S Roth

Delayed ("secondary") cerebral energy failure after acute hypoxia-ischemia in the newborn piglet: continuous 48-hour studies by phosphorus magnetic resonance spectroscopy

ABSTRACT: Phosphorus (31P) spectra from the brains of severely birth-asphyxiated human infants are commonly normal on the first day of life. Later, cerebral energy failure develops, which carries a serious prognosis. The main purpose of this study was to test the hypothesis that this delayed (“secondary”) energy failure could be reproduced in the newborn piglet after a severe acute reversed cerebral hypoxicischemic insult. Twelve piglets were subjected to temporary occlusion of the common carotid arteries and hypoxemia [mean arterial Po2 3.1 (SD 0.6) kPa]. Mean cerebral phosphocreatine concentration [PCr]/inorganic orthophosphate concentration [Pi] decreased from 1.40 (SD 0.29) to 0.01 (SD 0.02), and nucleotide triphosphate concentration [NTP]/exchangeable phosphate pool concentration [EPP] decreased from 0.19 (SD 0.02) to 0.06 (SD 0.04) (p<0.001 for each decrease). On reperfusion and reoxygenation of the brain, mean [PCr]/[Pi] and [NTP]/[EPP] returned to baseline. Observations continuing for the next 48 h showed that [PCr]/[Pi] again decreased, in spite of normal arterial Po2, mean arterial blood pressure, and blood glucose, to 0.62 (SD 0.61) at 24 h (p<0.01) and 0.49 (SD 0.37) at 48 h (p<0.001). [NTP]/[EPP] also decreased, but to a lesser degree. Intracellular pH remained unchanged. These findings appeared identical with those seen in birth-asphyxiated human infants. No changes in cerebral metabolite concentrations took place in six control piglets. The severity of secondary energy failure, as judged by the lowest [PCr]/[Pi] recorded at 24-48 h, was directly related to the extent of acute energy depletion, obtained as the time integral of reduction in [NTP]/[EPP] (p<0.0001). This animal model of secondary energy failure may prove useful for testing cerebroprotective strategies.

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.

RELATION BETWEEN ULTRASOUND APPEARANCE OF THE BRAIN OF VERY PRETERM INFANTS AND NEURODEVELOPMENTAL IMPARIMENT AT EIGHT YEARS

The relation between the ultrasound appearance of the brain and neurodc.velopmenial outcome aT eight years oi age was investigated in 206 infants born berwecn 1979 and 1992 at <3 3 wecks gestation (600 to ZSOOg birthweights). Only 4 prr cent of the 112 infants with normal scans at discharge from the neonatal unir developed major. disabling impairment. No signiiicant adverse effect of uncomplicated periventricular haemorrhage was detected. The probability of a major impairment in infants with ventricular dilatation or hydroccphalus was 27 per cent, and 69 per cent in those with cerebral atrophy. 4‐1 per cent of the children demonstrated significant differcnccs in their cognitive processing skills, which appeared capable of affecting learning and may possibly habc been caused by undetected hyposic‐ischaemic damage 10 callosal fibres.

Relation of deranged neonatal cerebral oxidative metabolism with neurodevelopmental outcome and head circumference at 4 years

Cerebral oxidative metabolism was studied using phosphorus magnetic resonance spectroscopy during the first week of life and neurodevelopmental outcome was assessed at 4 years in 62 infants who had clinical and/or biochemical evidence consistent with birth asphyxia (critically impaired intrapartum gas exchange). Twenty‐one died and the neurodevelopmental status of the 41 who survived was assessed by a range of tests at age 4 years. The minimum recorded values for the cerebral phosphocreatine:inorganic phosphate concentration ratio (an index of oxidative metabolism) were related to outcome. The results showed significant relations between the extent of derangement of neonatal oxidative metabolism and a range of adverse outcomes, including death, and at 4 years reduced head growth and the presence and severity of neuromotor impairments, overall neurodevelopmental impairments, and cognitive functioning. Strong correlations between the extent of derangement of neonatal oxidative metabolism and outcome at 1 and 4 years were also shown. We conclude that the severities of adverse outcomes at 1 and 4 years of age were closely related to the extent of cerebral energy derangement in the first week of life, and we also conclude that primary intrapartum hypoxic‐ischaemic cerebral injury was generally responsible for the events that led to death, microcephaly, and impaired

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.

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 · 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 · 100 g-1. Alterations in CBV also occurred ranging from −0.44 to 0.40 (median 0) mL · 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 · min-1, respectively (n = 9); for mean cerebral oxygen delivery, values were 2.71 (0.89) and 3.15 (0.73) mL · 100 g-1 · 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 · 100 g-1 · kPa-1 (n = 16); these changes were not statistically significant. We conclude that (1) surfactant administration caused small, transient perturbations in cerebral oxyhemoglobin concentration and CBV, and (2) no important alterations in cerebral blood flow, cerebral oxygen delivery, or response of CBV to changes in arterial carbon dioxide tension were detected.

The neurodevelopmental outcome of term infants with different intrauterine growth characteristics

The objective of this study was to test the hypothesis that neurodevelopmental outcome would differ between two groups of small-for-gestational age infants born at term showing different in utero growth characteristics during the third trimester. The design was a prospective cohort study done at a tertiary referral centre. The 76 subjects who fulfilled the inclusion criteria had an estimated fetal weight below the 10th centile for their gestation. Subsequent to enrolment, repeat ultrasound scans were performed weekly to determine growth velocity. Twenty-three infants whose change in fetal abdominal circumference between first and last scan was greater than -1.5 standard deviation scores (SDS) were assigned to the intrauterine growth retardation group (IUGR) while 53 infants whose fetal abdominal circumference changed less than 1.5 SDS were assigned to the small-for-gestational-age (SGA) group. Ten infants with normal intrauterine growth were enrolled as controls. Following delivery all infants had a neurological examination and a cranial ultrasound scan. At 1 year, 75 infants (87%) were traced and reassessed (49 SGA, 18 IUGR and eight controls) with a neurological examination and a developmental assessment. At birth, impairments were found in 27 (51%) of the SGA, 13 (57%) of the IUGR groups and one (10%) of the controls. At 1 year, 18 (37%) of the SGA subjects, six (33%) of the IUGR subjects and one (13%) of the control infant were impaired, including three (6%) of the SGA subjects and one (6%) of the IUGR subjects who were disabled. We conclude that in term fetuses with an estimated birthweight below the 10th centile for their gestation, the pattern of growth in the third trimester does not affect outcome at 1 year. In spite of optimum obstetric management, nearly one-third of the combined SGA and IUGR term fetuses had suffered some, albeit minor, neurological damage.

Neurodevelopmental status at 1 year predicts neuropsychiatric outcome at 14–15 years of age in very preterm infants

BACKGROUND Neurodevelopmental and behavioural problems have been repeatedly reported in very preterm survivors, often showing themselves later in childhood as poor school performance. Early identification of problems would mean that appropriate remedial therapy can be implemented. We have previously shown that neurodevelopmental status at 1 year was predictive of outcome at 8 years in a cohort of preterm infants. The aim of this paper was to see if neurodevelopmental outcome in adolescence could be predicted by assessment by 1 year in the same cohort of preterm infants. STUDY DESIGN Prospective cohort study. SUBJECTS 150 adolescents, born before 33 weeks gestation. OUTCOME MEASURES Neurological examination, developmental quotient, vision and hearing by 1 year. At 14-15 years, neurological examination, school performance questionnaire, Schonnell test of reading age, a premorbid adjustment score, Rutter behavioural score and for those born from 1981, cognitive tests (WISC-R). RESULTS A highly significant relationship existed between neurological status by 1 year and the need for extra educational provision, overall neurodevelopmental status, cognitive function in those that had their IQs measured and premorbid adjustment score of prepsychotic symptoms in adolescence. However, status at 1 year was not predictive of adolescent reading age or behavioural score. CONCLUSIONS Neurodevelopmental assessment at 1 year is predictive of school performance and outcome in the adolescent period.

56 RELATION BETWEEN CEREBRAL HAEMODYNAMICS AND OUTCOME IN BIRTH ASPHYXIATED NEWBORN INFANTS STUDIED BY NEAR INFRARED SPECTROSCOPY (NIRS)

The purpose of this study was to measure cerebral blood flow (CBF), cerebral blood volume (CBV) and its response to changes in arterial carbon dioxide tension (CBVR) by NIRS in 21 term newborn infants who had suffered birth asphyxia. All had clinical and biochemical (base deficit ≥ 15 mmol/l) evidence of asphyxia and were studied during ihc first 24 hours. Eight of the 21 infants died and neurodevelopmental examination in survivors at one year of age showed that 7 had major neurological impairments; the remaining 6 infants were normal or had minor impairments. Results (mean ± SEM) were as follows:Values for CBF and CBV were significantly higher than previously defined normal values and for CBVR lower. The extern of the abnormalities was related to the severity of adverse outcome (ANOVA p<0.05).

Follow-up by questionnaire?

Recently, proposals have been made to include larger numbers of infants and reduce the cost of obtaining follow-up information pertaining to modern perinatal management. These proposals have been made in response to requests from purchasers and providers of health care as well as the obstetricians and neonatologists actively engaged in delivery of the service. These initiatives are welcome, but care must be taken to provide objective, meaningful data. In addition to standardised recording including by questionnaire, standardised data collection designed to identify relevant impairments must be the primary objective; the nature and extent of disability at particular ages can then be assigned but it is misleading to regard disability as the principle outcome measure.