Respiratory hospitalizations and respiratory syncytial virus prophylaxis in special populations

Palivizumab utilization, compliance, and outcomes were examined in infants with preexisting medical diseases within the Canadian Registry Database (CARESS) to aid in developing guidelines for potential “at-risk” infants in the future. Infants who received ≥1 dose of palivizumab during the 2006–2010 respiratory syncytial virus (RSV) seasons at 29 sites were recruited and utilization, compliance, and outcomes related to respiratory infection/illness (RI) events were collected monthly. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for premature infants ≤35 completed weeks gestational age (GA) who met standard approval criteria (group 1) compared to those with medical disorders (group 2) using Cox proportional hazards regression models with adjustment for potential confounding factors. Of 7,339 registry infants, 4,880 were in group 1 and 952 in group 2, which included those with Down syndrome (20.3%), upper airway anomalies (18.7%), pulmonary diseases (13.3%), and cystic fibrosis (12.3%). Group 2 were older at enrolment (10.2 ± 9.2 vs. 3.5 ± 3.1 months, p < 0.0005), had higher GA (35.9 ± 6.0 vs. 31.0 ± 5.4 weeks, p < 0.0005), and were less compliant with treatment intervals (69.4% vs. 72.6%, p = 0.048). A greater proportion of group 2 infants were hospitalized for RI (9.0% vs. 4.2%, p < 0.0005) and RSV (2.4% vs. 1.3%, p = 0.003) (unadjusted). Being in group 2 was associated with an increased risk of RI (HR = 2.0, 95%CI 1.5–2.5, p < 0.0005), but not RSV hospitalization (HR = 1.6, 95%CI 0.9–2.8, p = 0.106). In infants receiving palivizumab, those with underlying medical disorders, though not currently approved for prophylaxis, are at higher risk for RI events compared with preterm infants. However, risk of RSV hospitalizations is similar.     

Disease-related response to inhaled nitric oxide in newborns with severe hypoxaemic respiratory failure

Inhaled nitric oxide (iNO) has been shown to improve oxygenation in severe persistent pulmonary hypertension of the newborn (PPHN). However, PPHN is often associated with various lung diseases. Thus, response to iNO may depend upon the aetiology of neonatal acute respiratory failure. A total of 150 (29 preterm and 121 term) newborns with PPHN were prospectively enrolled on the basis of oxygenation index (OI) higher than 30 and 40, respectively. NO dosage was stepwise increased (10–80 ppm) during conventional mechanical or high-frequency oscillatory ventilation while monitoring the oxygenation. Effective dosages ranged from 5 to 20 ppm in the responders, whereas iNO levels were unsuccessfully increased up to 80 ppm in the nonresponders. Within 30 min of iNO therapy, OI was significantly reduced in either preterm neonates (51 ± 21 vs 23 ± 17, P < .0001) or term infants with idiopathic or acute respiratory distress syndrome (45 ± 20 vs 20 ± 17, P < .0001), `idiopathic' PPHN (39 ± 14 vs 14 ± 9, P < .0001), and sepsis (55 ± 25 vs 26 ± 20, P < .0001) provided there was no associated refractory shock. Improvement in oxygenation was less significant and sustained (OI = 41 ± 16 vs 28 ± 18, P < .001) in term neonates with meconium aspiration syndrome and much less (OI = 58 ± 25 vs 46 ± 32, P < .01) in those with congenital diaphragmatic hernia. Only 21 of the 129 term newborns (16%) required extracorporeal membrane oxygenation (57% survival). Survival was significantly associated with the magnitude in the reduction in OI at 30 min of iNO therapy, a gestational age ≥34 weeks, and associated diagnosis other than congenital diaphragmatic hernia. Conclusion, iNO improves the oxygenation in most newborns with severe hypoxaemic respiratory failure including preterm neonates. However, response to iNO is disease-specific. Furthermore, iNO when combined with adequate alveolar recruitment and limited barotrauma using exogenous surfactant and HFOV may obviate the need for extracorporeal membrane oxygenation in many term infants. Received: 24 April 1997 / Accepted in revised form 3 January 1998     

Growth hormone treatment increases CO2 response, ventilation and central inspiratory drive in children with Prader-Willi syndrome

We studied whether the beneficial effects of growth hormone (GH) treatment on growth and body composition in PWS are accompanied by an improvement in respiratory function. We measured resting ventilation, airway occlusion pressure (P_0.1) and ventilatory response to CO₂ in nine children, aged 7–14 years, before and 6–9 months after the start of GH treatment. During GH treatment, resting ventilation increased by 26%, P_0.1 by 72% and the response to CO₂ by 65% (P < 0.002, <0.04 and <0.02, respectively). This observed increase in ventilatory output was not correlated to changes in body mass index. Conclusion Treatment of children with Prader-Willi syndrome (PWS) seems to have a stimulatory effect on central respiratory structures. The observed increase in ventilation and inspiratory drive may contribute to the improved activity level reported by parents of PWS children during growth hormone therapy. Received: 28 April 1998 / Accepted: 6 April 1999     

A comparison of cytokine responses in respiratory syncytial virus and influenza A infections in infants

Respiratory syncytial virus (RSV) infection is a major cause of bronchiolitis in infants while influenza A infection usually manifests as upper respiratory tract infection. We hypothesised that the immunological responses of infants to RSV infection and influenza A infection are different. This prospective study was undertaken to compare the cytokine responses during RSV and influenza A infection. Sera and nasopharyngeal aspirates (NPA) were collected from infants with a coryzal illness with or without wheeze who were admitted to the paediatric wards during 1998. Cytokines, adhesion molecules, RANTES, IgE and eosinophil cationic protein (ECP) were measured by enzyme linked immunosorbent assay or fluorescence enzyme immunoassay. The diagnosis of RSV and influenza infections was based on direct immunofluorescence and viral culture. Of the 39 infants studied, RSV infection was confirmed in 11 patients and Influenza A in 10 patients. All RSV patients and one influenza A patient had wheeze during the infection. The serum concentrations of interleukin (IL)-4 and IL-5, regulated upon activation normal T cell expressed and secreted (RANTES) and soluble intercellular adhesion molecule 1 (sICAM-1) in infants with RSV infection were significantly higher than those with influenza A infection (all P < 0.02). The concentration of tumour necrosis factor-α (TNF-α) in NPA was significantly lower in infants with RSV infection (P < 0.01). Conclusion A predominant T helper cell type 2 cytokine and related immunological response was observed in infants with respiratory syncytial virus infection whereas a predominant pro-inflammatory cytokine response was observed in infants with influenza A infection. This may explain the different clinical manifestations of the two viral infections in infants. Received: 17 April 2000 / Accepted: 13 September 2000     

Home oxygen therapy in infants with bronchopulmonary dysplasia: a prospective study

We followed the clinical course of 21 infants with bronchopulmonary dysplasia enrolled in a prospective home O₂ therapy programme during a 4-year-period. Mean gestational age was 28.5 weeks (range, 25–36 weeks) and mean birth weight 1093 g (range 630–2750 g). Infants were regularly monitored to maintain pulse oximeter O₂ saturation over 94%–95%. The source of O₂ was liquid oxygen and was delivered by nasal cannula. During the follow up oxygenation was assessed by SatO₂ measurement, cardiac function by Doppler echocardiography and respiratory function by the occlusion technique. All patients had an ophthalmological follow up. The mean age of the infants at discharge was 3.7 months (range 1.7–8.6) and mean weight 2830 g (range 2150–3780 g). At discharge 8 infants had right ventricular hypertrophy (RVH) and four of them had pulmonary hypertension. Mean duration of home O₂ therapy was 97 days (range 15–320 days) and the mean age of discontinuation of O₂ was 6.9 months (range 3–14.7 months). The cardiological follow up was benign: the ECG signs of RVH disappeared by 12 months of age in six out of eight infants and the right ventricular pulmonary pressure, as measured by the Doppler method, normalised in the four patients in whom it was detected. No relationship was found between respiratory mechanics and the duration of O₂ therapy. Weight gain was poor with mean growth at the 3rd percentile for females and just below the 3rd percentile for males. Twelve of the 21 infants required 25 rehospitalizations. No one presented deterioration of retinopathy of prematurity that was present in 16 infants at discharge; at 12 months retinopathy was resolved in 14 infants. A total of 2025 hospital days were saved, representing a significant financial saving. Conclusion Home O₂ therapy permits the safe early discharge of O₂-dependent BPD infants and it reduces significantly the length of time spent in hospital which represents a considerable financial saving. Received: 17 December 1996 and in revised from: 15 April 1997 / Accepted: 29 April 1997     

Early nasal continuous positive airway pressure treatment reduces the need for intubation in very low birth weight infants

Nasal continuous positive airway pressure (CPAP) applied shortly after birth is said to be an effective treatment of respiratory distress in very low birth weight infants (VLBW). We tested the hypothesis that the use of early nasal CPAP (applied as soon as signs of respiratory distress occurred, usually within 15 min after birth) reduces the need for intubation, the duration of intermittent mandatory ventilation and the incidence of bronchopulmonary dysplasia. All liveborn VLBW infants (birth weight < 1500 g) admitted to our tertiary neonatal intensive care unit in 1990 (historical controls) and in 1993 (early nasal CPAP group) entered the study. The intubation rate was significantly lower after introduction of nasal CPAP (30% vs 53%, P = 0.016). Median duration of intubation was 4.5 days (interquartile range 3–7 days) before versus 6.0 days (2.8–9 days) after nasal CPAP was introduced (P = 0.73). The incidence of bronchopulmonary dysplasia was not reduced significantly (32% vs 30%, P = 0.94). Survival until discharge was 89.5% before versus 92.9% after introduction of nasal CPAP (P = 0.54). Conclusion Early nasal CPAP is an effective treatment of respiratory distress in VLBW infants, significantly reducing the need for intubation and intermittent mandatory ventilation, without worsening other stan dard measures of neonatal outcome. We found no significant decrease in the incidence of bronchopulmo nary dysplasia. Received: 5 February 1996 and in revised form: 12 September 1996 / Accepted: 23 October 1996     

Comparison of two inspiratory: expiratory ratios during high frequency oscillation

The aim of this study was to compare gas exchange and volume delivery during high frequency oscillation at two frequently used inspiratory:expiratory (I:E) ratios: 1:2 and 1:1, other oscillatory settings being kept constant. A group of 13 infants with respiratory distress syndrome, median gestational age 28 weeks (range 23–36) and postnatal age 1 day (range 1–8) were studied. At the I:E ratio of 1:1 compared to 1:2 the median paCO₂ was lower, P < 0.05 (30 mmHg, range 22–47 vs 34 mmHg, range 27–46) and the volume delivered higher, P < 0.01 (2.6 ml/kg, range 1.2–5.6 vs 2.0 ml/kg, range 1.0–3.9). There was no significant difference in oxygenation levels at the two I:E ratios. In a related in vitro study, changing the I:E ratio from 1:2 to 1:1 increased the mean airway pressure by a median of 8.6% (range 2.9–28.1%). Conclusion Routinely maintained longer expiratory than inspiratory times during high frequency oscillation should be discouraged. Received: 6 November 1998 / Accepted: 30 March 1999     

Respiratory syncytial virus infection in 406 hospitalized premature infants: results from a prospective German multicentre database

Premature birth, chronic lung disease of prematurity (CLD), congenital heart disease and immunodeficiency predispose to a higher morbidity and mortality in respiratory syncytial virus (RSV) infection. This study describes the preterms hospitalised with RSV infection from the prospective German DSM RSV Paed database. The DMS RSV Paed database was designed for the prospective multicentre documentation and analysis of clinically relevant aspects of the management of inpatients with RSV infection. This study covers six consecutive RSV seasons (1999–2005); the surveillance took place in 14 paediatric hospitals in Germany. Of the 1,568 prospectively documented RSV infections, 26% (n = 406) were observed in preterms [vs. 1,162 children born at term (74%)] and 3% (n = 50) had CLD, of which 49 had received treatment in the last 6 months (‘CLDplus’). A significantly higher proportion in the preterm group had congenital heart disease, nosocomial infection, and neuromuscular impairment. There were significantly more children older than 24 months in the preterm group. The attributable mortality was 0.2% (n = 2) in children born at term vs. 1.2% (n = 5) in the preterm group (p = 0.015) [preterm plus CLD 8.0% (n = 4 of 50); McIntosh grade 1, 8.6% (n = 3 of 35) and McIntosh Grade 4, 15% (n = 3 of 20)]. Eight patients were categorized as ‘palivizumab failures’. In the multivariate analysis, premature birth, CLD_plus, and nosocomial infection were significantly and independently associated with the combined outcome ‘complicated course of disease’. In conclusion, this is the first prospective multicentre study from Germany that confirms the increased risk for severe RSV disease in preterms, in particular in those with CLD treated in the last 6 months before the onset of the infection. From the perspective of our results, the statements of the German Society of Paediatric Infectious Diseases considering the use of passive immunisation (2003) seem reasonable.     

Outcome of very low birthweight infants after introducing a new standard regime with the early use of nasal CPAP

In this paper, a retrospective study was performed to find out whether the introduction of early nasal continuous positive airway pressure (nCPAP) as a new standard regime of very low birthweight infants will lead to a decreasing tracheal intubation and ventilation rate, as well as to a lower incidence of bronchopulmonary dysplasia in a tertiary-level perinatal centre. Ninety-three infants (study group) with early nCPAP as the first respiratory support were compared to 63 infants (historical control group) born before the use of early nCPAP. No statistically significant differences were found in the baseline characteristics. The main results of the study include reduced intubation mainly in infants with a birthweight <1,000 g (study group): 58% vs. 81% (p < 0.05). The mean duration of ventilation was 248 h (control group) vs. 128 h (study group) (p < 0.001) and 437 h vs. 198 h in infants <1,000 g (p < 0.001). There was significantly reduced incidence of bronchopulmonary dysplasia from 55% to 18% for all surviving infants (p < 0.001), and for infants <1,000 g, it was 90% vs. 30% (p < 0.001). No significant differences for other outcome criteria were noted, but a significant reduction in the use of central i.v. lines, fluids, drugs, volume expansion, sedation, catecholamines, surfactant, steroids and buffer, as well as antibiotics, was observed (p < 0.05). Therefore, we can conclude that early nCPAP is an easy-to-use and safe procedure for very low birthweight infants to treat respiratory distress.     

Neonatal neutropenia associated with maternal hypertension poses a risk for nosocomial infection

One hundred and six neonates of 24–32 weeks gestation born to hypertensive mothers and 106 concurrent control infants of normotensive mothers were evaluated to determine the relationship between maternal hypertension and neonatal neutropenia and the risk of nosocomial infection developing in neutropenic infants.. Complete blood counts were performed on both cohorts and retrospectively evaluated. Neutropenia was diagnosed using published reference ranges for infants with birth weight ≤1500 g and >1500 g. Evidence of nosocomial infection based on a positive blood culture with supportive clinical signs of sepsis was documented. The incidence of neutropenia among infants of hypertensive mothers was not significantly different from that among infants of normotensive mothers (21% vs 24%), but the duration of neutropenia was significantly longer in the infants of hypertensive mothers (P = 0.0001). Nosocomial infection was more frequent in neutropenic than the non-neutropenic hypertensive mothers' infants (55% vs 12%, P = 0.0002). Conclusion Although there is no difference in the incidence of neonatal neutropenia between infants of hypertensive mothers and those of normotensive mothers, the former group has an increased risk of nosocomial infection in neutropenic infants of hypertensive mothers. This may be related to prolonged neutropenia which was found in these infants in the present study. Received: 24 August 1997 and in revised form: 30 March 1998 / Accepted: 1 April 1998     

International variation in the management of infants hospitalized with respiratory syncytial virus

Respiratory syncytial virus (RSV) is a frequent cause of hospitalization among infants. To compare patient management in Europe, the United States, and Australia, we analyzed the charts of 1,563 pediatric patients hospitalized with laboratory-confirmed RSV lower respiratory infections during recent RSV seasons. Half of patients had been seen initially as outpatients. Median duration of hospitalization was 4 days in Australia, Finland, the United Kingdom, and the United States, and 8 or 9 days in Belgium, France, Germany, Italy, and the Netherlands. In a linear regression model that included clinical findings, underlying conditions, prematurity, and age, the leading variable associated with length of stay was “hospitalization in continental Europe”. This geographic factor conferred a 1.8-fold longer stay (95% CI: 1.7–1.9) than hospitalization elsewhere. Utilization of nine supportive therapies for RSV varied widely among hospitals, even within the same country. The individual hospital was strongly associated with the use of every therapy studied, independent of patient characteristics and clinical status. Conclusion Management of RSV patients varies markedly by country and hospital. Multicenter RSV trials that measure length of stay should standardize criteria for “readiness for discharge”. It may be appropriate to limit international trials to countries with similar median stays for RSV. Variability within multicenter trials could be further controlled by standardizing the use of other therapies and the diagnosis of complications. Received: 29 April 1997 / Accepted in revised form: 11 August 1997     

Respiratory control in children with Prader-Willi syndrome

  Physiological parameters of infants and children with Prader-Willi syndrome were examined in order to clarify whether there were indicators of disturbed respiratory control mechanisms in the pre-obesity stage of the syndrome. From January 1993 to March 1995 in eight patients with Prader-Willi syndrome (five boys, three girls, aged 6 weeks – 12.5 years),␣polysomnography was performed and compared with 28 children matched for gestational age, sex, birth weight and age at sleep study. The recordings included thoracic and abdominal breathing movements, nasal airflow, tcPO₂, tcPCO₂, oxygen saturation, EEG, EOG and ECG. Respiratory responses to hypercapnia during quiet sleep were obtained from five Prader-Willi patients and ten peers. The Prader-Willi group showed an increased number of apnoeas per hour of sleep, a decreased nadir of oxygen saturation, increased maximum of the instantaneous heart rate and decreased respiratory responses to hypercapnia during quiet sleep. Conclusion These findings indicate a primary dis‐turbance of central respiratory control in patients with Prader-Willi syndrome which may be worsened by the development of obesity. Received: 26 January 1996 / Accepted: 21 July 1996     

Oral iron is sufficient for erythropoietin treatment of very low birth-weight infants

The aim of this study was to compare two different doses and means of administration of iron in recombinant human erythropoietin (rHuEPO)-treated very low birth-weight (VLBW) infants. VLBW infants (n = 41) were randomized to one of three groups. Fourteen infants were treated with rHuEPO (300 IU/kg three times a week s.c.) and oral iron (ferrofumarate, 6 mg of iron/kg per day). Another 14 infants received the same erythropoietin dose and intramuscular iron (ferroxypolymaltose, once 12 mg of iron/kg weekly). Thirteen infants were treated with the same dose of intramuscular iron but did not receive rHuEPO. After the 3-week study period, haemoglobin concentrations and reticulocyte counts were similar in the rHuEPO-treated groups and both were higher than in the group not receiving rHuEPO (P < 0.001). In both rHuEPO-treated groups the transferrin receptor concentration increased from 6.8–7.2 mg/l to 10.5–11.3 mg/l. Conclusion In erythropoietin-treated very low birth weight infants the iron need for erythropoiesis can be met by oral administration of iron. Received: 17 November 1997 and in revised form: 6 March 1998 / Accepted: 30 April 1998     

Antenatal ambroxol treatment does not prevent the respiratory distress syndrome in premature infants

The effectiveness of ambroxol in the prevention of neonatal respiratory distress syndrome and in reducing the need for intermittent mandatory ventilation and oxygen therapy was studied in 88 mothers whose infants was born between 24 and 34 weeks of gestation and who were randomized either for treatment with ambroxol (group A = 42) or served as control (group B = 46). There were no significant differences in the mean gestational age, birth weight or Apgar score between the two groups. We found no significant differences in occurrence of respiratory distress syndrome (55% vs 45%), in support by intermittent mandatory ventilation (71% vs 72%) or oxygen therapy (74% vs 75%) at 12 h of age between groups A and B. Conclusion This study does not suggest the efficacy of antenatal ambroxol treatment both for the prevention of neonatal respiratory distress syndrome and for the reduction of its severity. Received: 12 October 1995 and in revised form: 30 August 1996 / Accepted: 10 September 1996     

Prevention of vitamin K deficiency bleeding: efficacy of different multiple oral dose schedules of vitamin K

There is consensus that late vitamin K deficiency bleeding (VKDB) should be prevented by vitamin K prophylaxis. One single dose of 1 mg vitamin K₁ is effective if given i.m. or s.c., but not if given orally. Repeated oral doses might be as effective as the parenteral dose but the optimal dose regimen remains to be established. Different oral dose schedules are presently used in different countries. In Australia, Germany, The Netherlands and Switzerland active surveillance data on late VKDB were collected in a similar manner and failure rates compared. Identical case definitions were used. There were three basic strategies for oral and one for parenteral vitamin K prophylaxis for healthy newborns in the four countries: (1) daily supplementation of low dose vitamin K (25 μg) for breast-fed infants (The Netherlands); (2) 3 × 1 mg orally [Australia (January 1993 – March 1994) and Germany (December 1992 – December 1994)]; (3) 1 mg vitamin K i.m. (Australia since March 1994); and (4) 2 × 2 mg vitamin K (new mixed micellar preparation) (Switzerland). The respective failure rates per 100,000 live births (including cases given all recommended doses and those given incomplete prophylaxis) were for strategy: (1) 0.2 (0–1.3) in The Netherlands; (2) 2.3 (95% CI 1.6–3.4) in Germany and 2.5 (1.1–4.8) in Australia (oral prophylaxis); (3) Australia (i.m. prophylaxis) 0 (0–0.9); and (4) 3.6 (0.7–10.6) in Switzerland. The failure rates for complete prophylaxis only were: strategy (1) 0 (0–0.7) in The Netherlands; (2) 1.8 (1.1–2.8) in Germany and 1.5 (0.5–3.6) in Australia; (3) Australia (i.m.) 0 (0–0.9); and (4) 1.2 (0–6.5) in Switzerland. Conclusions The Australian data confirm that three oral doses of 1 mg vitamin K are less effective than i.m. vitamin K prophylaxis. A daily low oral dose of 25 μg vitamin K₁ following an initial oral dose of 1 mg after birth for exclusively breast-fed infants may be as effective as parenteral vitamin K prophylaxis. The effectiveness of the “mixed-micellar” preparation of vitamin K₁ needs further study. Received: 12 April 1996 / Accepted: 21 July 1996     

Prophylaxis for respiratory syncytial virus with respiratory syncytial virus-immunoglobulin intravenous among preterm infants of thirty-two weeks gestation and less: reduction in incidence, severity of illness and cost

OBJECTIVE: To determine the impact of respiratory syncytial virus (RSV) prophylaxis among preterm infants of < or =32 weeks gestation by comparing the severity of illness and cost of RSV-related care during the two winter seasons before (1994 to 1995, 1995 to 1996) with the two seasons after initiation of prophylaxis (1996 to 1997, 1997 to 1998). METHODS: Preterm infants of < or =32 weeks gestation at risk for hospitalization with RSV infection were identified retrospectively from the infants hospitalized in our neonatal units. Infants were included if they (1) were born 6 months before or during four winter seasons (1994 to 1998), (2) were discharged from the neonatal unit and (3) had remained in the university outpatient clinic system during at least the first winter of life. Preterm infants of < or =32 weeks gestation hospitalized with RSV were identified from our RSV database (which includes cost of hospitalization, duration of hospital stay, pediatric intensive care unit stay and intubation). Infants receiving prophylaxis were identified prospectively. RESULTS: The incidence of hospitalization with RSV was significantly lower among the cohort of infants born after initiation of prophylaxis: 8.7% (17 of 195) vs. 22% (35 of 159), P = 0.00049 by two tailed Fisher's exact test. Among the cohort of infants born after initiation of prophylaxis (n = 195), 100 infants received prophylaxis. The gestational and chronologic ages of the prophylaxis-treated infants were significantly lower than those of the non-prophylaxis-treated infants (n = 95). The prophylaxis-treated infants also were more likely to have bronchopulmonary dysplasia. Only 1 (1%) of the prophylaxis-treated infants required hospitalization for RSV. Comparison of the cohort of infants born before initiation of prophylaxis to the cohort born after initiation of prophylaxis (includes prophylaxis-treated and non-prophylaxis-treated infants) revealed a significant reduction in severity of illness and cost. The length of stay in the cohort born before initiation of prophylaxis was reduced 83.8%: 373.6 days per 100 infants at risk vs. 60.5 (P = 0.00055). The length of stay in the pediatric intensive care unit was reduced 92.7%: 218.2 days per 100 infants at risk vs. 15.9 (P = 0.00029). The duration of intubation was reduced 95.6%: 187.4 days per 100 infants at risk vs. 8.2 (P = 0.00024). The dollars spent for RSV-related care (hospitalizations and prophylaxis) per 100 infants at risk for RSV was reduced 65% in the cohort of infants born after prophylaxis: $670,590 per 100 infants at risk vs. $234,596 (P = 0.00056). This reduction remained significant (64.9%) if the cost of ribavirin (drug and administration fees) was excluded from the cost of hospitalization. CONCLUSIONS: These data reveal that RSV prophylaxis significantly reduced the incidence of RSV hospitalizations and severity of illness as well as the cost of RSV-related care among these infants.     

Effect of caffeine on respiratory muscle strength and lung function in prematurely born,ventilated infants

The aims of this study were to determine whether caffeine administration increased respiratory muscle function and if this was associated with lung function improvement in prematurely born infants being weaned from mechanical ventilation. Respiratory muscle function was assessed by measurement of the maximum pressures generated during occlusions at end inspiration (Pemax) and end expiration (Pimax) and lung function by measurement of lung volume (functional residual capacity (FRC)) and respiratory system compliance (CRS) and resistance (RRS) in 18 infants with a median gestational age of 28 (range 24–36) weeks. Measurements were made immediately prior to caffeine administration (baseline) and 6 h later. Six hours after caffeine administration compared to baseline, the median Pemax (p = 0.017), Pimax (p = 0.004), FRC (p < 0.001), CRS (p = 0.002) and RRS (p = 0.004) had significantly improved. Our results suggest that caffeine administration facilitates weaning of prematurely born infants from mechanical ventilation by improving respiratory muscle strength.     

Elevated platelet activating factor in the tracheal aspirate at birth and signs of intra-uterine inflammation in infants with neonatal pulmonary emphysema

To investigate the pathophysiology of the neonatal pulmonary emphysema, we assayed platelet activating factor (PAF) in the tracheal aspirates of the low birth weight infants. A total of 29 neonates (birth weight <1750 g) who required mechanical ventilation were enrolled. Tracheal aspirates were obtained within 48 h and blood samples collected within 24 h of life. PAF was assayed on the basis of its ability to cause aggregation of washed rabbit platelets. PAF was significantly elevated in four infants who showed pulmonary emphysema within the 1st week of life (median 24 pg/g lipid phosphorus, range 9.9–200) compared with those detected in the other three groups of infants; infants with respiratory distress syndrome (RDS) in whom chronic lung disease (CLD) did not develop (median 1.8 pg/g lipid phosphorus, range 0–30; P < 0.05), infants without RDS nor CLD (median 0.64 pg/g lipid phosphorus, range 0–14; P < 0.05) and infants with other types of CLD (median 1.1 pg/g lipid phosphorus, range 0–1.8; P < 0.01). The four infants who developed pulmonary emphysema within the 1st week of life, had significantly elevated serum IgM and neutrophilia at birth. The increased amount of PAF in the tracheal aspirates shows the presence of inflammation in the lung at birth. The elevated serum IgM level and neutrophilia indicate that the inflammation begins in utero. Conclusion Our data suggest that neonatal pulmonary emphysema is caused by intra-uterine inflammation increasing platelet activating factor in the lungs. Platelet activating factor may play a role in aggravating the process of pulmonary emphysema. Received: 20 July 1998 / Accepted: 14 February 1999     

Ventilation in special situations. Mechanical ventilation in bronchiolitis

Bronchiolitis is a prevalent viral disease in infants. Many of these infants require hospital admission and mechanical ventilation due to respiratory failure or apnea. The clinical and pathophysiological spectrum of this disease can range from two extremes, obstructive and restrictive disease, on which the indication for mechanical ventilation and the modality used should be based. Non-invasive ventilation is especially indicated in both obstructive and hypoxemic restrictive patterns and a pressure-controlled modality is recommended. In obstructive patterns, air trapping must be monitored, while in restrictive patterns the addition of positive end-expiratory pressure (PEEP) is indicated. High-frequency oscillatory ventilation is indicated in restrictive patterns with sever hypoxemia despite conventional ventilatory support or in cases of significant air leak syndromes. In all cases, a permissive hypercapnia strategy is recommended to prevent barotrauma. Sedation and muscle relaxation should be considered to facilitate adaptation to the ventilator and to try to limit the risks of air trapping, air leak, and barotrauma.     

新生儿和婴儿呼吸道合胞病毒致急性下呼吸道感染临床特征和疾病负担

目的了解上海地区新生儿和婴儿呼吸道合胞病毒（RSV）感染的严重程度及疾病负担,为RSV感染的监测及临床防治提供科学依据。方法回顾性收集2012年3月至2013年2月复旦大学附属儿科医院内科和新生儿科住院并确诊为急性下呼吸道感染（ALRI）≤1岁患儿的病历,截取人口学资料、临床特征、病死率、并发症、住院时间和费用等指标,并采用严重度指数(SI)进行RSV感染严重程度综合评价。分为新生儿组和婴儿组,并进一步分为单一感染和混合感染亚组进行分析。 结果1 726例ALRI≤1岁患儿中RSV阳性913例（52.9%）进入分析。新生儿组295例,婴儿组618例。①SI评分新生儿组高于婴儿组,(2.5±0.2) vs (1.9±0.1)分,P<0.05;较重度和重度比例新生儿组显著高于婴儿组,但单一感染和混合感染亚组间差异无统计学意义。②RSV感染的≤1岁患儿病死率为5.0％,新生儿组病死率与婴儿组差异无统计学意义,婴儿组合并基础疾病患儿病死率高。③机械通气比例两组间差异无统计学意义,婴儿组混合感染亚组高于单一感染亚组。④并发症情况：新生儿组呼吸暂停和脓毒症发生率较高,新生儿组混合感染亚组脓毒症发生率显著高于单一感染亚组。⑤住院天数新生儿组与婴儿组差异无统计学意义,合并基础疾病者显著高于未合并疾病疾病患儿;住院费用婴儿组显著高于新生儿组,新生儿混合感染亚组显著高于单一感染亚组,合并基础疾病患儿显著高于未合并基础疾病患儿。 结论RSV感染新生儿的重症比例和并发症的发生率较高,婴儿组住院费用较高。混合感染和合并基础疾病是影响RSV感染严重程度和疾病负担的重要因素。