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Background: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic-ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. Method(s): In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 mug/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Result(s): Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. Conclusion(s): In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.Copyright © 2018, International Pediatric Research Foundation, Inc.

Background: Impaired cerebral autoregulation in preterm infants makes circulatory management important to avoid cerebral hypoxic-ischemic injury. Dobutamine is frequently used as inotropic treatment in preterm neonates, but its effects on the brain exposed to cerebral hypoxia are unknown. We hypothesized that dobutamine would protect the immature brain from cerebral hypoxic injury. Method(s): In preterm (0.6 gestation) fetal sheep, dobutamine (Dob, 10 mug/kg/min) or saline (Sal) was infused intravenously for 74 h. Two hours after the beginning of the infusion, umbilical cord occlusion (UCO) was performed to produce fetal asphyxia (Sal+UCO: n = 9, Dob+UCO: n = 7), or sham occlusion (Sal+sham: n = 7, Dob+sham: n = 6) was performed. Brains were collected 72 h later for neuropathology. Result(s): Dobutamine did not induce cerebral changes in the sham UCO group. UCO increased apoptosis and microglia density in white matter, hippocampus, and caudate nucleus, and astrocyte density in the caudate nucleus. Dobutamine commenced before UCO reduced microglia infiltration in the white matter, and microglial and astrocyte density in the caudate. Conclusion(s): In preterm hypoxia-induced brain injury, dobutamine decreases neuroinflammation in the white matter and caudate, and reduces astrogliosis in the caudate. Early administration of dobutamine in preterm infants for cardiovascular stabilization appears safe and may be neuroprotective against unforeseeable cerebral hypoxic injury.Copyright © 2018, International Pediatric Research Foundation, Inc.

Objective: This study aimed to determine the additional diagnostic information provided by prenatal (fetal) magnetic resonance imaging (pMRI) following tertiary ultrasound (US) for fetal cranial abnormalities in complicated monochorionic gestations. Method(s): Women with complicated monochorionic gestations complicated by twin-twin transfusion syndrome, co-twin demise (CD), selective intrauterine growth restriction, and/or twin anaemia-polycythaemia sequence who were referred for pMRI after tertiary US were included. Additional diagnostic information by pMRI that changed prognostic counselling was the primary outcome. Result(s): Thirty-three women with 48 live fetuses had pMRI at a median of 25 weeks (range: 21-29). Three of ten survivors of spontaneous CD, one of eight survivors of CD after twin-twin transfusion syndrome and 1/30 co-survivors had diagnostic information added by pMRI that altered counselling; US was normal in two and in the other three underrepresented parenchymal injury (5/33 = 15%; 95% confidence interval +/-0.27-0.03). Additional findings included occipital lobe infarction, hemispheric injury, dural sinus thrombosis, ischaemia-producing polymicrogyria and intraventricular haemorrhage. Another 8/33 women had additional information provided by pMRI that did not alter counselling. Conclusion(s): Prenatal magnetic resonance imaging resulted in changed prognostic counselling in 5/33 pregnancies. Evaluation of incorporation of pMRI into routine surveillance of complicated monochorionic gestations is needed. © 2017 John Wiley & Sons, Ltd.

Fetal growth restriction (FGR) is a common complication of pregnancy and, in severe cases, is associated with elevated rates of perinatal mortality, neonatal morbidity, and poor neurodevelopmental outcomes. The leading cause of FGR is placental insufficiency, with the placenta failing to adequately meet the increasing oxygen and nutritional needs of the growing fetus with advancing gestation. The resultant chronic fetal hypoxia induces a decrease in fetal growth, and a redistribution of blood flow preferentially to the brain. However, this adaptation does not ensure normal brain development. Early detection of brain injury in FGR, allowing for the prediction of short- and long-term neurodevelopmental consequences, remains a significant challenge. Furthermore, in FGR infants the detection and diagnosis of neuropathology is complicated by preterm birth, the etiological heterogeneity of FGR, timing of onset of growth restriction, its severity, and coexisting complications. In this review, we examine existing and emerging diagnostic tools from human and preclinical studies for the detection and assessment of brain injury in FGR fetuses and neonates. Increased detection rates, and early detection of brain injury associated with FGR, will offer opportunities for developing and assessing interventions to improve long-term outcomes.Copyright © 2017 International Pediatric Research Foundation, Inc.

Objective: This study aimed to determine the additional diagnostic information provided by prenatal (fetal) magnetic resonance imaging (pMRI) following tertiary ultrasound (US) for fetal cranial abnormalities in complicated monochorionic gestations. Method(s): Women with complicated monochorionic gestations complicated by twin-twin transfusion syndrome, co-twin demise (CD), selective intrauterine growth restriction, and/or twin anaemia-polycythaemia sequence who were referred for pMRI after tertiary US were included. Additional diagnostic information by pMRI that changed prognostic counselling was the primary outcome. Result(s): Thirty-three women with 48 live fetuses had pMRI at a median of 25 weeks (range: 21-29). Three of ten survivors of spontaneous CD, one of eight survivors of CD after twin-twin transfusion syndrome and 1/30 co-survivors had diagnostic information added by pMRI that altered counselling; US was normal in two and in the other three underrepresented parenchymal injury (5/33 = 15%; 95% confidence interval +/-0.27-0.03). Additional findings included occipital lobe infarction, hemispheric injury, dural sinus thrombosis, ischaemia-producing polymicrogyria and intraventricular haemorrhage. Another 8/33 women had additional information provided by pMRI that did not alter counselling. Conclusion(s): Prenatal magnetic resonance imaging resulted in changed prognostic counselling in 5/33 pregnancies. Evaluation of incorporation of pMRI into routine surveillance of complicated monochorionic gestations is needed. © 2017 John Wiley & Sons, Ltd.

Fetal growth restriction (FGR) is a common complication of pregnancy and, in severe cases, is associated with elevated rates of perinatal mortality, neonatal morbidity, and poor neurodevelopmental outcomes. The leading cause of FGR is placental insufficiency, with the placenta failing to adequately meet the increasing oxygen and nutritional needs of the growing fetus with advancing gestation. The resultant chronic fetal hypoxia induces a decrease in fetal growth, and a redistribution of blood flow preferentially to the brain. However, this adaptation does not ensure normal brain development. Early detection of brain injury in FGR, allowing for the prediction of short- and long-term neurodevelopmental consequences, remains a significant challenge. Furthermore, in FGR infants the detection and diagnosis of neuropathology is complicated by preterm birth, the etiological heterogeneity of FGR, timing of onset of growth restriction, its severity, and coexisting complications. In this review, we examine existing and emerging diagnostic tools from human and preclinical studies for the detection and assessment of brain injury in FGR fetuses and neonates. Increased detection rates, and early detection of brain injury associated with FGR, will offer opportunities for developing and assessing interventions to improve long-term outcomes.Copyright © 2017 International Pediatric Research Foundation, Inc.