Intrauterine inflammation, cerebral oxygen consumption and susceptibility to early brain injury in very preterm newborns.
BACKGROUND
In utero exposure to inflammation results in elevated cerebral oxygen consumption. This increased metabolic demand may contribute to the association between chorioamnionitis and intraventricular haemorrhage (P/IVH). We hypothesised that intrauterine inflammation imposes an elevated cerebral metabolic load and increased fractional oxygen extraction (cFTOE) with cFTOE further increased in the presence of early P/IVH.


METHODS
Eighty-three infants ≤30 weeks gestation were recruited. Exposure to intrauterine inflammation was determined by placental histology. Total internal carotid blood flow (Doppler ultrasound) and near infrared spectroscopy were measured and cerebral oxygen delivery (mcerbDO2), consumption (mcerbVO2) and cFTOE were calculated on days 1 and 3 of life. Primary outcome was defined as death or P/IVH >grade II (cranial sonograph) by day 3.


RESULTS
Infants exposed to intrauterine inflammation had higher total internal carotid blood flow (92 vs 63 mL/kg/min) and mcerbDO2 (13.7 vs 10.1 mL/kg/min) than those not exposed to inflammation. Newborns with P/IVH had both higher oxygen consumption and extraction compared with those without sonographic injury regardless of exposure to intrauterine inflammation. Further, in preterms exposed to inflammation, those with P/IVH had higher consumption (6.1 vs 4.8 mL/kg/min) and extraction than those without injury. These differences were observed only on day 1 of life.


CONCLUSIONS
Although P/IVH is multifactorial in preterm newborns, it is likely that cerebral hypoxic-ischaemia plays a central pathophysiological role. These data provide a mechanistic insight into this process and suggests that the increased cerebral metabolic load imposed by the presence of inflammation results in a higher risk of critical hypoxic ischaemia in the preterm with increased susceptibility to significant P/IVH.
Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, South Australia, Australia Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Michael J
MJ
Stark
Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Nicolette A
NA
Hodyl
Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, South Australia, Australia.
Kiran Kumar
KK
Belegar V
Department of Neonatal Medicine, Women's and Children's Hospital, Adelaide, South Australia, Australia Robinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Chad C
CC
Andersen
D001921:Brain / Q000378:metabolism*; D002343:Carotid Artery, Internal / Q000000981:diagnostic imaging; D002543:Cerebral Hemorrhage / Q000503:physiopathology*; D002821:Chorioamnionitis / Q000503:physiopathology*; D005113:Extraction, Obstetrical / Q000706:statistics & numerical data; D005260:Female; D006801:Humans; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology; D007231:Infant, Newborn; D007234:Infant, Premature / Q000502:physiology*; D019344:Lactic Acid / Q000097:blood; D008297:Male; D010100:Oxygen / Q000378:metabolism; D010101:Oxygen Consumption / Q000502:physiology*; D011247:Pregnancy; D012039:Regional Blood Flow / Q000502:physiology; D019265:Spectroscopy, Near-Infrared; D018608:Ultrasonography, Doppler
D019344:Lactic Acid; D010100:Oxygen
Neonatology; cerebral fractional oxygen extraction; intra-uterine inflammation; intraventricular haemorrahge