accuracy has been validated using cardiac magnetic resonance imaging.74 Measurement of superior vena cava flow has been proposed as an alternative method of assessing the adequacy of systemic flow, because it is not confounded by atrial or ductal shunts.75 Although cardiac magnetic resonance imaging data have raised some questions about measurement accuracy, the relationship between superior vena cava flow and outcomes shows a consistent trend.74 Reduced flow in the superior caval vein is common in premature infants in the first 24 hours, reaching a nadir between 8 and 12 hours, which coincides with increased systemic vascular resistance Neonates with the lowest flow are at greatest risk of intraventricular hemorrhage (Fig 15.5).76 When 3-year neurodevelopmental assessment was performed, low superior caval venous flow remained significantly associated on multiple logistic regression analysis, when adjusted for gestation and birth weight, with an abnormal developmental quotient and the combined end point of death and abnormal developmental quotient.77 Both blood pressure and systemic flow are important determinants of the likelihood of altered perfusion, and neither should be monitored nor treated in isolation, without consideration of the influence of the other Decisions about circulatory adequacy should include a comprehensive assessment of systemic perfusion, and echocardiography assessment of cardiac output may be an invaluable adjunct tool Other bedside tools such as near-infrared spectroscopy, noninvasive cardiac output monitoring, and heart rate variability have been explored in selected patient populations and may continue to evolve into additional adjunctive monitoring modalities, although further investigation is needed FIG 15.5 Box plot of the lowest superior caval vein (SVC) flow in the first 24 hours for neonates who developed severe intraventricular hemorrhage (N = 18) versus those who did not develop an intraventricular hemorrhage (N = 99) IVH, Intraventricular hemorrhage (From Kluckow M, Evans N Low superior vena cava flow and intraventricular haemorrhage in preterm infants Arch Dis Child Fetal Neonatal Ed 2000;82[3]:F188–F194.) Cardiovascular Problems Unique to the Preterm Infant Hemodynamically Significant Arterial Duct Patency of the arterial duct is a common problem in preterm babies, especially those born with extremely low weight Although functionally essential for the normal fetal circulation, persistent ductal patency may have significant effects in preterm infants that include pulmonary overcirculation and systemic hypoperfusion Persistent patency is found in approximately half of babies born at less than 29 weeks’ gestation and/or weighing less than 800 g.78,79 Biology of Normal Closure Ductal closure is not immediate, particularly in infants born with extremely low weights, and occurs in two stages Functional closure, which is a dynamic process that may be reversed if the ambient conditions change to favor patency, depends on the vasoconstricting action of humoral and biochemical factors on the muscular layer of the duct This constriction results in the development of a zone of profound hypoxia in the media, which is the sentinel stimulus for irreversible closure Anatomic closure depends on the architectural remodeling of the ductal wall.80 It consists of extensive neointimal thickening, and loss of smooth muscle cells from the inner media.81 The remodeling effects start at the pulmonary end, progressing toward the aortic insertion.82 Both vasodilator prostaglandins, especially PgE2 and nitric oxide, oppose ductal closure during fetal life.83,84 In the second trimester, intimal cushions are formed that closely resemble the pathologic intimal thickening seen in atherosclerotic disease.85 The media is supplied with oxygen from either the lumen or its mural vessels The thickness of the avascular zone, adjacent to the lumen, plays a critical role in determining the degree of hypoxia and subsequent remodeling of the ductal wall Constriction of the circumferential and longitudinal muscle in the ductal wall leads to compaction, increased avascular thickness, and limits luminal supply of oxygen to both the avascular zone and the medial muscle.81 The resultant hypoxia induces expression of vascular endothelial growth factor or cell death, depending on its severity The geographic distribution of expression corresponds