Normal range for blood flow velocity in cerebral arteries of newly born term infants.

A cross-sectional study of 128 healthy full term infants was made using duplex Doppler ultrasonography in order to establish a normal range for cerebral blood flow velocity (CBFV) in the first week of life. Recordings were made from both the anterior (ACA) and middle cerebral arteries (MCA). There was a statistically significant increase in CBFV in both the ACA and MCA over the first four days of life, which was particularly obvious in the first 24 h. There is a close relationship between measurement of CBFV from the ACA and the MCA, although the velocity tends to be higher in the MCA.

Patent ductus arteriosus and cerebral circulation in preterm infants.

The diagnosis of patent ductus arteriosus (PDA) was determined by Doppler examinations of the descending aorta and/or main trunk of the pulmonary artery in a cohort of 120 preterm infants. 55 per cent of the infants had Doppler echocardiographic evidence of ductal patency on the first day of life and this proportion fell to 30 per cent on the second day and 21 per cent on the third day. The incidence remained constant for the rest of the first week. Infants with PDA were significantly more likely to develop periventricular leukomalacia (PVL) than infants without PDA, but the incidence of periventricular haemorrhage was not increased. The cerebral haemodynamic effects of ductal patency were evaluated. Infants with PVL were found to have a significantly higher incidence of retrograde flow in the anterior cerebral artery during diastole, but the study was unable to demonstrate any significant difference in cerebral blood flow velocity between the infants with and without PDA.

Cerebral blood flow velocity recordings and the prediction of intracranial haemorrhage and ischaemia.

Doppler ultrasound was used to study prospectively cerebral and cardiovascular hemodynamics in a cohort of 120 preterm infants to see whether it was possible to predict infants at increased risk of developing cerebral pathology. The infants were divided into four outcome groups: Group I (n = 65, median gestation = 30 weeks) did not develop periventricular haemorrhage (PVH) nor periventricular leukomalacia (PVL) Group II (n = 43, median gestation = 28 weeks) developed PVH as the first or only cerebral lesion Group III (n = 7, median gestation = 29 weeks) developed PVL as the first or only cerebral lesion Group IV (n = 5, median gestation = 28 weeks) developed PVH and PVL simultaneously. Cerebral blood flow velocity (CBFV) and aorta blood flow velocity (ABFV) recordings made before the onset of PVH or PVL were compared between the four groups on each postnatal day but it was not possible to demonstrate a statistically significant difference between these variables in the four outcome groups. We conclude, therefore, that it is not possible to identify the infants who will go on to develop haemorrhage or ischaemic lesions on the basis of Doppler cerebral haemodynamic studies.

Evaluation of C. reactive protein values in neonatal sepsis.

C. reactive protein (CRP) estimations were performed prospectively on 30 consecutive admissions of very low birth weight infants to a Regional neonatal intensive care unit. The samples were analysed by a recently described, rapid intralipid agglutination assay and by a reference turbidimetric technique. Two hundred and ninety samples were assayed by both techniques. The intralipid agglutination was positive on two occasions when the reference method found normal levels. No false negative reactions occurred. Bacterial micro-organisms were isolated on 32 occasions but 19 of the organisms were considered to represent bacterial colonisation or contamination. The CRP remained negative in 17 cases. There were 13 episodes of clinical deterioration associated with positive bacterial cultures. In each of the six infants with severe systemic infections (septicaemia (4), meningitis (1), and osteomyelitis (1)), the levels were raised. In five of these infants the CRP was elevated before, or at the time of, the clinical deterioration. The CRP remained normal during seven (54%) of the culture positive events. We believe that the CRP estimations provide additional information in the evaluation of the infant with suspected sepsis. Serial measurements are helpful in distinguishing bacterial contamination from invasive infection but are not helpful in predicting infection during the pre-clinical phase. The intralipid agglutination technique is a rapid and reliable test and could be performed on the neonatal unit outside normal laboratory hours.

Severe birth asphyxia and abnormal cerebral blood-flow velocity.

Thirty-four fullterm infants with postasphyxial encephalopathy (PAE) were studied with ultrasound to assess cerebral blood-flow velocity (CBFV). A control group of 126 healthy infants also had CBFV recordings during the first week of life. Measurements for the majority of the asphyxiated group fell into two abnormal patterns in relation to the control group: four had low CBFV (less than 2 SD below the mean) and 17 had high CBFV (greater than or equal to 2 SD above the mean); all had severe PAE. Median age at the first high measurement was 26 hours. There were no statistically significant differences between infants with normal and abnormal CBFV in measurements of PaCO2 or mean arterial blood-pressure. A Pourcelot Resistance Index (PRI) less than 0.55 was common in the presence of high CBFV, but never seen with low measurements. 21 of the 34 infants died of their asphyxial insult and four of the survivors have severe cerebral palsy at a median age of two years. Three of the four with low CBFV died, and no infant with CBFV greater than 3 SD survived without severe impairment. The positive predictive value of CBFV measurements less than 2 SD or greater than 3 SD for death or severe impairment is 94 per cent, compared with 83 per cent for low PRI alone. The authors believe that high CBFV is the result of vasoparalysis of cerebral arterioles and that it represents a form of irreversible cerebral injury.

Cerebral haemodynamic effects of changes in positive end expiratory pressure in preterm infants.

The effects of changes in positive end expiratory pressure (PEEP) on cerebral blood flow velocity, arterial blood gases, and mean arterial pressure were studied in newborn infants. In mechanically ventilated premature infants with severe respiratory disease, an increase in PEEP from 2 to 6 cm H2O was associated with an increase in cerebral blood flow velocity. There was no significant change in mean arterial blood pressure. There was a significant increase in PaO2 and PaCO2 for every stepwise rise in PEEP. Multivariate regression analysis showed that 72% of the effect on cerebral blood flow velocity was attributable to PaCO2 alone and that any change in blood pressure was not likely to contribute to these changes. There was no evidence that changes in PEEP within the commonly used range adversely affected the neonatal cardiovascular or cerebral circulations.

Transient hyperoxia and cerebral blood flow velocity in infants born prematurely and at full term.

Little is known about the effects of hyperoxia on the cerebral circulation of human infants. Using duplex Doppler we measured the changes in cerebral blood flow velocity in a group of full term (n = 15) and premature infants (n = 17, median gestational age 31 weeks) in response to a transient threefold increase in oxygen tension. Measurements of blood gas tensions as well as blood pressure and cerebral blood flow velocity were made over a period of 20 minutes on three occasions for each infant; during normal oxygenation, hyperoxia, and normal oxygenation. There was a fall in cerebral blood flow velocity in 15 of the 17 premature infants with hyperoxia and the median reduction was 0.06 cm/second for every 1 kPa increase in oxygen tension. There was no significant change in either PCO2 or blood pressure during the period of hyperoxia. The cerebral blood flow velocity fell in all 15 infants born at full term during hyperoxia, but there was a simultaneous and significant reduction in PCO2 at the same time as the hyperoxia. Analysis of variance suggested that in the infants born at full term the change in carbon dioxide had most effect in the reduction of cerebral blood flow velocity, rather than the hyperoxia itself. We conclude that in premature infants, cerebral vascular resistance may be altered by a fall in cerebral blood flow velocity in the presence of hyperoxia.

Resistance index, blood flow velocity, and resistance-area product in the cerebral arteries of very low birth weight infants during the first week of life.

Cerebral artery Doppler ultrasound recordings, and intra-arterial pressure measurements have been made from 27 very low birth weight infants during the first week of life. These data were used to calculate Pourcelot's resistance index (RI), mean blood flow velocity, and resistance-area product (RAP), in both the anterior and middle cerebral arteries. There was a good degree of correlation between recordings from different sites on the same occasion, but absolute values were site dependent. Over the first three days of life there was a significant increase in blood flow velocity in each of the vessels, and a significant fall in RI and RAP.

Blood pressure measurements in very low birth weight infants over the first week of life.

Intra-arterial blood pressure measurements recorded during the first week of life in 32 stable very low birth weight infants (20 of birth weight up to 1250 g and 12 with birth weight 1251-1500 g) were reviewed. None of the infants received inotropic drugs or were given infusions of colloids to manipulate the blood pressure during the periods from which the recordings were taken. The mean systolic, mean and diastolic blood pressure measurements for infants of birth weight greater than 1250 g were significantly higher than those recorded in the infants of birth weight of up to 1250 g (figure 1). The mean blood pressure (calculated by adding one third of the pulse pressure to the diastolic pressure) in the larger infants showed a significant increase with increasing postnatal age, but this increase was not apparent in the smaller infants (figure 2). Figure 3 shows the range of systolic, mean and diastolic blood pressure values that were recorded. The mean values were remarkably constant with diastolic blood pressure varying between 31 and 34 mmHg, mean blood pressure between 35 mmHg and 40 mmHg, and systolic blood pressure between 46 mmHg and 52 mmHg. Intra-arterial lines provide a convenient and accurate route for blood pressure monitoring. It is important that a normal range of blood pressure values in the very low birth weight infant is established so that hypotension, with the potential risk of cerebral ischemia, can be avoided.

Plasma bile acids in patients with peroxisomal dysfunction syndromes: analysis by capillary gas chromatography-mass spectrometry.

Six patients with disorders of peroxisomal function have been studied. Two presented in the neonatal period with the classical features of the Zellweger syndrome, two had incomplete Zellweger phenotypes, one infantile Refsum's disease and one rhizomelic chondrodysplasia punctata. Plasma bile acid profiles were determined using capillary gas chromatography-mass spectrometry. In all patients, except the case of chondrodysplasia punctata, 27-carbon and 29-carbon bile acids were present. The compounds identified included trihydroxycoprostanic acid (THCA), dihydroxycoprostanic acid (DHCA), C24-, C25- and C26-hydroxylated derivatives of THCA, a 27-carbon acid with four nuclear hydroxy groups and 3 alpha,7 alpha,12 alpha-trihydroxy-27a,27b-dihomo-5 beta-cholestan-26, 27b-dioic acid (C29-dicarboxylic acid). THCA was present at a low concentration in the patient with infantile Refsum's disease; the concentration of DHCA and the C29 dicarboxylic acid were considerably higher. The presence of abnormal bile acids in patients with Zellweger syndrome and infantile Refsum's disease could be explained by the absence of peroxisomes from their hepatocytes. In chondrodysplasia punctata the cause of peroxisomal dysfunction must be different, since normal bile acid synthesis is preserved.