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Background: In mechanically ventilated preterm infants with respiratory distress syndrome (RDS), exogenous surfactant application has been demonstrated both to decrease DNA-synthesis but also and paradoxically to increase epithelial cell proliferation. However, the effect of exogenous surfactant has not been studied directly on alveolar type II cells (ATII cells), a key cell type responsible for alveolar function and repair., Objective: The aim of this study was to investigate the effects of two commercially available surfactant preparations on ATII cell viability and DNA synthesis., Methods: Curosurf® and Alveofact® were applied to two ATII cell lines (human A549 and mouse iMATII cells) and to primary rat ATII cells for periods of up to 24 h. Cell viability was measured using the redox indicator resazurin and DNA synthesis was measured using BrdU incorporation., Results: Curosurf® resulted in slightly decreased cell viability in all cell culture models. However, DNA synthesis was increased in A549 and rat ATII cells but decreased in iMATII cells. Alveofact® exhibited the opposite effects on A549 cells and had very mild effects on the other two cell models., Conclusion: This study showed that commercially available exogenous surfactants used to treat preterm infants with RDS can have profound effects on cell viability and DNA synthesis.

Background and Aim: Preterm birth is the major cause of infant mortality and morbidity in both developed and developing countries. In Europe, the prevalence rate of premature birth ranges from 5.5 to 11.4% - an average of 7.1% of all live births. In this report, we aim to compare the current health and social policies, as well as practices in 13 EU member states., Materials and Methods: Using desk research, relevant information was gathered from each of the 13 European countries with regard to the prevalence of preterm birth, the cost of preterm birth to healthcare budgets, and the relevant policies, guidelines and practices in place at the national and, in some cases, regional level. The information comes from a range of sources, including government and parent association websites, published scientific literature and media reports., Results: Despite the growing prevalence and increasing costs, neonatal and preterm infant health rank low on the policy agendas of EU member states., Conclusion: Based on the findings, there are a number of recommendations that should be considered. The European Union should (i) recognize the growing challenge of prematurity in Europe and its significant impact on infant morbidity and mortality, (ii) improve neonatal health through the development and implementation of coordinated EU health and social policies, (iii) address the lack of comparable European data on prematurity, including prevalence, mortality, acute morbidity and long-term impairment, (iv) also increase the standard of neonatal care across Europe by supporting the development and implementation of European medical guidelines and quality standards, (v) support the development of European postgraduate training programmes in Peri- and Neonatology in order to increase the quality and availability of trained healthcare professionals., (© 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.)

Background: Perinatal brain injury in preterm infants is a major cause of neurological handicap. The role of the neurotrophin receptor p75 (p75(NTR)) in the pathogenesis and repair of neonatal excitotoxic brain injury is unknown. Depending on a complex interplay of neurotrophin signalling, p75(NTR) can, in addition to its trophic function, also induce apoptosis., Hypothesis: We hypothesised that excitotoxicity increases p75(NTR) expression and p75(NTR) knockout (KO) mice have a significantly smaller lesion size upon excitotoxicity as compared to wild-type (WT) mice., Methods: We used an established animal model of neonatal excitotoxic brain injury mimicking several key aspects of human preterm brain damage. We subjected five-day-old WT and KO mice to excitotoxic injury by means of a single intracranial ibotenate injection (N-methyl-D-aspartate receptor agonist, NMDAR) into one brain hemisphere. Lesion size, number of activated caspase-3- and apoptosis-inducing factor (AIF)-positive cells were determined as outcome parameters. Gender analyses were taken into account retrospectively., Results: NMDAR-mediated excitotoxicity induced an upregulation of p75(NTR) expression in the peri-lesion area. Lesion size was significantly increased in female KO as compared to male KO animals. Knockout of p75(NTR) reduced the number of activated caspase-3 but not AIF-positive cells after NMDAR-mediated excitotoxic injury independently of gender., Conclusion: Since NMDAR-mediated excitotoxic brain injury induced p75(NTR) expression and caspase-3-activated apoptosis in p75(NTR) KO animals was decreased, we conclude that activation of p75(NTR) contributes to NMDAR-mediated apoptosis in the neonatal brain. An increase in lesion size in female animals after excitotoxic brain injury suggests that in females p75(NTR) seems to play a dual role., (Copyright © 2010 Elsevier B.V. All rights reserved.)

Objective: Mild hypothermia after perinatal hypoxic-ischemic encephalopathy (HIE) reduces neurologic sequelae without significant adverse effects, but studies are needed to determine the most-efficacious methods., Methods: In the neo.nEURO.network trial, term neonates with clinical and electrophysiological evidence of HIE were assigned randomly to either a control group, with a rectal temperature of 37°C (range: 36.5-37.5°C), or a hypothermia group, cooled and maintained at a rectal temperature of 33.5°C (range: 33-34°C) with a cooling blanket for 72 hours, followed by slow rewarming. All infants received morphine (0.1 mg/kg) every 4 hours or an equivalent dose of fentanyl. Neurodevelopmental outcomes were assessed at the age of 18 to 21 months. The primary outcome was death or severe disability., Results: A total of 129 newborn infants were enrolled, and 111 infants were evaluated at 18 to 21 months (53 in the hypothermia group and 58 in the normothermia group). The rates of death or severe disability were 51% in the hypothermia group and 83% in the normothermia group (P=.001; odds ratio: 0.21 [95% confidence interval [CI]: 0.09-0.54]; number needed to treat: 4 [95% CI: 3-9]). Hypothermia also had a statistically significant protective effect in the group with severe HIE (n=77; P=.005; odds ratio: 0.17 [95% CI: 0.05-0.57]). Rates of adverse events during the intervention were similar in the 2 groups except for fewer clinical seizures in the hypothermia group., Conclusion: Systemic hypothermia in the neo.nEURO.network trial showed a strong neuroprotective effect and was effective in the severe HIE group.

Objective: To evaluate the efficacy of systemic hypothermia when applied within 10 hours after birth to neonates with hypoxic-ischemic encephalopathy (HIE)., Study Design: Ninety-three term infants with moderate-to-severe HIE were randomly assigned to either systemic hypothermia (n = 46) or conventional treatment (n = 47). Hypothermia was induced within 10 hours after birth, decreasing rectal temperature to 33.5°C for 72 hours, followed by slow rewarming to 36.5°C. Neurodevelopmental outcome was assessed at 18 months old. The primary outcome was death or moderate-to-severe disability., Results: Outcome data were available for 82 infants. Death or moderate-to-severe disability occurred in 21 of 44 infants (47.7%) in the control group and in 7 of 38 infants (18.4%) in the hypothermia group (P = 0.01) at 18 months. The primary outcome was not different whether hypothermia was started within 6 hours or 6 to 10 hours after birth. Subgroup analysis suggested that systemic hypothermia improved long-term outcome only in infants with moderate HIE (P = 0.009), but not in those with severe HIE. No severe hypothermia-related adverse events were observed., Conclusion: Systemic hypothermia reduced the risk of disability in infants with moderate HIE, in accordance with earlier studies. Hypothermia was induced within 6 hours in most infants, but delaying the onset to 6 to 10 hours after birth did not negatively affect primary outcome. Further studies with a large number of patients are needed to confirm that delayed cooling is equally effective.

Objective: The purpose of this study was to evaluate the efficacy and safety of erythropoietin in neonatal hypoxic-ischemic encephalopathy (HIE), by using a randomized, prospective study design., Methods: A total of 167 term infants with moderate/severe HIE were assigned randomly to receive either erythropoietin (N = 83) or conventional treatment (N = 84). Recombinant human erythropoietin, at either 300 U/kg (N = 52) or 500 U/kg (N = 31), was administered every other day for 2 weeks, starting <48 hours after birth. The primary outcome was death or disability. Neurodevelopmental outcomes were assessed at 18 months of age., Results: Complete outcome data were available for 153 infants. Nine patients dropped out during treatment, and 5 patients were lost to follow-up monitoring. Death or moderate/severe disability occurred for 35 (43.8%) of 80 infants in the control group and 18 (24.6%) of 73 infants in the erythropoietin group (P = .017) at 18 months. The primary outcomes were not different between the 2 erythropoietin doses. Subgroup analyses indicated that erythropoietin improved long-term outcomes only for infants with moderate HIE (P = .001) and not those with severe HIE (P = .227). No negative hematopoietic side effects were observed., Conclusion: Repeated, low-dose, recombinant human erythropoietin treatment reduced the risk of disability for infants with moderate HIE, without apparent side effects.

Objective: Nerve growth factor (NGF), a neurotrophin, is induced in lung cells by proinflammatory cytokines, and has a role in bronchial hyperreactivity and lung tissue repair. Ventilation induced lung injury, on the other hand, is known to increase the levels of proinflammatory cytokines in the lungs. We investigated whether, and to what extent, various degrees of lung injury induced by short-term ventilation affect NGF levels in the lung tissue of adolescent rabbits., Methods: The rabbits were randomized to different modes of ventilation: (1) CON: normal ventilation for 30 min; (2) NVT: normal ventilation for 6 hr; (3) HFQ: ventilation for 6 hr at double frequency, but normal tidal volume (VT); and (4) HVT: 6 hr ventilation at double VT but normal frequency., Results: NGF protein was detected in bronchoalveolar lavage fluid (BALF) and lung tissue in all animals. Ventilation for 6 hr significantly increased NGF levels, in both BALF and lung tissue, in the HFQ and HVT groups as compared to control (P < 0.05). The maximum increase in BALF NGF was seen in the HVT group (P = 0.02 vs. CON and NVT groups, and P = 0.05 vs. HFQ). A parallel increase in interleukin 1-beta (IL1-beta) was observed. Expression of the high-affinity NGF-receptor, tropomyosin-related kinase A (TrkA), was also upregulated in these two groups., Conclusion: Injurious modes of mechanical ventilation upregulate NGF and its receptor TrkA in rabbit lungs, and IL1-beta may be a mediator for this response. We speculate that this increase in NGF level may translate into the development of bronchial hyperreactivity.

Recent evidence suggests that the current ILCOR guidelines regarding hypothermia for the treatment of neonatal encephalopathy need urgent revision. In 2005 when the current ILCOR guidelines were finalised one large (CoolCap trial, n=235) and one small RCT (n=67), in addition to pilot trials, had been published, and demonstrated that therapeutic hypothermia after perinatal asphyxia was safe. The CoolCap trial showed a borderline overall effect on death and disability at 18 months of age, but significant improvement in a large subset of infants with less severe electroencephalographic changes. Based on this and other available evidence, the 2005 ILCOR guidelines supported post-resuscitation hypothermia in paediatric patients after cardiac arrest, but not after neonatal resuscitation. Subsequently, a whole body cooling trial supported by the NICHD reported a significant overall improvement in death or disability. Further large neonatal trials of hypothermia have stopped recruitment and their final results are likely to be published 2009-2011. Many important questions around the optimal therapeutic use of hypothermia remain to be answered. Nevertheless, independent meta-analyses of the published trials now indicate a consistent, robust beneficial effect of therapeutic hypothermia for moderate to severe neonatal encephalopathy, with a mean NNT between 6 and 8. Given that there is currently no other clinically proven treatment for infants with neonatal encephalopathy we propose that an interim advisory statement should be issued to support and guide the introduction of therapeutic hypothermia into routine clinical practice.

Background: Inflammation and reactive oxygen species (ROS) are important in the development of perinatal brain injury. The ROS-generating enzyme NADPH oxidase (Nox2) is present in inflammatory cells and contributes to brain injury in adult animal models., Hypothesis: NADPH oxidase contributes to ROS formation and development of injury in the immature brain and inhibition of NADPH oxidase attenuates perinatal brain injury., Methods: We used animal models of term hypoxia-ischemia (HI) (P9 mice) as well as ibotenate-induced excitotoxic injury (P5 mice) mimicking features of periventricular leukomalacia in preterm infants. In vitro microglia cell cultures were used to investigate NADPH oxidase-dependent ROS formation. In vivo we determined the impact 1) of HI on NADPH oxidase gene expression 2) of genetic (gp91-phox/Nox2 knock-out) and 3) of pharmacological NADPH oxidase inhibition on HI-induced injury and NMDA receptor-mediated excitotoxic injury, respectively. Endpoints were ROS formation, oxidative stress, apoptosis, inflammation and extent of injury., Results: Hypoxia-ischemia increased NADPH oxidase subunits mRNA expression in total brain tissue in vivo. In vitro ibotenate increased NADPH oxidase-dependent formation of reactive oxygen species in microglia. In vivo the inhibition of NADPH oxidase did not reduce the extent of brain injury in any of the animal models. In contrast, the injury was increased by inhibition of NADPH oxidase and genetic inhibition was associated with an increased level of galectin-3 and IL-1beta., Conclusion: NADPH oxidase is upregulated after hypoxia-ischemia and activated microglia cells are a possible source of Nox2-derived ROS. In contrast to findings in adult brain, NADPH oxidase does not significantly contribute to the pathogenesis of perinatal brain injury. Results obtained in adult animals cannot be transferred to newborns and inhibition of NADPH oxidase should not be used in attempts to attenuate injury.

Enhanced glutamate release and inflammation play an important role in the pathogenesis of developmental brain injury. Although N-methyl-d-aspartate receptor (NMDAR) antagonists potently attenuate neonatal brain damage in several animal models, they can also impact trophic functions in the developing brain. As a consequence, high-affinity NMDAR antagonists have been shown to trigger widespread apoptotic neurodegeneration in the newborn brain. Dextromethorphan (DM), a low-affinity NMDAR antagonist with anti-inflammatory properties, may be neuroprotective against excitotoxic and inflammation-enhanced excitotoxic brain injury, without the associated stimulation of apoptotic degeneration. Using an established newborn mouse model of excitotoxic brain damage, we determined whether systemic injection of DM significantly attenuates excitotoxic lesion size. We investigated several doses and time regimens; a dose of 5 microg/g DM given in a combination of both pre-injury and repetitive post-injury treatment proved most effective. DM treatment significantly reduced lesion size in gray and white matter by reducing cell death as shown by a decreased Fluoro-Jade B staining and caspase-3 activation. Pre-treatment with interleukin-1beta and lipopolysaccharide enhanced NMDAR-mediated excitotoxic brain injury and microglial cell activation. This sensitizing effect was abolished by DM treatment, as the effectiveness of DM in reducing lesion size and microglial cell activation was similar to phosphate-buffered saline-pre-treated controls. In all cases, no gender-specific differences were detected. DM treatment did not trigger any apoptotic neurodegeneration (caspase-3 cleavage, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling, Fluoro-Jade B staining). Although functional parameters were not measured, our data corroborate reports that DM is neuroprotective and that it may therefore improve functional outcome following perinatal brain injury.

Background: Periventricular leukomalacia (PVL) is a major cause of neurological handicap in pre-term infants. At present, there are no effective or causal therapies available. Thyroid hormones play an essential role in brain development and are reported to be decreased in pre-terms and following brain injury in adults., Hypothesis: Excitotoxic brain damage of newborn mice decreases thyroid hormone concentrations. Exogenous T3 administration restores thyroid hormone levels and reduces perinatal brain damage in an animal model of PVL., Design and Method: To create white and gray matter (WM/GM) lesion mimicking several key aspects of PVL, we injected ibotenic acid (Ibo), a glutamate analog, into the right hemisphere (intracranially (i.c.)) of 5-day-old mice. T3 (10 microg/kg body weight (bw)) was injected intraperitoneally (i.p.) 1 h or repeatedly 1/24/48/72/96 h post-insult. We determined lesion size, number of apoptotic cells in WM/GM and serum T3/T4 concentration at 24 and 120 h after injury. Serum T3/T4 concentration was also determined before and 1 and 2h after T3 administration., Results: Excitotoxic brain damage did not alter serum T3/T4 concentrations within 120 h of injury. Serum T3 levels were distinctly elevated within 1 h of T3 injection; however, this elevation was relatively short-lived (half-life estimated to be less than 12 h). Neither single nor repetitive T3 treatment regimen reduced excitotoxic lesion size, but it did reduce apoptosis., Conclusions: T3 replacement does not prevent excitotoxic cell death, but it does reduce developmental neuronal apoptosis, which could participate to the beneficial neuropsychological effects of hormone therapy. Further study is therefore warranted.

The purpose of this study was to characterize the effects of doubling minute ventilation (either by doubling ventilator frequency [Freq] or tidal volume [V T]) and of normal minute ventilation prolonged to 12-fold duration, synchronously at biophysical, biochemical/cellular, histological, and transcriptional levels in a model of mild lung injury. A prospective, randomized study was performed on adolescent New-Zealand white rabbits. The rabbits were randomly assigned to one of the following groups: control (normal minute ventilation for 0.5 hours); 1 x V T, 12-fold prolongation at normal V T (normal minute ventilation for 6 hours [12 x 0.5 hours]); 2 x Freq at normal V T (double minute ventilation for 6 hours); and 2 x V T at normal Freq (double minute ventilation for 6 hours). Normocapnia was maintained throughout the experiment. At the biophysical level, gas exchange (alveolar-arterial O2-tension difference [ AaDO2]) deteriorated by 23, 51, and 95%, and respiratory compliance decreased by 6.0, 18.4, and 26% in the 1 x V T, 2 x Freq, and 2 x V T group, respectively, during 6 hours of ventilation. Concomitantly, at the biochemical-cellular level, interleukin-8 (IL-8) in the bronchoalveolar lavage fluid increased 44-fold, 150-fold, and 275-fold ( P = 0.02), respectively. The white blood cell count decreased significantly in all three intervention groups. At the histological level, the influx of leukocytes as well as the tissue water content increased in proportion to the degree of injury. At the transcriptional level, lung IL-8 mRNA expression increased 11-fold in the 2 x V T group ( P = 0.002), 9-fold ( P = 0.02) in the 2 x Freq group, and 4-fold in the 1 x V T group as compared with control. Not only doubling V T, but also doubling Freq at normal V T injures the lung significantly, although to a lesser extent. A concept of weighted risk for increases of V T and Freq is proposed.

Using an established mouse model of human periventricular leukomalacia, we investigated whether EPO could reduce excitotoxic damage. When administered 1 h following intracerebral injection of 10 microg ibotenic acid at day 5 of life, both a single injection of EPO (5000 IU/kg bw) and repetitive administrations of EPO reduced white and gray matter lesion size. The therapeutic window for protection was small as the protective effect of EPO was lost when EPO administration was delayed to 4 h post-insult. EPO-mediated upregulation of EPO-R, but not EPO, mRNA was observed within 4 h of the excitotoxic insult. The EPO effect was gender independent. Minor hematopoetic effects were observed following EPO treatment. We conclude that a single dose of EPO is sufficient to reduce excitotoxic brain injury and may therefore possess therapeutic relevance in the clinical setting.

Granulocyte-colony stimulating factor (G-CSF) has been shown to reduce brain lesion size and mortality in adult mice after hypoxic-ischemic injury. Another hematopoietic growth factor, stem cell factor (SCF), has been shown to be up-regulated in the brains of adult rodents following brain damage, where it stimulates postlesional neurogenesis. Injection of the excitotoxic agent ibotenate into the brain of newborn mice produces a brain lesion characterized by neuronal death and white matter cysts, which is similar to periventricular leucomalacia. The aim of the present study was to investigate whether administration of SCF and G-CSF is neuroprotective against ibotenate lesions in neonatal mice. Contrary to our expectations, cortical and white matter brain lesions induced by ibotenate were enhanced following the administration of 50 microg/kg SCF or 200 microg/kg G-CSF. Dose-response studies indicated that G-CSF could increase grey matter lesions even at lower dosages (22 and 66 microg/kg). Administration of SCF and G-CSF in combination also increased cortical and white matter lesions, to 133 +/- 8% and 187 +/- 12%. In the undamaged brain, G-CSF or G-CSF+SCF treatment had no effect on apoptosis in the grey or white matter; however, these treatments significantly increased apoptosis in the damaged brain. Our data clearly demonstrate that G-CSF and SCF are not neuroprotective and result in deleterious enhancement of excitotoxic brain damage in newborn mice. We conclude that G-CSF and SCF should be used cautiously in newborn infants with brain lesions; if they are used, long term neurologic and neurodevelopmental follow-up is warranted.

The effectiveness of hypothermia in preventing ischemic brain damage depends on when it is started. The purpose of this study was to investigate the effects of temperature reduction during a hypoxic-ischemic (HI) insult on brain injury and signalling pathways of neuronal cell death and survival. Seven-day-old mice were subjected to left common carotid artery ligation and hypoxia (10% oxygen) at different temperatures (37, 36 or 34 degrees C) for 50 min. Brain injury at 7 days post-HI was significantly reduced from 67.4% at 37 degrees C to 31.6% at 36 degrees C and 10% at 34 degrees C, with no observable injury in the cortex of the 34 degrees C group. Cytochrome c release, caspase-3 activation and apoptosis-inducing factor translocation from mitochondria to nuclei were all significantly inhibited after intraischemic temperature reduction. Concurrently, the cell survival signalling pathway involving Akt was significantly sustained (the phosphorylated form of Akt was maintained) when the hypoxia temperature was decreased. These results indicate that intraischemic hypothermia diminished apoptosis through inhibition of both caspase-dependent and caspase-independent neuronal cell death pathways and promoted cell survival by inhibition of phosphorylated Akt dephosphorylation in the neonatal brain, thereby preventing neuronal cell death.

Objectives: Exchanging amniotic fluid (AF) with perfluorocarbon (PFC) may serve as a medium for fetoscopic surgery. This study evaluates the distribution and physiologic effects of intraamniotic PFC as a medium for fetoscopy., Methods: Fetuses of 17 pregnant rabbits underwent either exchange of the AF with PFC, electrolyte solution (ES), or control. The quality of vision during fetoscopy was assessed in AF and PFC. After 6 h, we determined the distribution of PFC in the maternofetal unit., Results: Quality of vision during fetoscopy was better in PFC than with AF. There was no difference in fetal survival between the study groups. PFC was demonstrated on X-ray in the pharynx of 4 fetuses, and the esophagus in 1., Conclusions: PFC provided an ideal medium for fetoscopy without fetal compromise., (Copyright (c) 2005 S. Karger AG, Basel.)

Background: Instilling perfluorooctyl bromide (PFOB) into the fetal lung may lead to alveolar distension., Objective: The aim of the study was to evaluate the safety of PFOB instillation into fetal lungs and to determine the radiographic distribution and tissue concentration of PFOB in New Zealand white rabbits., Methods: Sibling fetuses of pregnant (day 27) New Zealand white rabbits were randomized to intratracheal instillation of 1 mL PFOB with tracheal ligation, instillation without ligation, and unmanipulated controls. The maternal animals were killed directly after instillation, at 3 or 6 hours (n = 10 each). For each study cohort, we determined fetal lung/body weight (FLBW) ratios, the radiographic distribution of PFOB, as well as pulmonary PFOB and water content by tissue distillation. PFOB concentrations in maternal and fetal tissues were assessed by gas chromatography., Results: The relative amount of fetal lung PFOB recovered by fractional distillation was highest in ligated (25%) and lower in unligated lungs (9%). Extrapulmonary PFOB was found in the fetal brain (2.0 +/- 0.7 ppm), but not in any other fetal or maternal tissues. Mean FLBW ratios were highest in ligated fetuses, followed by unligated fetuses and controls. PFOB partially displaced fetal lung water. PFOB was visible in the lungs of all treated fetuses. Fetal survival between manipulated and unmanipulated fetuses did not differ., Conclusions: After prenatal intrapulmonary instillation, some PFOB remains in the lung, even if the trachea is not ligated, and may exert distending pressure on the alveoli.

Background/purpose: Fetal tracheal occlusion (TO) accelerates lung growth but decreases surfactant production. We have previously shown that instillation of perfluorooctylbromide (PFOB) into fetal rabbit lungs leads to lung growth similar to TO. This study compares neonatal lung mechanics and surfactant production after prenatal intrapulmonary PFOB instillation vs TO., Methods: In each of 18 pregnant rabbits on gestational day 27, sets of 4 fetuses underwent either (1) intrapulmonary instillation of 1 mL PFOB, (2) TO, (3) instillation of 1 mL 0.9% NaCl (saline), and (4) hysteroamniotomy without fetal manipulation (control). Fetuses were born by cesarean delivery after 48 hours. Fetuses of 12 rabbits were mechanically ventilated for 15 minutes to evaluate lung compliance and airway resistance. Pulmonary surfactant protein B (SP-B) was quantified by immunohistochemistry in fetuses of the remaining 6 rabbits., Results: Compliance was decreased in the TO group after cesarean delivery (0.33 +/- 0.13 mL/cm H2O) compared with PFOB (0.59 +/- 0.12 mL/cm H2O), saline (0.50 +/- 0.12 mL/cm H2O), and control (0.52 +/- 0.10 mL/cm H2O) fetuses. Mean fetal lung to body weight ratio was higher in TO and PFOB fetuses compared with saline and control. Higher water content and lower numbers of surfactant protein B-positive cells were found in the TO-treated fetuses., Conclusions: Both prenatal intrapulmonary instillation of PFOB and TO accelerate lung growth, but TO is associated with decreased postnatal lung compliance, possibly influenced by decreased surfactant production and increased fluid retention. Conversely, instillation of PFOB preserved lung compliance and surfactant synthesis.

We investigated whether premature infants nursed at the upper range of normal body temperature are more capable of maintaining their nasopharyngeal and rectal temperature when exposed to a 1 degrees C increase or a 1 degrees C decrease of incubator temperature. In a randomized controlled trial, premature infants were exposed to a 1 degrees C increase (T + 1 degrees C; n = 10), or to a 1 degrees C decrease (T - 1 degrees C; n = 10) of incubator temperature. Nasopharyngeal, rectal, and skin temperatures as well as heat flux at various sites, heart rate, and activity were measured over a 6-hour period. The absolute changes in core temperatures, Tnasoph and Trectal, were significantly greater in the T + 1 degrees C compared with T - 1 degrees C (T + 1 degrees C versus T - 1 degrees C: Tnasoph 0.44 +/- 0.31 degrees C and 0.18 +/- 0.14 degrees C respectively; p < 0.001; T(rectal) 0.43 +/- 0.30 degrees C and 0.25 +/- 0.10 degrees C, respectively; p < 0.01) when exposed to the increase or decrease in incubator temperature. Premature infants are less able to cope with increases in incubator temperature given that rectal and nasopharyngeal temperature change more when environmental temperature is increased.

The study's aim was to evaluate whether prenatal instillation of perfluorooctylbromide (PFOB, a perfluorocarbon) into the lungs of fetal rabbits leads to increased lung growth. Hysteroamniotomy was performed in eight pregnant New Zealand white rabbits on gestational day 27. In each mother, four fetuses were randomized to undergo either 1) endotracheal intubation and intrapulmonary instillation of 1 ml PFOB, 2) intrapulmonary instillation of 1 ml 0.9% NaCl solution (saline), 3) no fetal manipulation (control), or 4) tracheal occlusion (TO). The distribution of PFOB was documented radiographically. The fetuses were born by cesarean section after 48 h, sacrificed, weighed, and their lungs excised. Fetal lung to body weight ratios (FLBW) were determined, and the lungs were snap frozen for histomorphologic analysis and lung tissue distillation. On macroscopic inspection, PFOB-filled and tracheally-occluded lungs were markedly larger than saline-filled and control lungs. Mean FLBW was higher in fetuses treated with intrapulmonary instillation of PFOB (0.037+/-0.009), compared with fetuses receiving saline (0.027+/-0.008) or the unmanipulated controls (0.028+/-0.008). FLBW was highest after TO (0.049+/-0.008). After 48 h, in-vivo radiographs did not demonstrate any residual PFOB. Average dry fetal left lung weight (in g) was much higher in the TO (0.064+/-0.029) and PFOB (0.062+/-0.016) fetuses compared with the saline (0.054+/-0.017) and control (0.043+/-0.012) groups. Alveolar architecture on microscopy was similar between all groups, although the alveolar septae appeared thicker and more cellular after PFOB treatment and TO. We concluded that prenatal intrapulmonary PFOB instillation leads to increased lung growth in the late gestation rabbit model. Although PFOB instillation resulted in lower wet FLBW than TO, the increase in dry lung weight is comparable. This novel technique may be a less invasive and less noxious treatment strategy for pulmonary hypoplasia associated with diaphragmatic hernia.

Hypothermia is possibly the single most effective method of neuroprotection developed to date. However, the mechanisms are not completely understood. The aim of this study was to investigate the effects of post-ischemic hypothermia on brain injury and apoptotic neuronal cell death as well as related biochemical changes after neonatal hypoxia-ischemia (HI). Seven-day-old rats were subjected to left common carotid artery ligation and hypoxia (7.8%) for 1 h. Systemic hypothermia was induced immediately after hypoxia-ischemia, and body temperature was maintained at 30 degrees C for 10 h. The normothermic group was kept at 36 degrees C. Brain infarct volumes and neuronal loss in the CA1 area of the hippocampus were significantly reduced at 72 h post-HI in the hypothermia group. Cytochrome c release and activation of caspase-3 and -2 at 24 h post-HI were significantly diminished by hypothermia. The numbers of cytochrome c- and TUNEL-positive cells in the cortex and dentate gyrus of the hippocampus were significantly reduced in the hypothermia group compared with the normothermia group at 72 h post-HI. These results indicate that hypothermia may, at least partially, act through inhibition of the intrinsic pathway of caspase activation in the neonatal brain, thereby preventing apoptotic cell death.

Objectives: (a) To investigate in a newborn animal model whether nasopharyngeal temperature is more closely related to epidural brain temperature than rectal temperature and (b) to investigate in human neonates whether measurement of nasopharyngeal temperature is dependent on the measurement site and other conditions., Design and Setting: (a) Animal experiment in newborn piglets, at an institute for surgical research. (b) Prospective study in human neonates, at a neonatal intensive care unit of a tertiary care university hospital. ANIMALS AND PATIENTS: (a) Nineteen tracheostomized ventilated newborn piglets. (b) Twenty-two spontaneously breathing human newborns nursed either in an incubator or a cot., Measurements and Results: (a) In the piglets nasopharyngeal temperature (Tnasoph) measured at the nose-ear distance, defined as distance from the inner brim of the nostril to the tragus and inner rim of the meatus accusticus, most closely reflected epidural temperature (Tepidur) at the epidural surface (r2 = 0.89), followed by skin temperature at the temple, rectal temperature (Trectum) at 2 cm depth, and esophageal temperature (Tesoph) in the middle esophagus. Tnasoph did not significantly differ before and after tracheostomy. (b) In the newborns Tnasoph was significantly lower than Trectum. Measurements of Tnasoph at nose-ear distance within a feeding tube had a high precision and were unaffected by breathing or head turning. A nasopharyngeal probe was imaged by magnetic resonance imaging in four newborns of various body weight; its tip when inserted to a depth equal to nose-ear distance was anatomically closest to the brain base but separated from it by tissue layer 2.2 cm thick., Conclusions: Tnasoph measured at a position anatomically closest to the brain reflects epidural brain temperature more closely than Trectum. When measured at nose-ear distance it is unaffected by breathing or head turning. Measuring Tnasoph within a feeding tube and standardizing the measuring position is crucial for its use as brain temperature analogue.

Objective: To study the impact of lung water content and its reduction by a topically applied diuretic on respiratory and lung tissue mechanics in comparison with surfactant administration in surfactant-deficient newborn piglets with lavage-induced lung injury., Design: Controlled, randomized study., Setting: Animal research facility., Subjects: Newborn piglets. TREATMENT Piglets were surfactant depleted by lung lavage and, after a pretreatment period, randomly treated with intratracheal furosemide, furosemide and surfactant, or with surfactant alone., Measurements and Main Results: Dynamic compliance (C(DYN)), static compliance (C(ST)), stress-adaptation pressures (P(DIFF)) and post mortem lung water content were determined. Static compliance in the furosemide-surfactant group was not significantly higher than in the surfactant group. At the end of the study, C(ST) did not differ between the three groups because C(ST) in the furosemide group had increased to values similar to those of the surfactant-containing treatment groups: C(ST) F+S: 0.73 +/- 0.2 mL/cm H2O/kg body weight (BW); C(ST) S: 0.61 +/- 0.11 mL/cm H2O/kg BW; and C(ST) F: 0.60 +/- 0.19 mL/cm H2O/kg BW). Compliance was inversely and P(DIFF) was directly correlated to lung water (LW) content (C(ST) vs. LW: r2 = .59, p = .001; C(DYN) vs. LW: r2 = .49, p = .006; P(DIFF) vs. LW: r2 = .37, p = .059), independent of the type of treatment. Changes in C(ST) and C(DYN) were inversely related to changes in P(DIFF). Intrapulmonary furosemide was more rapidly absorbed when administered to the surfactant-depleted lung alone compared with the mixture with surfactant, and intrapulmonary furosemide had a rapid systemic effect., Conclusion: Although the combination of surfactant with a diuretic failed to increase respiratory compliance to a significantly larger extent than surfactant alone, furosemide at the end of the study increased respiratory compliance to a level similar to surfactant-containing treatments. Lung water content and, to a lesser extent, the absence or presence of surfactant appeared to determine lung mechanics, and its impact on lung mechanics was similar to surfactant administration.

Objective: To assess the physiological effects and adverse side-effects of induced hypothermia in asphyxiated newborn infants as a base for future controlled, randomized trials., Design: Retrospective chart analysis with historical controls., Setting: Tertiary neonatal intensive care unit of the University of Cape Town, South Africa., Patients: Twenty-one asphyxiated newborns treated with induced hypothermia between September 1997 and February 1998 were compared to 15 asphyxiated newborn infants admitted during March to August 1997. The two groups of infants did not differ in patient characteristics or severity of asphyxia (comparison group vs hypothermia group: Apgar at 5 min 5.3 +/- 3.1 vs 5.2 +/- 2.3; base deficit 15.6 +/- 6.3 vs 11.5 +/- 7.2 and Thompson neurological score 10.1 +/- 4.0 vs 9.1 +/- 3.6)., Interventions: Hypothermia was induced by placing a cap formed from coolpacks, at a temperature of about 10 degrees C, around the head of asphyxiated newborn infants to maintain the nasopharyngeal temperature between 34 and 35 degrees C. Hypothermia was maintained for 3 days., Measurements and Results: In the comparison group 4/15 infants died and in the hypothermia group 4/21 died. Hypothermia was induced at a median of 6.0 h (range 45 min to 53 h) post-partum, maintained for an average of 80 h (median 77.5 h, range 22 to 185 h) and resulted in an average nasopharyngeal temperature of 34.6 +/- 0.5 degrees C. Hypothermia reduced abdominal skin temperature from 36.3 +/- 0.5 degrees C to 35.1 +/- 0.35 degrees C (p = 0.0001), heart rate from 139 +/- 21 to 121 +/- 13 beats/min (p < 0.0001) and respiratory rate from 67 +/- 11 to 56 +/- 9 breaths/min (p = 0.005). Neither episodes of bradycardia nor dysrhythmias, apnea, clinical signs of bleeding diathesis in the hypothermia group nor differences in the frequency of hypoglycaemia and urinary output, blood in urine or tracheal secretion between the two groups were observed. In the survivors the neurological score, assessed at day 2 and day 5, fell from 10.9 +/- 3.5 to 8.1 +/- 4.5 in the hypothermia group and rose from 8.1 +/- 2. 5 to 9.0 +/- 3.1 in the comparison group (p = 0.003)., Conclusions: Adverse effects of mild hypothermia induced for 3 days in asphyxiated newborns were significantly less than expected from previous reports on neonates with accidental hypothermia.

Background: Neonatal sepsis is a common and life-threatening disorder, particularly among preterm infants. Early initiation of antibiotic therapy is frequently delayed because the first clinical signs of sepsis are non-specific and there are no reliable early laboratory indicators. We investigated the time course of expression and the prognostic power of the early inflammatory mediators interleukin-1 receptor antagonist (IL-1ra), interleukin-6 (IL-6), and circulating intercellular adhesion molecule-1 (cICAM-1) before clinical diagnosis of sepsis., Methods: In a prospective multicentre study, we monitored 182 very-low-birthweight infants in six intensive-care units for occurrence of sepsis. During routine or clinically indicated blood sampling, an additional sample was collected for measurement of IL-1ra, IL-6, cICAM-1, and C-reactive protein (CRP). Infants were grouped into those with proven sepsis, no infection, or unclassified. The mean study duration was 34 days. Whenever sepsis occurred, a study period of 10 days was defined: day 0 was the day of clinical diagnosis of sepsis; days -4 to -1 were the 4 days before diagnosis; days +1 to +5 were the 5 days after. We compared the concentrations of the immune mediators during the 10-day study period with group-specific baseline values from before day -4., Findings: 101 infants were included in the analysis: 21 with proven sepsis, 20 with no infection, and 60 unclassified. We excluded 57 because of incomplete datasets and 24 who had early-onset sepsis. IL-1ra and IL-6 increased significantly 2 days before diagnosis of sepsis; maximum median increases within the study period were 15-fold for IL-1ra and 12-fold for IL-6. The diagnostic sensitivities of IL-1ra, IL-6, and CRP concentrations on day 0 of diagnosis were 93%, 86%, and 43%, respectively; corresponding values on day -1 were 64%, 57%, and 18%. The specificities of IL-1ra, IL-6, and CRP concentrations were 92%, 83%, and 93%. cICAM-1 had a specificity of only 64%., Interpretation: IL-1ra and IL-6 are superior to cICAM-1 and CRP as predictors of sepsis 1 or more days before clinical diagnosis. Ad-hoc measurement of these cytokines could allow earlier initiation of antibiotic therapy with corresponding improvement in outcome in very-low-birthweight infants with sepsis.

Objective: Recent studies have suggested direct pulmonary effects of furosemide in asthmatics and infants with bronchopulmonary dysplasia. We tested the hypothesis that intratracheally administered furosemide also increases respiratory compliance in children after cardiac surgery, and investigated whether furosemide has a topical and/or systemic action., Study Design: Prospective study with intra-individual control. In twelve infants and toddlers (age: 10 +/- 8 months, weight: 6.9 +/- 3 kg) mechanically ventilated for compromised lung mechanics after cardiac surgery, 0.5 mg/kg furosemide was intratracheally administered to the lungs. Lung mechanics were serially assessed using a computerised system (Sensormedics 2600) during a 2 h control and 2 h intervention period. Urine output was measured by an indwelling bladder catheter and levels of furosemide were determined in blood and tracheal aspirates., Results: Static compliance improved within 30 min in all patients, reached a maximum of 44 (20-85)% above baseline and remained improved throughout the study (p < 0.05). An immediate, short and significant diuretic effect of intratracheally applied furosemide was observed. Furosemide levels 1 h after intervention were 795 ng/ml in the blood and 431 micrograms/ml (i.e. 1000-fold higher) in the tracheal aspirate. Changes in compliance were correlated only to urine output values over the 2 h (r = 0.82, p = 0.044, n = 9) after furosemide administration., Conclusion: We conclude that intratracheally applied furosemide improves static compliance in infants and toddlers with compromised lung mechanics after cardiac surgery. We demonstrated that furosemide is absorbed from the lung and has a systemic effect within 15 min after its intratracheal instillation.

The shape of the volume-pressure (V/P) curve indicates alveolar collapse if it is convex to the pressure axis and indicates overdistension if it is concave. Positive end-expiratory pressure (PEEP) should either improve or decrease compliance and oxygenation in neonates ventilated for respiratory distress syndrome (RDS), depending on predominance of either alveolar collapse or overdistension. To test this hypothesis, we determined quasistatic V/P curves in 13 preterm neonates and characterized their shape by an alveolar distension index (ADI) at PEEP levels of 2, 4, and 6 cm H2O. We calculated the ADI dividing the V/P ratio at a low tidal volume by the V/P ratio at a high tidal volume. This ADI was then related to the effect of PEEP changes on respiratory compliance and alveolar to arterial oxygen tension difference (AaDO2). ADI was assumed to indicate alveolar collapse if less than 1 and overdistension if more than 1. An increased PEEP in neonates with alveolar collapse (ADI less than 1) decreased AaDO2 more (12 vs 10 mm Hg/cm PEEP, not significant) and decreased compliance less (3 vs 17%/cm PEEP; P < 0.05) than in those neonates with alveolar overdistension (ADI more than 1). Conversely, a decreased PEEP in neonates with alveolar overdistension increased compliance more (19 vs 5%; not significant) and increased AaDO2 less (7 vs 26 mm Hg; P < .01) than in those with alveolar collapse. AaDO2 and compliance changes after PEEP alterations were significantly correlated to the ADI before PEEP alterations (P < 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Brain temperature depends on the balance of cerebral heat production and heat loss via cerebral circulation and head surface. We investigated whether brain temperature and heat loss via the head surface differed in neonates with abnormal cerebral metabolism or circulation. We measured the core temperature of the head noninvasively by the zero-gradient method, skin temperature of the head, the heat flux from the head, and esophageal and operative environmental temperature in seven healthy neonates, seven neonates with cerebral damage, and two neonates with cerebral hypoperfusion caused by an incurable congenital heart disease. Cerebral blood flow velocity in the anterior cerebral artery and systemic blood pressure were also measured. Brain temperature profile was measured in two premature infants with external ventricular drainage. Core temperature of the head, considered to represent brain temperature, was up to 1.5 degree C higher in infants with cerebral hypoperfusion than in normal neonates. The core temperature of the head was higher than the esophageal temperature in all except two infants with the most severe cerebral damage. The difference between core temperature of the head and esophageal temperature was 0.72 +/- 0.12 degree C in normal neonates, 0.16 +/- 0.4 degree C in infants with cerebral damage, and ranged from 0.9 to 1.2 degree C in infants with cerebral hypoperfusion. The relationship of core of the head to esophageal temperature discriminated between all 16 newborn infants according to their brain pathologic condition, except one infant with a mild ischemic-hypoxic encephalopathy. In conclusion, brain temperature depends on cerebral perfusion and level of brain injury.(ABSTRACT TRUNCATED AT 250 WORDS)

We evaluated a bedside method of assessing respiratory compliance from chest expansion, which is judged by eye and classified into three tidal volume categories, and from the inflation pressure read on the respirator's manometer. Compliance assessed by this method was compared with the compliance measured by the injection technique in 45 randomly chosen newborns ventilated for various diseases. The compliance assessed from chest expansion and inflation pressure correlated significantly with the measured compliance (r = 0.86, p < 0.001). Interobserver reliability was acceptable for clinical practice and improved within 6 months of training (weighted kappa = 0.67 versus 0.86). Within ten individuals, changes of compliance assessed by this method were also significantly correlated with those of measured compliance (r = 0.85, p < 0.01). This method, termed "optical compliance," is instantaneously and always available for all patients on ventilators without any additional apparatus and thus might improve the assessment of respiratory function in routine care and emergency situations.

Postterm and growth-retarded fetuses share a common problem which can be characterized by a discrepancy between the supply of oxygen and nutrients to, and the demand of the fetus. But, this "insufficient" placental exchange function may also extend to and affect its thermal homeostasis; e.g. when the capacity of convective (placenta) pathways is shifted towards conductive (surface) pathways for heat loss. Therefore, fetal scalp heat flux measurements, where heat serves as an intrinsic tracer for metabolic activity and placental exchange function, promised a new kind of information. In 81 pregnant women during labor we measured fetal scalp heat flux by means of an heat flux transducer attached to the fetal head and after the cervix had dilated to 3 cm. In the healthy fetuses we found a positive linear relationship between scalp heat flux and different anthropometric variables such as body length (r = 0.432, n = 65, P less than 0.01), head circumference and gestational age. In comparison, postmature and growth-retarded fetuses showed higher heat flux values than appropriately grown fetuses of the same length head size and gestational age. Moreover, in those fetuses scalp heat flux decreased by approximately 4 watt/m2 during the second stage and differed in this regard from the control group who showed stable values during labor and delivery. We conclude that scalp heat flux measurements may indicate disturbances of placental exchange before acute hypoxia occurs.

Compliance of the respiratory system (CRS) is rarely measured in the critically ill neonate. Instead, inflation pressure (dP), amount of ventilation (dPxfr) and optical CRS are used as indirect parameters to characterize lung mechanics. In 30 randomly chosen newborns ventilated for various causes we investigated which of these bedside methods most accurately represents the compliance of the respiratory system. The correlation coefficient was much higher for the optically determined compliance (r = 0.91) than for the amount of ventilation (r = 0.67) or the inflation pressure alone (r = 0.46) versus the measured static compliance of the respiratory system.

In 40 deliveries a new variable, heat flux from the fetal scalp, was recorded and correlated with fetal outcome. The heat flux from the fetus, which reflects the temperature gradient between the warmer fetus and the mother was measured by a transducer attached to the fetal scalp after rupture of the membranes. In the last 20 min before delivery we found a statistically significant correlation (p less than 0.05) between heat flux from the fetus and pH of umbilical artery blood. Heat flux in the group with higher pH differed significantly from those with lower pH. We conclude that heat flux measurements could be developed and used for fetal monitoring.

A modified method for registering non-nutritive sucking behaviour with and without taste stimulation enabled us to study taste perception of premature babies. We wanted to study how babies who had no extrauterine taste experience reacted to one or more stimuli with water and 33% glucose. Eight randomly selected healthy newborns (three of them being SGA without further symptoms), exclusively fed by gastric tube, were studied. The mean gestational age at the time of the study was 35.5 weeks. They were studied five times with water and five times with glucose just before feeding. In seven babies the sucking response to glucose was greater than that to water from the first trial onwards. Sucking response increased with repeated glucose stimulation, but remained the same with water stimulation. The eighth baby behaved completely differently. We concluded from our results that premature babies with a postconceptional age of 35 weeks can discriminate between sweet and not-sweet. The greater sucking response to glucose than to water at the first trial implies a genetic factor in the preference for sweet in humans.

The role of histamine in physiological and pathological states has not been fully elucidated. In the pathological state histamine release can be induced by several mechanisms. The most frequent events are IgE-mediated release, complement-mediated release and release by chemical agents. During inflammation histamine is set free and contributes to the course of inflammatory processes, either enhancing or inhibiting inflammatory reactions. In order to look for a target in the glomerulum we examined H2 receptor binding to isolated glomerular cells using 3H-cimetidine as ligand. Two binding sites were detected, a low affinity site with a kD = 6.3 microM and a high affinity site exhibiting a kD = 0.18 microM. These findings are comparable to properties of 3H-cimetidine receptor binding to brain membranes.

During mechanical ventilation, inadvertent positive end-expiratory pressure (PEEP) can have deleterious effects, including decreasing lung compliance and alveolar ventilation. To detect and quantitate inadvertent PEEP in 10 preterm neonates receiving mechanical ventilation, we clamped the connection between the endotracheal tube and the respirator at end-expiration and, after about 5 seconds, measured the airway pressure resulting from the trapped gas that emptied into the airways and the measuring system. To study the effect of decreasing inadvertent PEEP on lung mechanics and gas exchange, we measured the compliance of the respiratory system and blood gases. Inadvertent PEEP greater than 1 cm H2O was detected in 19 of 29 measurements. Decreasing inadvertent PEEP by lengthening the expiratory time increased the compliance of the respiratory system (r = -0.74, n = 10, P less than 0.02). Decreasing inadvertent PEEP by greater than 1 cm H2O (mean 2.1 +/- 0.8 cm H2O) in six newborn infants increased respiratory compliance from 0.57 +/- 0.09 to 0.73 +/- 0.13 ml/cm H2O, or approximately 30%, and lowered Pco2 from 40.6 +/- 14.4 to 38.2 +/- 14.1 mm Hg despite a reduction in the level of ventilation set on the respirator. Knowing the amount of inadvertent PEEP and its effects can help improve mechanical ventilation in newborn infants.

Using the adenylate cyclase assay after Ross we examined hormone sensitivity of isolated glomerular cells. cAMP production was increased 1.3--1.6-fold by stimulation with isoproterenol, 1.5--1.8 times by prostaglandin E1 and 1.4--1.5 times by histamine. The isoproterenol reaction could be completely inhibited by propranolol, the histamine effect was abolished by the H2-blocking agent cimetidine. As control we applied sodium fluoride, which directly activates the catalytic adenylate cyclase unit, increasing the activity 1.8--2.7 times (depending on the method of homogenization). These findings could reflect some physiological or pathophysiological implications, which are discussed in the present report.

Transcutaneous PO2, heart rate, and aortic blood pressure were measured i 10 mechanically-ventilated newborn infants to assess the degree and course of hypoxaemia, and to monitor the cardiovascular and respiratory changes during tracheal toilet. Five infants weighed less than 1250 (mean 994), g and 5 infants weighed greater than 1750 (mean 2216) g. During tracheal suction the TcPO2 fell from 68 +/- 27 (mean +/- SD) to 43 +/- 23 mmHg, and the heart rate from 144 +/- 8 to 123 +/- 25 beats/minute, but the blood pressure increased from 44 to +/- 24 to 49 +/- 24 mmHg. Hypoxaemia (TcPO2 less than 50 mmHg) occurred in 7 of 8 initially well-oxygenated infants when suctioned. The decrease in TcPO2 was similar for both groups of infants. It was greater in infants with controlled ventilation and an F1O2 greater than or equal to 0.8 than in infants with intermittent mandatory ventilation and an F1O2 less than 0.8. The TcPO2 fall correlated well with the TcPO2 during the control period but not during the time that the infants were disconnected from the respirator. A critical re-evaluation of routine tracheal toilet is needed.

The possible existence of a chemical substance with cross-reactivity to digoxin antibodies in the neonatal serum or plasma was investigated in this study. Our data show that in contrast to previous reports, the levels of a "digoxin-like substance" in the serum or plasma of healthy newborns are negligible and probably would not affect the reliability of digoxin radioimmunoassay tests.

The compliance of the respiratory system (Crs) has been measured by an airway occlusion technique in 78 healthy newborn infants [gestational age (GA) 36.2 +/- 2.9 weeks, range 28-41 weeks; birth weight (BW) 2.418 +/- 0.879 kg, range 0.830-4.350 kg; body height (BH) 45.2 +/- 4.4 cm, range 33-52 cm in the first 8 h after birth (206.2 +/- 100.8 min, range 45-480 min). The prediction equations were (Crs, ml/cm H2O): Crs = 0.087.GA -1.173 (r = 0.49, p less than 0.0001), Crs = 0.372.BW +1.067 (r = 0.62, p less than 0.0001), Crs = 0.076.BH -1.493 (r = 0.61, p less than 0.0001). The Crs values were very similar to the values measured in curarized newborn infants and quoted in the literature. There was only one newborn infant with a Crs of less than 1 ml/cm H2O (GA = 34 weeks, BW = 0.830 kg, BH = 33 cm, Crs = 0.909 ml/cm H2O).