Incidence Of Chronic Lung Disease Research Articles

Improvement of Short- and Long-Term Outcomes for Very Low Birth Weight Infants: Edmonton NIDCAP Trial

Our objective was to determine the impact of Newborn Individualized Developmental Care and Assessment Program (NIDCAP)-based care on length of stay of very low birth weight (VLBW) infants. Secondary outcome measures were days of ventilation, incidence of chronic lung disease, and 18-month neurodevelopmental outcomes. This cluster-randomized, controlled trial took place in a large NICU in Canada, with follow-up evaluation at 18 months of age, from September 1999 to September 2004. One hundred VLBW singleton infants and 10 VLBW twin sets were assigned randomly to NIDCAP-based or control care, and 90% participated in follow-up assessments. The intervention was NIDCAP-based care (N = 56), that is, care by NIDCAP-educated staff members and behavioral observations. The control group (N = 55) received standard NICU care. Statistical analyses were adjusted for cluster randomization. Although the intervention was not blinded, the pediatricians making the decisions to discharge the infants were not involved in the study, and the follow-up staff members were blinded with respect to group. NIDCAP group infants had reduced length of stay (median: NIDCAP: 74 days; control: 84 days; P = .003) and incidence of chronic lung disease (NIDCAP: 29%; control: 49%; odds ratio: 0.42 [95% confidence interval: 0.18-0.95]; P = .035). At 18 months of adjusted age, NIDCAP group infants had less disability, specifically mental delay (NIDCAP: 10%; control: 30%; odds ratio: 0.25 [95% confidence interval: 0.08-0.82]; P = .017). NIDCAP-based care for VLBW infants improved short- and long-term outcomes significantly.

Early intervention in management of very preterm growth‐restricted fetuses: 2‐year outcome of infants delivered on fetal indication before 30 gestational weeks

To describe the outcome of growth-restricted fetuses with absent or reversed end-diastolic flow (ARED) in the umbilical artery delivered on fetal indication before 30 gestational weeks. Between 1998 and 2004, 42 fetuses with intrauterine growth restriction (IUGR) and ARED in the umbilical artery were delivered liveborn by Cesarean section on fetal indication before 30 gestational weeks. The median gestational age at delivery was 27 + 1 (range, 24 + 4 to 29 + 5) weeks. An additional four fetuses died in utero at a median gestational age of 24 + 2 (range, 23 + 5 to 25 + 4) weeks. Neonatal morbidity, infant mortality and major neurological morbidity of liveborn infants were compared with those in two control groups: all 371 liveborn infants delivered at < 30 weeks during the corresponding time period (Group A) and a subset of these, 42 matched infants without IUGR (Group B). Thirty-two fetuses (76%) [corrected] were delivered within 48 h of the occurrence of ARED (25 absent, seven reversed end-diastolic flow). The remaining 10 fetuses (five absent, five reversed end-diastolic flow) were monitored for a median of 6.5 (range, 3-18) days before delivery. One infant died in the neonatal period and three during the first year of postnatal life (2-year survival 90%). The incidence of chronic lung disease was higher in the ARED Group than in Control Groups A and B (P = 0.001 and P = 0.03, respectively). There were no differences between the groups in the occurrence of necrotizing enterocolitis, cerebral hemorrhage or retinopathy of prematurity. Cerebral palsy was diagnosed in 14% of the index group compared with 11% and 17% of Control Groups A and B (P > 0.05). Very preterm growth-restricted fetuses with umbilical artery ARED delivered on fetal indication, in most cases before the occurrence of severe changes in the ductus venosus velocity waveforms and/or fetal heart rate tracings, showed high 2-year survival and low morbidity.

Ventilator Gas Flow Rates Affect Inspiratory Time and Ventilator Efficiency Index in Term Lambs

Background: Despite increasing survival in the smallest preterm infants, the incidence of chronic lung disease has not decreased. Research into ventilatory strategies has concentrated on minimising barotrauma, volutrauma and atelectotrauma, but little attention has been paid to the role of bias gas flow rates and the potential for rheotrauma or shear stress injury. Ventilated preterm infants frequently receive relatively high gas flow rates. Objectives: We hypothesised that altering bias gas flow rates would change the efficiency of ventilation and thereby affect ventilatory parameters. Methods: We tested this hypothesis using an artificial lung followed by ventilation of 8 term lambs. Results: Between flows of 2 and 15 l/min, inflation time (Ti) in the artificial lung was inversely related to the bias gas flow rate. In the ventilated lambs, Ti was inversely related to flow rates up to 10 l/min, with no statistically significant effect at flow rates >10 l/min. There were no adverse effects on gas exchange or cardiovascular parameters until a flow rate of 3 l/min was used, when inadequate gas exchange occurred. Conclusions: Ti is inversely associated with the bias gas flow rate. Flow rates much lower than those used in many neonatal units seem to provide adequate ventilation. We suggest that the role of ventilator gas flow rates, which may potentially influence shear stress in ventilator-induced lung injury, merits further investigation.

To tube or not to tube babies with respiratory distress syndrome

The use of mechanical ventilation in premature infants with respiratory distress syndrome (RDS) and respiratory failure often results in barotrauma, volutrauma and chronic lung disease (CLD). Research indicates that early surfactant therapy and initiation of nasal continuous positive airway pressure (CPAP) for these infants significantly reduces the need for mechanical ventilation and the incidence of CLD. Different CPAP delivery systems exist, each with some practical and clinical advantages and disadvantages. Clinical trials indicate that optimal management of neonatal RDS could be improved by early surfactant treatment followed immediately by extubation and stabilization on CPAP. Evidence suggests a synergistic effect between early surfactant administration (within 2 h of birth) and rapid extubation to nasal CPAP with a significant reduction in the need for mechanical ventilation and its associated morbidities.

Patterns of Respiratory Disease During the First 2 Postnatal Weeks in Extremely Premature Infants

Pulmonary disease among infants of <28 weeks' gestation (extremely low gestational age newborns) often has the following pattern: the infant starts out with little need for supplemental oxygen and ventilatory support in the first postnatal week but then has pulmonary deterioration in the second postnatal week, with an increased need for supplemental oxygen and respiratory support. We evaluated the antecedents and correlates of patterns of early lung disease, with particular emphasis on pulmonary deterioration, in a large cohort study (the Extremely Low Gestational Age Newborn [ELGAN] study). We examined data collected prospectively on 1340 infants born between 2002 and 2004 at 23 to 27 completed weeks of gestation and who survived to 14 days. Pulmonary deterioration was defined as receipt of fraction of inspired oxygen < 0.23 on any day between days 3 and 7 and receipt of fraction of inspired oxygen > or = 0.25 on day 14. One fifth (20%) of the infants had consistently low fraction of inspired oxygen, approximately two fifths (38%) had pulmonary deterioration, and the remaining approximately two fifths (43%) had consistently high fraction of inspired oxygen (early and persistent lung dysfunction). Compared with infants who had consistently low fraction of inspired oxygen, infants who experienced pulmonary deterioration had lower gestational ages and lower birth weights, had higher scores for neonatal acute physiology, and received more intensive modes of respiratory support. Gender, multifetal pregnancy, cesarean delivery, antenatal steroids, chorioamnionitis, and funisitis were not associated with pulmonary deterioration. The incidence of chronic lung disease, defined as oxygen therapy at 36 weeks' postmenstrual age, was 17% in the consistently low fraction of inspired oxygen group, 51% in the pulmonary deterioration group, and 67% in the early and persistent pulmonary dysfunction group. The incidence of death in these 3 groups before 36 weeks' postmenstrual age was 1%, 3%, and 5%, respectively. Nearly 40% of extremely low gestational age newborns experience pulmonary deterioration in the first 2 postnatal weeks, and half of these infants develop chronic lung disease. Indicators of developmental immaturity and illness severity were associated with both pulmonary deterioration and chronic lung disease. Studying the antecedents of pulmonary deterioration might provide new insights about chronic lung disease pathogenesis.

Urinary Aldosterone Excretion and Renal Function in Extremely-Low-Birth-Weight Infants following Acute Furosemide Therapy

Background: Increased activity of the renin-angiotensin-aldosterone system (RAAS) has been reported in the neonatal period. Until now, it has been demonstrated that the RAAS of healthy neonates responds to acute furosemide challenge while no data concerning the responsiveness of RAAS in extremely low birth weight (ELBW) infants are available. Objective: To assess urinary aldosterone excretion (UAE) and renal function in ELBW infants who received diuretics for the purpose of reducing the incidence of chronic lung disease (CLD). Methods: Infants with birth weights ≤1,000 g, at high risk to develop CLD, were studied in a prospective observational study. UAE and renal function were investigated before and after administration of furosemide given in a single dose of 2 mg/kg. Results: UAE and renal function were evaluated in 20 ELBW infants. Diuretic administration resulted in a significant rise in UAE and urinary sodium, potassium and chloride excretion. No change occurred in creatinine clearance, while urine volume increased significantly. Conclusions: ELBW infants respond to acute furosemide challenge by increasing urine volume, urinary electrolytes and UAE.

Comparison of neonatal outcome for inborn and outborn very low‐birthweight preterm infants

The aim of the present study was to compare the neonatal outcome of very low-birthweight (VLBW) preterm infants with regard to inborn and outborn status in a medical center of Southern Taiwan, where short-distance neonatal transport is the rule and maternal transport was not well established. This retrospective study included outborn VLBW preterm infants admitted to the neonatal intensive care unit of Chang Gung Memorial Hospital at Kaohsiung after neonatal transport during the period from 1999 through 2003. An equal number of inborn preterm infants matched for gender and birthweight were included as controls. Infants with lethal congenital anomalies or who died in the delivery room were excluded. Data were collected from reviewing medical charts. A total of 34 inborn VLBW infants and 34 outborn VLBW infants with neonatal transport were included. Chronic lung disease (CLD) was significantly more frequent in the outborn group according to McNemar test (P = 0.0124) and logistic regression. Logistic regression also showed that outborn status (P = 0.0173) and birthweight (P = 0.0024) were the two most important risk factors for development of CLD. Well-trained short distance neonatal transport is useful and valuable for VLBW infants with gestation age of 27-34 weeks in Southern Taiwan. The respiratory outcome, however, was poor in the outborn group in terms of incidence of CLD. To improve the respiratory outcome, further modification of respiratory care during transportation or antenatal maternal transport is crucial.

A Randomized Controlled Trial on Parenteral Nutrition, Oxidative Stress, and Chronic Lung Diseases in Preterm Infants

To evaluate the effect of trace elements (TEs), when added to total parenteral nutrition (TPN) solutions, on peroxides load, and to test the hypothesis that protection of TPN from light can decrease peroxides load and is associated with improvement in oxidant-related clinical outcomes in preterm infants. A total of 80 preterm infants were randomized to 1 of 4 groups (n=20 each): group 1 received a mixture of dextrose and amino acids; group 2 received a mixture of dextrose, amino acids, and lipid emulsion; group 3 received dextrose, amino acids, lipid emulsion, and multivitamins (MVP); and group 4 received dextrose, amino acids, lipid emulsion, MVP, and TEs. Each group was subdivided into photo-protected and photo-exposed subgroups (n=10 each). Using ferrous oxidation of xylenol orange technique, we measured the baseline level of excreted urinary peroxides before and 48 hours after starting TPN. We examined the association among light protection, urinary peroxides, and clinical outcomes of these infants. Baseline urinary peroxides ranged between 5.5 and 24.8 micromol/L. A significant increase in urinary peroxides was observed in all groups after receiving TPN. The use of TEs did not affect peroxide production. In regression analysis, the addition of MVP (P<0.0001) and the exposure to light (P=0.02) were significantly associated with increased urinary peroxides. In the overall population, light exposure was associated with a significant increase in the incidence of chronic lung disease (adjusted OR 9.26, confidence interval 1.2-73; P=0.03) but had no effect on mortality, necrotizing enterocolitis, or sepsis. TEs in TPN solutions have no effect on the production of urinary peroxides. Addition of MVP and exposure of TPN to light are the 2 major sources of peroxides in TPN. Protection from ambient light is associated with a decrease in chronic lung disease.

A Randomized Controlled Trial of Post-extubation Bubble Continuous Positive Airway Pressure Versus Infant Flow Driver Continuous Positive Airway Pressure in Preterm Infants with Respiratory Distress Syndrome

To compare the efficacy and safety of bubble continuous positive airway pressure (CPAP) and Infant Flow Driver (IFD) CPAP for the post-extubation management of preterm infants with respiratory distress syndrome (RDS). A total of 140 preterm infants at 24 to 29 weeks' gestation or with a birth weight of 600 to 1500 g who were ventilated at birth for RDS were randomized to receive either IFD CPAP (a variable-flow device) or bubble CPAP (a continuous-flow device). A standardized protocol was used for extubation and CPAP. No crossover was allowed. The primary outcome was successful extubation maintained for at least 72 hours. Secondary outcomes included successful extubation maintained for 7 days, total duration of CPAP support, chronic lung disease, and complications of prematurity. Seventy-one infants were randomized to bubble CPAP, and 69 were randomized to IFD CPAP. Mean gestational age and birth weight were similar in the 2 groups, as were the proportions of infants who achieved successful extubation for 72 hours and for 7 days. However, the median duration of CPAP support was 50% shorter in the infants on bubble CPAP. Moreover, in the subset of infants who were ventilated for less than 14 days, the infants on bubble CPAP had a significantly lower extubation failure rate. There was no difference in the incidence of chronic lung disease or other complications between the 2 study groups. Bubble CPAP is as effective as IFD CPAP in the post-extubation management of infants with RDS; however, in infants ventilated for < or = 14 days, bubble CPAP is associated with a significantly higher rate of successful extubation. Bubble CPAP also is associated with a significantly reduced duration of CPAP support.

Reduction in the Incidence of Chronic Lung Disease in Very Low Birth Weight Infants: Results of a Quality Improvement Process in a Tertiary Level Neonatal Intensive Care Unit

Our objective was to reduce the incidence of chronic lung disease by introducing potentially better practices in our delivery room and NICU. We compared the incidences of chronic lung disease in infants with birth weights of 501 to 1500 g in 2002 and 2005, after implementation of the changes. Medical records for infants of 501 to 1500 g who were born in 2002 and 2005 were reviewed for maternal characteristics, care of the infant in the delivery room and the NICU (including surfactant usage, duration of ventilation, duration of continuous positive airway pressure therapy, and duration of oxygen treatment), length of stay, and short-term clinical outcomes (eg, pneumothorax, severe intracranial hemorrhage, retinopathy of prematurity, and weight gain). There was a significant reduction in our incidence of chronic lung disease, from 46.5% in 2002 to 20.5% in 2005. The number of infants discharged from the hospital with oxygen therapy also decreased significantly, from 16.4% in 2002 to 4.1% in 2005. The overall relative risk reduction for chronic lung disease in 2005, compared with 2002, was 55.8%. By using a quality improvement process that included avoidance of intubation, adoption of new pulse oximeter limits, and early use of nasal continuous positive airway pressure therapy, we demonstrated a significant reduction in the incidence of chronic lung disease in infants with birth weights of <1500 g in 2005, in comparison with 2002. These results have persisted to date. There were no significant short-term complications.

Very Early Surfactant Without Mandatory Ventilation in Premature Infants Treated With Early Continuous Positive Airway Pressure: A Randomized, Controlled Trial

Chronic lung disease is one of the most frequent and serious complications of premature birth. Because mechanical ventilation is a major risk factor for chronic lung disease, the early application of nasal continuous positive airway pressure has been used as a strategy for avoiding mechanical ventilation in premature infants. Surfactant therapy improves the short-term respiratory status of premature infants, but its use is traditionally limited to infants being mechanically ventilated. Administration of very early surfactant during a brief period of intubation to infants treated with nasal continuous positive airway pressure may improve their outcome and further decrease the need for mechanical ventilation. Our goal was to determine if very early surfactant therapy without mandatory ventilation improves outcome and decreases the need for mechanical ventilation when used in very premature infants treated with nasal continuous positive airway pressure soon after birth. Eight centers in Colombia participated in this randomized, controlled trial. Infants born between 27 and 31 weeks' gestation with evidence of respiratory distress and treated with supplemental oxygen in the delivery room were randomly assigned within the first hour of life to intubation, very early surfactant, extubation, and nasal continuous positive airway pressure (treatment group) or nasal continuous airway pressure alone (control group). The primary outcome was the need for subsequent mechanical ventilation using predefined criteria. From January 1, 2004, to December 31, 2006, 279 infants were randomly assigned, 141 to the treatment group and 138 to the control group. The need for mechanical ventilation was lower in the treatment group (26%) compared with the control group (39%). Air-leak syndrome occurred less frequently in the treatment group (2%) compared with the control group (9%). The percentage of patients receiving surfactant after the first hour of life was also significantly less in the treatment group (12%) compared with the control group (26%). The incidence of chronic lung disease (oxygen treatment at 36 weeks' postmenstrual age) was 49% in the treatment group compared with 59% in the control group. All other outcomes, including mortality, intraventricular hemorrhage, and periventricular leukomalacia were similar between the groups. In premature infants treated with nasal continuous positive airway pressure early after birth, the addition of very early surfactant therapy without mandatory ventilation decreased the need for subsequent mechanical ventilation, decreased the incidence of air-leak syndrome, and seemed to be safe. Reduction in the need for mechanical ventilation is an important outcome when medical resources are limited and may result in less chronic lung disease in both developed and developing countries.

Changing Use of Surfactant Over 6 Years and Its Relationship to Chronic Lung Disease

Our goals were to identify the trend of surfactant use over a 6-year period and to determine whether a relationship exists between the incidence of chronic lung disease in infants born weighing <1000 g who receive surfactant and those who do not. Data regarding surfactant use, incidence of chronic lung disease, nasal continuous positive airway pressure use and duration, and demographic data were collected from the Alere (formerly ParadigmHealth) database from 2001 to 2006 (n = 3086). Groups were compared by using chi(2) test, analysis of variance, or Student's t test. Use of surfactant has decreased over time from 67% in 2001 to 59.9% in 2006. Infants who received surfactant were more likely to develop chronic lung disease. Those who received >1 dose of surfactant were more likely to develop chronic lung disease when compared with infants treated with only 1 dose. Chronic lung disease rates have risen over time from 47.8% in 2001 to 57.8% in 2006. There was no difference in survival between groups. Despite the findings that surfactant use decreased during the study period and the rate of chronic lung disease increased, the data do not support a connection. Infants who receive surfactant are more likely to develop chronic lung disease, and chronic lung disease rates are stable in those infants not treated with surfactant. It is concerning, however, that 60% of infants not receiving surfactant developed chronic lung disease.

Risk Model of Thoracic Aortic Surgery in 4707 Cases From a Nationwide Single-Race Population Through a Web-Based Data Entry System

The objective of this study was to collect integrated data from nationwide hospitals using a web-based national database system to build up our own risk model for the outcome from thoracic aortic surgery. The Japan Adult Cardiovascular Surgery Database was used; this involved approximately 180 hospitals throughout Japan through a web-based data entry system. Variables and definitions are almost identical to the STS National Database. After data cleanup, 4707 records were analyzed from 97 hospitals (between January 1, 2000, and December 31, 2005). Mean age was 66.5 years. Preoperatively, the incidence of chronic lung disease was 11%, renal failure was 9%, and rupture or malperfusion was 10%. The incidence of the location along the aorta requiring replacement surgery (including overlapping areas) was: aortic root, 10%; ascending aorta, 47%; aortic arch, 44%; distal arch, 21%; descending aorta, 27%; and thoracoabdominal aorta, 8%. Raw 30-day and 30-day operative mortality rates were 6.7% and 8.6%, respectively. Postoperative incidence of permanent stroke was 6.1%, and renal failure requiring dialysis was 6.7%. OR for 30-day operative mortality was as follows: emergency or salvage, 3.7; creatinine >3.0 mg/dL, 3.0; and unexpected coronary artery bypass graft, 2.6. As a performance metric of the risk model, C-index of 30-day and 30-day operative mortality was 0.79 and 0.78, respectively. This is the first report of risk stratification on thoracic aortic surgery using a nationwide surgical database. Although condition of these patients undergoing thoracic aortic surgery was much more serious than other procedures, the result of this series was excellent.

Decreased Use of Postnatal Corticosteroids in Extremely Preterm Infants without Increasing Chronic Lung Disease

Background: Postnatal corticosteroidsare effective in preventing chronic lung disease in preterm infant. There are concerns that corticosteroid use may be associated with an increased risk of impaired neurodevelopment. Objective: To examine the effect of change in practice with the use of postnatal corticosteroids over an 8-year period in extremely preterm babies on the incidence of chronic lung disease (CLD) and cerebral palsy at 1 year of age. Methods: Babies of birth weight <1,000 g or gestational age <28 weeks admitted from 1997 to 2004 were included in this retrospective analysis. The study period was divided into two eras: group 1: 1997–2000, group 2: 2001–2004. Data were collected from the neonatal database, individual records and from the Growth and Development Unit. The outcome measure of CLD was defined as oxygen dependency at 36 weeks postmenstrual age. Data for postnatal corticosteroid usage were collected for the number of babies per year, and total dose. Results: 389 group 1 babies were compared to 368 group 2 babies. There was a significant decrease in the use of dexamethasone from 27% in group 1 to 13% in group 2 (p = 0.0001), and total dose – mg/kg (4.5 ± 2.9 vs. 2.6 ± 1.6, p = 0.0001). The incidence of CLD and need for home oxygen was similar between groups. The incidence of cerebral palsy reduced from 10.4% in group 1 to 6.6% in group 2, though this was not statistically significant (OR 0.63; 95% CI 0.3, 1.2.). Conclusion: Decreased postnatal corticosteroid use had no impact on the incidence of CLD or need for home oxygen therapy. The trend towards a reduced rate of cerebral palsy requires further investigation.

Cochrane review: Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants

AbstractBackgroundRespiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although the use of intermittent positive pressure ventilation (IPPV) in neonates with respiratory failure saves lives, its use is associated with lung injury and chronic lung disease (CLD). Conventional IPPV is provided at 30‐80 breaths per minute, while a newer form of ventilation called high frequency oscillatory ventilation (HFOV) provides 'breaths' at 10 ‐ 15 cycles per second. This has been shown to result in less lung injury in experimental studies.ObjectivesThe objective of this review is to determine the effect of the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation (CV) in preterm infants who are mechanically ventilated for respiratory distress syndrome (RDS), on the incidence of chronic lung disease, mortality and other complications associated with prematurity and assisted ventilation.Search strategySearches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal hand searching by the Cochrane Collaboration, mainly in the English language. The search was updated in April 2007.Selection criteriaRandomised controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who were given IPPV. Randomisation and commencement of treatment needed to be as soon as possible after the start of IPPV and usually in the first 12 hours of life.Data collection and analysisThe methodological quality of each trial was independently reviewed by the various authors. The standard effect measures are relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) to produce one outcome were calculated. For all measures of effect, 95% confidence intervals were used. In subgroup analyses the 99% CIs are also given for summary RRs in the text. Meta‐analysis was performed using a fixed effects model. Where heterogeneity was over 50%, the random effects RR is also given.Main resultsFifteen eligible studies of 3,585 infants were included. Meta‐analysis comparing HFOV with CV revealed no evidence of effect on mortality at 28 ‐ 30 days of age or at approximately term equivalent age. These results were consistent across studies and in subgroup analyses. The effect of HFOV on CLD in survivors at term equivalent gestational age was inconsistent across studies and the reduction was of borderline significance overall. Subgroups of trials showed a significant reduction in CLD with HFOV when high volume strategy for HFOV was used, when piston oscillators were used for HFOV, when lung protective strategies for CV were not used, when randomisation occurred at two to six hours of age, and when inspiratory:expiratory ratio of 1:2 was used for HFOV. In the meta‐analysis of all trials, pulmonary air leaks occurred more frequently in the HFOV group.In some studies, short‐term neurological morbidity with HFOV was found, but this effect was not statistically significant overall. The subgroup of two trials not using a high volume strategy with HFOV found increased rates of Grade 3 or 4 intraventricular haemorrhage and of periventricular leukomalacia. An adverse effect of HFOV on long‐term neurodevelopment was found in one large trial but not in the five other trials that reported this outcome. The rate of retinopathy of prematurity is reduced overall in the HFOV group.Authors' conclusionsThere is no clear evidence that elective HFOV offers important advantages over CV when used as the initial ventilation strategy to treat preterm infants with acute pulmonary dysfunction. There may be a small reduction in the rate of CLD with HFOV use, but the evidence is weakened by the inconsistency of this effect across trials and the overall borderline significance. Future trials on elective HFOV should target those infants who are at most risk of CLD (extremely preterm infants), compare different strategies for generating HFOV and CV, and report important long‐term neurodevelopmental outcomes.Plain language summaryInsufficient evidence exists to support the routine use of high frequency oscillatory ventilation (HFOV) instead of conventional ventilation for preterm infants with lung disease who are given positive pressure ventilation.High frequency oscillatory ventilation is a way of providing artificial ventilation of the lungs that theoretically may produce less injury to the lungs and therefore reduce the rate of chronic lung disease. This review of the evidence from fifteen randomised controlled trials showed variable results between studies and no clear overall benefit or harm resulting from HFOV.

Protocol for administering continuous positive airway pressure in neonates

Continuous positive airway pressure (CPAP) is a simple, inexpensive and gentle mode of respiratory support in preterm very low birth weight (VLBW) infants. It helps by preventing the alveolar collapse and increasing the functional residual capacity of the lungs. Since it results in less ventilator induced lung injury than mechanical ventilation, it should theoretically reduce the incidence of chronic lung disease in VLBW infants. Various devices have been used for CPAP generation and delivery. The relative merits and demerits of these devices and the guidelines for CPAP therapy in neonates are discussed in this protocol.

Multiple Courses of Indomethacin and Neonatal Outcomes in Premature Infants

The objective of this retrospective cohort study was to determine patent ductus arteriosus (PDA) closure rate with multiple short courses (three doses) of postnatal indomethacin and compare neonatal outcomes in infants who received two versus three courses of indomethacin for PDA closure. Infants <34 weeks' gestational age born between January 2000 and December 2004 at the University of Maryland Medical Center and who received two or more short courses of indomethacin were included. Outcome measures were ductal closure rate and neonatal outcomes. Of 61 infants who were identified to have received two or more courses of indomethacin, 26 infants closed their ductus after the second course (response rate, 42%). Of the 35 infants who failed ductal closure after two courses, 11 infants had their ductus ligated and 23 received a third course of indomethacin. Of 23 who received a third course, 10 closed their ductus (response rate, 43%). There was no significant difference in the incidence of chronic lung disease, severe retinopathy of prematurity, necrotizing enterocolitis, renal function, or mortality between infants who received two and those who received three courses of indomethacin. Infants exposed to three courses of indomethacin had a statistically nonsignificant increased incidence of periventricular leukomalacia (p = 0.08; adjusted odds ratio = 4.8; 95% CI, 0.8-30) and remained in the hospital for a longer duration (p = 0.02) compared to infants exposed to two courses of indomethacin. We conclude that multiple courses of indomethacin may be associated with a ductal closure. However, the requirement for a third course may be associated with an increased risk of periventricular leukomalacia.

Adjunctive therapies in chronic lung disease: Examining the evidence

Chronic lung disease (CLD) or bronchopulmonary dysplasia (BPD) is one of the most common long-term complications in very premature infants. The incidence of CLD has been increasing over the past two decades in parallel with an improvement in the survival of this population. We have witnessed a revolution in the therapies that are used, either to manage these infants' respiratory distress syndrome (RDS) with an aim to prevent CLD or to manage the established condition. Several devices and strategies have been developed to provide respiratory support with minimal risk of lung injuries. Multiple adjunctive agents have also been used either to reduce the risk of CLD or to mitigate its course. There is considerable evidence supporting the use of exogenous surfactant, but unfortunately many other therapies currently used for CLD, either preventative or as a treatment, are based on very little or no evidence. The gold standard to assess a given therapy is the randomised controlled trial (RCT), designed to look at clinically meaningful outcomes and long-term safety. In this context, we discuss the support - or lack thereof - for the adjunctive therapies used in relation to CLD. Many of the therapies have been examined as systematic reviews by the Cochrane Neonatal Review Group. These reviews are noted in the references and can be easily accessed at the following website sponsored by the National Institute of Child Health and Human Development: www.nichd.nih.gov/cochrane/default.cfm.

Reduction in ventilator-induced lung injury improves outcome in congenital diaphragmatic hernia?

The purpose of this historical study was to compare the outcome for two treatment strategies, for neonates with congenital diaphragmatic hernia (CDH). The records of 65 infants born between 1991 and 2005 with CDH from a single tertiary care perinatal centre in the United Kingdom were retrospectively reviewed. Conventional mechanical ventilation (CMV) and systemic vasodilators were used from 1991 to 1995 (era 1). High frequency oscillatory ventilation (HFOV) and nitric oxide (NO) were used between 1996 and 2005 (era 2). Main outcome measures were survival and incidence of chronic lung disease. The results showed that the survival rate was 38% (8/21) in era 1 and 73% (32/44) in era 2, 95% CI for difference -59 to -10%. The incidence of chronic lung disease in survivors was 45% (5/11) in era 1 and 30% (9/30) in era 2, 95% CI for difference -18 to 49%. These data show significantly improved survival with elective use of HFOV and NO compared to CMV and systemic vasodilators. The survival results for CDH at St George's Hospital are comparable to those published from other institutions. The results may reflect a reduction in ventilator-induced lung injury with HFOV compared to CMV.

Uteroplacental insufficiency decreases p53 serine-15 phosphorylation in term IUGR rat lungs

Intrauterine growth restriction (IUGR) increases the incidence of chronic lung disease (CLD). The molecular mechanisms responsible for IUGR-induced acute lung injury that predispose the IUGR infant to CLD are unknown. p53, a transcription factor, plays a pivotal role in determining cellular response to stress by affecting apoptosis, cell cycle regulation, and angiogenesis, processes required for thinning of lung mesenchyme. Because thickened lung mesenchyme is characteristic of CLD, we hypothesized that IUGR-induced changes in lung growth are associated with alterations in p53 expression and/or modification. We induced IUGR through bilateral uterine artery ligation of pregnant rats. Uteroplacental insufficiency significantly decreased serine-15-phosphorylated (serine-15P) p53, an active form of p53, in IUGR rat lung. Moreover, we found that decreased phosphorylation of lung p53 serine-15 localized to thickened distal air space mesenchyme. We also found that IUGR significantly decreased mRNA for targets downstream of p53, specifically, proapoptotic Bax and Apaf, as well as Gadd45, involved in growth arrest, and Tsp-1, involved in angiogenesis. Furthermore, we found that IUGR significantly increased mRNA for Bcl-2, an antiapoptotic gene downregulated by p53. We conclude that in IUGR rats, uteroplacental insufficiency induces decreased lung mesenchymal p53 serine-15P in association with distal lung mesenchymal thickening. We speculate that decreased p53 serine-15P in IUGR rat lungs alters lung phenotype, making the IUGR lung more susceptible to subsequent injury.