Effects of antenatal glucocorticoids on cerebral substrate metabolism in the preterm ovine fetus

McCallum, Jeremy D.; Smith, Norman; Schwab, Matthias; Coksaygan, Turhan; Reinhardt, Bettina; Nathanielsz, Peter W.; Richardson, Bryan

doi:10.1016/j.ajog.2007.05.007

Cited by 14 publications

(13 citation statements)

References 20 publications

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“…), and so increased glucose and an associated rise in insulin levels may drive an increase in cerebral metabolic rate and oxygen demand, as is speculated to occur after betamethasone exposure in term fetal sheep (McCallum et al . ). This in turn may have contributed to increased neural activity.…”

Section: Discussionmentioning

confidence: 97%

The effects of dexamethasone on post‐asphyxial cerebral oxygenation in the preterm fetal sheep

Lear

Koome

Davidson

et al. 2014

The Journal of Physiology

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Key pointsr Mothers at risk of preterm delivery are routinely given synthetic glucocorticoids such as dexamethasone to help mature fetal lungs and improve survival after birth.r We have previously shown that dexamethasone given after an acute episode of asphyxia in preterm fetal sheep is associated with greater brain injury.r In this study we found that fetal exposure to dexamethasone after asphyxia in preterm fetal sheep was associated with reduced intracerebral oxygenation during the critical latent phase of recovery.r In the secondary phase, maternal dexamethasone was associated with increased epileptiform transient activity and evidence of greater mitochondrial oxidation.r These findings suggest that fetal exposure to the synthetic glucocorticoid dexamethasone is associated with a critical mismatch between the brain's demand for oxygenation and the supply of oxygen that may contribute to greater brain injury.Abstract Exposure to clinical doses of the glucocorticoid dexamethasone increases brain activity and causes seizures in normoxic preterm fetal sheep without causing brain injury. In contrast, the same treatment after asphyxia increased brain injury. We hypothesised that increased injury was in part mediated by a mismatch between oxygen demand and oxygen supply. In preterm fetal sheep at 0.7 gestation we measured cerebral oxygenation using near-infrared spectroscopy, electroencephalographic (EEG) activity, and carotid blood flow (CaBF) from 24 h before until 72 h after asphyxia induced by 25 min of umbilical cord occlusion. Ewes received dexamethasone intramuscularly (12 mg 3 ml -1 ) or saline 15 min after the end of asphyxia. Fetuses were studied for 3 days after occlusion. During the first 6 h of recovery after asphyxia, dexamethasone treatment was associated with a significantly greater fall in CaBF (P < 0.05), increased carotid vascular resistance (P < 0.001) and a greater fall in cerebral oxygenation as measured by the difference between oxygenated and deoxygenated haemoglobin (delta haemoglobin; P < 0.05). EEG activity was similarly suppressed in both groups. From 6 to 10 h onward, dexamethasone treatment was associated with a return of CaBF to saline control levels, increased EEG power (P < 0.005), greater epileptiform transient activity (P < 0.001), increased oxidised cytochrome oxidase (P < 0.05) and an attenuated increase in [delta haemoglobin] (P < 0.05). In conclusion, dexamethasone treatment after asphyxia is associated with greater hypoperfusion in the critical latent phase, leading to impaired intracerebral oxygenation that may exacerbate neural injury after asphyxia.

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Section: Discussionmentioning

confidence: 97%

The effects of dexamethasone on post‐asphyxial cerebral oxygenation in the preterm fetal sheep

Lear

Koome

Davidson

et al. 2014

The Journal of Physiology

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“…There are abundant animal data demonstrating that hypoxemia results in central redistribution of blood flow in the fetus (Donofrio et al, 2003 and Pearce, 2006; Vyas et al, 1990 and Wladimiroff, 1987). Although less is known about the effects of hypoglycemia on the fetal cerebral circulation, there are data to indicate that glycemic state can influence cerebral hemodynamics in the fetus (Makowski et al, 1972, McCallum et al, 2008 and Pardo et al, 1999). The precise relationship between arterial oxygen and glucose content and cerebral vasodilation is not clear in these animal models and certainly not in human fetuses.…”

Section: Discussionmentioning

confidence: 99%

Cerebral Blood Flow Characteristics and Biometry in Fetuses Undergoing Prenatal Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

McElhinney

Benson

Brown

et al. 2010

Ultrasound in Medicine & Biology

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Children with hypoplastic left heart syndrome (HLHS) are at risk for neurodevelopmental dysfunction; prenatal factors may play a role in this predilection. Cerebral blood flow profiles are abnormal in fetuses with HLHS, raising the possibility that cerebral hemodynamics in utero may be related to neurodevelopmental abnormalities. Prenatal aortic valvuloplasty for fetal aortic stenosis with evolving HLHS is technically feasible and improves left heart hemodynamics. This study aimed to assess the effects of prenatal intervention on cerebral blood flow profiles and head circumference in fetuses with evolving HLHS. Seventy fetuses underwent prenatal aortic valvuloplasty for evolving HLHS (median 23 weeks gestation). Among 46 fetuses that had successful valvuloplasty and available data, middle cerebral artery (MCA) pulsatility (PI) and resistive (RI) indices were abnormal (Z-scores −1.7 ± 1.1 and −2.2 ± 1.4, p < 0.001). Early post-valvuloplasty (n = 33) and at late gestation follow-up (n = 28), MCA PI and RI Z-scores remained low with no difference from pre- or early postintervention. Fetal head circumference was normal, as were umbilical artery PI and RI Z-scores. Cerebral blood flow characteristics are abnormal in mid-gestation fetuses with evolving HLHS, suggesting low cerebral vascular impedance. The mechanisms and significance of these abnormalities are unknown. Prenatal aortic valvuloplasty did not have a major impact on these indices.

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“…The increased cerebral metabolic load and hemodynamic fluctuations imposed by intrauterine inflammation may help explain the clinical observation that the risk of white matter injury is increased when there is inflammation and/or infection present, even without a clear role for cytokines (49). On the other hand, while antenatal steroids decreases the risk of GM-IVH, their administration to pregnant ewes decreases fetal CBF without increasing COE, which may be detrimental to brain oxygenation in conjunction with other hypoxic stressors (118).…”

Section: Preterm Brain Injury and Cerebral Hemodynamicsmentioning

confidence: 98%

Cerebral vascular regulation and brain injury in preterm infants

Brew

Walker

Wong

2014

American Journal of Physiology-Regulatory, Integrative and Comp

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Cerebrovascular lesions, mainly germinal matrix hemorrhage and ischemic injury to the periventricular white matter, are major causes of adverse neurodevelopmental outcome in preterm infants. Cerebrovascular lesions and neuromorbidity increase with decreasing gestational age, with the white matter predominantly affected. Developmental immaturity in the cerebral circulation, including ongoing angiogenesis and vasoregulatory immaturity, plays a major role in the severity and pattern of preterm brain injury. Prevention of this injury requires insight into pathogenesis. Cerebral blood flow (CBF) is low in the preterm white matter, which also has blunted vasoreactivity compared with other brain regions. Vasoreactivity in the preterm brain to cerebral perfusion pressure, oxygen, carbon dioxide, and neuronal metabolism is also immature. This could be related to immaturity of both the vasculature and vasoactive signaling. Other pathologies arising from preterm birth and the neonatal intensive care environment itself may contribute to impaired vasoreactivity and ineffective CBF regulation, resulting in the marked variations in cerebral hemodynamics reported both within and between infants depending on their clinical condition. Many gaps exist in our understanding of how neonatal treatment procedures and medications have an impact on cerebral hemodynamics and preterm brain injury. Future research directions for neuroprotective strategies include establishing cotside, real-time clinical reference values for cerebral hemodynamics and vasoregulatory capacity and to demonstrate that these thresholds improve long-term outcomes for the preterm infant. In addition, stimulation of vascular development and repair with growth factor and cell-based therapies also hold promise.

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Effects of antenatal glucocorticoids on cerebral substrate metabolism in the preterm ovine fetus

Cited by 14 publications

References 20 publications

The effects of dexamethasone on post‐asphyxial cerebral oxygenation in the preterm fetal sheep

The effects of dexamethasone on post‐asphyxial cerebral oxygenation in the preterm fetal sheep

Cerebral Blood Flow Characteristics and Biometry in Fetuses Undergoing Prenatal Intervention for Aortic Stenosis with Evolving Hypoplastic Left Heart Syndrome

Cerebral vascular regulation and brain injury in preterm infants

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