Bronchopulmonary dysplasia - prevalence, severity and predictive factors in a national cohort of extremely premature infants.

AIM: To study prevalence and predictive factors of bronchopulmonary dysplasia (BPD) in a cohort of preterm infants with a high incidence of prenatal steroid and surfactant treatment. METHODS: BPD was analysed in a national cohort of infants with gestational age (GA) of 22-27 completed weeks (wks) or birth weight (BW) of 500-999 g. Of 464 infants who were transferred to a NICU, 377 infants with GA ≤ 30 wks and survived beyond 28 days were included in the study. RESULTS: Moderate or severe BPD was strongly related to GA. Of infants with GA 22-25 wks, 67.3% developed BPD compared to 36.6% at GA 26-30 wks. Overall, moderate and severe BPD was significantly more common in boys (63.3%) than in girls (36.6%) (p = 0.0004), but female gender was not a protective factor in infants with GA 22-25 wks. In multivariate analyses, BPD was significantly associated with gender, surfactant treatment and treatment for PDA. CONCLUSIONS: BPD remains a severe complication of extreme prematurity in spite of prenatal steroids and surfactant treatment. Whether associations with surfactant and PDA treatment simply reflect severity of early lung disease or have causal relationships should probably be studied in randomized controlled trials.

Neonatal mortality and morbidity in extremely preterm small for gestational age infants: a population based study.

AIM: To assess if growth restricted (small for gestational age, SGA) extremely preterm infants have excess neonatal mortality and morbidity. METHODS: This was a cohort study of all infants born alive at 22-27 weeks' post menstrual age in Norway during 1999-2000. Outcomes were compared between those who were SGA, defined as a birth weight less than the fifth percentile for post menstrual age, and those who had weights at or above the fifth percentile. RESULTS: Of 365 infants with a post menstrual age of <28 weeks, 31 (8%) were SGA. Among infants with a post menstrual age of <28 weeks, only chronic lung disease was associated with SGA status (OR 2.7, 95% CI 1.0 to 7.2). SGA infants with a post menstrual age of 26-27 weeks had excess neonatal mortality (OR 3.8, 95% CI 1.3 to 11), chronic lung disease and a significantly higher mean number of days (age) before tolerating full enteral nutrition. SGA infants with a post menstrual age of 22-25 weeks had an excess risk of necrotising enterocolitis. CONCLUSION: Extremely preterm SGA infants had excess neonatal mortality and morbidity in terms of necrotising enterocolitis and chronic lung disease.

Mometasone furoate nasal spray in the treatment of perennial non-allergic rhinitis: a nordic, multicenter, randomized, double-blind, placebo-controlled study.

In order to evaluate the efficacy and safety of mometasone furoate nasal spray (MFNS) in patients with perennial non-allergic rhinitis (PNAR) a phase III, double-blind, randomized, placebo-controlled, Nordic multicenter study was performed at 16 sites (7 in Sweden, 3 in Denmark, 3 in Finland and 3 in Norway). A total of 329 patients (age 18-82 years) with a mean duration of PNAR of 9 years were included in the study. The total duration of the study was 11 weeks: 2 weeks of screening, 6 weeks of treatment and 3 weeks of follow-up. Inclusion criteria were unspecific rhinitis symptoms and exclusion criteria were a positive skin prick test as well as intolerance to aspirin or non-steroidal anti-inflammatory drugs. Endoscopy was performed to exclude patients with structural anomalies and nasal polyps. The primary efficacy variable was the subject's total overall evaluation. In the intention-to-treat (ITT) group of patients (n = 329) the improvement rates were 56% (MFNS) and 49% (placebo). In the per-protocol (PP) group (n = 251) the corresponding figures were 58% and 47%. Stratifying for groups of patients having moderate symptoms, the results were 54% vs 43% in the ITT group and 56% vs 41% in the PP group. The therapeutic response showed greater improvement in total nasal score as recorded by the investigator in the groups treated with MFNS as compared to the placebo group (p = 0.09 [PP], p = 0.14 [ITT]). Adverse events occurred during the study, upper respiratory tract infections and headache being the most frequently reported, but there was no statistically significant difference between MFNS and placebo. The results of this study indicate that MFNS is a safe and effective treatment for patients with PNAR.

[Clinical risk index for small premature infants]. / Klinisk risikoindeks for små premature.

BACKGROUND: The clinical risk index for babies (CRIB) is a score given to extremely small prematures as a tool for expressing initial sickness. It was developed in order to compare results among different neonatal intensive care units (NICUs). MATERIAL AND METHODS: The CRIB score was determined for prematures with birth weight < or = 1,000 g born at the Central Hospital in Akershus during the 1995-99 period. The results are measured as the survival rate until discharge. RESULTS: 45 babies where treated at our NICU during this five-year period. Median gestation age was 27 weeks (range: 23-32 weeks), median birth weight was 875 g (range: 475-1,000 g), median CRIB was 4 (range: 1-16). The survival rate until discharge was 89%. To validate the CRIB score as a predictor for hospital mortality, a receiver-operating curve (ROC) was constructed. The area under the ROC curve was 0.93. INTERPRETATION: CRIB proved to be a good predictor for hospital mortality and seems a useful indicator for initial sickness.

[Respiratory syncytial virus infections in hospitalized children in Akershus]. / Infeksjon med respiratorisk syncytialvirus hos hospitaliserte barn i Akershus.

INTRODUCTION: The study describes hospitalisations for RSV infections among children < 15 years. MATERIAL AND METHODS: The study is a population-based retrospective analysis of admission data from February 1993 through January 2000 of children who tested positive for RSV in nasopharyngeal aspirates. RESULTS: 1,002 cases were identified of which 69.5% were < 1 year old children. Estimated annual incidence of RSV infection requiring hospitalisation was 2.1/1,000 Children < 15 years, 24.9/1,000 infants < 1 year, and 28.4/1,000 infants < 6 months old. Males were more likely to be hospitalised than females. The overall mortality was 0.5%. Premature infants with birthweight < or = 1,000 g had the highest hospitalisation rates, the longest hospital stay and most complications. However, surprisingly many complications occurred among previously healthy infants. INTERPRETATION: Recommendations for RSV prophylaxis among preterm infants should be investigated in a larger study. Development of an RSV vaccine should be a priority.

[Hallway patients in hospital departments of internal medicine in 1998 and 1999]. / Korridorpasienter i indremedisinske avdelinger i 1998 og 1999.

BACKGROUND: Patient beds in corridors because of limited room capacity is a well-known phenomenon in many Norwegian hospitals. MATERIAL AND METHODS: Questionnaires were sent to all departments of internal medicine in Norway (n = 62) in 1998 and in 1999. RESULTS: Nearly 50 of 60 departments had to use patient beds in corridors regularly. There was no change in the number of such beds from 1998 to 1999. INTERPRETATION: The use of patient beds in corridors of departments of internal medicine in Norwegian hospitals in extensive.

[Hallway patients--consequences or the quality of care and patient integrity]. / Korridorpasienter--konsekvenser for behandlingskvalitet og pasientintegritet.

BACKGROUND: Because of the limited capacity in Norwegian hospitals, many patient beds are located in corridors. Does this affect quality of care and patient integrity? MATERIAL AND METHODS: The National Board of Health sent a questionnaire to all Norwegian hospitals with departments of internal medicine (n = 62). The questionnaire had statements on how corridor patients affect quality of care and patient integrity. We asked the head doctor and head nurse to fill in the questionnaire together. 60 questionnaires (97%) were returned. RESULTS: There was 88%-100% agreement to the following statements: Corridor patients reduce quality of care and increase risk of mistakes and accidents. The risk of infections increases. Time spent per patient by doctor and nurse is reduced. These drawbacks affect all patients, but corridor patients the most. The quality of professional and personal conversation is reduced. Some corridor patients do all their personal hygiene in the corridor. Corridor patients' diagnosis can be recognised by passing persons. INTERPRETATION: The results document that having in-patients in corridors has a negative effect on quality of care and patient integrity.

Cardiopulmonary function in premature infants with bronchopulmonary dysplasia--a 2-year follow up.

Twenty-three premature infants (GA 28.8 +/- 0.5 weeks) with bronchopulmonary dysplasia (BPD) and 14 premature infants (controls, GA 33.0 +/- 1.2 weeks) with moderate respiratory distress syndrome or with mild respiratory disturbances, were evaluated for impairment of cardiopulmonary function at 50 and 120 weeks corrected age. Respiratory system compliance was reduced in both groups, but improved with advancing age. Respiratory system resistance was initially increased, especially in the BPD group, but improved gradually. Maximum flow at functional residual capacity (VmaxFRC ml/s) indicated, nevertheless, severe peripheral obstruction (flow < 84 ml/s) in 16/20 of infants with BPD and in 7/12 of control infants at 50 weeks corrected age. At 120 weeks corrected age none of the control patients had severe peripheral pulmonary obstruction (flow < 120 ml/s), while this was still found in 5/13 infants with BPD. Doppler echocardiography indicated cardiac involvement (shortened pulmonary acceleration time) in patients with the most severe peripheral pulmonary obstruction. Pulmonary morbidity was also higher in the BPD group, and these infants were shorter and weighed less than the control infants. CONCLUSION. Measurements of maximum flow at functional residual capacity as well as cardiac evaluation are essential elements in follow up of infants with severe BPD.

Pulmonary effects after surfactant treatment in premature infants with severe respiratory distress syndrome.

To understand the mechanisms behind the improved oxygenation after intratracheal surfactant instillation, the immediate effects of lung volume and pulmonary mechanics were analyzed. All infants studied were enrolled in multicenter trials in which surfactant therapy was instituted according to a rescue protocol. Infants received either synthetic surfactant (Exosurf) or modified porcine surfactant (Curosurf). Measurements of lung volume and pulmonary mechanics were successfully performed in 12 patients with a birth weight of 1.3 +/- (SD) 1.4 weeks. Functional residual capacity (FRC) and pulmonary mechanics were measured during mechanical ventilation. The FRC increased significantly by 70% (median), from 7.10 +/- (SD) 2.8 ml/kg to 11.5 +/- 3.3 ml/kg after surfactant instillation. However, a concomitant decrease in specific compliance was also seen. These findings could suggest that this immediate increase in FRC is initially nonuniform. However, since no significant correlation between changes in FRC and improvement in arterial-to-alveolar oxygen tension ratio is seen, other effects of surfactant must also be considered. These could include local and/or systemic changes in hemodynamics, such as decreased shunting as well as various effects on gas diffusion.

Pulmonary effects of closure of patent ductus arteriosus in premature infants with severe respiratory distress syndrome.

UNLABELLED: The pulmonary effects of closure of a patent ductus arteriosus (PDA) were investigated in 11 premature infants with severe respiratory distress syndrome. Successful closure of a PDA did not improve the short-term severity of pulmonary disease (24 and 48 h after treatment) as judged by the arterial/alveolar oxygen tension ratio or the amount of ventilatory support. Also, pulmonary mechanics measured 24 h before, 24 and 48 h after treatment, were not statistically different. CONCLUSION: Infants with severe respiratory disease requiring high ventilation pressure and high oxygen concentration, where structural changes in the lungs are already established, will rarely show short-term improvement in pulmonary disease as a result of closure of a PDA. The overall clinical condition may, however, improve as a result of reduced cardiovascular strain. Earlier treatment of a PDA could reduce the ventilation period and the possible risk of developing chronic lung disease.

Cerebral blood flow autoregulation after moderate hypoxemia in the newborn piglet.

The isotope-labelled microsphere method was used to study blood flow autoregulation in the brainstem (BS), cerebellum (CBL), cerebrum (CBR) and choroid plexus (ChPl) in 21 newborn piglets exposed to hypoxemia and/or hypovolemia. One group of piglets (n = 7) was made hypoxemic by breathing 10% O2 for 10 min, a second group (n = 8) was studied during hypoxemia (10% O2, 10 min), followed by hypovolemia (bleeding 20% of estimated blood volume). A third group of piglets (n = 6) was made hypovolemic by bleeding 20%. Hypoxemia significantly impaired the autoregulatory capacity in CBL and CBR resulting in a pressure-passive flow pattern. Hypovolemia alone did not produce any significant cerebral vascular response in BS, CBL and CBR, not even when hypovolemia was preceded by hypoxemia, indicating a rapid restoration of the autoregulatory capacity of the cerebral vasculature after hypoxemia of moderate duration. The hypotension seen both during hypoxemia and hypovolemia was gradually compensated for and normalized within 60 min. However, animals exposed to both hypoxemia and hypovolemia were still hypotensive 60 min after the hypoxemic insult. Cardiac output (CO) was not affected by hypoxemia, but was consistently reduced in hypovolemia. We therefore speculate that in the newborn a reduced CO might be a more specific parameter for hypovolemia than a low blood pressure.

Effect of intraventricular hemorrhage on pulmonary function in newborn piglets.

Intracranial hemorrhage in the premature infant is often associated with respiratory failure and need for mechanical ventilation. We therefore addressed the question of possible interactions with and pulmonary consequences of intraventricular hemorrhage. Newborn piglets were studied during intraventricular hemorrhage simulated by intraventricular blood infusion. Infusion volume amounted to 8% of estimated brain weight. Respiratory rate, minute ventilation, lung resistance and dynamic lung compliance, as well as arterial blood gases, arterial and intraventricular pressures were measured. The piglets were mechanically ventilated with a low basal rate of 20 breaths per minute throughout the study. All piglets experienced significant rise in intraventricular pressure and respiratory failure during the study. Respiratory failure was mainly a result of a reduction in respiratory frequency and minute ventilation until apnea. However, a rise in lung resistance was also noted while lung compliance did not change. We conclude that increased need for mechanical ventilation during intracranial hemorrhage is primarilty a consequence of hypoventilation. The increase seen in lung resistance could also suggest that intraventricular hemorrhage causes an element of bronchiolar constriction. Furthermore, these effects are not only a result of the increase in intraventricular pressure, but specific effects of blood components within the central nervous system must be considered.

Incidence and prediction of bronchopulmonary dysplasia in a cohort of premature infants.

A prospective study on the incidence of bronchopulmonary dysplasia (BPD) in premature infants is reported. A cohort of premature infants with gestational ages < or = 32 weeks, treated during 1989, was followed for one year. Of a total study population of 117 infants, 23 (19.6%) developed BPD, defined as oxygen dependence at 28 postnatal days. However, only 15 infants (12.8%) needed supplementary oxygen at the age of 36 gestational weeks and 5 infants (4.2%) needed supplementary oxygen periodically at one year of age. BPD was found to account for a significant part of both the total and late mortality in the cohort. Measurements of pulmonary mechanics were performed at 3 +/- 1 and 12(13) +/- 1 days of life in a subgroup of 26 infants with RDS who required assisted ventilation for 4 days or longer. No significant difference in lung compliance or resistance could be found during the first examination between infants who later developed BPD and infants with RDS only. At the second examination, infants who later developed BPD had significantly lower lung compliance (0.48 +/- 0.23 ml/cmH2O) than infants in the RDS group (1.50 +/- 0.72 ml/cmH2O) (p < 0.001). Measurements of pulmonary mechanics could be of importance for early prediction of infants at risk of BPD.

[Natural and synthetic surfactant in the treatment of neonatal respiratory distress syndrome]. / Naturlig og syntetisk surfaktant i behandling av neonatalt åndenødssyndrom.

The results of treatment of severe respiratory distress syndrome in premature infants with gestational age < or = 32 weeks are reported. During the two-year period 1991-92, the department participated in both the Osiris study (Exosurf) and the Curosurf 4 study (Curosurf). Five of the 23 infants treated with Exosurf died and 16 survived without major sequelae. 14 of the 25 infants treated with Curosurf died and six survived without major sequelae. Four of the infants treated with Curosurf developed severe retinopathy of prematurity. During the study period this complication occurred in one additional patient who was not eligible for inclusion in the study. The results show the need to study differences in the physiological effects of surfactants more closely, in order both to improve the basis for selection of surfactant for individual patients, and to define the indications for treatment. The results raise the question of whether such studies should continue to include control patients.

Effect of hypoxemia and hypovolemia on retinal and choroidal blood flow in the newborn piglet.

The effect of hypoxemia and/or hypovolemia on ocular blood flow was studied in paralyzed and mechanically ventilated newborn piglets with the isotope-labelled microsphere method. Twenty-six piglets were studied in four different groups. One group of piglets (n = 6) was made hypoxemic by breathing 10% O2, a second group (n = 7) and a third group (n = 7) were studied during hypoxemia (10% O2), followed by hypovolemia (bleeding 20 and 30% of estimated blood volume, respectively). A fourth group of piglets (n = 6) was made hypovolemic by bleeding 20% of estimated blood volume. Hypoxemia resulted in a 2- to 3-fold increase in retinal blood flow (RBF), while hypovolemia did not change RBF, not even when preceded by a period of hypoxemia. In the case of choroidal blood flow (ChBF), the increase caused by hypoxemia was only 10-40%. Although ChBF decreased significantly during hypovolemia, no significant correlation between mean arterial blood pressure and ChBF was found. The results indicate that autoregulation is normally seen in RBF, but probably not in ChBF. However, during hypoxemia autoregulation was found neither in RBF nor in ChBF.

[Mortality and morbidity among infants with extremely low birth weight]. / Overlevelse og sykelighet blant ekstremt for tidlig fødte barn.

We reviewed outcomes in 65 infants with extremely low birth weight who were treated at our perinatal center from January 1981 through December 1989. Included in the study were infants whose gestational age was less than or equal to 26 weeks and whose birth weight was less than or equal to 750 grams. The outcomes were compared for three periods, 1981-83 (n = 16), 1984-86 (n = 20) and 1987-89 (n = 29). There was no significant difference in survival rate during the study period (19 vs 25 vs 31%). However, significantly more children now survive the first 24 hours of life.

Effects of endotracheal tube size and ventilator settings on the mechanics of a test system during intermittent flow ventilation.

The effect of varying the size of standard neonatal endotracheal tubes on delivered tidal volumes (VT), resistance (R), dynamic compliance (Cdyn), and resistive work of breathing (WOB) was measured in a test system during intermittent flow ventilation at different ventilator settings. The experiments were performed with a Sechrist infant ventilator connected to a Dräger Test Lung via standard neonatal endotracheal tubes. R, inspiratory (Ri), and expiratory resistance (Re) as well as WOB were significantly affected by endotracheal tube size. The calculated difference in Re between endotracheal tubes of 2.5 and 3.5 mm I.D. was 93 cm H2O/L/S (mean value for all studies). Cdyn and VT were also affected by endotracheal tube size. However, although statistically significant differences were found in Cdyn (mean, 0.584 mL/cm H2O and 0.567 mL/cm H2O) and VT (mean, 13.0 mL and 12.7 mL) for the tube sizes 3.5 mm and 2.5 mm I.D., respectively, the absolute numerical differences were small. Also, ventilator settings with respect to the peak inspiratory pressure (PIP) - positive end-expiratory pressure (PEEP) difference had a significant influence on Cdyn for both tube sizes. On the other hand, flow and inspiratory time adjustments had no significant effect on ventilatory parameters. Endotracheal tube size and ventilator settings should be considered when comparing the pulmonary function tests in intubated and non-intubated newborn infants.