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 4774 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. (Pediatr Res 25445-451, 1989) Abbreviations 31P MRS, phosphorus magnetic resonance spectroscopy PCr, phosphocreatine Pi, inorganic orthophosphate PME, phosphomonoester PDE, phosphodiester total P, total mobile phosphorus pHi, intracellular pH BE, base excess SDS, standard deviation score GQ, Griffiths general quotient PVL, periventricular leukomalacia energy metabolism in the brain tissue of newborn infants (1, 2). pH, can also be estimated.In previous investigations, we found that abnormalities indicating abnormal oxidative phosphorylation were detectable in the brain after birth asphyxia (3) and in the presence of cerebral echodensities detected by ultrasound that are associated with various forms of hypoxic-ischemic brain injury (4). In the latter study, it was shown that evidence of severely abnormal oxidative phosphorylation was related to subsequent loss of brain tissue. The purpose of the present investigation was to explore the prognostic significance of abnormalities of oxidative phosphorylation for survival and for neurodevelopmental status at 1 y of age in a group of infants suspected of hypoxic-ischemic brain injury.

In the gestational age range studied, adverse neurodevelopmental outcome depends primarily on the type of the intracranial lesion rather than on gestational age.

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

The study suggests that women with PKU should start a Phe-restricted diet before conception. Maintenance of maternal blood Phe within the target range predicts good offspring outcomes, but variations even within that range should be avoided.

SUMMARY 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. RÉSUMÉ Relaiions entre les aspecis échographiques du cervean chez: les grands prématurés et l'altération dévelopmeriial à huit ans La relation entre I'aspect échographique du cerveau et le devenir neurodévelopmental á láge de huit ans a été recherché chez 206 nourrissons entre 1979 et 1992 à moins de 33 semaines de gestation (poids de naissance 600‐25OOg). Seulement 4 pour cent des 112 nourrissons avec une échographie normale à la sortie de l'unitè de soins intensifs nèonataus préntérent des troubles majeurs, incapacitants. Aucun effet négatif de I'hémorragie périventriculaire non compliquée ne fut détectée. La probabilité d'un trouble majeur chez les enfants avec dilatation ventriculaire ou hydrocéphalie fut de 27 pour cent, et 69 pour cent en cas d'atrophie cérébrale. 44 pour cent des enfants présentérent des differences significatives dans leurs attitudes cognitives. apparaissant capables d'affecter les apprentissages et pouvant avoir été cause par des domrnages hypoxiques ischémiqucs des fibres calleuses ayant passé inaperçus. ZUSAMMENFASSUNG Relation zwischen Ultraschallbefund des Gehirns bei viel zu früh geborenen kindern und entwicklungsneurologischen Störungen im Alter VON acht Jahren Bei 206 Kindern, die zwischen 1979 und 1992 mit einem Gestationsalter von < 33 Wochen geboren wurden (Geburtsgewicht 600‐2500g), wurde die Relation zwischen Ultraschallbefund des Gchirns und entwicklungsneurologischem Outcome im Alter von acht Jahren untersucht. Nur 4 Prozent der 112 Kinder mit normalen Befunden bei der Entlassung von der Neugeborenenstation entwickclten schwerwiegende Behinderungen. Unkomplizierte periventrikuläre Blutungen hatten keinc signifikanten negativen Folgen. Bei Kindern mit Ventrikelerweiterung oder Hydrozephalus betrug die Wahscheinlichkeit einer schweren Störung 27 Prozent und bei Kindern mit cerebraler Atrophic 69 Prozent. 44 Prozent der Kinder wiesen signifikante Unterschiede bei der kognitiven Verarbeitung auf, was einen möglichen Einfluβ auf das Lernen hatte und was vielleicht durch eine nicht erkannte hyposämisch‐ischämische Schädigung der Fasern des Corpus calosum. RESUMEN Relación entre el aspeclo del cerebro a los ultrasonidos en lactantes muy a pretér...