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Biomedical subjects

A M Costello

Publications and source records attributed to A M Costello.

At least 37 records · Page 2Linked to original sources

Hypoglycaemia: a common problem among uncomplicated newborn infants in Nepal.

Among a cross-sectional sample (stratified by weight and age after birth) of 226 uncomplicated term newborns from the delivery and postnatal wards of a busy government maternity hospital in Kathmandu, the period prevalence of hypoglycaemia (corrected blood glucose of < 2.6 mmol/l) during the first 50 hours after birth was 38 per cent. (This compares with a reported prevalence rate of 12 per cent from studies of uncomplicated term newborns in the UK.) Hypothermia, young maternal age, low birth weight and early sampling after birth were independent risk factors for hypoglycaemia. Of 31 infants studied longitudinally during the same period, 27 (87 per cent) had at least one blood glucose measurement of < 2.6 mmol/l and 25 (81 per cent) a rectal temperature of < 35.5 degrees C. Fourteen infants (44 per cent) had three or more episodes of hypoglycaemia and seven infants (22 per cent) had three or more episodes of hypothermia. Hypoglycaemia is a common, preventable and neglected problem in many maternity hospitals in developing countries. Simple low-cost measures to reduce the incidence of hypoglycaemia may have a major impact on early infant mortality and neurodevelopmental sequelae of perinatal origin.

Adolescent↗

Development of IgG responses to mycobacterial antigens.

Recent studies link mycobacterial and human heat shock protein antigens with autoimmune diseases. Little is known about the development of antibody responses to these antigens in children. IgG responses to mycobacterial antigens were studied in children living in the UK (an environment low in mycobacteria) who had not received BCG vaccination. Age curves of IgG response to sonicates from different species of mycobacteria were similar suggesting that the greater part of the developing IgG response is to the common antigens shared by all mycobacteria. The major part of the IgG response was to carbohydrate antigens: lipoarabinomannan is a mycobacterial cell wall carbohydrate and was confirmed as a major immunodominant antigen. Infants showed a marked early response to the mycobacterial 65 kilodalton (kDa) and 70 kDa heat shock proteins, but not to the human 65 kDa heat shock protein. The early IgG response to heat shock proteins may reflect cross reactivity to proteins released by a wide variety of bacteria (possibly from breakdown in the gut) or recognition of other immunodominant antigens with high levels of cross reactivity to self.

Age Factors↗

Relationship between neurodevelopmental status of very preterm infants at one and four years.

The neurodevelopmental status of 171 very preterm infants was assessed at one and four years of age. At one year 17 had major impairments and 14 had minor ones. At four years the numbers had increased to 25 with major and 25 with minor impairments. Infants with no impairments at one year had a 4 per cent probability of a major impairment at four years, whereas infants with a major impairment had a 94 per cent probability. Infants who later proved to have major neuromotor impairments had been accurately identified at one year, as had infants with sensorineural hearing-loss. Infants with minor impairments of tone and reflexes at one year did not develop cerebral movement disorder, but as a group their scores on tests of cognitive functioning were low. An additional group of infants with cognitive impairments was identified who were unimpaired at one year. The emergence of cognitive deficits largely accounted for the increase in impairments between one and four years.

Child, Preschool↗

Growth velocity and stunting in rural Nepal.

In a community based study, height and weight increments of 441 Nepali children aged 0-6 years were measured before harvest and six months later and compared with centile standards derived from American children. Low mean growth velocities for height were found only in children under 2 years of age, and for weight during the first 18 months. The mean height for age standard deviation score for the 12-23 months age group was already -2.8 at first measurement. The effect of the initial thinness of the child on subsequent height and weight velocity was reciprocal: thin children seemed to catch up weight at the expense of height. These results suggest that stunting is caused largely by a reduced growth velocity during the nutrition dependent infantile phase of growth, with some additional impairment and delay in onset of the early childhood phase of growth hormone dependent growth, especially in thin children. Nutritional interventions after the second year of life are unlikely to alter the prevalence of linear growth retardation in poor communities. Growth velocity may be more useful than static anthropometry to assess the impact of such interventions.

Age Factors↗

Prediction in very preterm infants of satisfactory neurodevelopmental progress at 12 months.

This study was performed to find out how well ultrasound brain-scanning and neurological examination of very preterm infants, together and separately, predicted normal neurodevelopmental progress at 12 months corrected age. 111 infants born at less than 33 weeks gestation were scanned at discharge from the neonatal unit, and neurological examinations were performed at a gestation-equivalent age at or near term. During the first year of life repeated neurological and developmental testing was carried out. At 12 months a diagnosis of normal progress or of major or minor neurodevelopmental disorders was made. 56 (50 per cent) infants with both a favourable ultrasound scan and normal neurological findings had a 98 per cent (90 to 99 per cent) probability of normal progress at 12 months, and a 100 per cent (93 to 100 per cent) probability of having no major disorder. Separately, ultrasound scanning and neurological examination were not such good predictors of normal outcome, although they selected larger groups of infants with high probabilities of progressing normally. Ultrasound brain-scanning and neurological examination can be used in combination to identify potentially normal preterm infants when they are discharged to their homes.

Central Nervous System↗

Precision of ultrasound diagnosis of pathologically verified lesions in the brains of very preterm infants.

Abnormalities detected by a mechanical sector scanner were compared 'blind' with autopsy findings in the brains of 56 infants born at less than 33 weeks gestation. Intraventricular haemorrhage was found in 53 of 112 hemispheres and had been accurately diagnosed by ultrasound (sensitivity 91 per cent; specificity 81 per cent). Isolated germinal layer haemorrhage was less successfully identified (sensitivity 61 per cent; specificity 78 per cent); false-positive diagnoses were partly due to difficulty in distinguishing haemorrhage from the normal choroid plexus in extremely preterm infants. Haemorrhagic parenchymal lesions were correctly identified in nine infants (sensitivity 82 per cent; specificity 97 per cent). Only 11 of 39 hemispheres with histological evidence of hypoxic-ischaemic injury, without marked bleeding, were correctly identified by ultrasound (sensitivity 28 per cent), mainly because of failure to detect small areas of periventricular leucomalacia and diffuse gliosis. 10 hemispheres with periventricular echodensities thought to represent leucomalacia showed no histological evidence of hypoxic-ischaemic injury (specificity 86 per cent). Ventricular dilatation in seven infants was always associated with evidence of hypoxic-ischaemic injury at autopsy.

Brain↗

Prediction of neurodevelopmental impairment at four years from brain ultrasound appearance of very preterm infants.

The neurodevelopmental status of 171 very preterm infants whose brains had been scanned prospectively with ultrasound was assessed blind at four years using a wide range of tests, including tests of cognitive function. Highly significant correlations were found between the ultrasound appearance of the brain and outcome. The probability of a major neurodevelopmental impairment among the 137 children who had a normal ultrasound scan or uncomplicated periventricular haemorrhage at discharge from the unit was 7 per cent; and for any neurodevelopmental impairment (major plus minor) it was 22 per cent. The probabilities for major, or any, neurodevelopmental impairment among the 18 children who had ventricular dilatation were 33 and 50 per cent, respectively; and for the 16 with hydrocephalus and/or cerebral atrophy (loss of brain-tissue from any cause) the probabilities were 56 and 69 per cent. Impairments predicted from lesions detected by ultrasound were largely neurological. There was no evidence that cognitive impairments could be predicted among infants free of neurological impairments.

Atrophy↗

Probability of neurodevelopmental disorders estimated from ultrasound appearance of brains of very preterm infants.

The neurodevelopmental status of 342 very preterm infants who had undergone prospective ultrasound brainscans was assessed at a median corrected age of 52 weeks. The probabilities for neurodevelopmental disorders were calculated according to the ultrasound findings. The results showed that the probability of a major or minor disorder was low for infants whose scans did not show periventricular haemorrhage or markedly increased parenchymal echodensities in the first week of life, and for those whose scans at discharge gave no evidence of ventricular dilatation, hydrocephalus or cerebral atrophy. By contrast, the probability of a disorder was very high for infants with markedly increased parenchymal echodensities in the first week, and for infants with evidence of cerebral atrophy at discharge. The majority of the infants could be assigned, on the basis of the ultrasound scan at discharge, either to a large group who were at low risk of neurodevelopmental disorders or to a small group who were at high risk; the remainder were at intermediate risk. These findings may be used as a guide to the prognosis for other infants whose ultrasound scans show similar appearances.

Atrophy↗

Brain intracellular pH and metabolism during hypercapnia and hypocapnia in the new-born lamb.

1. The effects of hypercapnia and hypocapnia on brain intracellular pH (pHi) and metabolism were investigated in new-born lambs under barbiturate anaesthesia. 2. 31P nuclear magnetic resonance (n.m.r.) spectroscopy was used to determine brain pHi and the relative concentrations of compounds containing mobile phosphorus nuclei including phosphocreatine (PCr), nucleoside triphosphates (NTP) and inorganic phosphate (Pi). Simultaneous measurements were made of the molar ratio of glucose to oxygen uptake by the brain. 3. During normocapnia (arterial partial pressure of CO2 Pa, CO2, 39 +/- 1 mmHg mean +/- S.E. of mean, n = 9) brain pHi was 7.13 +/- 0.02. Hypercapnia (Pa, CO2, 98 +/- 3 mmHg) was associated with a fall in brain pHi to 6.94 +/- 0.03 (n = 19, P less than 0.001), whereas no significant change in brain pHi occurred during hypocapnia (Pa, CO2, 16 +/- 1 mmHg; brain pHi 7.15 +/- 0.01). 4. During hypercapnia there was an increase in the ratio of Pi to NTP from 1.09 +/- 0.08 to 1.47 +/- 0.06 (P less than 0.001) and a decrease in the ratio PCr/Pi from 1.60 +/- 0.08 to 0.93 +/- 0.04 (P less than 0.001). There was a linear correlation between Pi/NTP and brain pHi. 5. Alterations in arterial PCO2 had no significant effect on the molar ratio of glucose to oxygen uptake by the brain, which remained close to unity. 6. The change in brain pHi observed during hypercapnia can be accounted for by the known physico-chemical buffering capacity of brain tissue. Homoeostasis of brain pHi during hypocapnia provides further evidence that additional regulatory mechanisms operate in these circumstances. 7. The observed changes in PCr and Pi can be accounted for in part by the [H+] dependence of the creatine kinase reaction.

Animals↗

Cerebral energy metabolism studied with phosphorus NMR spectroscopy in normal and birth-asphyxiated infants.

Phosphorus (31P) nuclear magnetic resonance spectroscopy was used to study intracellular metabolism in the brains of 6 normal newborn infants and 10 infants who had been asphyxiated during delivery. In the normal infants spectral peaks mainly attributable to adenosine triphosphate, phosphocreatine (PCr), phosphodiesters plus phospholipids, and inorganic orthophosphate (Pi) were always detected, together with an additional large peak in the phosphomonoester region indicating the presence of a metabolite or metabolites (probably largely phosphoethanolamine) which may be involved in rapid growth of the brain. In the asphyxiated infants, data obtained on the first day of life showed no differences from those in normal infants, but by the second to ninth days inverse changes in the concentrations of PCr and Pi had caused a significant reduction in PCr/Pi. This latency suggest the possibility of effective early treatment before irreversible metabolic damage sets in. Mean intracellular pH when PCr/Pi was minimal was 7.17 +/- 0.10. Values for PCr/Pi below 0.80 were associated with a very bad prognosis for survival and early neuro-developmental outcome.

Adenosine Diphosphate↗