Chronic Lung Disease In Survivors Research Articles

Prenatal stomach position and volume in relation to postnatal outcomes in left-sided congenital diaphragmatic hernia.

ObjectiveTo examine the association between prenatal stomach position (SP) grade and stomach volume (SV) and the need for pulmonary hypertension (PH) treatment after birth in prenatally diagnosed left‐sided congenital diaphragmatic hernia (CDH), live born >34 weeks.MethodsIn retrospect, SP grade and SV were determined in fetuses with isolated left‐sided CDH from 19 weeks gestational age (GA) onwards at three different time periods (≤24 weeks' GA: US1, 24–30 weeks' GA: US2; ≥30 weeks' GA: US3). Primary outcome was need for treatment of PH after birth. Secondary analyses included the predictive value of SP and SV for other respiratory outcomes and postnatal defect size.ResultsA total of 101 fetuses were included. SP grade was significantly associated with need for treatment of PH (US1, US2, and US3: p < 0.02). Also, prenatal SP grade was positively associated with defect size and development of chronic lung disease (CLD) in survivors. No association was found between SV and respiratory morbidities or postnatal defect size.ConclusionSP grade in left‐sided CDH fetuses is associated with an increased need for PH treatment, a larger postnatal defect size and CLD in survivors. We consider SP determination a valuable contribution to the prenatal assessment of left‐sided CDH.

The validity of the observed-to-expected lung-to-head ratio in congenital diaphragmatic hernia in an era of standardized neonatal treatment; a multicenter study.

ObjectiveTo assess the predictive value of observed‐to‐expected lung‐to‐head ratio (O/E LHR) for survival and chronic lung disease (CLD) in survivors of left‐sided congenital diaphragmatic hernia (CDH) in an era of standardized neonatal treatment, and to evaluate the predictive value of the O/E LHR trajectory for survival.MethodsThis retrospective cohort study was performed in two high‐volume CDH centers in the Netherlands in prenatally detected, isolated left‐sided CDH patients born between 2008 and 2014. O/E LHR and liver position were determined using 2D‐ultrasonography at three time points during gestation from 19 weeks onwards. Ultrasound measurements were performed on stored ultrasound data by one single experienced operator blinded to postnatal outcome.ResultsOf the 122 included cases, 77.9% survived of whom 38.9% developed CLD. A significant association was found between the first measured O/E LHR and survival and development of CLD in survivors. Prenatal liver position did not have additional predictive value. No significant association was found between the trajectory of the O/E LHR and survival.ConclusionIn an era of standardized neonatal treatment for neonates with CDH, the first measured O/E LHR per patient significantly predicts survival and development of CLD in survivors in isolated left‐sided CDH infants. © 2017 The Authors. Prenatal Diagnosis published by John Wiley & Sons, Ltd.

Preferential Streaming of the Ductus Venosus Toward the Right Atrium Is Associated With a Worse Outcome Despite a Higher Rate of Invasive Procedures in Human Fetuses With Left Diaphragmatic Hernia

Preferential streaming of the ductus venosus (DV) toward the right atrium has been observed in fetuses with left diaphragmatic hernia (LDH). The purpose of this retrospective study was to compare survival rates to discharge between a group with preferential streaming of the DV toward the right heart and a group in which this abnormal flow pattern was not present. We retrospectively searched our patient records for fetuses with LDH in whom liver position, DV streaming and postnatal outcome information was available. 55 cases were found and divided into two groups: Group I fetuses exhibited abnormal DV streaming toward the right side of the heart; group II fetuses did not. Various prognostic and outcome parameters were compared. 62 % of group I fetuses and 88 % of group II fetuses survived to discharge (p = 0.032). Fetoscopic tracheal balloon occlusion (FETO) was performed in 66 % of group I fetuses and 23 % of group II fetuses (p = 0.003). Postnatal ECMO therapy was performed in 55 % of group I fetuses and 23 % of group II infants (p = 0.025). Moderate to severe chronic lung disease in survivors was observed in 56 % of the survivors of group I and 9 % of the survivors of group II (p = 0.002). Preferential streaming of the DV toward the right heart in human fetuses with left-sided diaphragmatic hernia was associated with a poorer postnatal outcome despite a higher rate of invasive pre- and postnatal procedures compared to fetuses without this flow abnormality. Specifically, abnormal DV streaming was found to be an independent predictor for FETO.

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.

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.

Sequential Meta-analysis of Past Clinical Trials to Determine the Use of a New Trial

Clinical trials can be stopped early based on interim analyses or sequential analyses. In principle, sequential analyses can also be used to decide whether enough evidence has been gathered in completed trials to make further trials unnecessary. We demonstrate such an application through a retrospective analysis of clinical trials comparing ventilation methods for the treatment of preterm newborns. We identified 5 recent trials that compared high-frequency ventilation with conventional mechanical ventilation in the treatment of preterm newborns. Death or chronic lung disease and chronic lung disease in survivors were the primary clinical outcomes of interest. We applied sequential meta-analyses to these 5 studies. After including the first study of the last 5 trials in a sequential meta-analysis, the boundary of "no clinically relevant effect" was crossed for both outcomes (death or chronic lung disease). A sensitivity analysis using a reduction in the size of assumed clinically relevant effect showed the same findings after 2 trials. Sequential meta-analyses showed that a lack of clinically relevant effect had been established after the first of the 5 trials. If such an analysis had been conducted after the first or second of these clinical trials, it might have led to changes in the study design of subsequent trials or even to a reassessment of the need for further trials.

Antenatal Glucocorticoid Treatment Decreases Mortality and Chronic Lung Disease in Survivors among 23- to 28-Week Gestational Age Preterm Infants

The purpose of this study was to analyze the influence of antenatal glucocorticoid therapy (AGT) on mortality and chronic lung disease (CLD) in surviving preterm infants 23 to 28 weeks gestational age (WGA). This was a multicenter, prospective, observational study. A total of 2448 infants 23 to 28 WGA were born in 2002 to 2003; 27.7% did not receive AGT, 18.8% were exposed to partial AGT, and 53.5% were exposed to complete AGT. A total of 883 died and 22.9% of 1537 survivors were affected by CLD. Unadjusted univariate analysis showed AGT was associated with a reduction in mortality (p<0.001), either with partial or complete AGT courses, and also with a reduction in CLD in survivors (p<0.001), but only with complete AGT courses. In logistic regression analysis adjusted for confounding factors and a propensity score for AGT, AGT was significant and independently associated with a reduction of mortality, but only for complete AGT course (odds ratio [OR], 0.64; 95% confidence interval [CI], 0.47 to 0.87; p=0.004), and with a decrease in CLD if a complete AGT course was administered (OR, 0.63; 95% CI, 0.45 to 0.89; p=0.009). A complete course of AGT in 23 to 28 WGA pregnancies is associated with decreased rates of neonatal mortality and CLD disease in surviving infants.

Elective high frequency oscillatory ventilation versus conventional ventilation for acute pulmonary dysfunction in preterm infants.

Respiratory failure due to lung immaturity is a major cause of mortality in preterm infants. Although intermittent positive pressure ventilation (IPPV) saves lives, lung distortion during 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 seconds. This has been shown to result in less lung injury in experimental studies. The objective of this review is to determine whether the elective use of high frequency oscillatory ventilation (HFOV) as compared to conventional ventilation in preterm infants who are mechanically ventilated for the respiratory distress syndrome decreases the incidence of chronic lung disease (CLD) without adverse effects. Searches were made of the Oxford Database of Perinatal Trials, MEDLINE, EMBASE, previous reviews including cross references, abstracts, conferences and symposia proceedings, expert informants, journal handsearching by the Cochrane Collaboration, mainly in the English language. Expert informant's search in the Japanese language was made by Prof. Y. Ogawa. Randomized controlled trials comparing HFOV and CV in preterm or low birth weight infants with pulmonary dysfunction, mainly due to RDS, who are to be given IPPV. Randomization and commencement of treatment should have been as soon as possible after the start of IPPV and usually in the first 12 hours of life. The methodological quality of each trial was independently reviewed by the various authors. Each author extracted data separately; they were compared and differences were resolved. The standard method of the Cochrane Neonatal Review Group was used to synthesize the data using relative risk (RR) and risk difference (RD). From 1/RD the number needed to treat (NNT) for benefits, and number needed to harm (NNH) for adverse effects, were calculated. Meta-analysis of the six eligible studies comparing HFOV with CV revealed that there is no difference in mortality. There are trends toward decreases in CLD in survivors at 28-30 days, 'death or CLD at 28-30 days' and CLD in survivors at 36-37 weeks postmenstrual age or discharge in the HFOV group. However, there are trends towards increases in severe (grades 3 & 4) intraventricular hemorrhage (IVH) and in periventricular leukomalacia (PVL) in the HFOV group. HFOV results in a small increase in any air leak syndrome (ALS), [summary RR 1.20 (1.03, 1.39)]. Only 2 trials have included neurodevelopmental follow up and more survivors in the HFOV group are abnormal [summary RR 1.26 (1.01, 1.58)]. In the subgroup of four trials where a high volume strategy (HVS) was used, HFOV results in more favourable pulmonary outcomes. There are significantly lower rates of CLD in survivors at 28-30 days [summary RR 0.53 (0.36, 0.76)] and of 'death or CLD at 28-30 days' [summary RR 0.56 (0.40, 0.77) with a non-significant trend towards a reduction in oxygen use at 36-37 weeks postmenstrual age or discharge [summary RR 0.74 (0.55, 1.01)]. There were no differences in the rates of IVH or PVL. Of the four trials in the subgroup using surfactant routinely, three also used the HVS. The trends in results were similar with surfactant to those for the HVS subgroup analysis. One trial suggests that HFOV may reduce the cost of in-hospital care. In the subgroup of two trials (HIFI 1989, Rettwitz-Volk 1998) not using a HVS there is no effect of HFOV on the rate of CLD; however, there is an increase in the rate of PVL [summary RR 1.64 (1.02, 2.64). The overall meta-analyses is dominated by the large HIFI study which did not use the HVS recommended on the basis of animal studies, and in which surfactant was not available. Studies which used HVS have shown some benefits in short term measures of CLD without an in

Surfactant therapy for respiratory distress syndrome in premature neonates: a comparative review.

Exogenous surfactant therapy has been part of the routine care of preterm neonates with respiratory distress syndrome (RDS) since the beginning of the 1990s. Discoveries that led to its development as a therapeutic agent span the whole of the 20th century but it was not until 1980 that the first successful use of exogenous surfactant therapy in a human population was reported. Since then, randomized controlled studies demonstrated that surfactant therapy was not only well tolerated but that it significantly reduced both neonatal mortality and pulmonary air leaks; importantly, those surviving neonates were not at greater risk of subsequent neurological impairment. Surfactants may be of animal or synthetic origin. Both types of surfactants have been extensively studied in animal models and in clinical trials to determine the optimum timing, dose size and frequency, route and method of administration. The advantages of one type of surfactant over another are discussed in relation to biophysical properties, animal studies and results of randomized trials in neonatal populations. Animal-derived exogenous surfactants are the treatment of choice at the present time with relatively few adverse effects related largely to changes in oxygenation and heart rate during surfactant administration. The optimum dose of surfactant is usually 100 mg/kg. The use of surfactant with high frequency oscillation and continuous positive pressure modes of respiratory support presents different problems compared with its use with conventional ventilation. The different components of surfactant have important functions that influence its effectiveness both in the primary function of the reduction of surface tension and also in secondary, but nonetheless just as important, role of lung defense. With greater understanding of the individual surfactant components, particularly the surfactant-associated proteins, development of newer synthetic surfactants has been made possible. Despite being an effective therapy for RDS, surfactant has failed to have a significant impact on the incidence of chronic lung disease in survivors. Paradoxically the cost of care has increased as surviving neonates are more immature and consume a greater proportion of neonatal intensive care resources. Despite this, surfactant is considered a cost-effective therapy for RDS compared with other therapeutic interventions in premature infants.

High-frequency oscillatory ventilation in pediatric respiratory failure: a multicenter experience.

The use of high-frequency oscillatory ventilation (HFOV) has increased dramatically in the management of respiratory failure in pediatric patients. We surveyed ten pediatric centers that frequently use high-frequency oscillation to describe current clinical practice and to examine factors related to improved outcomes. Retrospective, observational questionnaire study. Ten tertiary care pediatric intensive care units. Two hundred ninety patients managed with HFOV between January 1997 and June 1998. None. Patients were classified according to presence or absence of preexisting lung disease, symptomatic respiratory syncytial virus infection, or presence of cyanotic heart disease or residual right-to-left intracardiac shunt. In addition, patients for whom HFOV acutely failed were analyzed separately. Those patients with preexisting lung disease were significantly smaller, had a significantly higher incidence of pulmonary infection as the triggering etiology, and had a significantly greater duration of conventional ventilation before institution of HFOV compared with patients without preexisting lung disease. Stepwise logistic regression was used to predict mortality and the occurrence of chronic lung disease in survivors. In patients without preexisting lung disease, the model predicted a 70% probability of death when the oxygenation index (OI) after 24 hrs was 28 in the immunocompromised patients and 64 in the patients without immunocompromise. In the immunocompromised patients, the model predicted a 90% probability of death when the OI after 24 hrs was 58. In survivors without preexisting lung disease, the model predicted a 70% probability of developing chronic lung disease when the OI at 24 hrs was 31 in the patients with sepsis syndrome and 50 in the patients without sepsis syndrome. In the patients with sepsis syndrome, the model predicted a 90% probability of developing chronic lung disease when the OI at 24 hrs was 45. Given the number of centers involved and the size of the database, we feel that our results broadly reflect current practice in the use of HFOV in pediatric patients. These results may help in deciding which patients are most likely to benefit from aggressive intervention by using extracorporeal techniques and may help identify high-risk populations appropriate for prospective study of innovative modes of supporting gas exchange (e.g., partial liquid breathing or intratracheal pulmonary ventilation).

Pulmonary Sequelae at Six Months following Extracorporeal Membrane Oxygenation

Mechanical assisted ventilation for neonatal respiratory failure is associated with residual lung disease. Because ECMO rests the lungs, it has been suggested that ECMO will prevent chronic lung disease in survivors. To determine whether or not ECMO survivors have evidence of pulmonary sequelae, we studied 19 infants who were treated with ECMO for neonatal respiratory failure. Ten infants still required supplemental oxygen or pulmonary medications or both to treat clinical lung disease during the first six months of life. Thoracic gas volume was normal. Pulmonary mechanics in ECMO survivors were compared with those of 13 preterm infants with BPD at similar age. We conclude that a significant proportion of ECMO survivors have residual abnormalities in pulmonary mechanics at 6 months of age. We speculate that neonatal lung injury due to meconium aspiration and other causes is a more important determinant of abnormal pulmonary sequelae than the method of treatment.