Abnormal cerebral haemodynamics in perinatally asphyxiated neonates related to outcome.

AIM: To measure changes in cerebral haemodynamics during the first 24 hours of life following perinatal asphyxia, and relate them to outcome. METHODS: Cerebral blood volume (CBV), its response (CBVR) to changes in arterial carbon dioxide tension (PaCO(2)), and cerebral blood flow (CBF) were measured using near infrared spectroscopy (NIRS) in 27 term newborn infants with clinical and/or biochemical evidence consistent with perinatal asphyxia. RESULTS: Both CBF and CBV were higher on the first day of life in the infants with adverse outcomes, and a CBV outside the normal range had a sensitivity of 86% for predicting death or disability. The mean (SD) CBVR on the first day of life was 0.13 (0.12) ml/100 g/1/kPa, which, in 71% of infants, was below the lower 95% confidence limit for normal subjects. CONCLUSION: An increase in CBV on the first day of life is a sensitive predictor of adverse outcome. A reduction in CBVR is almost universally seen following asphyxia, but is not significantly correlated with severity of adverse outcome.

Relation between ultrasound appearance of the brain of very preterm infants and neurodevelopmental impairment at eight years.

The relation between the ultrasound appearance of the brain and neurodevelopmental outcome at eight years of age was investigated in 206 infants born between 1979 and 1982 at < 33 weeks gestation (600 to 2500g birthweights). Only 4 per cent of the 112 infants with normal scans at discharge from the neonatal unit developed major, disabling impairment. No significant adverse effect of uncomplicated periventricular haemorrhage was detected. The probability of a major impairment in infants with ventricular dilatation or hydrocephalus was 27 per cent, and 69 per cent in those with cerebral atrophy. 44 per cent of the children demonstrated significant differences in their cognitive processing skills, which appeared capable of affecting learning and may possibly have been caused by undetected hypoxic-ischaemic damage to callosal fibres.

Effect of indomethacin on cerebral oxidized cytochrome oxidase in preterm infants.

To determine the effect of i.v. indomethacin on cerebral intracellular oxygenation, as judged by changes in the concentration of oxidized cytochrome oxidase, studies were performed using near-infrared spectroscopy on 15 infants of 23 to 29 wk gestation, aged 8 to 30 d, who required the drug for closure of a patent ductus arteriosus. Indomethacin caused significant (p < 0.01) falls in cerebral blood flow, oxygen delivery, and blood volume and its reactivity to changes in arterial carbon dioxide tension, as previously reported. In 11 of the 15 infants, significant (p < 0.01) falls of 0.18 to 0.92 mumol.L-1 in the concentration of oxidized cytochrome oxidase were observed. Parallel experiments on synaptosomes derived from rat brain showed that indomethacin was most unlikely to have had a direct effect on mitochondrial respiration. These results are consistent with the hypothesis that the observed falls in the concentration of oxidized cytochrome oxidase resulted from hemodynamic perturbations that reduced cerebral intracellular oxygenation.

Cerebral hemodynamic effects of treatment with modified natural surfactant investigated by near infrared spectroscopy.

The purpose of this study was to investigate the effects on cerebral hemodynamics of administering modified natural surfactant (Curosurf, 200 mg.kg-1) to infants requiring mechanical ventilation for hyaline membrane disease. Observations were made using near infrared spectroscopy on 20 infants for between 26 and 109 (median 57) min before and 22 to 112 (median 46) min after surfactant instillation. Changes in cerebral oxyhemoglobin concentration and cerebral blood volume (CBV) were monitored continuously; cerebral blood flow, oxygen delivery, and the response of CBV to changes in arterial carbon dioxide tension were measured while the infants were stable shortly before and after surfactant was given. Cerebral oxyhemoglobin concentration fell transiently in all infants immediately after surfactant by a median of -0.21 (range -0.46 to 0.05) mL x 100 g-1, but quickly recovered so that the median change during the 10 min after surfactant was 0.01 (-0.46 to 0.46) mL x 100 g-1. Alterations in CBV also occurred ranging from -0.44 to 0.40 (median 0) mL x 100 g-1, which represented -12 to 16% of total CBV; these changes rapidly resolved. When the infants were stable before and after surfactant, the values for mean (SD) cerebral blood flow were 20.5 (7.5) and 23.1 (5.2) mL.100 g-1 x min-1, respectively (n = 9); for mean cerebral oxygen delivery, values were 2.71 (0.89) and 3.15 (0.73) mL x 100 g-1 x min-1 (n = 9); and for response of CBV to changes in arterial carbon dioxide tension, they were 0.14 (0.09) and 0.11 (0.11) mL x 100 g-1 x kPa-1 (n = 16); these changes were not statistically significant.(ABSTRACT TRUNCATED AT 250 WORDS)

Experimentally measured optical pathlengths for the adult head, calf and forearm and the head of the newborn infant as a function of inter optode spacing.

The Differential Pathlength Factor (DPF) has been measured for several different tissues. The results showed that the DPF varied with the type of tissue studied, and in the case of the adult calf with sex. However, the DPF for all tissues studied was constant once the inter optode spacing exceeded 2.5 cm. Thus, measurements can be made by NIR spectroscopy at a range of inter optode spacings, and a single DPF used in the calculation of chromophore concentration. The results also showed that the major source of error in the DPF lay in the measurement of the inter optode spacing. To improve accuracy, two options are possible. Firstly, some means of continuous measurement of inter optode spacing could be incorporated in the NIR instrumentation. The better alternative would be an instrument incorporating a method of directly measuring the optical pathlength at each wavelength. This could be done either by time of flight measurement, or if it can be validated, by phase shift measurement.

New non-invasive methods for the investigation of cerebral oxidative metabolism and haemodynamics in newborn infants.

Magnetic resonance spectroscopy and near infrared spectroscopy provide complimentary information about cerebral oxidative metabolism and haemodynamics and are valuable methods for investigating normal brain development and the pathogenesis of perinatal brain injury. Magnetic resonance spectroscopy can be used to measure in brain tissue the concentrations of important phosphorus compounds that are involved in oxidative metabolism, notably adenosine triphosphate, phosphocreatine and inorganic orthophosphate: intracellular pH can also be estimated. Abnormalities indicating impaired oxidative phosphorylation have been detected in a range of situations where hypoxic-ischaemic brain injury was known or suspected to have occurred, such as birth asphyxia and periventricular leucomalacia. Following acute cerebral injury a latent period of many hours has frequently been found before evidence of impaired oxidative phosphorylation developed, suggesting the possibility of effective early treatment. The extent of the metabolic impairment was related to long term outcome. Near infrared spectroscopy provides cotside information about cerebral oxygenation and haemodynamics. Quantitative information can be obtained about oxyhaemoglobin, deoxyhaemoglobin and the redox state of cytochrome aa3. Methods have been described for calculating cerebral blood flow, oxygen delivery, blood volume and carbon dioxide reactivity; and maturational changes are being defined. In birth-asphyxiated babies, abnormalities are detectable well before oxidative phosphorylation becomes impaired.

Quantification of concentration changes in neonatal human cerebral oxidized cytochrome oxidase.

The oxygenation of cerebral cytochrome oxidase in vivo was investigated in eight newborn preterm infants. Near-infrared spectroscopy was used to quantify changes in the concentration of oxidized cytochrome oxidase ([CytO2]) observed during alterations in arterial oxygen saturation (SaO2) in the range of 85-99% and of carbon dioxide tension (PaCO2) in the range of 4.3-9.6 kPa. No relation was found between changes in SaO2 and [CytO2]. Alterations in PaCO2 were positively related both to changes in [CytO2] and total cerebral hemoglobin concentration [( Hb]t). The changes in [CytO2] ranged from 0.09 to 0.33 (median 0.21) mumol.l-1.kPa-1. The ratio [CytO2]/[Hb]t ranged from 0.06 to 0.12 (median 0.08). The relation of delta [CytO2] to the change in cerebral blood volume (delta CBV) was calculated: delta [CytO2]/delta CBV ranged from 0.09 to 0.18 (median 0.11) mumol/ml. These results define a fraction of cerebral cytochrome oxidase in the newborn infant that is oxidized after an increase in PaCO2 but demonstrate that a change in SaO2 in the range studied was not sufficient by itself to change [CytO2]. They differ from results of studies in adults; this may reflect significant differences between adult and neonatal brain.

Effect of intervention on development of hip posture in very preterm babies.

Preterm babies are physiologically hypotonic, which causes their posture to be flattened when lying in the prone position. This flattened posture may persist beyond term. In a prospective, randomised, controlled, double blind trial of postural support carried out on 45 babies born at less than 33 weeks of gestation, we showed that infants positioned with specific hip support during the period of intensive care had significantly fewer features of flattened posture at the age equivalent to term.

Response of cerebral blood volume to changes in arterial carbon dioxide tension in preterm and term infants.

The response of cerebral blood volume (CBVR) to a small induced change in arterial carbon dioxide tension was studied by near-infrared spectroscopy in 17 newborn infants born from 26 wk of gestation to term. All 17 infants were undergoing mechanical ventilation but had apparently normal brains. The CBVR per kPa change in arterial carbon dioxide tension within the range 3.9 to 9.6 kPa was calculated from the change in total cerebral Hb concentration ([TCHb]) using the equation: delta CBV = delta [TCHb] x 0.89/[H] where [H] is the large vessel Hb concentration. A least-squares regression line with 95% confidence limits was derived for CBVR against gestational age. A highly significant linear increase in CBVR was found: mean CBVR from the regression increased from 0.07 mL.100 g-1.kPa-1 at 26 wk to 0.51 mL.100 g-1.kPa-1 at 40 wk.