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Hemodynamic antecedents of peri/intraventricular hemorrhage in very preterm neonates

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Summary

Novel hemodynamic monitoring technologies have contributed to the understanding of developmental cardiovascular physiology and pathophysiology in general, and of developmental hemodynamics in particular. Hemodynamic disturbances play a significant role in the pathogenesis of peri/intraventricular hemorrhage (P/IVH) in preterm infants. Immaturity of the myocardium, delayed and incomplete cardiopulmonary transition, sustained patency of the ductus arteriosus, and unintended consequences of respiratory and cardiovascular supportive care are all likely to be involved in the presentation of low cardiac output syndrome and decreased organ blood flow in a large number of very preterm neonates (gestational age ≤28 weeks). Forebrain vessels in very preterm infants may not have achieved a “high-priority vasculature” status at the time of delivery; in these patients, forebrain perfusion is not protected during the compensated phase of shock. Reperfusion may be attenuated by the careful use of medications decreasing cerebrovascular reactivity, thus providing a potential target for the development of careful pharmacological support of transitional hemodynamics in selected patients at high risk for the development of P/IVH.

Introduction

Transition from the fetal to postnatal circulation can be challenging, especially for very preterm infants (gestational age <28 weeks). Accordingly, if the process of immediate postnatal transition is significantly affected, the chances of cardiopulmonary failure and/or brain injury increase. The mechanisms of brain injury in preterm infants are complex and multifactorial but also include hemodynamic derangements as a potentially significant contributing factor. The premature cardiovascular system has inherent vulnerabilities. For instance, the immaturity of the myocardium results in, among other things, a greater sensitivity to high afterload and the persistence of fetal shunts affects the loading conditions of the heart. Furthermore, the unintended consequences of our supportive care can further compromise cardiovascular function. For example, our interventions in the delivery room, such as the timing of cord clamping, influence the effective circulating blood volume. In addition, positive pressure ventilation can compromise ventricular function and venous return. Changes in blood oxygen and carbon dioxide (CO2) concentrations as a result of the provision of supplemental oxygen and positive pressure ventilation, respectively, can also affect the vascular system in general and the cerebral vascular bed in particular. All of the above factors, directly or through their effects on the cardiovascular system, could alter cerebral hemodynamics and oxygen delivery, predisposing the vulnerable brain of the premature infant to peri/intraventricular hemorrhage (P/IVH). In this article, we first review the normal cardiovascular transition from fetal to postnatal life with a special focus on cerebral blood flow (CBF). We then discuss the impact of the altered immediate postnatal circulatory transition and the accompanying events that precede and likely are involved in the development of P/IVH.

Section snippets

Cardiac function and CBF during fetal life

Although much of our understanding about fetal circulation comes from studies in lamb models, recent Doppler studies in the human fetus have shed light on some of the differences of the circulatory adaptation between the lamb and the human. Close to half of the oxygenated blood coming from the placenta in the umbilical vein bypasses the liver via the ductus venosus, and, from the inferior vena cava it preferentially flows through the foramen ovale into the left atrium thereby supplying the most

Hemodynamic changes at birth

At birth there are three major events significantly affecting the cardiovascular system: lung aeration, exposure to higher oxygen tension and separation from the placental circulation. In the fetal lamb model, ventilation with a gas mixture that does not alter blood gases results in no change in CBF [3]. Once oxygen is given, however, significant decrease in CBF occurs. Cord occlusion results in a slight but non-significant increase in CBF. Therefore, in the lamb, CBF decreases at birth,

Cerebral blood flow and oxygenation and P/IVH

The pattern of changes in CBF in extremely preterm infants who later develop P/IVH is different from those who do not. When CBF was measured by NIRS on the first postnatal day, the infants who later developed severe P/IVH had significantly lower CBF than the controls [13]. Studies of SVC flow also indicate that low SVC flow, a surrogate of CBF, is a risk factor for developing P/IVH [14]. Furthermore, changes in CFOE reveal that preterm infants who later develop P/IVH have a greater rise in CBF

Underlying causes of the initial postnatal cerebral ischemia

The exact cause or causes of the observed cerebral ischemia during the first few hours after birth in the subset of the extreme preterm infants who later develop P/IVH is unknown. It is possible that structural immaturity of the brain and/or its response to extreme transitional changes lead to ischemia. However, accumulating evidence implicates circulatory impairment as the primary cause of low perfusion with immaturity of the brain likely playing a mostly permissive role.

Using SVC flow as a

Underlying causes of reperfusion

With the resolution or correction of the initial physiologic and/or iatrogenic events resulting in systemic and/or cerebral hypoperfusion, CBF increases. Accordingly, following the early, low cardiac output state in the immediate postnatal period (first 12–24 h), cardiac function normalizes and CBF increases in most very preterm neonates [18]. In a subset of extremely preterm infants with a more immature and thus vulnerable cardiovascular and cerebral status and/or who are born depressed

Conclusions

Extremely preterm infants are in the state of compensated shock at and immediately after birth. A subset of these patients is especially vulnerable to the development of P/IVH, likely due to an unappreciated severity of immaturity and/or the clinical presentation upon delivery. There is growing evidence that the cardiovascular compromise in these patients is not easily recognizable and that the shock is multifactorial in etiology involving hypovolemia, myocardial compromise, abnormal

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