Cerebral glucose metabolism measured by positron emission tomography in term newborn infants with hypoxic ischemic encephalopathy.

Total and regional cerebral glucose metabolism (CMRgl) was measured by positron emission tomography with 2-((18)F) fluoro-2-deoxy-D-glucose ((18)FDG) in 20 term infants with hypoxic ischemic encephalopathy (HIE) after perinatal asphyxia. All infants had signs of perinatal distress, and 15 were severely acidotic at birth. Six infants developed mild HIE, twelve moderate HIE, and two severe HIE during their first days of life. The positron emission tomographic scans were performed at 4-24 d of age (median, 11 d). One hour before scanning, 2-3.7 MBq/kg (54-100 microCi/kg) (18)FDG was injected i.v. No sedation was used. Quantification of CMRgl was based on a new method employing the glucose metabolism of the erythrocytes, requiring only one blood sample. In all infants, the most metabolically active brain areas were the deep subcortical parts, thalamus, basal ganglia, and sensorimotor cortex. Frontal, temporal, and parietal cortex were less metabolically active in all infants. Total CMRgl was inversely correlated with the severity of HIE (p < 0.01). Six infants with mild HIE had a mean (range) CMRgl of 55.5 (37.7-100.8) micromol.min(-1).100 g(-1), 11 with moderate HIE had 26.6 (13.0-65.1) micromol.min(-1).100 g(-1), and two with severe HIE had 10.4 and 15.0 micromol.min(-1).100 g(-1), respectively. Five of six infants who developed cerebral palsy had a mean (range) CMRgl of 18.1 (10.2-31.4) micromol.min(-1).100 g(-1) compared with 41.5 (13.0-100.8) micromol.min(-1).100 g(-1) in the infants with no neurologic sequela at 2 y. We conclude that CMRgl measured during the subacute period after perinatal asphyxia in term infants is highly correlated with the severity of HIE and short-term outcome.

Ten-year follow-up of children born before 29 gestational weeks: health, cognitive development, behaviour and school achievement.

Since the mid-1990s several studies have reported poor school performance in extremely preterm infants. The necessity to provide a full picture of the child's situation has been indicated. In a southern Swedish population 32,120 infants were born during the 2-y period 1985-1986. In total, 121 infants (0.4%) were reported liveborn before the 29th gestational wk and 12 (0.04%) were reported stillborn. Only 65 infants (50%) survived to the age of 10 y. The aim of this study was to evaluate the situation of extremely preterm (EPT) children at school, compared with that of full-term (FT) control children, at the age of 10 y. Health, cognitive development, school achievement and behaviour were measured. Ninety-two percent of the preterm children had no major neurological disability and most were in good health. The EPT children had an IQ of 90 +/- 15 vs 106 +/- 15 (mean +/- SD) for the FT children (p <0.001), and on the test of Visual-Motor Integration, the EPT children had 93.3 +/- 12.2 vs 109.6 +/- 14.2 for FT peers (p < 0.001). On both tests the differences between the groups corresponded to approximately one standard deviation. Thirty-eight percent of the EPT children performed below grade level at school. Thirty-two percent had general behavioural problems and 20% had attention deficit hyperactivity disorder, compared with 10% and 8%, respectively, in the FT group. EPT children require interventions to support their development and reduce behavioural problems.

Early cerebral metabolic and electrophysiological recovery during controlled hypoxemic resuscitation in piglets.

We tested the hypothesis that controlled hypoxemic resuscitation improves early cerebral metabolic and electrophysiological recovery in hypoxic newborn piglets. Severely hypoxic anesthetized piglets were randomly divided into three resuscitation groups: hypoxemic, 21% O2, and 100% O2 groups (8 in each group). The hypoxemic group was mechanically ventilated with 12-18% O2 adjusted to achieve a cerebral venous O2 saturation of 17-23% (baseline; 45 +/- 1%). Base excess (BE) reached -22 +/- 1 mM at the end of hypoxia. During a 2-h resuscitation period, no significant differences in time to recovery of electroencephalography (EEG), quality of EEG at recovery, or extracellular hypoxanthine concentrations in the cerebral cortex and striatum were found among the groups. BE and plasma hypoxanthine, however, normalized significantly more slowly during controlled hypoxemic resuscitation than during resuscitation with 21 or 100% O2. We conclude that early brain recovery during controlled hypoxemic resuscitation was as efficient as, but not superior to, recovery during resuscitation with 21 or 100% O2. The systemic metabolic recovery from hypoxia, however, was delayed during controlled hypoxemic resuscitation.

Hypoxic-ischaemic encephalopathy is associated with regional changes in cerebral blood flow velocity and alterations in cardiovascular function.

Doppler-derived indices of cerebral blood flow velocity (CBFV) and echocardiographic parameters of left ventricular function were measured in 18 patients with hypoxic-ischaemic encephalopathy HIE (group I) and in 28 normal controls (group II). Group-I infants had a subnormal distribution of CBFV values increasing over the first 85 h postnatally. CBFV values were constantly higher in the internal carotid than in the anterior cerebral artery. During the first 24 h postnatally, pulsatility and resistance indices of cerebral blood flow were significantly higher in group-I patients. From 30 to 85 h after birth, resistance indices were lower in group-I infants with severe HIE. Depressed left ventricular function and/or hypotension was documented in 50% of group-I patients.

Changing trend in perinatal management and outcome of extremely low birthweight (ELBW) infants.

Perinatal care of the extremely preterm and low birthweight (ELBW) infant is founded on basic principles of physiology and knowledge about the prevailing pathophysiological mechanisms. New therapies in clinical care are usually introduced non-uniformly, so more often there is a gradual rather than a sudden change in the development of perinatal care, conceivably involving also an important learning process. This was confirmed in an evaluation of respiratory care for ELBW infants (n = 325) over a 9-year period (1986-1994). Although birthweight (mean 815 g) and degree of immaturity at birth (mean 26.7 weeks of gestation) did not change over the years, our trend analysis showed that the survival rate increased from 47% to 70% (p < 0.04) and the percentage of survivors without bronchopulmonary dysplasia and/or major intracranial haemorrhages (ICH grades 3 and 4) increased from 67% to 87% (p < 0.006). We suggest that besides medical treatment per se, refinement and tuning of nursing and medical care procedures will also affect the total outcome of ELBW infants.

Changes in lung volume and static expiratory pressure-volume diagram after surfactant rescue treatment of neonates with established respiratory distress syndrome.

The effect of natural surfactant on respiratory system mechanics in infants with respiratory distress syndrome (RDS) is incompletely understood, possibly because the analysis has usually been confined to the tidal breath. We studied 11 paralyzed neonates weighing 540 to 1,850 g before and approximately 30 min after surfactant, which was instilled at 4 to 41 h of age. Diagrams relating airway pressure to expired volume were obtained by having the infant exhale passively through a flowmeter, starting at 30 and ending at 0 cm H20 of pressure. An interrupter intermittently stopped the flow so that pressure could be recorded under static conditions. FRC was measured by sulfur hexafluoride washout, and TLC was calculated from FRC and the pressure-volume (P-V) curve. Ventilation homogeneity was assessed from the washout curve as pulmonary clearance delay (PCD). TLC increased by 10% or more in five infants, but it remained unchanged in the others. Median TLC was 19 ml/kg before and 21.5 ml/kg after surfactant (p = 0.39). The P-V curve became markedly steeper at low pressures after surfactant in most infants, the slope of the steepest segment, i.e., maximal compliance, increasing from 0.65 to 1.22 ml/cm H20/kg (medians, p = 0.008). Dynamic compliance (Cdyn) was unchanged at 0.28 ml/cm H20/kg, whereas specific dynamic compliance (Cdyn/FRC) decreased (p = 0.04). There was no significant immediate change in PCD. The findings imply that during the first 30 min surfactant acted mainly by stabilizing already ventilated air spaces.

Extremely low-birth-weight infants less than 901 g: development and behaviour after 4 years of life.

In a long-term, prospective, control study, 20 extremely low-birth-weight (ELBW) infants with birth weights between 500 and 900 g (mean 755 (SD 109) g) and gestational ages between 24 and 30 weeks (mean 26.2 (SD 1.8) weeks) were compared with 20 full-term infants at 4 years of age for growth, health, development and quality of life. Four of 20 (20%) ELBW children had major neurological disorders, which were all identified at the 1-year assessment. Seventeen (85%) ELBW children had cognitive development, assessed with the Griffiths mental development scale, within the normal range for age but lower than for full-term controls. The greatest deviations between ELBW and full-term children were found in locomotor and visual-motor integration functions. Eight ELBW children in all (40%), four with recurrent respiratory tract infections after neonatal mechanical ventilation and the four children with major neurological disorders had a higher rate of visits to physicians and hospital admissions. The behavioural symptom interview showed an increased rate of hyperactivity and difficulties in concentrating but not of general behavioural deviations in the ELBW group. Only by school age can all aspects of an extremely early birth be evaluated, but at 4 years of age, 85% of the ELBW children in our group had a good quality of life according to Scheffzek's categorizations.

Low risk of seizure recurrence after early withdrawal of antiepileptic treatment in the neonatal period.

The risk of seizure recurrence within the first year of life was evaluated in infants with neonatal seizures diagnosed with a combination of clinical signs, amplitude-integrated electroencephalogram (EEG) monitoring, and standard EEG. Fifty eight of 283 (4.5%) neonates in tertiary level neonatal intensive care had seizures. The mortality in the infants with neonatal seizures was 36.2%. In 31 surviving infants antiepileptic treatment was discontinued after one to 65 days (median 4.5 days). Three infants received no antiepileptic treatment, two continued with prophylactic antiepileptic treatment. Seizure recurrence was present in only three cases (8.3%)--one infant receiving prophylaxis, one treated for 65 days, and in one infant treated for six days. Owing to the small number of infants with seizure recurrence, no clinical features could be specifically related to an increased risk of subsequent seizures. When administering antiepileptic treatment, one aim was to abolish both clinical and electrographical seizures. Another goal was to minimise the duration of treatment and to keep the treatment as short as possible. It is suggested that treating neonatal seizures in this way may not only reduce the risk of subsequent seizure recurrence, but may also minimise unnecessary non-specific prophylactic treatment for epilepsy.

OSCILLO-oscillating air mattress in neonatal care of very preterm babies.

In this pilot study a new device for respiratory stimulation with undulating oscillations and high frequency vibrations via an air mattress was tested as an additional therapy in 12 preterm infants with recurrent apnoeic episodes. The mean birthweight of the study population was 1760 g and gestational age 31.1 weeks. it was shown that an oscillating air mattress is an effective additional mode of treatment for apnoeic episodes in preterm infants. There was a clear reduction in rate of apnoeas in all 12 infants being transitory in 2 and more persistent in 10 infants. Besides restlessness in a few cases no side effects were observed. Whether this mode of treatment could lessen the need for drug medication with xanthines will require a larger randomized investigation.

Predictive value of early continuous amplitude integrated EEG recordings on outcome after severe birth asphyxia in full term infants.

The background pattern in single channel amplitude integrated EEG recordings (aEEG) was recorded in 47 infants within the first six hours after birth to see if this could predict outcome after birth asphyxia. The aEEG background pattern during the first six hours of life was continuous and of normal voltage in 26 infants. All these infants survived; 25 were healthy, one had delayed psychomotor development. A continuous but extremely low voltage pattern was present in two infants, both of whom survived with severe handicap. Five infants had flat (mainly isoelectric) tracings during the first six hours of life; four died in the neonatal period, and one survived with severe neurological handicap. Burst-suppression pattern was identified in 14 infants, of whom five died, six survived with severe handicap, and three were healthy at follow up. The type of background pattern recorded within the first six postnatal hours in the aEEG tracings predicted outcome correctly in 43 of 47 (91.5%) infants. Use of aEEG monitoring can predict outcome, with a high degree of accuracy, after birth asphyxia, within the first six hours after birth. The predictive value of a suppression-burst pattern was, however, somewhat lower than the other background patterns. The aEEG seems to be a feasible technique for identifying infants at high risk of subsequent brain damage who might benefit from interventionist treatment after asphyxia.

Airway and body surface sensors for triggering in neonatal ventilation.

Failure of neonatal patient triggered ventilation may reflect a delay in delivery of flow relative to the inspiratory effort of the infant. Transmission of diaphragmatic contraction to the sensor site (patient delay) and further transmission to and within the sensing device (device delay) both contribute to the delay in triggering. Patient and device delays were studied for different sensing systems in 36 infants, 24 of whom were intubated. Device delay was long (> 40 ms) with a conventional apnoea monitor compared with sensors placed at the airway opening (2 ms), the inspiratory (12 ms) and expiratory (3 ms) pressure transducers of the ventilator, the Graseby capsule (8 ms), strain gauges (3 ms) and oesophageal pressure (6 ms). In near normal infants, the sum of patient and device delays for the latter sensors was less than 20 ms and a minor component of the total delay. However, in severe lung disease the total delay may be more than 100 ms even for airway sensors.

Extremely low-birth-weight infants less than 901 g. Growth and development after one year of life.

In a long-term prospective control study, 20 extremely low-birth-weight infants with birth weights between 500 and 900 g (mean 755 +/- 109 g) and gestational ages between 24 and 30 weeks (mean 26.2 +/- 1.8 weeks) were compared with 20 full-term infants, after the first year of life for growth, development and continuing morbidity after discharge from the intensive care unit. The total rate of neurological abnormalities was 17%; the rate of infantile post-hemorrhagic hydrocephalus requiring shunt operations was 8.7%, while 13% had retinopathy of prematurity with vision deficit, but none was blind. The hospital readmission rate was 70%, but for most infants only one or a few readmissions were needed whereas three infants with chronic lung disorders required frequent hospital readmissions, mainly for respiratory infections. Apart from 4 infants with major cerebral neonatal complications, 16 of 20 extremely low-birth-weight infants (80%) showed development within the normal range at one year of age, although with delay in some areas in comparison with full-term control infants. Follow-up into preschool and school age is in progress. We cautiously suggest that the results at the one year follow-up do indicate a possible favourable long-term outcome for many of these extremely low-birth-weight infants with normal cognitive development and with no major neurological sequelae.

Neonatal care of very low birth weight pre-term infants in the 1990's in Sweden.

Refinement of optimal neonatal intensive care for the very pre-term infants with risk of developing neonatal complications including retinopathy of prematurity (ROP) has been under development since the late 1980's. During the last decade better methods for supporting the respiration including surfactant treatment has contributed to the increased survival rate which today is more than 50% for infants born between 24 and 28 completed weeks of gestation. Improvement in the 'environmental engineering' in the neonatal intensive care unit is necessary to improve the longterm outcome regarding disabilities and handicaps including ROP. Clinical research in neonatology clearly shows that a high quality medical and nursing care is required for these infants.

Prevention of excess neonatal morbidity associated with group B streptococci by vaginal chlorhexidine disinfection during labour. The Swedish Chlorhexidine Study Group.

Streptococcus agalactiae transmitted to infants from the vagina during birth is an important cause of invasive neonatal infection. We have done a prospective, randomised, double-blind, placebo-controlled, multi-centre study of chlorhexidine prophylaxis to prevent neonatal disease due to vaginal transmission of S agalactiae. On arrival in the delivery room, swabs were taken for culture from the vaginas of 4483 women who were expecting a full-term single birth. Vaginal flushing was then done with either 60 ml chlorhexidine diacetate (2 g/l) (2238 women) or saline placebo (2245) and this procedure was repeated every 6 h until delivery. The rate of admission of babies to special-care neonatal units within 48 h of delivery was the primary end point. For babies born to placebo-treated women, maternal carriage of S agalactiae was associated with a significant increase in the rate of admission compared with non-colonised mothers (5.4 vs 2.4%; RR 2.31, 95% CI 1.39-3.86; p = 0.002). Chlorhexidine reduced the admission rate for infants born of carrier mothers to 2.8% (RR 1.95, 95% CI 0.94-4.03), and for infants born to all mothers to 2.0% (RR 1.48, 95% CI 1.01-2.16; p = 0.04). Maternal S agalactiae colonisation is associated with excess early neonatal morbidity, apparently related to aspiration of the organism, that can be reduced with chlorhexidine disinfection of the vagina during labour.

Acute changes in cerebral oxygenation and cerebral blood volume in preterm infants during surfactant treatment.

Following administration of surfactant a marked depression in aEEG activity occurs for about 10 minutes; the mechanism of this depression is unknown. In view of this, twenty-nine preterm infants were investigated with near infrared spectroscopy (NIRS) to evaluate rapid changes in total cerebral haemoglobin concentration and cerebral oxyhaemoglobin concentration during rescue treatment with natural surfactant. During surfactant instillation there was a short-lasting hypoxaemia as demonstrated by pulseoximetry as well as a considerable fall in arterial blood pressure. With NIRS, tissue hypoxia was demonstrated by a drop in cerebral oxyhaemoglobin concentration. The marked drop in arterial blood pressure occurring immediately following surfactant was not matched by a drop in total cerebral haemoglobin concentration. This suggests that cerebral blood volume and hence cerebral blood flow was maintained. In the following minutes there was an improvement in cerebral oxygenation as indicated by the rise in cerebral oxyhaemoglobin concentration in nearly all the infants.