title: Reduced fetal cerebral oxygen consumption is associated with smaller brain size in fetuses with congenital heart disease.
abstract: BACKGROUND
  Fetal hypoxia has been implicated in the abnormal brain development seen in newborns with congenital heart disease (CHD). New magnetic resonance imaging technology now offers the potential to investigate the relationship between fetal hemodynamics and brain dysmaturation.
  
  
  RESULTS
  We measured fetal brain size, oxygen saturation, and blood flow in the major vessels of the fetal circulation in 30 late-gestation fetuses with CHD and 30 normal controls using phase-contrast magnetic resonance imaging and T2 mapping. Fetal hemodynamic parameters were calculated from a combination of magnetic resonance imaging flow and oximetry data and fetal hemoglobin concentrations estimated from population averages. In fetuses with CHD, reductions in umbilical vein oxygen content (P<0.001) and failure of the normal streaming of oxygenated blood from the placenta to the ascending aorta were associated with a mean reduction in ascending aortic saturation of 10% (P<0.001), whereas cerebral blood flow and cerebral oxygen extraction were no different from those in controls. This accounted for the mean 15% reduction in cerebral oxygen delivery (P=0.08) and 32% reduction cerebral Vo2 in CHD fetuses (P<0.001), which were associated with a 13% reduction in fetal brain volume (P<0.001). Fetal brain size correlated with ascending aortic oxygen saturation and cerebral Vo2 (r=0.37, P=0.004).
  
  
  CONCLUSIONS
  This study supports a direct link between reduced cerebral oxygenation and impaired brain growth in fetuses with CHD and raises the possibility that in utero brain development could be improved with maternal oxygen therapy.
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Liqun
authors.initials: L
authors.lastname: Sun
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Christopher K
authors.initials: CK
authors.lastname: Macgowan
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: John G
authors.initials: JG
authors.lastname: Sled
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Shi-Joon
authors.initials: SJ
authors.lastname: Yoo
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Cedric
authors.initials: C
authors.lastname: Manlhiot
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Prashob
authors.initials: P
authors.lastname: Porayette
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Lars
authors.initials: L
authors.lastname: Grosse-Wortmann
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Edgar
authors.initials: E
authors.lastname: Jaeggi
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Brian W
authors.initials: BW
authors.lastname: McCrindle
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: John
authors.initials: J
authors.lastname: Kingdom
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Edward
authors.initials: E
authors.lastname: Hickey
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.).
authors.forename: Steven
authors.initials: S
authors.lastname: Miller
authors.affiliation: From Department of Ultrasound, International Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China (L.S.); Division of Pediatric Cardiology, Department of Pediatrics (L.S., S.-J.Y., C.M., P.P., L.G.-W., E.J., B.W.M., M.S.), Department of Physiology and Experimental Medicine (C.K.M., J.G.S.), Department of Diagnostic Imaging (S.-J.Y., L.G.-W., M.S.), Department of Cardiovascular Surgery (E.H.), and Department of Pediatric Neurology (S.M.), University of Toronto and Hospital for Sick Children, Toronto, ON, Canada; and Department of Obstetrics and Gynecology, University of Toronto and Mount Sinai Hospital, Toronto, ON, Canada (J.K.). mike.seed@sickkids.ca.
authors.forename: Mike
authors.initials: M
authors.lastname: Seed
mesh_terms: D000328:Adult; D001921:Brain / Q000196:embryology* / Q000378:metabolism* / Q000473:pathology; D016022:Case-Control Studies; D002560:Cerebrovascular Circulation / Q000502:physiology; D003430:Cross-Sectional Studies; D005260:Female; D005333:Fetus / Q000378:metabolism*; D006330:Heart Defects, Congenital / Q000378:metabolism*; D006439:Hemodynamics / Q000502:physiology; D006801:Humans; D008279:Magnetic Resonance Imaging; D009929:Organ Size; D010092:Oximetry; D010101:Oxygen Consumption / Q000502:physiology*; D011247:Pregnancy; D011263:Pregnancy Trimester, Third; D011446:Prospective Studies; D012039:Regional Blood Flow / Q000502:physiology
keywords: brain; heart diseases; hemodynamics; magnetic resonance imaging; pediatrics