J Baudin

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

ABSTRACT: 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 hypoxicischemic injury, the prognosis for survival without serious multiple impairments is very poor, and that when ATP/ total phosphorus is reduced, death is almost inevitable.

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 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

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 probabilité 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 probabilité 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.

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.

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.

INCREASED PERIVENTRICULAR ECHCDENSITIES IN VERY PRETERM INFANTS AND PREDICTION OF EARLY NEURCDEVELOPMENTAL OUTCOME

Increased periventricular echodensities in preterm infants appear usually to be transient, but occasionally evolve into cystic periventricular leukomalacia. The purpose of this investigation was to find out whether the detection of increased echodensities improved the prognostic significance of abnormalities detected in the brain of very preterm infants by ultrasound scanning. In 1983, the brains of 122 infants born at less than 33 weeks of gestation who were admitted to the Neonatal Unit of University College Hospital were repeatedly scanned. Classification of the results was as previously described (1), but in addition the absence (n=103) or presence (n=19) and degree (+ or ++) of increased periventricular echodensities was noted. Neurodevelopmental assessments (1) were performed on all the infants at 1 year of age. The table shows the prevalence of neurodevelopmental abnormalities (including both major and minor abnormalities) at follow-up.The results provided no evidence that the presence of increased periventricular echodensities aided the assignment of prognosis.1. Stewart AL et al. Arch Dis Child 1983; 58: 598-604.

107 MOTOR TESTS OF INTERHEMISPHERIC CONTROL AND COGNITIVE FUNCTION IN VERY PRETERM INFANTS AT EIGHT YEARS

We have previously reported that damage to the posterior corpus callosum might explain some of the subtle cognitive processing deficits found later in many preterm infants. To test this hypothesis we carried out motor tests of interhemispheric control in 197 consecutively examined very preterm infants(<33 weeks gestation) at eight years. In addition to the Kaufman Assessment Battery for Children (K-ABC) and other studies, two tests of mirrorwise(Tm) and alternate(Ta) forearm diadochokinetic (pronation-supination) movements were performed. The alternate movement represents the most complicated form of interhemispheric control and reciprocal inhibition. The time difference between the two movements (Ta-Tm) is considered to give an indication of the efficiency of transfer of motor information between the hemispheres (particularly the posterior corpus callosum). There was a significant and linear relation between this time difference and the Kaufman Mental Processing Composite (K-MPC) score (p<0.002, DF 2). We conclude that the corpus callosum has an important role in cognitive development and posterior corpus callosum efficiency is related to cognitive outcome.

40 ULTRASOUND BRAIN-SCANS IN VERY PRETERM INFANTS AND OUTCOME AT 18 MONTHS AND 4 YEARS OF AGE

We have previously reported close associations between the results of ultrasound brain-scans in infants born at less than 33w gestation and their neurodevelopmental status at 18 months of age (Stewart AL et al, Arch Dis Child 1983; 58: 598-604). To find out whether this status had changed at 4 years, neurological examinations and tests of cognitive function were carried out (see table).In general, neurodevelopmental status at 18 months was substantiated at 4 years. Disorders recognised at 4 years in previously unaffected infants included deficits of vision and of cognitive function, behavioural disorders and epilepsy. 4 infants no longer had minor disorders but as a group infants assigned this status at 18 months (usually because of abnormalities of tone and reflexes) scored worse on tests of cognitive function than infants considered to be normal at 18 months.

49 NEUROLOGICAL IMPAIRMENT AT ONE YEAR PREDICTS NEUROLOGICAL AND COGNITIVE OUTCOME AT EIGHT YEARS IN VERY PRETERM INFANTS

We have previously reported the prediction of neurodevelopmental outcome at 4 years from the results of neurodevelopmental assessment at one year in a cohort of very preterm (<33 weeks) infants (1). At one year infants were classified by ihe presence of neurological impairment (major, with disability; minor, without disability) and the results of developmental testing (DQ). To investigate prediction ai 8 years, 95% of the cohort were re-examined at a mean age of 98 (SD ±4) months with clinical and neurological examinations, tests of hearing, vision, visuo-motor integration (Beery), cognitive functioning (WISC-R, K-ABC) and school achievement (K-ABC). The main results were:Multiple regression analysis showed that neurological impairment at one year was a highly significant independent predictor of outcome at 8 years (p<0.001) whereas DQ at one year was not.1. Stewart el al., Dev Med Child Neurol. 1988;30:53-63