The Relationship Between Systemic Hemodynamic Perturbations and Periventricular-Intraventricular Hemorrhage—A Historical Perspective
Section snippets
Neuropathology
The primary lesion in PV–IVH is bleeding from vessels within the periventricular subependymal germinal matrix (GM) located between the caudate nucleus and thalamus at the level of the foramen of Monro.2, 9 The matrix is a transitional gelatinous region that provides poor support for a large, immature network of blood vessels primarily supplied by Heubner's artery, a branch of the anterior cerebral artery. Venous drainage includes the terminal, choroidal, and thalamostriate veins that lead to
Cerebral Autoregulation and Pressure-Passive Circulation
Cerebral autoregulation is the intrinsic ability of the cerebral blood vessels to maintain relatively constant cerebral blood flow (CBF) over a range of systemic blood pressures. As cerebral perfusion pressure decreases, cerebrovascular resistance also decreases by alterations in the diameter of the precapillary arterioles, maintaining CBF.2, 16, 17 This adaptive ability has a limited capacity and will result in a decrease of CBF when the blood pressure falls below a certain threshold and an
Evaluation of the Cerebral Circulation
Application of the Doppler ultrasound technique in the early 1980s to measure cerebral arterial blood flow velocity (CBFV) through the anterior fontanel facilitated the ability to link systemic events to the pathogenesis of PV–IVH.7 Measurements were obtained from the pericallosal artery (terminal branch of the anterior cerebral artery) as it courses around the genu of the corpus callosum, as well as from the right or left middle cerebral artery transcranially through the coronal suture.
Pathogenesis
The pathogenesis of PV–IVH is complex, and predisposing factors include a combination of vascular, intravascular, and extravascular influences1, 2 (Fig 2). From earlier report, several reasons pointed to a critical role for intravascular factors and specifically perturbations in mean arterial blood pressure (ABP) as a major mechanism of capillary rupture and hemorrhage (see appendix). First, the cerebral circulation of the sick infant was considered pressure passive.21, 22, 23, 24, 25 Second,
Periventricular White Matter Injury (WMI) Associated With PV–IVH
The etiology of the periventricular cerebral intraparenchymal lesion was unclear in the early 1980s. The earlier notion was that the intraparenchymal lesion represented an “extension” of hemorrhage from the germinal matrix or lateral ventricle into previously normal periventricular white matter. However, subsequent neuropathologic data indicated that the intraparenchymal lesions represent regions of hemorrhagic necrosis.3, 14, 15, 43 The pathogenesis of the WMI associated with hemorrhage
Perturbations on the Arterial Side
Several studies had established an association between RDS and PV–IVH by the early 1980s.46, 47 However, the mechanism(s) that linked these 2 comorbidities of prematurity were unclear. Using Doppler ultrasound, we described an association between fluctuations in CBFV and subsequent PV–IVH in preterm infants with RDS.35 Thus, in a study of preterm infants weighing < 1500 g and requiring mechanical ventilation for RDS, 21 of 23 infants (91%), with a beat-to-beat fluctuating CBFV pattern measured
Conventional Mechanical Ventilation
Mechanical ventilation can directly or indirectly affect CBF through modulating cardiac output by impeding venous return or through changes in the acid–base balance. Elevated mean airway pressure can impede venous return, which may increase central venous pressure and intracranial venous pressure as well as decrease cardiac output.71, 72, 73, 74, 75 This situation increases the risk for hypoperfusion, particularly in vulnerable regions, such as the periventricular white matter. Importantly, the
General Considerations
According to the data accumulated over the years, several factors should be considered when assessing the risk for PV–IVH, starting with the condition of the infant at delivery. The infant's condition seems to be influenced in part by the administration of antenatal glucocorticoids80, 81, 82, 83, 84 and/or the presence of histologic chorioamnionitis/fetal vasculitis.85 The single most important “intervention” shown to reduce significantly the development of PV–IVH has been a short course of
Future Directions
In recent years, WMI, often in the absence of PV–IVH, is the predominant finding observed on magnetic resonance imaging in very low birth weight infants.1, 2 Because antenatal glucocorticoids significantly reduce IVH, the target population should be those VLBW infants delivered rapidly or emergently with minimum intrapartum care. In addition, close attention to blood pressure should be a priority to avoid hypotension and/or perturbations. It is this group of infants who may derive benefit from
References (99)
- et al.
Hemorrhagic-ischemic cerebral injury in the preterm infant: Current concepts
Clin Perinatol
(2002) Anterior fontanel: Window to the neonatal brain
J Pediatr
(1982)Neonatal cerebral blood flow velocity measurement
Clin Perinatol
(1985)- et al.
Germinal matrix-intraventricular hemorrhage in the premature newborn: Management and outcome
Neurol Clin
(2003) Autoregulation of cerebral blood flow in newborn babies
Early Hum Dev
(2005)- et al.
Autoregulation of cerebral blood flow in the newborn dog
Brain Res
(1980) - et al.
Heterogeneity of cerebral vasoreactivity in preterm infants supported by mechanical ventilation
J Pediatr
(1989) - et al.
Intraventricular hemorrhage following volume expansion after hypovolemic hypotension in the newborn beagle
J Pediatr
(1982) - et al.
Mean arterial blood pressure changes in premature infants and those at risk for intraventricular hemorrhage
J Pediatr
(1990) - et al.
The associations of rapid volume expansion and intraventricular hemorrhage in the preterm infant
J Pediatr
(1980)
Relationship of uric acid concentrations and severe intraventricular hemorrhage/leukomalacia in the premature infant
J Pediatr
Pneumothorax and cerebral haemorrhage in preterm infants
Lancet
Manual of Neonatal Respiratory Care
The effect of patent ductus arteriosus on flow velocity in the anterior cerebral arteries: Ductal steal in the premature newborn
J Pediatr
Cerebral hemodynamic change and intraventricular hemorrhage in very low birth weight infants with patent ductus arteriosus
Ultrasound Med Biol
Surfactant administration acutely affects cerebral and systemic hemodynamics and gas exchange in very-low-birth-weight infants
J Pediatr
Relationship between mean airway pressure, cardiac output, and organ blood flow with normal and decreased respiratory compliance
J Pediatr
Early randomized intervention with high-frequency jet ventilation in respiratory distress syndrome
J Pediatr
Antenatal corticosteroids and cranial ultrasonographic abnormalities
Am J Obstet Gynecol
Evidence from multicenter networks on the current use and effectiveness of antenatal corticosteroids in low birthweight infants
Am J Obstet Gynecol
Use of steroids in the perinatal period
Paediatr Resp Rev
Labor and delivery characteristics and risks of cranial ultrasonographic abnormalities among very-low-birth-weight infantsThe Developmental Epidemiology Network Investigators
Am J Obstet Gynecol
Effect of maternal glucocorticoid exposure on risk of severe intraventricular hemorrhage in surfactant-treated preterm infants
J Pediatr
Prevention of intraventricular hemorrhage in preterm infants by phenobarbitone: A controlled trial
Lancet
Vitamin E supplementation reduces frequency of periventricular hemorrhage in very preterm infants
Lancet
Ethamsylate reduces the incidence of periventricular haemorrhage in very low birthweight babies
Lancet
Neurology of the Newborn
Outcome of neonatal intraventricular hemorrhage with periventricular echodense lesions
Ann Neurol
Intraventricular hemorrhage in preterm infants: Declining incidence in the 1980's
Pediatrics
Trends in neonatal morbidity and mortality for very low birthweight infant
Am J Obstet Gynecol
Cerebral blood flow velocity in the human newborn: The value of its determination
Pediatrics
Origin of intraventricular haemorrhage in the preterm infant
Arch Dis Child
Developmental Pathology of the Neonate
Human germinal matrix: Venous origin of hemorrhage and vascular characteristics
AJNR Am J Neuroradiol
Are venous circulatory abnormalities important in the pathogenesis of hemorrhagic and/or ischemic cerebral injury?
Pediatrics
Periventricular intraparenchymal cerebral hemorrhage in preterm infants: The role of venous infarction
J Pathol
Periventricular intraparenchymal echodensities in the premature newborn: Critical determinant of neurologic outcome
Pediatrics
Control of cerebral circulation in the high-risk neonate
Ann Neurol
Cerebral pressure autoregulation and vasoreactivity in the newborn rat
Pediatr Res
Autoregulation of cerebral blood flow in the preterm fetal lamb
Pediatr Res
Impaired autoregulation of cerebral blood flow in the distressed newborn infant
J Pediatr
Cerebral intravascular oxygenation correlates with mean arterial pressure in critically ill premature infants
Pediatrics
Fluctuating pressure-passivity is common in the cerebral circulation of sick premature infants
Pediatr Res
Impaired autoregulation in preterm infants identified by using spatially resolved spectroscopy
Pediatrics
Postnatal adaptation of cerebral blood flow using near infrared spectroscopy in extremely preterm infants undergoing high-frequency oscillatory ventilation
Acta Paediatr
Cerebral blood flow is independent of mean arterial blood pressure in preterm infants undergoing intensive care
Pediatrics
Hypotensive extremely low birth weight infants have reduced cerebral blood flow
Pediatrics
Beagle puppy model of intraventricular hemorrhage
J Neurosurg
Mean arterial blood pressure and neonatal cerebral lesions
Arch Dis Child
Cited by (36)
The impact of prematurity and associated comorbidities on clinical outcomes in neonates with congenital heart disease
2022, Seminars in PerinatologyCitation Excerpt :The Vermont Oxford Network database in 2020 reported a 27% overall incidence of IVH and 8% severe IVH rate in VLBW infants (Nightingale Internet Reporting System 2020), with 80–90% diagnosed in the first 72 hours of life.23 In the transitional period after birth, changes in lung compliance associated with respiratory distress syndrome, surfactant administration, and positive pressure ventilation may increase central venous pressure and further contribute to impedance of venous return and subsequent cerebral ischemia and hemorrhage (periventricular hemorrhagic infarction).24 While some protection against IVH may be conferred by administration of antenatal steroids, initiation of delayed cord clamping, and appropriate thermoregulation,25 IVH remains a challenging complication of prematurity.
Neonatal Hypertension
2022, Clinics in PerinatologyCitation Excerpt :In those with severe acute hypertension, defined as showing evidence of end-organ dysfunction, intravenous agents should be used.48 To avoid cerebral ischemia or hemorrhage, care should be taken to avoid rapid reduction of blood pressure, particularly in those with severe acute hypertension and in premature infants who are at higher risk because of immaturity of the periventricular circulation.62 As with other medications in the neonatal population pharmacokinetic data and information on drug efficacy and side effect profiles within the neonatal population are generally lacking.
The hypertensive neonate
2020, Seminars in Fetal and Neonatal MedicineCitation Excerpt :As with all patients with severe hypertension, care should be taken to avoid rapid reduction of BP, which may result in cerebral ischemia or hemorrhage. This complication may be more likely to occur in premature infants because of immaturity of the periventricular circulation [76]. In the setting of severe hypertension, oral agents should be avoided given their variable duration of effect, onset of action, and unpredictable response.
Neurocritical care of premature infants
2020, Biomedical JournalCitation Excerpt :In human, GM starts to involute around 28-week gestation and often disappears at term. Predisposing factors of PIVH include a GM with an immature vasculature, a pressure passive cerebral circulation, and hemodynamic perturbations in sick premature infants [24]. In >90% of the cases, PIVH occurs during the first 3 postnatal days when the immature cardiorespiratory system is challenged to make the hemodynamic adaptation from fetal-to-neonatal life that comes too early [18].
Intracranial hemorrhage in neonates: A review of etiologies, patterns and predicted clinical outcomes
2018, European Journal of Paediatric Neurology