in utero and requires a healthy placenta. A common manifestation of abnormal placental development is impaired fetal growth. While placental pathology is the final common denominator in many cases of fetal growth restriction, a variety of discreet lesions have been described involving both the maternal and fetal circulations at their confluence in the placenta. Detailed examination of the placenta provides a means of elucidating the pathophysiology of poor fetal growth. This is an essential step in developing effective strategies for the prediction, prevention, and possible treatment of the growth restricted fetus.
Pub.: 16 Oct '10, Pinned: 27 Aug '17
Abstract: Intrauterine growth restriction (IUGR), a condition that occurs due to various reasons, is an important cause of fetal and neonatal morbidity and mortality. It has been defined as a rate of fetal growth that is less than normal in light of the growth potential of that specific infant. Usually, IUGR and small for gestational age (SGA) are used interchangeably in literature, even though there exist minute differences between them. SGA has been defined as having birth weight less than two standard deviations below the mean or less than the 10th percentile of a population-specific birth weight for specific gestational age. These infants have many acute neonatal problems that include perinatal asphyxia, hypothermia, hypoglycemia, and polycythemia. The likely long-term complications that are prone to develop when IUGR infants grow up includes growth retardation, major and subtle neurodevelopmental handicaps, and developmental origin of health and disease. In this review, we have covered various antenatal and postnatal aspects of IUGR.
Pub.: 22 Jul '16, Pinned: 27 Aug '17
Abstract: This study reviewed the screening, diagnosis, prophylaxis, and treatment of intrauterine growth restriction using the PubMed database for key words and the Cochrane database for systematic reviews. Identification of risk factors and measurement of symphysis-fundus height are currently the screening standards. Diagnosis is verified by ultrasonography. Accuracy of diagnosis may be improved by using customized fetal growth curves, symphysis-fundus height charts, and 3-dimensional ultrasonographic evaluation and measuring umbilical artery Doppler dimensional ultrasonographic evaluation measuring umbilical artery Doppler impedance. Prophylaxis with acetylsalicylic acid, started in the first or second trimester or combined with heparin before conception, may reduce the incidence of growth restriction in specific groups at high risk. Active management may reduce incidence in patients with mild to moderate asthma, and targeted treatment of infections may also be beneficial. Antenatal corticosteroid treatment also reduces the perinatal morbidity and mortality associated with IUGR. Bed rest has no demonstrated beneficial effects.
Pub.: 14 Feb '06, Pinned: 27 Aug '17
Abstract: Wall shear stress (WSS), the frictional force between blood and endothelium, is an important determinant of vascular function. It is generally assumed that WSS remains constant at a reference value of 15 dyn/cm(2). In a study of small rodents, we realized that this assumption could not be valid. This review presents an overview of recent studies in large and small animals where shear stress was measured, derived from velocity measurements or otherwise, in large vessels. The data show that large variations exist within a single species (human: variation of 2-16 N/m(2)). Moreover, when we compared different species at the same location within the arterial tree, an inverse relationship between animal size and wall shear stress was noted. When we related WSS to diameter, a unique relationship was derived for all species studied. This relationship could not be described by the well-known r(3) law of Murray, but by the r(2) law introduced by Zamir et al. in 1972. In summary, by comparing data from the literature, we have shown that: (i) the assumption of a physiological WSS level of approximately 15 dyn/cm(2) for all straight vessels in the arterial tree is incorrect; (ii) WSS is not constant throughout the vascular tree; (iii) WSS varies between species; (iv) WSS is inversely related to the vessel diameter. These data support an "r(2) law" rather than Murray's r(3) law for the larger vessels in the arterial tree.
Pub.: 16 Dec '06, Pinned: 27 Aug '17
Abstract: Late-onset intrauterine growth restriction (IUGR) results from a failure of the placenta to supply adequate nutrients and oxygen to the rapidly growing late-gestation fetus. Limitations in current monitoring methods present the need for additional techniques for more accurate diagnosis of IUGR in utero. New magnetic resonance imaging (MRI) technology now provides a noninvasive technique for fetal hemodynamic assessment, which could provide additional information over conventional Doppler methods.The objective of the study was to use new MRI techniques to measure hemodynamic parameters and brain growth in late-onset IUGR fetuses.This was a prospective observational case control study to compare the flow and T2 of blood in the major fetal vessels and brain imaging findings using MRI. Indexed fetal oxygen delivery and consumption were calculated. Middle cerebral artery and umbilical artery pulsatility indexes and cerebroplacental ratio were acquired using ultrasound. A score of ≥ 2 of the 4 following parameters defined IUGR: (1) birthweight the third centile or less or 20% or greater drop in the centile in estimated fetal weight; (2) lowest cerebroplacental ratio after 30 weeks less than the fifth centile; (3) ponderal index < 2.2; and (4) placental histology meets predefined criteria for placental underperfusion. Measurements were compared between the 2 groups (Student t test) and correlations between parameters were analyzed (Pearson's correlation). MRI measurements were compared with Doppler parameters for identifying IUGR defined by postnatal criteria (birthweight, placental histology, ponderal index) using receiver-operating characteristic curves.We studied 14 IUGR and 26 non-IUGR fetuses at 35 weeks' gestation. IUGR fetuses had lower umbilical vein (P = .004) and pulmonary blood flow (P = .01) and higher superior vena caval flow (P < .0001) by MRI. IUGR fetuses had asymmetric growth but smaller brains than normal fetuses (P < .0001). Newborns with IUGR also had smaller brains with otherwise essentially normal findings on MRI. Vessel T2s, oxygen delivery, oxygen consumption, middle cerebral artery pulsatility index, and cerebroplacental ratio were all significantly lower in IUGR fetuses, whereas there was no significant difference in umbilical artery pulsatility index. IUGR score correlated positively with superior vena caval flow and inversely with oxygen delivery, oxygen consumption, umbilical vein T2, and cerebroplacental ratio. Receiver-operating characteristic curves revealed equivalent performance of MRI and Doppler techniques in identifying IUGR that was defined based on postnatal parameters with superior vena caval flow area under the curve of 0.94 (95% confidence interval, 0.87-1.00) vs a cerebroplacental ratio area under the curve of 0.80 (95% confidence interval, 0.64-0.97).MRI revealed the expected circulatory redistribution in response to hypoxia in IUGR fetuses. The reduced oxygen delivery in IUGR fetuses indicated impaired placental oxygen transport, whereas reduced oxygen consumption presumably reflected metabolic adaptation to diminished substrate delivery, resulting in slower fetal growth. Despite brain sparing, placental insufficiency limits fetal brain growth. Superior vena caval flow and umbilical vein T2 by MRI may be useful new markers of late-onset IUGR.
Pub.: 18 Oct '15, Pinned: 27 Aug '17
Abstract: The endothelial cells of the umbilical vessels are frequently used in mechanobiology experiments. They are known to respond to wall shear stress (WSS) of blood flow, which influences vascular growth and remodeling. The in vivo environment of umbilical vascular WSS, however, is not well characterized. In this study, we performed detailed characterization of the umbilical vascular WSS environments using clinical ultrasound scans combined with computational simulations. Doppler ultrasound scans of 28 normal human fetuses from 32nd to 33rd gestational weeks were investigated. Vascular cross-sectional areas were quantified through 3D reconstruction of the vascular geometry from 3D B-mode ultrasound images, and flow velocities were quantified through pulse wave Doppler. WSS in umbilical vein was computed with Poiseuille's equation, whereas WSS in umbilical artery was obtained via computational fluid dynamics simulations of the helical arterial geometry. Results showed that blood flow velocity for umbilical artery and vein did not correlate with vascular sizes, suggesting that velocity had a very weak trend with or remained constant over vascular sizes. Average WSS for umbilical arteries and vein was 2.81 and 0.52 Pa, respectively. Umbilical vein WSS showed a significant negative correlation with the vessel diameter, but umbilical artery did not show any correlation. We hypothesize that this may be due to differential regulation of vascular sizes based on WSS sensing. Due to the helical geometry of umbilical arteries, bending of the umbilical cord did not significantly alter the vascular resistance or WSS, unlike that in the umbilical veins. We hypothesize that the helical shape of umbilical arteries may be an adaptation feature to render a higher constancy of WSS and flow in the arteries despite umbilical cord bending.
Pub.: 28 Jul '16, Pinned: 27 Aug '17
Abstract: The aim of obstetric management is to identify growth-restricted foetuses at risk of severe intrauterine hypoxia, to monitor their health and to deliver when the adverse outcome is imminent. After 30-32 gestational weeks, a Doppler finding of absent or reverse end-diastolic flow in the umbilical artery of a small-for-gestational age foetus is in itself an indication for delivery. In very preterm foetuses, the intrauterine risks have to be balanced against the risk of prematurity. All available diagnostic information (e.g., Doppler velocimetry of umbilical artery, foetal central arteries and veins and of maternal uterine arteries; foetal heart rate with computerised analysis of short-term variability; amniotic fluid amount; and foetal gestational age-related weight) should be collected to support the timing of delivery. If possible, the delivery should optimally take place before the onset of late signs of foetal hypoxia (pathological foetal heart rate pattern, severely abnormal ductus venosus blood velocity waveform, pulsations in the umbilical vein).
Pub.: 27 Oct '09, Pinned: 25 Aug '17
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