Neonatal electrocortical brain activity and cerebral tissue oxygenation during non-acidotic, normocarbic and normotensive graded hypoxemia.

OBJECTIVE: Neonates are commonly exposed to isolated hypoxemic episodes. In order to identify the risk of this, we correlated cerebral oxygen delivery and electrocortical brain activity during isolated graded and repetitive hypoxemia in 1-week-old piglets. METHODS: Six halothane-anesthetized piglets were subjected to two episodes of graded hypoxemia of 45 min duration. The fractional concentration of inspired oxygen (FiO(2)) was stepwise decreased at 15 min intervals from 0.21 to 0.15, 0.10 and 0.05. A second identical hypoxemic event was induced after 1 h of normoxemia (FiO(2) 0.21). Mean arterial pressure (MAP) and pH were maintained at baseline values during the whole experiment. We measured near infrared spectroscopy parameters (cerebral oxidized cytochrome aa(3) (Cytaa3), total hemoglobin (tHb: oxy- +deoxyhemoglobin)) corresponding to cerebral blood volume (CBV), carotid blood flow (Q(car)), intra-arterial oxygen saturation (SaO(2)), and mean maximal EEG amplitude and relative spectral power. RESULTS: Delta (delta) power increased significantly and the EEG amplitude dropped below 10 and 5 microV at the end of the first and the second hypoxemic period (PaO(2) 2.68+/-1.08 (P<0.05) and 2.87+/-0.58 kPa, respectively). Both EEG variables normalized during recovery (FiO(2) 0.21). Q(car), CBV and Cytaa3 were not changed. CONCLUSION: Acute isolated hypoxemia has to be sustained to induce neuronal hypofunction in normotensive animals. Hypoxic hypoxemia led to acute changes in neuronal activity, whereas cellular oxygenation remained unaffected.

Tissue oxygen saturation measured by near infrared spectrophotometry correlates with arterial oxygen saturation during induced oxygenation changes in neonates.

The aim of this study was to compare quantitatively the changes in tissue oxygen saturation (TOS), determined by two algorithms (TOSc and TOSa) based on near-infrared spectrophotometry, to the changes in arterial oxygen saturation (SaO2) measured by pulse oximetry. TOSc is an algorithm derived by the manufacturer (Critikon) based on a modified Beer-Lambert law; TOSa, our own algorithm, uses the diffusion approximation of light transport for the semi-infinite boundary condition. Slow changes of more than 3% in SaO2 were carried out in 20 mechanically ventilated neonates by altering the inspired oxygen fraction. For each change the regression lines of TOSc versus SaO2, TOSa versus SaO2 and TOSc versus TOSa were calculatcd. For each infant the mcan slope, intercept and r2 of these lines were determined. In 18 preterm infants we obtained median 9.5 (range one to 13) measurements corresponding to a total of 166 measurements. The mean SaO2 was 91.6 (SD 2.3)%, TOSc was 64.7 (SD 7.2)% and TOSa was 71.4 (SD 11.0)%. Changes in TOSc and TOSa were strongly correlated to changes in SaO2 (r2 = 0.86 and r2 = 0.87). TOSc considerably but systematically underestimated the size of the change: delta TOSc = 0.49 delta SaO2. TOSa quantified changes reasonably correctly: delta TOSa = 0.90 delta SaO2. Changes in TOSc and TOSa were highly correlated (r2 = 0.98). These results are promising, but the large inter-individual variation requires further work.

[Ultrasonically established cystic periventricular leukomalacia (PVL): incidence and associated factors in Switzerland 1995-1997]. / Sonographisch nachgewiesene zystische periventrikuläre Leukomalazie (PVL): Inzidenz und assoziierte Faktoren in der Schweiz 1995-1997.

BACKGROUND: Cystic periventricular leukomalacia (PVL) is an ischemic brain lesion that mainly affects preterm infants and causes severe neurological damage. Diagnosis is made by cranial ultrasonography. Objectives of this study were to determine the incidence, to identify associated factors and to evaluate the frequency of neurological abnormality at discharge. PATIENTS AND METHODS: Infants with PVL in Switzerland were systematically registered (Swiss Pediatric Surveillance Unit, Swiss Neonatal Network) over three years (1995 to 1997). They were compared to a control group matched for gestational age. RESULTS: Over the three year period 40 infants with PVL defined as at least 2 cysts with diameter = 2 mm in the periventricular region were registered (35 of them were preterm babies). In comparison with the matched controls the infants with PVL had received significantly less frequently antenatal corticosteroids (44 vs 78%, Event Rate Ratio 0.57, 95% Confidence Interval 0.38-0.68), they had lower umbilical cord arterial pH and lower Apgar scores; there was a trend to arterial hypotonia and hypocapnia associated with PVL. The infants of the study group needed more often mechanical ventilation or nasal CPAP (92% versus 67%; ERR 1.38, CI 1.07-1.77) and had more often intracranial hemorrhage (39 versus 14%; ERR 2.8, CI 1.13-6.96). 56% of the infants with PVL were considered abnormal at the neurological examination at discharge compared to 28% in the control group (p < 0.02). CONCLUSION: The incidence of PVL in Switzerland is 1.2% for preterm infants with a birth weight less than 1500 g. Cranial ultrasonography on infants at risk for PVL is important because 44% of the infants with PVL didn't show neurologic abnormalities at discharge.

Cyclical fluctuations in blood pressure, heart rate and cerebral blood volume in preterm infants.

Many recently published papers describe cyclical changes of cerebral circulatory variables, mainly in cerebral blood flow velocity (CBFV) performed with Doppler sonography. In this paper we focus on another important variable of cerebral circulation: on cerebral blood volume (CBV) measured by near infrared spectrophotometry (NIRS). In a retrospective analysis of NIRS measurements in 20 preterm infants (median 27 3/7 weeks of gestation), the dominating frequencies and prevalence of cyclical changes of CBV and its possible correlation with peripheral circulatory variables (mean arterial pressure and heart rate) was examined. In 19 out of the 20 infants cyclical changes of CBV were found within a frequency range of 2-4.7 cycles/min which is comparable to the results of the Doppler studies describing fluctuations in CBFV. A dominating frequency of heart rate (HR), was found only in 12 out of 20 infants, and it was with 2.1-3.8 cycles/min in a similar range compared to CBV. In mean arterial blood pressure (MABP), however we detected cycles with longer periods every 1-2.5 min in 14 out of 20 infants. There was a significant coherence between MABP/CBV and HR/CBV. The area under the coherence curve, however, was significantly larger between MABP and CBV as compared to HR and CBV (P = 0.0007, Wilcoxon signed-rank test).

The influence of a clear layer on near-infrared spectrophotometry measurements using a liquid neonatal head phantom.

It is difficult to test near-infrared spectrophotometry instruments in vivo. Therefore we constructed a liquid phantom which mimics the neonatal head. It consists of a spherical 3.5 mm thick layer of silicone rubber simulating skin and bone and a 0.5 mm thick clear layer of polypropylene imitating cerebrospinal fluid. It acts as container for a liquid solution with Intralipid, 60 micromol l(-1) haemoglobin and yeast. The solution was oxygenated using oxygen and then deoxygenated by the yeast. From the instrumental (Critikon 2020) algorithm, we found that with increasing scattering (0.5%, 1%, 1.5% and 2% Intralipid concentration) the reading was increasingly offset from the expected value of 0 micromol l(-1) by 55.7, 68.6, 76.5 and 80.4 micromol l(-1) (oxyhaemoglobin) and 16.0, 24.4, 29.6 and 31.7 micromol l(-1) (deoxyhaemoglobin). This reduced the range of the oxygen saturation reading from the expected 100% to 31.5, 21.1, 14.3 and 11.5%. Haemoglobin concentration changes were increasingly underestimated by a factor of two to four. For a second algorithm based on the diffusion approximation the offsets were smaller: oxyhaemoglobin 11.4, 17.8, 22.5 and 25.1 micromol l(-1) and deoxyhaemoglobin 1.3, 3.4, 5.2 and 6.0 micromol l(-1). The range of the oxygen saturation reading was higher: 41.3, 29.2, 23.4 and 16.6%. Concentration changes were underestimated by a factor of six to ten. This study demonstrates the need to develop algorithms which take into consideration anatomical structures.

Regional differences of cerebral hemoglobin concentration in preterm infants measured by near infrared spectrophotometry.

Near infrared spectrophotometry has been used to measure total cerebral hemoglobin concentration (micromol/l) as a major indicator of the oxygen transport capacity in neonates. The aim of this study was to find out how the position of the probe influences the quality of the measurement and the actual cerebral hemoglobin concentration-values. We studied 10 healthy preterm infants with a mean gestational age of 31.5 weeks and a birthweight of 1513 g. The data were collected by a two channel near infrared spectrophotometry system using a geometrical principle to measure absolute cerebral hemoglobin concentration. The incoming signal of the light emitting diode as a value allows a prediction of the quality of the measurement: a high value refers to a high signal/noise ratio. Starting from the centre of the forehead (0%) for each measurement the probe was moved by 2.5% of the headcircumference to the left respectively right side of the head up to 20%. The cerebral hemoglobin concentration-values increased from 87 respectively 93 micromol/l up to 164 respectively 173 micromol/l on the right respectively left side, while the light emitting diode signal-values decreased from 21 respectively 21 down to 10 respectively 11, the more laterally the probe was moved. There were two plateaus of these variables in the frontal (0-5%) respectively lateral (15-20%) region. A further investigation on a solid phantom for premature heads showed that hair has either no or a contrary effect on the cerebral hemoglobin concentration-values than expected. The extracerebral tissue (soft tissue, skull, cerebrospinal fluid layer) is discussed to have a significant influence on the light attenuation in adult heads. Still there is no evidence for a significant effect on prematures, because this overlying tissue is much thinner and more translucent than the one in adults. Absolute cerebral hemoglobin concentration measured by near infrared spectrophotometry is substantially influenced by the position of the probe at the infant's head. Considering our results we recommend placing the probe at 2.5% of the headcircumference away from the centre of the forehead for the measurement of cerebral hemoglobin concentration in premature infants.

Development of bladder and bowel control: significance of prematurity, perinatal risk factors, psychomotor development and gender.

UNLABELLED: Development of bladder and bowel control from 6 months to 6 years was investigated in 140 preterm children and a control group of 349 healthy term children. Structured parental interviews and neurodevelopmental assessments were carried out when the child was 1, 3, 6, 9, 12, 18 and 24 months, and at yearly intervals thereafter. Even though preterm children were put on the potty at significantly earlier ages and significantly more frequently than term children, they expressed their need for evacuation and attained day and night bladder and bowel control at the same corrected age as term children. Initiation and intensity of toilet-training were not significantly correlated with the development of bladder and bowel control. Gestational age, being too small for gestational age, adverse perinatal conditions and mild to moderate neurological impairment did not affect the occurrence of the child's initiative and the development of bladder and bowel control. Neither developmental and intelligence quotients at the age of 1 to 3 years nor the socioeconomic status of the families influenced the age at which the child became clean and dry. Girls were significantly more advanced in expressing their needs and gaining bladder and bowel control than boys in both the preterm and term groups. CONCLUSION: Development of bladder and bowel control is largely a maturational process which cannot be accelerated by an early onset or a high intensity of training. It is not affected by prematurity, adverse perinatal events or mild to moderate neurological impairment, nor is it related to psychomotor development or actual Swiss socioeconomic conditions.

Cerebral blood flow and neurological outcome in the preterm infant.

UNLABELLED: Cerebral blood flow (CBF) studies have provided some insight into pathophysiological mechanisms of cerebral damage in newborn children; their value in predicting brain damage, however, remains elusive. The purpose of our study was to evaluate the role of CBF measurements in predicting developmental outcome in preterm neonates at 18 months. Preterm babies with a gestational age of less than 34 weeks and a birth weight of less than 1500 g (n = 71) were enrolled in the study. CBF was measured by the noninvasive intravenous 133Xe method on three different occasions. We classified our measurements into three groups: depending on the time when performed group 1: between 2 and 36 h (n = 52); group 2: between 36 and 108 h (n = 44); group 3: between 108 and 240 h (n = 41). At the age of 18 months neurodevelopment testing was performed according to the Bayley mental and motor scales. Surviving infants had a higher mean CBF over the three groups than non surviving children (15.2 +/- 3.5 ml/100 g brain tissue/min vs 13.0 +/- 2.1 ml/100 g brain tissue/min, P < 0.05). There was no correlation of CBF with mental or motor development in our study population in either of the three groups. CONCLUSION: In preterm infants basal CBF is higher in surviving than in non surviving infants, but there is no correlation of resting CBF and later neurological outcome.

CO2 reactivity of the cerebral hemoglobin concentration in healthy term newborns measured by near infrared spectrophotometry.

CO2 reactivity of cerebral hemoglobin concentration was studied in 16 healthy term neonates on days 1 and 4 after birth using the near infrared spectrophotometry (NIRS) technique. The aim was to establish data on the physiological range of CO2 reactivity in healthy newborns and to investigate the influence of postnatal age on it. The CO2 reactivity measured by NIRS is expressed as the change of the total cerebral hemoglobin concentration (tHbR) per change of CO2 tension in micromol/l/kPa. We evaluated CO2 reactivity during increases and decreases of transcutaneous CO2 partial pressure and found in our methodological setting the data of the increases more reliable. In all infants but 1 we found a tHbR on day 1 with a mean value of 8.19 micromol/l/kPa (-1.39 to 18.87), in all infants on day 4 with a mean value of 9.54 micromol/l/kPa (2.76-25. 88). There is a trend to higher values between day 1 and day 4 (difference = 2.25 micromol/l/kPa; p = 0.08). The noninvasive NIRS technique enabled us to test the cerebrovascular CO2 reactivity of the tHbR for the first time in healthy term newborns. Data on its physiologic range and variability are presented and compared to findings from ventilated infants and other age groups. As the CO2 reactivity might be an indicator for infants at risk of cerebral damage, it is necessary to have data on the physiological range of this parameter.

Movement quality in preterm infants prior to term.

Quality of spontaneous movement behavior (fluency, spatio-temporal variation and sequencing) was studied from birth to term in high-risk preterm (n = 18), low-risk preterm (n = 18) and term (n = 20) infants. Cranial ultrasonography was performed during the first week of life and the child's general health was considered. The results were as follows: (1) In their first week of life, preterm infants displayed lower scores on all quality parameters when compared to term infants (p < 0.001). (2) Quality of spatiotemporal variation and sequencing decreased up to term (p < 0.01). These findings could be attributed to maturational differences, too early exposure to an extrauterine environment, and cerebral lesions.

Comparison of absolute cerebral haemoglobin concentration in neonates measured directly and by the oxygen swing method both based on near infrared spectrophotometry.

The total cerebral haemoglobin concentration (tHb in mumol/l) as a major indicator of the oxygen transport capacity is investigated in neonates. Two methods to determine tHb by near infrared spectrophotometry (NIRS) have evolved so far: The first method requires a slow oxygenation change with reference to arterial oxygen saturation (tHbo-method). The second method is based on a geometrical principle and a two channel NIRS instrument (tHbg-method). The aim of this study was to compare both methods quantitatively. 15 clinically stable preterm infants needing supplemental oxygen were included in this study. For each method the measurements of three infants were excluded due to unsatisfactory measurement quality. The remaining 9 neonates had a mean gestational age of 29 (range 25.1 to 31.4) weeks, birthweight of 1272 (740 to 1690) g and a postnatal age of 2.6 (0.5 to 5) days. In each infant 6 tHbo measurements were carried out. During each tHbo measurement the mean of the continuously available tHbg (Cerebral Redox Monitor 2020, Johnson & Johnson Medical) was calculated. The mean of all successful tHbo and corresponding tHbg was determined for each infant. The mean tHbg was 151 mumol/l (range 62 to 223 mumol/l) and the mean tHbo was 59 mumol/l (27 to 113 mumol/l). The regression line between the two methods was tHbg = 1.34 x tHbo + 72 mumol/l. The r was 83.6%. The correlation suggests, that both methods can be applied to measure tHb. However, it has to be taken into account that the tHbg-method returns significantly higher values than the tHbo-method.

Effect of nursing in the head elevated tilt position (15 degrees) on the incidence of bradycardic and hypoxemic episodes in preterm infants.

OBJECTIVE: We investigated whether nursing in the head elevated tilt position (HETP), compared with the horizontal position, has any effect on the incidence of bradycardic and hypoxemic episodes in preterm infants. METHODS: Twelve spontaneously breathing preterm infants with idiopathic recurrent apnea were studied in a randomized controlled crossover trial. Nine infants were treated with aminophylline. Each spent a total of 24 hours in the horizontal prone position and a total of 24 hours in HETP (prone, 15 degrees). The position was changed in random order every 6 hours. Thoracic impedance, heart rate, and arterial oxygen saturation were recorded continuously. The frequency of isolated hypoxemia (arterial saturation <80%), of isolated bradycardia (heart rate <90 beats per minute), and of mixed events was analyzed and compared without knowledge of the allocated position. RESULTS: In total, there were significantly fewer bradycardic and/or hypoxemic episodes (28.2%) in HETP compared with the horizontal position (mean difference, 13.35 episodes/24 hours; 95% confidence interval [CI]: 5.9- 20.8). The decrease was largest for isolated hypoxemic episodes (48.5%; mean difference, 11.74 episodes/24 hours; 95% CI: 6.1-17.4). Isolated bradycardic episodes (mean difference, 2.27 episodes/24 hours; 95% CI: -0.78-5.31) and mixed events were not decreased significantly in HETP. CONCLUSIONS: Nursing in a moderately tilted position (15 degrees) reduces hypoxemic events in preterm infants. This intervention is easy to apply, quickly reversible, and can be combined with drugs such as aminophylline.

Continuous noninvasive measurement of cerebral arterial and venous oxygen saturation at the bedside in mechanically ventilated neonates.

OBJECTIVES: To test the practicablity of a new spectrophotometric method using pulse oximetric techniques in combination with special filters for the noninvasive determination of cerebral arterial and venous oxygen saturation and oxygen extraction in neonatal intensive care unit patients. The spectrophotometer used three different wavelengths at a sampling rate of 100 Hz. DESIGN: Clinical evaluation of a new method and comparison with previously published data. SETTING: Design and construction of the special spectrophotometer at the Biomedical Engineering Laboratory of the Swiss Federal Institute of Technology. Measurements in the neonatal intensive care unit of the University Hospital, Zurich, Switzerland. PATIENTS: Convenience sample of 15 clinically stable newborn infants, who were mechanically ventilated and receiving supplemental oxygen. Median gestational age was 29 5/7 wks (range 26 3/ 7 to 36 0/7), median birth weight was 1555 g (720 to 2500), median postnatal age was 4 days (1 to 10). INTERVENTIONS: The emitter and receiver were placed on the forehead near the sagittal sinus, between 2 and 2.8 cm apart, and the pulsating light attenuations (arterial and venous pulse waves) were recorded. MEASUREMENTS AND MAIN RESULTS: Arterial and venous pulse waves were satisfactory in 10 of 15 infants. Mean cerebral arterial oxygen saturation was 89.9 +/- 5.4% (SD), mean cerebral venous oxygen saturation was 73.0 +/- 8.9%, and mean cerebral oxygen extraction was 16.9 +/- 11.7%. A linear regression analysis demonstrated a significant correlation between mean PCO2 and venous oxygen saturation (slope 1.0%/torr, p < .05) and between mean PCO2 and cerebral oxygen extraction (slope -1.3%/torr, p < .05). CONCLUSION: This new method has the potential for monitoring continuously, noninvasively, and simultaneously cerebral arterial and venous oxygen saturation and oxygen extraction in mechanically ventilated preterm infants.

The effect of behavioural states on cerebral oxygenation during endotracheal suctioning of preterm babies.

Near infrared spectroscopy (NIRS) was used to investigate the effect of behavioural states on changes of oxygenated (O2Hb), deoxygenated haemoglobin (HHb) and total haemoglobin (tHb), during endotracheal suctioning. In an open prospective design, NIRS measurements have been done during 20 suctioning episodes in 13 preterm neonates. Heart rate, arterial oxygen saturation, and carbon dioxide tension were monitored continuously. Behavioural state (BS) observations were made and documented as well. The statistical analysis showed that in patients who were active, with crying periods during suctioning (behavioural states 4-5), changes of oxygenated (p < 0.005) and deoxygenated haemoglobin (p < 0.05), as well as of arterial oxygen saturation (p < 0.05) and heart rate (p < 0.05) were significantly greater than in patients who were quiet with predominant behavioural state 1, 2 and 3. These results underline the influence of behavioural states on the physiological answers to endotracheal suctioning. NIRS proved to be a valuable tool to evaluate possible harmful effects of different suctioning techniques.

Differences in movement quality at term among preterm and term infants.

Significant differences in movement quality at term are reported in high-risk preterm (n = 18), low-risk preterm (n = 21) and term (n = 20) infants. Movement quality was judged using 2-minute video collection of general movements; three parameters of movement quality could be assessed reliably in a semiquantitative way: fluency, spatiotemporal variability and sequencing. The parameters fluency and variability correlated highly with each other (r = 0.47-0.99) while their correlations with sequencing were less (r = 0.42-0.67). Significant differences on all quality parameters were noted between term, low-risk preterm and high-risk preterm infants (p < 0.001-0.05). The findings indicate a significant impact of prematurity per se and brain damage on movement quality.

Body proportionality in growth-retarded VLBW infants.

The aim of this study was to investigate how intrauterine growth retardation affects body proportions in VLBW infants. The cohort consisted of 135 surviving and 80 deceased preterm infants weighing less than 1250 grams at birth. Gestational age varied between 24 and 36 weeks (mean age 29.7 and 27.5 weeks, respectively). Birth weight was more than 2 SD below the mean birth standard values in 32% of the surviving, and in 27% of the deceased infants. Reduction of weight, length and head circumference at birth was analysed using Z scores based on Swedish birth standards. Z scores of weight, length and head circumference were highly correlated in the surviving and the deceased infants (r = 0.78 to 0.94 and 0.65 to 0.97, respectively). Length was significantly more affected by growth retardation than weight. Weight and head circumference were proportionately reduced. Intrauterine growth retardation influences body proportions in VLBW infants differently than in larger preterm and term infants.

Does a profound change in toilet-training affect development of bowel and bladder control?

A major change in toilet-training was observed in two successive generations. The median onset of toilet-training was postponed by 13 months between the First Zürich Longitudinal Study (320 children born between 1954 and 1956) and the Second Zürich Longitudinal Study (309 children born between 1974 and 1984). Bladder control, both day and night, was not affected, but bowel control was delayed by 16 months, due not to a lack of training, but to the abandonment of maternal control. The results strongly confirm earlier findings that the development of bowel and bladder control is a maturational process which cannot be accelerated by early onset and high intensity of potty-training. The child's initiative proved to be a reliable indicator that the child was developmentally capable of being clean and dry. Girls were consistently earlier than boys, indicating different maturation rates. No significant correlations were noted between the socioeconomic status and start and intensity of toilet-training, onset of the child's initiative or development of bladder and bowel control.