title: Testing impact of perinatal inflammation on cerebral autoregulation in preterm neonates: evaluation of a noninvasive method.
abstract: Increased preterm delivery rate and survival of preterm infants of whom a considerable proportion survive with neurodevelopmental impairment calls for better knowledge of mechanisms associated with brain injury. This thesis focuses on cerebral autoregulation and is based on clinical studies of very preterm infants and experimental studies in newborn piglets. Maintaining adequate cerebral perfusion is critical to avoid brain injury. In healthy neonates, cerebral autoregulation ensures an almost unchanged cerebral perfusion within a narrow range of arterial blood pressures. When autoregulation is impaired, cerebral blood flow follows changes in arterial blood pressure passively. Both impaired cerebral autoregulation and perinatal inflammation have been associated with perinatal brain injury in preterm neonates. We hypothesized that impaired cerebral autoregulation might represent a hemodynamic link between inflammation and brain injury. We used an apparently well established non-invasive method based on frequency analysis between spontaneous changes in arterial blood pressure and cerebral oxygenation as measured with near-infrared spectroscopy. It turned out that the methodology was weak. This led us to evaluate the precision and validity of this method. We monitored 22 preterm neonates and demonstrated that reliable detection of impaired cerebral autoregulation requires several hours of monitoring. However, weighting measurements with large variations in blood pressure in favour of those with small increases the precision. This reduces the required monitoring time in each infant (study I). Furthermore, we used a piglet model to validate the method against a conventional measure of cerebral autoregulation and demonstrated a significant correlation with degree of impaired autoregulation (study II). To study a possible link between cerebral autoregulation and perinatal inflammation, cerebral autoregulation was measured in 60 infants in their first postnatal day. Foetal vasculitis was used as a marker of antenatal (preceding) inflammation. Level of interleukin-6 in postnatal blood samples was used as a marker of postnatal (concurrent) inflammation. Neither ante- nor postnatal inflammation affected cerebral autoregulation significantly. There was, however, a trend towards a more severely impaired autoregulation in infants with signs of antenatal inflammation. Postnatal inflammation was significantly associated with hypotension, and blood pressure was inversely associated with degree of impaired cerebral autoregulation (study III). Also, we made use of our piglet model to study (i) if hypovolaemia affects cerebral autoregulation, and (ii) a possible direct cerebrovascular effect of dopamine therapy. Hypovolaemia without hypotension did not seem to affect autoregulation significantly. Dopamine, the most frequently used antihypotensive drug in neonates, elicited an unexplained mismatch between cerebral oxygenation and perfusion, as perfusion increased while oxygenation was unaffected (study IV). This mismatch has formed the basis for an ongoing explanatory study. Based on the findings in the present thesis we conclude the following: Our non-invasive method has potential use in clinical research. However, low precision hampers its clinical application. In preterm infants with perinatal inflammation, cerebral blood flow is at most moderately affected by variations in arterial blood pressure, provided inflammation induced hypotension is prevented. In newborn piglets, hypovolaemia alone did not affect cerebral autoregulation significantly, and dopamine therapy elicited an unexplained mismatch between cerebral perfusion and oxygenation.
authors: Department of Neonatology, Copenhagen University Hospital, Rigshospitalet, Denmark. gitte.holst.hahn@gmail.com.
authors: Gitte Holst
authors: GH
authors: Hahn
mesh_terms: D000818:Animals; D001794:Blood Pressure; D002560:Cerebrovascular Circulation; D054022:Cerebrum / Q000098:blood supply / Q000503:physiopathology; D004298:Dopamine / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects; D006706:Homeostasis / Q000502:physiology*; D006801:Humans; D020896:Hypovolemia / Q000150:complications / Q000503:physiopathology; D007231:Infant, Newborn; D007249:Inflammation / Q000150:complications / Q000503:physiopathology*; D010101:Oxygen Consumption; D047928:Premature Birth / Q000503:physiopathology*; D019265:Spectroscopy, Near-Infrared; D013552:Swine
chemical_list: D015259:Dopamine Agents; D004298:Dopamine