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Biomedical subjects

O Pryds

Publications and source records attributed to O Pryds.

At least 19 recordsLinked to original sources

Perinatal risk factors of adverse outcome in very preterm children: a role of initial treatment of respiratory insufficiency?

AIM: To investigate risk factors of adverse outcome in a cohort of very preterm children treated mainly with nasal continuous positive airway pressure (CPAP) during the neonatal course. METHODS: In Denmark, preterm children are treated with nasal CPAP as a first approach to respiratory support. A national prospective study of all infants with a birthweight below 1000 g or a gestational age below 28 wk born in 1994-1995 was initiated to evaluate this approach. Of the 269 surviving children 164 (61%) were not treated with mechanical ventilation in the neonatal period. A follow-up of the children at 5 y of age was conducted. Data from the neonatal period and the 5-y follow-up were analysed. RESULTS: In multivariate analyses including 250 children, a severely abnormal neonatal brain ultrasound scan was predictive of cerebral palsy (OR = 19.9, CI 95%: 6.1-64.8) and intellectual disability (OR = 6.2, CI 95%: 2.3-16.5). A high Clinical Risk Index for Babies (CRIB) score (OR = 2.4, CI 95%: 1.1-5.5) and chronic lung disease (OR = 2.8, CI 95%: 1.2-6.9) were predictive of intellectual disability. In univariate analyses mechanical ventilation was associated with cerebral palsy (OR=4.3, CI 95%: 1.7-10.8) and intellectual disability (OR = 2.2, CI 95%: 1.2-4.2), but the associations became insignificant in multivariate analyses including chronic lung disease and a severely abnormal ultrasound scan. CONCLUSION: The associations between neonatal risk factors and adverse outcome in our cohort were very similar to those found in other cohorts with another initial treatment of respiratory insufficiency. We found no significant adverse effects of mechanical ventilation beyond what could be explained by associations with chronic lung disease and IVH 3-4/PVL.

Cerebral Palsy↗

The Danish national study in infants with extremely low gestational age and birthweight (the ETFOL study): respiratory morbidity and outcome.

AIM: To describe and analyse neonatal care, short and long-term morbidity with special reference to ventilatory support and chronic lung disease (CLD) in a population-based study. METHODS: During 1994 and 1995 a prospective, nation-wide, multicentre study was conducted, comprising 477 liveborn infants with gestational age (GA) < 28 wk and/or birthweight < 1000 g. Of these, 407 infants received active treatment. The ventilatory treatment was based on the principle of permissive hypercapnia and early nasal continuous positive airway pressure (NCPAP) supplemented with surfactant and ventilator therapy in case of CPAP failure. RESULTS: Among actively treated infants 85% received CPAP and 23% mechanical ventilation from the first day of life. A total of 269 infants (56%) survived to discharge. Of these, 195 had a GA < 28 wk. One-hundred and five survivors with GA < 28 wk survived with NCPAP as sole respiratory support. In surviving infants, periventricular leucomalacia/intraventricular haemorrhage grade 3-4 was found in 10%, retinopathy of prematurity grade > 2 in 4%, and oxygen requirement at 36 and 40 wk of postmenstrual age (CLD) in 16 and 5%, respectively. Three infants either died of CLD (n = 1) or required oxygen therapy beyond 43 wk of postmenstrual age. Logistic regression analysis showed significant associations between oxygen requirement at 40 wk and GA, septicaemia, mechanical ventilation, symptomatic patent ductus arteriosus and Clinical Risk Index for Babies score. Only the two last-mentioned factors proved significant in infants with GA < 28 wk. No infant died after discharge and 253 (94%) were followed up at 2 y of corrected age; one or more moderate to severe impairments were found in 66 (26%) of the examined children. CONCLUSION: Ventilatory treatment in extremely premature and extremely low-birthweight infants based on early NCPAP and permissive hypercapnia may result in comparable survival rates and sensorineural outcome; however, the incidence of CLD seems lower than that reported on conventional treatment.

Chronic Disease↗

The haemodynamic effects of dopamine and volume expansion in sick preterm infants.

AIM: To determine the haemodynamic effects of dopamine and volume expansion in preterm neonates. Effect parameters were mean arterial blood pressure (MABP), left ventricular output (LVO) and global cerebral blood flow (CBF). METHODS: In a randomised, clinical control trial 36 preterm neonates were randomised to receive either dopamine 5 microg/kg per min, volume expansion with albumin 20% 15 ml/kg or no treatment. Parameters were measured before and 2 h after initiation of treatment. RESULTS: Dopamine was effective in increasing MABP; both treatments increased LVO, whereas no significant difference between the treatment groups and the control group could be demonstrated with regard to CBF. CONCLUSION: No effect on global cerebral blood flow could be demonstrated in this study, despite significant effects on systemic circulatory parameters. However, the variance on the measurement of cerebral blood flow indicates that a small but clinically significant effect may have been overlooked.

Blood Pressure↗

Brain lesions in preterms: origin, consequences and compensation.

Twenty-nine high-risk preterm born children, from a cohort with cerebral blood flow (CBF) measurements in the first 2 d of life, were examined prospectively at the age of 5.5-7 y neurologically, neuropsychologically and by magnetic resonance imaging (MRI). They were compared to 57 control children in terms of neurology and neuropsychology. Abnormal MRI was found in 19 children. Low oxygen delivery to the brain was found in 63% of them, in contrast to 12.5% in those with normal MRI, indicating neonatal hypoxia-ischemia as an important factor. The MRI abnormalities were mainly periventricular lesions (n = 19), especially periventricular leucomalacia (PVL, n = 17). Three of the very preterm children had severe cerebellar atrophy in addition to relatively mild periventricular abnormalities. MRI showed specific morphological correlates for the major disabilities, e.g. spastic CP (involvement of motor tracts), mental retardation (bilateral extensive white matter reduction or cerebellar atrophy) and severe visual impairment (severe optic radiation involvement). A morphological correlate for minor disabilities, i.e. functional variations in motor performance or intelligence, was not found, with the exception that symptoms of attention deficit hyperactivity disorder were related to mild MRI abnormalities. This could mean that with respect to cognitive functions, mild or unilateral periventricular MRI lesions could be compensated. However, as among preterms without mental retardation (n = 19), IQ was generally and significantly lower than in the control group; other, more chronic pathogenetic factors, not detectable by MRI alone, may play a role.

Attention Deficit Disorder with Hyperactivity↗

Regional cerebral blood flow during seizures in neonates.

With the use of 99mTc-D, L,-hexamethylpropylenamine oxime and single photon emission computed tomography, regional cerebral blood flow was measured ictally in 12 mature infants with recurrent seizures and compared with a reference group of nine interictal studies. The study indicates that both clinical and electrical seizures in neonates are associated with a focal cerebral hyperperfusion of the same amount as seen in adults.

Brain↗

Cerebral blood flow in the newborn infant.

Studies of CBF have provided some insight into cerebrovascular physiology and pharmacology. However, the precise relation between CBF and cerebral damage remains elusive, and there is no definition of a threshold CBF below which ischaemic brain damage always occurs. Measurement of CBF thus does not currently provide a secure guide in the clinical management of sick infants. Further work, particularly using techniques like magnetic resonance imaging and NIRS, which provide data in addition to CBF measurements, may yet disclose strategies which manipulate CBF to reduce cerebral ischaemia. While cerebral injury remains a substantial problem in neonatal intensive care, such research is urgently needed.

Blood Pressure↗

Limited role for nitric oxide in mediating cerebrovascular control of newborn piglets.

AIMS: To investigate the effects of the nitric oxide (NO) synthase inhibitor L-nitro-arginine methyl ester (L-NAME) on cerebral blood flow, and its response to alterations in arterial carbon dioxide tension (CBF-CO2 reactivity). METHODS: Cerebral blood flow was measured six times at varying arterial carbon dioxide tension (PaCO2) using the intravenous 133Xenon clearance technique in eight mechanically ventilated piglets of less than 24 hours postnatal age. After the third measurement L-NAME was administered as a bolus (20 mg/kg) and subsequently infused (10 mg/kg/hour). RESULTS: PaCO2 ranged between 2.7-8.9 kPa. Cerebral blood flow decreased by 14.0% (95% confidence interval 1.9-27.4) after L-NAME. CBF-CO2 reactivity was 18.4% per kPa (95% CI 14.1-22.2) before L-NAME and 15.2%/kPa (95% CI 11.1-19.3) afterwards; the difference between the CBF-CO2 reactivities was 3.2%/kPa (95% CI -0.4-6.8): these were not significantly different. CONCLUSIONS: Inhibition of nitric oxide synthesis reduces cerebral blood flow no more than a 0.5-1.0 kPa fall in PaCO2. Nitric oxide is not an important mediator of CBF-CO2 reactivity.

Animals↗

Intrauterine growth retardation and premature delivery: the influence of maternal smoking and psychosocial factors.

OBJECTIVES: This study investigated the influence of psychosocial stress, maternal schooling, social support, psychological well-being, alcohol, and smoking on intrauterine growth retardation and premature delivery. METHODS: At a Copenhagen university hospital, 2432 pregnant women completed a questionnaire on general health, psychosocial stressors, and sociodemographic characteristics. RESULTS: In 212 cases (8.7%) the women delivered prematurely. Preterm delivery as associated with psychosocial stress (adjusted odds ratio [OR]=1.14 for each 1-point increase on the psychosocial stressor 5-point scale and 1.92 for the whole scale) and poor school education (adjusted OR=2.62 for 7-9 years of schooling, 1.91 for 10 years, and 1.0 for 11-13 years). In 152 cases (6.3%), infants had a birthweight below the 10th percentile. Intrauterine growth retardation was associated with smoking, daily drinking, school education, and social network variables. In a multiple logistic regression model, intrauterine growth retardation was associated with smoking habits (adjusted OR=2.40 for 0-9 cigarettes daily, 2.68 for 10-15 daily, and 2.88 for more than 15 daily). CONCLUSIONS: Psychosocial stressors and limited duration of schooling appeared to influence preterm delivery. Smoking habits influenced intrauterine growth retardation.

Adult↗

Local vascular CO2 reactivity in the infant brain assessed by functional MRI.

The local cerebral vascular response to hyperventilation was investigated in five distressed, intubated infants by means of a T2 sensitive gradient-echo MRI technique at 1.5 T. In one preterm infant, the MR signal change during hyperventilation was sparse. In four term infants, the mean MR signal of the brain slice investigated decreased by 1.2-2.6% per kPa change in PCO2 as a reflection of decreased cerebral blood flow during hyperventilation. Pixel-wise analysis revealed absence of vascular response in the basal ganglia, the thalamus or in the occipital region. In two adult controls, who hyperventilated voluntarily, the vascular reactivity was homogeneously distributed predominantly over the grey matter. The experiments demonstrate that local impairment of vascular CO2 reactivity in the distressed infant brain can be detected by T2 sensitive gradient-echo MRI, which is also known as functional MRI.

Adult↗

Brain lactate in preterm and growth-retarded neonates.

Glucose is the predominant cerebral energy source under physiological conditions, although other substrates may support cerebral metabolism. The present study was undertaken to determine if lactate is present in the immature human brain, and if so, whether or not concentrations of lactate differ between small-for-gestational-age and appropriate-for-gestational-age infants. Thirty stable, healthy infants with normal brains were investigated. As the only nutrient, all received milk enterally prior to the investigation, which was carried out without sedation. Mean gestational age was 35 completed weeks (range 28-41 weeks) and mean birth weight was 2170 g (range 855-4100 g). Proton nuclear magnetic resonance spectra from the striatal region were obtained while the infants were sleeping quietly. Lactate was present in all 10 preterm small-for-gestational-age and 10 of 13 preterm appropriate-for-gestational-age infants, and the concentration was inversely related to postmenstrual age (p < 0.002). In addition, lactate increased with the degree of growth retardation (p < 0.01). At present the significance of lactate is unclear. Lactate may be produced locally or in peripheral tissues, and may support brain metabolism.

Brain↗

Oxygen at birth and prolonged cerebral vasoconstriction in preterm infants.

To determine if the use of oxygen in the delivery room influences subsequent global cerebral blood flow (CBF), 70 infants of gestational age of less than 33 completed weeks were randomly assigned to receive room air (group I) or 80% oxygen (group II) during the initial stabilisation at birth. In group I supplemental oxygen was administered on clinical indications, when required. After being admitted to the neonatal intensive care unit all infants were treated according to our normal practice. At a postnatal age of 2 hours CBF was measured by xenon clearance. Seventy four per cent of the infants in group I were successfully stabilised without the need for supplemental oxygen. CBF was significantly higher in group I than in group II (CBF median (interquartile range): 15.9 (13.6-21.9) v 12.2 (10.7-13.8) ml/100 g/minute). Differences in oxygen exposure seemed to be the only explanation for the differences in CBF. No differences in short term outcome were found between the groups.

Blood Flow Velocity↗

Prenatal stressors of human life affect fetal brain development.

In a population-based study, 3021 women in a central Copenhagen district received a questionnaire on environmental and psychological factors during mid-gestation. Of these, 70 women were selected consecutively on the basis of moderate to severe stressful life-events (DSM-III-R categories 3 to 5), in combination with an inadequate social network. They were compared with 50 non-stressed women with an intact social network. Stress and smoking significantly affected birthweight and head circumference. When birthweight was corrected, stress remained a significant determinant of small head circumference, indicating a specific effect on brain development. Stress also led to a suboptimal Prechtl neonatal neurological score. These findings suggest the existence of a fetal stress syndrome with adverse effects on fetal development, including deficient brain development.

Brain↗

Low neonatal cerebral oxygen delivery is associated with brain injury in preterm infants.

Neonatal cerebral oxygen delivery was estimated in 93 preterm infants (gestational age < 34 weeks) who survived the neonatal period. Of these, 26 had developed neurological handicap at follow-up 1.7-4.6 years later. Neonatal cerebral oxygen delivery was dependent on gestational age, and was also related to the degree of intra-uterine growth retardation, carbon dioxide tension, and blood glucose concentration. Lower oxygen delivery was observed in infants who developed germinal layer haemorrhage or periventricular leucomalacia compared with infants with normal brains. However, as no information on cerebral metabolic demand or oxygen extraction is available, it is unclear whether decreased oxygen delivery is a contributing factor to brain damage or whether it is a marker of existing injury.

Birth Weight↗

Magnetic resonance imaging in juvenile Canavan disease.

We present a 2-year-old boy and a 6-year-old girl with mild Canavan disease (CD). Aspartoacylase activity in skin fibroblasts was deficient. Magnetic resonance imaging (MRI) of the brain did not show the prominent leucodystrophy previously reported in CD, but there was a hyperintense signal from the lentiform nuclei and the heads of the caudate nuclei on the T2-weighted MR images. This suggests a specific vulnerability of the corpus striatum in these patients. In the older patient, the white matter became affected at the age of 6 years. Proton magnetic resonance spectroscopy (1H-MRS) of white matter revealed a normal concentration of N-acetyl-L-aspartate (NAA) and a markedly decreased concentration of choline containing compounds (Cho) in the boy but a normal ratio of NAA to Cho in the girl. We conclude that deficient NAA catabolism affects myelin metabolism. This may present as changes in the striatum and/or as a low concentration of Cho before leucodystrophy appears on MRI.

Amidohydrolases↗

Comparison of the effects of phenobarbitone and morphine administration on EEG activity in preterm babies.

Continuously recorded amplitude-integrated EEG (aEEG) traces of 77 preterm babies were analysed retrospectively, to study the effect of different sedative drugs over a 24-h period. Thirty-seven babies were treated with phenobarbitone, 18 received morphine and 22 babies received no regular sedation. A "burst" was defined as a discharge of integrated amplitude greater than 10 microV and maximum interburst intervals in 10-min epochs over a 2-h period were measured. Maximum interburst was prolonged in babies given either morphine or phenobarbitone for sedation. Administration of a single dose of diazepam for intubation had a marked additive effect on the EEG depression caused by the base sedative and prolonged the effect for 11 to 12 h after drug administration. We conclude that the effect of sedative drugs must therefore be accounted for when interpreting records of quantified EEG for 12 to 24 h after drug administration.

Calcium↗

Estimation of cerebral venous saturation in newborn infants by near infrared spectroscopy.

The purpose of the study was to evaluate the near infrared spectroscopy technique for determination of the cerebral venous oxygen saturation. By tilting the patient's head down 15 degrees, changes in OD may be caused by changes in cerebral blood volume. On the assumption that increases in cerebral blood volume consist of venous blood only, cerebral venous oxygen saturation can be calculated as the measured change in oxygenated Hb divided by the change in total Hb. Two groups of mechanically ventilated, newborn infants were investigated: 10 asphyxiated, term infants and another 22 preterm infants with respiratory distress syndrome. All were monitored by near infrared spectroscopy during tilting, and cerebral blood flow was estimated by the 133Xe clearance technique immediately before tilting. Cerebral venous oxygen saturation could not be calculated in 13 preterm infants, as the blood volume remained constant during tilting. In the remaining 19, cerebral venous oxygen saturation averaged 0.67 (SD = 0.09) in asphyxiated infants and 0.53 (SD = 0.15) in preterm infants (p = 0.03). The corresponding values of cerebral blood flow were closely and inversely related to oxygen extraction calculated from cerebral venous saturation as estimated by near infrared spectroscopy.

Asphyxia Neonatorum↗

Changes in cerebral oxygenation and cerebral blood volume during endotracheal suctioning in ventilated neonates.

The effect of endotracheal suctioning on cerebral haemodynamics was investigated in 29 newborn infants with a mean gestational age of 31 weeks (range 25-40 weeks). Prior to one of two suctioning procedures, the inspiratory fraction of oxygen was increased by 10%. Brain oxygenation and total haemoglobin concentration were estimated continuously by near infrared spectroscopy. Mean arterial blood pressure, arterial blood oxygen saturation and carbon dioxide tension were recorded simultaneously. Brain oxygenation decreased in parallel with arterial oxygen saturation during suctioning. Preoxygenation ameliorated the decrease in brain oxygenation and arterial oxygen saturation whereas there was no benefit with regard to the changes in total haemoglobin concentration, carbon dioxide tension or mean arterial pressure. Changes in total haemoglobin concentration were related closely to concomitant changes in carbon dioxide tension (p less than 0.0001) but unrelated to changes in mean arterial pressure or arterial oxygen saturation. Our findings suggest that cerebral blood volume may react to changes in carbon dioxide tension during endotracheal suctioning in mechanically ventilated neonates. Apparently, preoxygenation prior to suctioning does not ameliorate the stress in normoxic infants.

Blood Pressure↗