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OBJECTIVE. The absence of cerebral autoregulation in preterm infants has been associated with adverse outcome, but its bedside assessment in the immature brain is problematic. We used spatially resolved spectroscopy to continuously measure cerebral oxygen saturation (expressed as a tissue-oxygenation index) and used the correlation of tissue-oxygenation index with spontaneous fluctuations in mean arterial blood pressure to assess cerebral autoregulation. PATIENTS AND METHODS. The tissue-oxygenation index and mean arterial blood pressure were continuously measured in very premature infants (n = 24) of mean (±SD) gestational age of 26 (±2.3) weeks at a mean postnatal age of 28 (±22) hours. The correlation between mean arterial blood pressure and tissue-oxygenation index in the frequency domain was assessed by using cross-spectral analysis techniques (coherence and transfer-function gain). Values of coherence reflect the strength of linear correlation, whereas transfer-function gain reflects the amplitude of tissue-oxygenation index changes relative to mean arterial blood pressure changes. RESULTS. High coherence (coherence ≥ 0.5) values were found in 9 infants who were of lower gestational age, lower birth weight, and lower mean arterial blood pressure than infants with coherence of CONCLUSIONS. High coherence between mean arterial blood pressure and tissue-oxygenation index indicates impaired cerebral autoregulation in clinically sick preterm infants and is strongly associated with subsequent mortality. Cross-spectral analysis of mean arterial blood pressure and tissue-oxygenation index has the potential to provide continuous bedside assessment of cerebral autoregulation and to guide therapeutic interventions.

INTRODUCTION. Very preterm birth (VPT; METHODS. We assessed 108 VPT individuals and 67 term-born controls at ages 18 to 19 years with the Eysenck Personality Questionnaire-Revised, short form (EPQ-RS). This questionnaire rates 3 dimensions of personality: extraversion (sociability, liveliness, sensation seeking); neuroticism (anxiety, low mood, low self-esteem); and psychoticism (coldness, aggression, predisposition to antisocial behavior). A fourth scale, “lie,” which measures dissimulation, is also derived. RESULTS. VPT individuals had significantly lower extraversion scores, higher neuroticism scores, and higher lie scores than term-born controls, after controlling for age at assessment and socioeconomic status. P scores were not significantly different between the 2 groups. There was a gender difference in that the increased neuroticism and decreased extraversion scores were accounted for mainly by VPT females. Associations between EPQ-RS scores and neonatal status, adolescent behavioral ratings, and body size at 18 to 19 years were assessed by using Kendall partial correlations, correcting for age at assessment and socioeconomic status. Gestational age, indices of neonatal hypoxia, and neonatal ultrasound ratings were not correlated with EPQ-RS scores. Birth weight was weakly associated with increased lie scores. Rutter Parents' Scale score, a measure of adolescent psychopathology, was associated with an increased neuroticism score. Poor social adjustment in adolescence was associated with an increased lie score. Height and weight at 18 to 19 years were not associated with EPQ-RS, but reduced occipitofrontal circumference was associated with both decreased extraversion and increased lie scores. CONCLUSIONS. Young adults who are born VPT have different personality styles from their term-born peers. This may be associated with an increased risk of psychiatric difficulties.

OBJECTIVE. The goal of this study was to evaluate the role of factors that may determine the efficacy of treatment with delayed head cooling and mild systemic hypothermia for neonatal encephalopathy.METHODS. A total of 218 term infants with moderate to severe neonatal encephalopathy plus abnormal amplitude-integrated electroencephalographic recordings, assigned randomly to head cooling for 72 hours, starting within 6 hours after birth (with the rectal temperature maintained at 34.5 ± 0.5°C), or conventional care, were studied. Death or severe disability at 18 months of age was assessed in a multicenter, randomized, controlled study (the CoolCap trial).RESULTS. Treatment, lower encephalopathy grade, lower birth weight, greater amplitude-integrated electroencephalographic amplitude, absence of seizures, and higher Apgar score, but not gender or gestational age, were associated significantly with better outcomes. In a multivariate analysis, each of the individually predictive factors except for Apgar score remained predictive. There was a significant interaction between treatment and birth weight, categorized as ≥25th or CONCLUSIONS. Outcomes after hypothermic treatment were strongly influenced by the severity of neonatal encephalopathy. The protective effect of hypothermia was greater in larger infants.

OBJECTIVES. The goals were to develop safe 4.7-T MRI examination protocols for newborn infants and to explore the advantages of this field strength in neonatal encephalopathy. METHODS. Nine ventilated newborn infants with moderate or severe encephalopathy were studied at 4.7 T, with ethical approval and informed parental consent. The custom-made, 4.7-T-compatible, neonatal patient management system included acoustic noise protection and physiologic monitoring. An adult head coil was used. Acquisition parameters for T2-weighted fast spin echo MRI and a variety of T1-weighted methods were adapted for MRI of neonatal brain at 4.7 T. The pulse sequences used had a radiofrequency specific absorption rate of RESULTS. Physiologic measures were normal throughout each scan. T2-weighted fast spin echo imaging provided better anatomic resolution and gray/white matter contrast than typically obtained at 1.5 T; T1-weighted images were less impressive. CONCLUSIONS. With appropriate safety precautions, MRI of newborn infants undergoing intensive care is as feasible at 4.7 T as it is at 1.5 T; our initial studies produced T2-weighted fast spin echo images with more detail than commonly obtained at 1.5 T. Although T1-weighted images were not adequately informative, additional pulse sequence optimization may be advantageous. A smaller neonatal head coil should also permit greater flexibility in acquisition parameters and even more anatomic resolution and tissue contrast. In neonatal encephalopathy, interpretation of the T2-weighted pathologic detail in combination with comprehensive neurodevelopmental follow-up should improve prognostic accuracy and enable more patient-specific therapeutic interventions. In addition, more precise relationships between structural changes and functional impairment may be defined.

OBJECTIVE. We sought to compare the prognostic utilities of early MRI spin-spin relaxometry and proton magnetic resonance spectroscopy in neonatal encephalopathy. METHODS. Twenty-one term infants with neonatal encephalopathy were studied at a mean age of 3.1 days (range: 1–5). Basal ganglia, thalamic and frontal, parietal, and occipital white matter spin-spin relaxation times were determined from images with echo times of 25 and 200 milliseconds. Metabolite ratios were determined from an 8-mL thalamic-region magnetic resonance spectroscopy voxel (1H point-resolved spectroscopy; echo time 270 milliseconds). Outcomes were assigned at age 1 year as follows: (1) normal, (2) moderate (neuromotor signs or Griffiths developmental quotient of 75–84), (3) severe (functional neuromotor deficit or developmental quotient RESULTS. Thalamic and basal ganglia spin-spin relaxation times correlated positively with outcome and predicted adversity. Although thalamic and basal ganglia spin-spin relaxation times were prognostic of adversity, magnetic resonance spectroscopy metabolite ratios were better predictors, and, of these, lactate/N-acetylaspartate was most accurate. CONCLUSIONS. Deep gray matter spin-spin relaxation time was increased in the first few days after birth in infants with an adverse outcome. Proton magnetic resonance spectroscopy was more prognostic than spin-spin relaxation time, with lactate/N-acetylaspartate the best measure. Nevertheless, both techniques were useful for early prognosis, and the potential superior spatial resolution of spin-spin relaxometry may define better the precise anatomic pattern of injury in the early days after birth.

OBJECTIVES. Fundamental questions remain about the precise temperature providing optimal neuroprotection after perinatal hypoxia-ischemia (HI). Furthermore, if hypothermia delays the onset of the neurotoxic cascade and the secondary impairment in cerebral energy generation, the “latent phase” may be prolonged, thus extending the period when additional treatments may be effective. The aims of this study were to investigate the effects of delayed systemic cooling at either 33°C or 35°C on the following: (1) latent-phase duration, and (2) cerebral metabolism during secondary energy failure itself, in the 48-hour period after transient HI. METHODS. Piglets were randomly assigned to the following: (1) HI-normothermic (HI-n) rectal temperature (Trectal; n = 12), (2) HI-Trectal 35°C (HI-35; n = 7), and (3) HI-Trectal 33°C (HI-33; n = 10). Groups were cooled to the target Trectal between 2 and 26 hours after HI. Serial magnetic resonance spectroscopy was performed over 48 hours. The effect of cooling on secondary energy failure severity (indexed by the nucleotide triphosphate/exchangeable phosphate pool [NTP/EPP] and phosphocreatine/inorganic phosphate [PCr/Pi] ratios) was assessed. RESULTS. Compared with HI-n, HI-35 and HI-33 had a longer NTP/EPP latent phase and during the entire study duration had higher mean NTP/EPP and PCr/Pi. The latent phase (both PCr/Pi and NTP/EPP) and the whole-brain cerebral energetics were similar for HI-35 and HI-33. During the hypothermic period, compared with HI-n, PCr/Pi was preserved in the cooled groups, but this advantage was not maintained after rewarming. Compared with HI-n, HI-35 and HI-33 had higher NTP/EPP after rewarming. CONCLUSIONS. Whole-body hypothermia for 24 hours at either 35 or 33°C, commenced 2 hours after resuscitation, prolonged the NTP/EPP latent phase and reduced the overall secondary falls in mean PCr/Pi and NTP/EPP during 48 hours after HI. Reducing the temperature from 35 to 33°C neither increased mean PCr/Pi and NTP/EPP nor further lengthened the latent phase.

Objectives. To investigate the effect of gestational age at birth on the frequency of ultrasound-detected brain lesions in infants born at Methods. Eight hundred forty-seven infants born at Results. Hemorrhagic lesions such as germinal matrix/intraventricular hemorrhage and hemorrhagic parenchymal infarction were more frequent in infants born at Conclusion. In the gestational age range studied, adverse neurodevelopmental outcome depends primarily on the type of the intracranial lesion rather than on gestational age.

“Sarah Parks … gave still-birth to a baby boy … A young doctor assisting the Parks' regular physician begged for an opportunity to experiment with an idea he had to rouse the lifeless infant. A tub of ice was ordered and the young doctor plunged the baby into it. Out came the screaming little Parks and he was named Gordon after the doctor who prodded him to life.”—Sir John Floyer, 1697 As this quotation shows, the use of cold water to stimulate the onset of respiration in depressed newborn infants has a long history. However, it was James Miller from New Orleans and Bjorn Westin from Stockholm who in the 1950s developed a scientific rationale for the use of hypothermia in “asphyxia neonatorum.” In a series of animal studies they demonstrated that rapid cooling in asphyxia prolonged survival by allowing the establishment of an equilibrium between cerebral oxygen demand and supply (reviewed in reference 1). They followed this in 1958 with a striking clinical study involving 10 severely depressed term infants.2,3 The infants all had Apgar scores of 1 at birth and they had failed to respond to conventional methods of resuscitation available at that time. The apneic infants were immersed in a specially constructed cold water bath with the aim of reducing core temperature rapidly. Cooling was stopped when spontaneous respirations commenced or when the rectal temperature approached 27°C. In 4 infants transfusions of oxygenated blood were also administered. The infants were then dried and allowed to rewarm spontaneously. One of the 10 infants died due to hyaline membrane disease but the remaining 9 survived, despite minimum core …

At the Toronto meeting of the American Academy of Pediatrics it was suggested that the Surgical Section be responsible for a portion of the program at the next annual meeting, the presentations to be in the form of a symposium. Articles relating to surgical conditions in infants and children frequently appear in current medical literature presenting opinions which are often divergent, or even conflicting, and members of the Academy have often commented on this apparent confusion. It seemed timely, therefore, to select several of the more common of these conditions and assign each to a member of the Surgical Section for a discussion which might reasonably be expected to represent one of the views more generally accepted by surgeons primarily interested in children. Complete unanimity is of course not to be expected nor desired, as an honest difference of opinion promotes healthy discussion and progress. Several of the comments on the presentations indicated that panel discussions on some of the subjects would be most interesting and might well be included in future programs. The close attention and favorable reaction of the audience was most gratifying, and it was regrettable that Dr. Potts who planned and coordinated the Symposium was prevented by illness from acting as chairman. Illness also prevented Dr. Wilkinson from presenting his discussion on "Bronchiectasis" but fortunately his time could be made available for the Honorary Life President of the Surgical Section, Dr. William E. Ladd, whose excellent address will be long remembered by all who heard it.