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D Azzopardi

Publications and source records attributed to D Azzopardi.

35 records · Page 2Linked to original sources

Persistent increases in cerebral lactate concentration after birth asphyxia.

In this prospective study proton magnetic resonance spectroscopy (1H MRS) was used to test the hypothesis that lactate can be detected later than 1 mo after birth in the brains of infants who display severe neurodevelopmental impairment 1 y after transient perinatal hypoxia-ischemia. Data were obtained from three groups of infants: 1) eight infants suffering birth asphyxia followed by perinatal encephalopathy and abnormal neurodevelopmental outcome at 1 y of age (defined as major neurologic impairment, Griffiths quotient <85%, and low optimality score); 2) 10 infants with signs of perinatal hypoxia-ischemia but normal neurodevelopmental outcome at 1 y; and 3) six control infants with uneventful perinatal courses and normal neurodevelopment at 1 y. Between one and four examinations (median 1) were performed at median (range) 11 (4-68) wk after birth, and the cerebral concentration ratio of lactate to creatine plus phosphocreatine (Cr) calculated from each spectrum. Lactate was detected later than the 1st mo after birth in seven of eight infants with abnormal neurodevelopmental outcome [maximum detected lactate/Cr was median (range) 0.44 (0.24-0.67)]. No lactate was detected later than the 1st mo after birth in infants with normal neurodevelopmental outcome, nor in five of six control subjects, although a small amount of lactate was detected in one control infant (lactate/Cr=0.04). These results suggest that the pathologic postasphyxial process, indicated by persistent cerebral lactate, may not be confined to the period immediately after injury.

Asphyxia Neonatorum↗

Magnetic resonance imaging of the brain in very preterm infants: visualization of the germinal matrix, early myelination, and cortical folding.

OBJECTIVE: To investigate preterm infants, we have installed in our neonatal intensive care unit a dedicated magnetic resonance (MR) imaging system which was specifically designed for neonatal use. The aim of this study was to describe the MR appearances of the brain in preterm infants who were first scanned between 25 and 32 weeks gestational age (GA) and to outline changes to the brains of these infants between their first scan and term. METHODS: Preterm infants of 25 to 32 weeks GA were imaged using the 1T neonatal MR system (Oxford Magnet Technology, Eyensham, Oxfordshire, England/Picker International, Cleveland, OH). The scanning protocol included T1-weighted conventional spin echo (repetition time [TR], 600; echo time, 20 ms), inversion recovery fast spin echo (TR, 3530; effective echo time, 30; inversion time, 950 ms), and T2-weighted fast spin echo (TR, 3500; effective echo time, 208 ms) sequences. RESULTS: Seventeen infants of median 28 weeks GA (range, 24 to 31 weeks) at birth were imaged a total of 53 times between birth and term. The median number of images per infant was two (range, 1 to 9). In infants of < 30 weeks GA, the germinal matrix was visualized at the margins of the lateral ventricles. It had a short T1 and short T2 and the bulk of it involuted at between 30 and 32 weeks GA. The white matter had a relatively homogeneous low signal except for bands of altered signal (probably originating from regions containing radial glia and migrating cells) which were most apparent anterolateral and posterolateral to the lateral ventricles. Myelination was seen in the posterior brainstem, cerebellum, and region of the ventrolateral nuclei of the thalamus. Infants had very little cortical folding at 25 weeks GA but this developed later in an orderly fashion. CONCLUSION: The neonatal MR system allowed extremely preterm infants to be studied safely with MR imaging. The images acquired demonstrated the germinal matrix, early myelination, and early cortical folding. Evolution of these features was demonstrated with serial studies.

Brain↗

Noninvasive characterization of neonatal adipose tissue by 13C magnetic resonance spectroscopy.

In vivo 13C magnetic resonance spectroscopy (MRS) was applied noninvasively to analyze the fatty acid composition of adipose tissue in 21 full-term newborn infants and 6 mothers. In order to assess the effects of gestational and postnatal age on adipose tissue composition, we studied preterm infants at birth, term infants at the ages of 6 wk and at 6 mon. We also investigated the influence of maternal diet on infant adipose tissue composition by studying the breast-fed infants of women who maintained either an omnivore or a vegan diet. Significant differences were observed in adipose tissue composition of neonates compared with their mothers. Neonates had more saturated and less unsaturated fatty acids than their mothers (P < 0.01). We also observed changes in adipose tissue composition with maturity. From birth to 6 wk of age 13C MR spectra showed a significant increase in the amount of unsaturated fatty acids, particularly polyunsaturated fatty acids (P < 0.01). Similarly, differences were seen as a result of gestational age. Preterm infants had relatively fewer unsaturated fatty acids than full-term infants. A greater proportion of these unsaturated fatty acids were polyunsaturated. Our results demonstrate that 13C MRS can be utilized to assess noninvasively neonatal adipose tissue lipid composition and to monitor the effects of developmental changes due to gestational age and oral feeding.

Adipose Tissue↗

Cerebral metabolism within 18 hours of birth asphyxia: a proton magnetic resonance spectroscopy study.

Proton magnetic resonance spectroscopy (1H MRS) was performed within 18 h of birth (median 13, range 4-18 h) on 16 term infants with clinical features of birth asphyxia. Ten infants with no evidence of birth asphyxia were studied as controls at 5-18 (median 8) h after birth. To detect delayed impairments in cerebral energy metabolism, 15 infants suspected of asphyxia underwent 31P MRS at 33-106 (median 62) h of age. Choline, creatine, and N-acetylaspartate (NAA) were detected in spectra located to the basal ganglia in all infants. Lactate was detected in 15 of the 16 infants suspected of asphyxia, but in only 4 of the 10 controls (p < 0.05, chi 2). Glutamine and glutamate (Glx) was detected in 11 infants suspected of asphyxia and in three controls, but this difference was not significant at the 5% level. The spectra revealed no other significant differences between asphyxiated infants and controls. In the asphyxiated infants, there was a negative correlation between the ratio of lactate to creatine in the first 18 h of life and phosphocreatine/inorganic phosphate (PCr/ P(i)) at 33-106 h (p < 0.001). Five severely asphyxiated infants had PCr/P(i) < 0.75 (median 0.53, range 0.14-0.65), indicating a poor neurodevelopmental prognosis, and a further infant died before PCr/Pi could be measured. Ten infants had PCr/P(i) > 0.75 (1.03, 0.76-1.49). Median lactate/creatine was 1.47 (range 0.67-3.81) in the six severely affected subjects, 0.38 (0-1.51) in the latter group, and 0 (0-0.6) in controls (p < 0.0005, Kruskall-Wallis). These results suggest that, after birth asphyxia, cerebral energy metabolism is abnormal during the period when 31P MRS characteristically gives normal results. 1H MRS might be of value in predicting which infants are likely to suffer a decline in cerebral high energy phosphate concentrations and subsequent neurodevelopmental impairment.

Asphyxia Neonatorum↗

Magnetic resonance spectroscopy in neonates.

Magnetic resonance spectroscopy allows noninvasive assessment of cerebral metabolism in newborn infants. 31P magnetic resonance spectroscopy has demonstrated that birth asphyxia leads to delayed impairment of cerebral energy metabolism and 1H magnetic resonance spectroscopy has shown lactate accumulation and a later decline in N-acetyl aspartate concentration. 13C magnetic resonance spectroscopy may help explain these observations.

Adult↗

Relation between cerebral oxidative metabolism following birth asphyxia, and neurodevelopmental outcome and brain growth at one year.

Studies of cerebral oxidative metabolism were carried out by phosphorous magnetic resonance spectroscopy during the first week of life in 52 infants with clinical and/or biochemical evidence of birth asphyxia. 15 infants died and the 37 survivors were assessed by a wide range of neurodevelopmental tests at one year of age. The minimum recorded values for cerebral phosphocreatine/inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed a significant relation between the extent of derangement of oxidative metabolism and the severity of adverse outcomes, including death, neurodevelopmental impairment and reduced head growth.

Adenosine Triphosphate↗

Virilisation of female preterm infants.

Two cases of hypertrophy of the clitoris in premature girls are reported; this was associated with persistently high concentrations of adrenal fetal zone androgens.

Adrenocorticotropic Hormone↗

Absolute quantitation of neonatal brain spectra acquired with surface coil localization.

Surface coils with strong coupling for both 31P and 1H were used to measure metabolite concentrations by in vivo NMR spectroscopy. Tissue water was used as an internal concentration reference and the 31P and 1H spatial sensitivities of the coils were matched. For such coils, sample loading does not necessarily have a significant effect on absolute quantitation results. The coils had proportionality constants which were almost independent of loading and the 1H and 31P flip angles at the coil centre produced by fixed length pulses were approximately equal over the range of loading conditions encountered in vivo. For 7 normal infants, of gestational plus postnatal age (GPA) 35 to 37 weeks, the nucleotide triphosphate concentration in the cerebral cortex was 3.7 +/- 0.6 mmol/L wet tissue (mean +/- SD). Further studies of normal infants down to 26 weeks GPA indicated that phosphorus metabolite concentrations increased significantly with GPA during this period. Concentrations were often low in the cerebral cortices of birth asphyxiated infants. In order to provide corroboration for the results from neonatal brain, data were acquired also from the resting, unexercised forearm muscles of 6 young adults and the measured adenosine triphosphate concentration was 6.3 +/- 0.8 Mmol/L wet tissue.

Adenosine Triphosphate↗

Magnetic resonance and near infrared spectroscopy for investigation of perinatal hypoxic-ischaemic brain injury.

Hypoxic-ischaemic injury to the brain is an important cause of perinatal death and seems to be the commonest cause of permanent neurodevelopmental disability in newborn infants who survive after intensive care. If this type of brain injury is to be prevented and treatment put on a rational basis, non-invasive methods are required for defining its mechanisms. This review has considered two such methods: magnetic resonance spectroscopy and near infrared spectroscopy. Magnetic resonance spectroscopy is used to measure, in brain tissue, the concentrations of the 'high energy' phosphorus metabolites that are dependent for their synthesis on the processes of oxidative phosphorylation. Intracellular pH can also be measured. Normal maturational changes in the brain have been defined and abnormalities detected in a range of conditions where hypoxic-ischaemic injury was suspected to have occurred. In laboratory animals the acute effects of curtailment of oxygen supply to the brain ('primary' energy failure) have been observed, and the effects of two commonly used treatments, infusions of sodium bicarbonate and glucose, have been tested. After resuscitation of newborn infants from severe intrapartum asphyxia, a latent period has often been noted before energy failure became detectable. This 'secondary' energy failure is due to a variety of damaging reactions initiated by the acute hypoxicischaemic episode and reperfusion of the brain. It is possible that in the future irreversible injury to brain cells following the episode may be prevented or ameliorated by the prompt use of cerebroprotective agents. The extent of abnormalities detected by magnetic resonance spectroscopy has prognostic implications: evidence of severe energy failure in the first days of life was regularly associated with subsequent death or with severe neurodevelopmental impairments. Many technical developments in magnetic resonance spectroscopy are under way, particularly employing proton (1H) spectroscopy, which will allow the intracerebral concentrations of a wide range of metabolites, including neurotransmitters, to be measured. The combination of spectroscopy with magnetic resonance imaging will permit quantitative data to be obtained from selected volumes within the brain. Near infrared spectroscopy is used to make observations at the cotside of the intracerebral concentrations of the chromophores oxyhaemoglobin, deoxyhaemoglobin, and oxidised cytochrome aa3, and it therefore provides information complementary to that obtained by magnetic resonance spectroscopy. Measurements can also be made of cerebral blood flow, cerebral blood volume, and other haemodynamic indices; in addition, the rea

Asphyxia Neonatorum↗

Phosphorus metabolites and intracellular pH in the brains of normal and small for gestational age infants investigated by magnetic resonance spectroscopy.

The brains of 30 normal preterm and term infants whose birth wt were appropriate for gestational age and 13 who were small for gestational age but healthy were studied by phosphorus magnetic resonance spectroscopy to determine values for metabolite concentration ratios and intracellular pH. In the AGA infants, phosphocreatine/inorganic orthophosphate increased between 28 and 42 wk of gestational plus postnatal age, suggesting a rise in the phosphorylation potential of brain tissue. At the same time, the concentration of phosphomonoester (mainly phosphoethanolamine) fell and that of phosphodiester (including phosphatidylethanolamine and phosphatidylcholine) increased. These changes reflected myelination and proliferation of membranes. Intracellular pH was approximately 7.1 and did not change with brain maturation. No differences were detected in these variables between the infants who were small for gestational age and those who were appropriate for gestational age.

Body Fluids↗

Prognosis of newborn infants with hypoxic-ischemic brain injury assessed by phosphorus magnetic resonance spectroscopy.

To investigate the prognostic significance of abnormalities of oxidative phosphorylation, the brains of 61 newborn infants born at 27-42 wk of gestation and suspected of hypoxic-ischemic brain injury were examined by surface-coil phosphorus magnetic resonance spectroscopy. Of these infants, 23 died, and the neurodevelopmental status of the 38 survivors was assessed at 1 y of age. Of the 28 infants whose phosphocreatine/inorganic orthophosphate (PCr/Pi) ratios fell below 95% confidence limits for normal infants, 19 died, and of the nine survivors, seven had serious multiple impairments (sensitivity 74%, specificity 92%, positive predictive value for unfavorable outcome 93%). Of the 12 infants with ATP/total phosphorus ratios below 95% confidence limits 11 died (sensitivity 47%, specificity 97%, positive predictive value 91%). Among the 46 infants with increased cerebral echodensities, PCr/Pi was more likely to be low, and prognosis poor, in infants whose echodensities were diffuse or indicated intraparenchymal hemorrhage than in infants whose echodensities were consistent with periventricular leukomalacia. We conclude that when reduced values for PCr/Pi indicating severely impaired oxidative phosphorylation are found in the brains of infants suspected of hypoxic-ischemic injury, the prognosis for survival without serious multiple impairments is very poor, and that when ATP/total phosphorus is reduced, death is almost inevitable.

Asphyxia Neonatorum↗