Objective. Dexamethasone is used in very low birth weight (VLBW) ventilator-dependent infants to prevent or decrease the severity of chronic lung disease. We reported a significant increase in respiratory compliance during a 7-day weaning course of moderately early dexamethasone therapy (0.5 mg/kg/d) in VLBW infants, along with a shorter duration of mechanical ventilation and O2 supplementation. Although 0.5 mg/kg/d has been the most commonly used dose in preterm infants, the use of a lower dose of dexamethasone may reduce potential adverse effects of steroid therapy. Quantification of dynamic pulmonary mechanics in VLBW infants who receive low-dose dexamethasone has not been reported. The objective of this study was to compare the effect of 2 dose regimens of dexamethasone on dynamic pulmonary mechanics, mean airway pressure (MAP), and fractional inspired oxygen concentration (Fio2) in intubated VLBW infants who were at risk for chronic lung disease.
Methods. We studied 47 VLBW (birth weight: 550-1290 g; gestational age: 24–30 weeks) ventilator-dependent infants at 7 to 14 days of age. Twenty-three infants were randomized to receive dexamethasone at 0.5 mg/kg/d intravenously for 3 days (high dose), 0.25 mg/kg/d for 3 days, and 0.1 mg/kg/d during the 7th day; 24 infants received low-dose dexamethasone as 0.2 mg/kg/d for 3 days and 0.1 mg/kg/d for 4 days. Respiratory compliance (Crs) and resistance were measured before and on days 2, 5, and 7 of dexamethasone therapy. We recorded airway pressure, flow, and tidal volume, and mechanical breaths were analyzed.
Results. Crs significantly increased during dexamethasone therapy in both groups of infants when compared with baseline (74% increase in the high-dose group and 66% increase in the low-dose group). Dexamethasone increased tidal volume and significantly reduced Fio2 and MAP in both groups of infants. A transient increase in blood pressure was noted in both groups.
Conclusions. Our findings indicate that 1) comparable significant increases in Crs are present in the low-dose dexamethasone as well as the high-dose dexamethasone groups on days 2, 5, and 7 of steroid therapy; and 2) MAP and Fio2 are significantly decreased during dexamethasone therapy in both groups of infants. We conclude that low-dose and high-dose dexamethasone, as used in this study, have comparable beneficial effects on dynamic pulmonary mechanics and subsequently on oxygen requirement and applied ventilatory support in VLBW infants.
- low-dose dexamethasone
- very low birth weight infants
- dynamic respiratory compliance
- mean airway pressure
Chronic lung disease (CLD) remains an important cause of mortality and morbidity in very low birth weight (VLBW) infants. The cause of CLD is multifactorial with major factors being 1) prematurity and incomplete development of the lung, 2) pulmonary volutrauma/barotrauma, 3) oxygen toxicity, 4) pulmonary edema, and 5) airway inflammation.1–6
The prevention of CLD has been an elusive pursuit to both clinical neonatology and research. Dexamethasone is used in neonatal intensive care units to help alleviate CLD. It has potent anti-inflammatory effects that are thought to alter the early course of CLD by 1) maintaining alveolar and capillary membrane stability, thereby preventing accumulation of fluid in the lung, 2) modulating cytokine expression and subsequent influx of inflammatory cells into the alveoli, and 3) inhibiting fibrosis during tissue repair.3–8
Previous dexamethasone trials focused on the use of 0.5 mg/kg/d of dexamethasone on a short-term basis or more commonly weaned over a longer duration of therapy (42 days), initiated at approximately 4 weeks of life.7–10 Dexamethasone has been shown to be useful in at least providing adequate improvement in pulmonary function necessary to wean ventilator-dependent infants. Recent trials have focused on the use of shorter courses of moderately early dexamethasone in an attempt to prevent or ameliorate CLD in VLBW infants,11–14 and 2 recent meta-analyses of randomized controlled trials13,14 reported a reduction in neonatal mortality and risk of CLD, in VLBW infants who received moderately early corticosteroid therapy (started at 7–14 days of age). However, when using corticosteroids, the lowest possible effective dose of dexamethasone should be considered because of the potential adverse effects, including neurologic adverse effects, of steroid therapy.
Pulmonary function testing has been used to define the changes seen in the development of CLD, to predict the likelihood of CLD based on pulmonary function test results, and to assess the efficacy of therapeutic interventions.11–15,18 In a previous randomized study, we reported a significant improvement in pulmonary mechanics, gas exchange, and clinical outcome11 in VLBW infants who were at risk for CLD and received a 7-day course of dexamethasone at 0.5 mg/kg/d with a weaning regimen started at 7 to 14 days of life. This moderately early dexamethasone therapy was associated with an increase in dynamic respiratory compliance (Crs; 50%–79% increase) along with a shorter duration of mechanical ventilation when compared with control infants. To our knowledge, quantification of dynamic pulmonary mechanics during low-dose dexamethasone therapy has not been reported. We hypothesized that a lower dose of moderately early dexamethasone (0.2 mg/kg/d) would also increase Crs as effectively as the higher dose (0.5 mg/kg/d), and perhaps with fewer side effects of systemic corticosteroid therapy. The objective of this study was to compare the effect of 2 different dose regimens of dexamethasone on dynamic respiratory mechanics, mean airway pressure (MAP), and fractional inspired oxygen concentration (Fio 2) in VLBW ventilator-dependent infants, almost 90% of whom were treated with surfactant but remained at risk for CLD.
A randomized, prospective clinical trial was conducted at the Newborn Intensive Care Unit of Los Angeles County–University of Southern California Medical Center. The study was approved by the institutional review board at our institution, and informed consent was obtained for each enrolled patient. Measurements of dynamic pulmonary mechanics, MAP, and Fio2 obtained in 47 infants (78% Hispanic) during a 3-year period ending in June 1996 are reported.
As in our previous study,11 infants were considered eligible for the study if they met the following criteria: 1) birth weight of 501 to 1500 g, 2) gestational age 24 to 32 weeks, 3) ventilator dependent at 7 to 14 days of age despite weaning trials, 4) ventilator rate ≥15 breaths/min, 5) Fio2 requirement of 0.30 or more to maintain a pulse oximeter oxygen saturation of 90% or higher, and 6) informed consent obtained. Infants with documented sepsis, systemic hypertension, congenital heart disease, renal failure, grade IV intraventricular hemorrhage (IVH), and multiple congenital anomalies or chromosomal abnormalities were excluded from the study.
Once inclusion criteria had been met, the infants were randomized to treatment with either a high-dose or a low-dose of dexamethasone in 2 divided daily doses. Group assignment was performed by blind drawing of random cards contained in opaque sealed envelopes. An outside investigator who was blinded to the randomized group assignment and who had no other contact with the patients evaluated dynamic pulmonary mechanics and pulmonary graphics in all patients. Twenty-three infants were randomized to receive a 7-day course of high-dose dexamethasone (0.5 mg/kg/d intravenously for 3 days, 0.25 mg/kg/d for 3 days, and 0.1 mg/kg/d during the 7th day); 24 infants received a 7-day course of low-dose dexamethasone (0.2 mg/kg/d intravenously for 3 days and 0.1 mg/kg/d for 4 days). This initial lower dose of dexamethasone (0.2 mg/kg/d) is equivalent to approximately 5 to 6 times the estimated cortisol replacement dose,19 and it is 60% lower than the initial higher dose of dexamethasone (0.5 mg/kg/d). Patient care, including ventilator and fluid management, was then at the discretion of the clinical team. A blood pH ≥7.25 was accepted, low-dose indomethacin was not used for prevention of IVH. For this study, administration of open-label dexamethasone was allowed after the study period when the attending neonatologist believed that it was indicated. No nebulized bronchodilators or diuretics were used in either group during the study period. In addition, none of the patients was receiving muscle relaxants at the time of the study.
The primary study endpoint was the measurement of dynamic respiratory mechanics before and during a 7-day course of moderately early dexamethasone (started at 7–14 days of age) at 2 different dose regimens in VLBW infants who were at risk for CLD. We also evaluated changes in MAP and Fio2 in both groups of infants before and on days 2, 5, and 7 of dexamethasone therapy.
Dynamic respiratory mechanics (PeDS; Medical Associated Services, Inc, Hatfield, PA) were measured before and on days 2, 5, and 7 of dexamethasone treatment. All measurements were done at bedside, with the patients lying supine, and endotracheal suctioning was performed before each study. The computerized neonatal pulmonary function system was used to record airway pressure, flow, and tidal volume. Air flow was measured with a heated Fleisch 00 pneumotachograph (dead space: 1.7 mL; resistance: 13.2 cm H2O/L/s) attached to the patient’s endotracheal tube and connected to a differential pressure transducer (Validyne MP45, Northridge, CA). The pneumotachograph was linear for gas flows up to 150 mL/s. Flow was digitally integrated to obtain tidal volume,11,18,20,21 and airway pressure was measured from a side port on the pneumotachograph. A water manometer was used to calibrate the pressure transducer, and the pneumotachograph was calibrated using constant flow rates and a flow meter. Flow and pressure signals were relayed to a computer and digitized at 75 Hz. In addition to tidal volume, we obtained measurements of Crs and respiratory resistance (Rrs). Pressure-volume and flow-volume loops were also analyzed. Crs and Rrs were calculated by 2-factor least mean square analysis from at least 10 accepted mechanical breaths as previously reported.11,18,21–23 The characteristics of breath-by-breath pressure-volume and flow-volume relationships11,18,21–23 were monitored to ensure that only those breaths that were complete and nondistorted by visual inspection of pulmonary graphics were used for analysis.
Ventilator settings, MAP, and Fio2 were recorded every 2 hours during mechanical ventilation. Infants were ventilated with a pressure limited, time-cycled ventilator (IV-100B Sechrist ventilator; Sechrist, Inc, Anaheim, CA, and Infant Star ventilator, Infrasonics, Inc, San Diego, CA). Proximal MAP was also measured using a ventilatory monitor (Pneumogard; Novametrix Medical Systems, Wallingford, CT), and a respiratory index score (Fio2 × MAP) was calculated for each patient. Seven infants from the total study population were receiving high-frequency oscillatory ventilation at the time of the study (SensorMedics 3100; SensorMedics, Inc, Yorba Linda, CA).
In addition, the influence of moderately early dexamethasone on the duration of mechanical ventilation, the occurrence of CLD (or bronchopulmonary dysplasia) defined as the need for oxygen supplementation at 36 weeks of corrected gestational age, and survival without CLD were evaluated. We monitored heart rate, blood pressure, transcutaneous Po2, and pulse oximeter oxygen saturation in all patients.24 Serum glucose and electrolytes, fluid intake, and urine output were recorded. The occurrence of pulmonary air leaks, septicemia, IVH, necrotizing enterocolitis, retinopathy of prematurity, spontaneous gastrointestinal perforation, and other clinical complications were evaluated.9–14,25 Hyperglycemia (serum glucose >180 mg/dL) and occurrence of hypertension (systolic blood pressure and diastolic blood pressure >2 standard deviations from mean values) were recorded.26 A chest radiograph, cranial ultrasound, and echocardiogram were obtained before enrollment and thereafter as often as clinically indicated.
We demonstrated a 50% or greater increase in Crs during a 7-day weaning course of dexamethasone starting at 0.5 mg/kg/d.11 For this study, we wish to establish that the average increase in dynamic compliance in the low-dose dexamethasone group is at worst 12% smaller than the average increase in dynamic compliance in the high-dose dexamethasone group. If the 2 treatment groups are equivalent, then an approximate sample size of 20 infants in each group was estimated to reject the null hypothesis (that the increase in the low-dose group is >12% smaller than the increase in the high-dose group) with a type I error of 0.05 and a type II error of 20% (80% power).
An intention-to-treat analysis was performed. Statistical differences for serial measurements of pulmonary mechanics, MAP, and Fio2 were evaluated using analysis of variance for repeated measures. When significant, the Bonferroni multiple comparison test was used to determine specific differences. The statistical significance of the differences between the 2 groups was evaluated with t tests for independent groups (2-tailed). Categorical variables were evaluated with the Pearson χ2 or Fisher exact test as appropriate.
During the study period, 59 patients were eligible for enrollment at 7 to 14 days of age, and 47 patients were enrolled. The other 12 eligible patients were not enrolled because of unavailability of the parents to provide consent (7 patients) or because of a parent’s refusal (5 patients). Twenty-three infants were randomized to the high-dose dexamethasone group, and 24 patients were randomized to the low-dose dexamethasone group. All randomized infants received the intended treatment, and all completed the 7-day treatment protocol, except for 1 patient in each group who had a few doses withheld because of suspected infection. The demographic data and baseline ventilator settings of the 47 patients who met eligibility criteria are shown in Table 1. Thirty-seven infants had a birth weight ≤1000 g: 78% of the study population in the high-dose group and 79% in the low-dose dexamethasone group. Only 2 infants from our study population had a birth weight ≤600 g. There were no significant differences between the 2 groups in birth weight, gestational age, postnatal age, MAP, or Fio2 (Table 1). Similarly, the use of antenatal steroids, Apgar scores at 1 and 5 minutes, and surfactant therapy were comparable between the groups. Measurements of dynamic pulmonary mechanics were obtained in 40 patients (20 in each group); 3 infants in the high-dose group and 4 infants in the low-dose dexamethasone group were changed to high-frequency oscillatory ventilation at the time of the study as part of clinical care, and pulmonary function tests were not done on them. Measurements of MAP and Fio2 were obtained in all 47 patients: 23 infants in the high-dose group and 24 infants in the low-dose dexamethasone group.
Dynamic Pulmonary Mechanics
The pulmonary function test results of the 2 different groups are shown in Figs 1 and 2. The Crs values significantly increased on days 2, 5, and 7 of therapy compared with baseline in the 0.5-mg (high-dose) dexamethasone group as well as in the 0.2-mg (low-dose) dexamethasone group (P < .001; Fig 1). When compared with their baseline value of 0.39 ± 0.01 mL/cm H2O/kg (mean ± standard error of the mean [SEM]), infants in the high-dose dexamethasone group had a significant increase in Crs of 59% on day 2, 67% on day 5, and 74% on day 7 of therapy (P < .001). From a baseline value of 0.41 ± 0.02 mL/cm H2O/kg, infants in the low-dose dexamethasone group had a significant increase in Crs of 41% on day 2, 56% on day 5, and 66% on day 7 (P < .001; Fig 1). Despite a somewhat more gradual improvement in Crs in the low-dose group, respiratory compliance changes in both groups were comparable and not significantly different at baseline and on days 2, 5, and 7 of dexamethasone therapy.
Similar changes were observed in the measurements of tidal volume in both groups (Fig 2). Tidal volume significantly increased on days 2, 5, and 7 (41% increase) compared with the baseline value (6.6 ± 0.4 mL/kg) in the high-dose dexamethasone group (P < .001); in the low-dose group, there was also a significant increase in tidal volume on days 2, 5, and 7 of therapy (39% increase) compared with a baseline value of 6.9 ± 0.3 mL/kg (P < .001; Fig 2). No significant changes in Rrs were noted in either group.
MAP and Fio2
MAP and Fio2 decreased in both groups of infants. In the high-dose dexamethasone group, MAP decreased significantly on days 2, 5, and 7 (a 53% decrease) of dexamethasone therapy compared with baseline (P < .001); in the low-dose dexamethasone group, MAP decreased on days 2, 5, and 7 (a 47% decrease) compared with baseline (P < .001; Fig 3). There was also a significant decrease in Fio2 requirements in both groups on days 2, 5, and 7 of dexamethasone therapy (P < .001; Fig 4). In the high-dose dexamethasone group, Fio2 decreased by 44% on day 7; in the low-dose group, the corresponding decrease in Fio2 was 39% on day 7 of dexamethasone therapy when compared with baseline (P < .001 in both groups). The decreases in MAP and Fio2 in both groups were comparable, and there were no significant differences between the groups at baseline and on days 2, 5, and 7 of dexamethasone therapy.
There was no significant difference between the 2 groups in survival, survival without CLD, duration of mechanical ventilation, or need for oxygen supplementation at 36 weeks of corrected gestational age (Table 2)). Three patients in the high-dose group and 3 infants in the low-dose dexamethasone group required oxygen and had CLD at 36 weeks (13.6% vs 13%; P = .95). Nine patients in the high-dose group were extubated at the end of the study period compared with 8 patients in the low-dose group (not significant). The acute complications noted during dexamethasone therapy were transient increases in blood pressure and glucose intolerance (serum glucose >180 mg/dL) in both groups (not significant). There were no significant differences in the incidence of sepsis, IVH, necrotizing enterocolitis, spontaneous gastrointestinal perforation, or retinopathy of prematurity between the 2 groups (Table 3)). After the study period, 5 patients (22%) in the high-dose group and 7 infants (29%) in the low-dose dexamethasone group were treated with dexamethasone at a later postnatal age, at the discretion of the attending neonatologist.
Our study showed that a 7-day course of moderately early dexamethasone treatment (2 different dose regimens) increased Crs and decreased oxygen requirement and ventilatory support (MAP) in VLBW infants who were at risk for CLD. The low-dose dexamethasone seems to be as effective as the higher dose of dexamethasone.
With the advent of exogenous surfactant therapy27 and the increased use of antenatal steroids,1,28–30 a milder form of CLD (new bronchopulmonary dysplasia) as defined by both clinical assessment and radiographic findings has evolved in VLBW infants with respiratory distress syndrome.5 However, the incidence of CLD remained unchanged, and, therefore, CLD remains a target for a number of therapeutic interventions, dexamethasone therapy being one of them. In this study, we randomized only patients who remained ventilator dependent after the first week of life despite antenatal corticosteroid/surfactant therapy.
In a randomized study,11 we reported a significant improvement in Crs in VLBW infants who received a 7-day course of 0.5 mg/kg/d dexamethasone with a weaning regimen started at 7 to 14 days of age (mean postnatal age: 9 days). Crs increased from a baseline value of 0.38 ± 0.02 mL/cm H2O/kg (mean ± SEM) to 0.57 ± 0.04 mL/cm H2O/kg on day 2 (50% increase) and continued to increase by 79% on day 7 of dexamethasone therapy. This improvement in pulmonary function translated in decreased MAP and Fio2 requirements, along with a decrease in the duration of mechanical ventilation and oxygen supplementation at 36 weeks of corrected gestational age when compared with control infants. Other randomized studies, including recent meta-analyses, provide good evidence to support the role of corticosteroids in reducing the risk of CLD in preterm infants.9,12–14,31 A limitation of our study is the lack of a control group. We decided not to have a control (or placebo) group because of our previous randomized study11 and the other published randomized trials documenting the beneficial effects of 0.5 mg/kg/d dexamethasone when our study was initiated.
Several different regimens of dexamethasone have been published; the late ones that focused on the early or moderately early use before CLD is well- established.11–14,31 However, there are concerns regarding significant short- and long-term side effects of corticosteroids in VLBW infants.11,13,14,25.31 Thus, different protocols have been published to try to avoid the side effects by using pulse therapy12 or by using short treatments of moderately early dexamethasone.11–13 Only a few studies compared different regimens directly,32 and in all previous randomized studies, moderately early dexamethasone was started with a dose of 0.5 mg/kg/d or higher.13 Because of concerns regarding abnormal growth and neurodevelopmental outcome (including increased risk of cerebral palsy) at 1 to 2 years in VLBW infants who are treated with high doses of dexamethasone very early after birth33 or with prolonged courses of high-dose dexamethasone (total dose approximately >7 mg/kg) tapered over 42 days,34 the lowest possible effective dose of dexamethasone should be considered when it becomes essential while treating intubated VLBW infants. We chose previously to use a 7-day course of dexamethasone (total dose: 2.35 mg/kg over 7 days), which was shown to be effective.11 Our current study evaluated the effects of a lower dose of dexamethasone on pulmonary mechanics and gas exchange in VLBW infants who remained ventilator dependent at 7 to 14 days of age despite surfactant treatment. We quantified changes in dynamic respiratory mechanics during a 7-day course of low-dose dexamethasone (total dose: 1 mg/kg over 7 days) and evaluated the clinical benefits of this therapy. This study directly compared the effects of low-dose and high-dose regimens of dexamethasone on pulmonary function, oxygenation, and ventilation in this vulnerable population.
In the current study, the improvement in pulmonary mechanics during low-dose and high-dose dexamethasone treatment was comparable and is consistent with previous reports.7,11,35,36 Previous investigators have pointed out the limitations of the dynamic method with an esophageal balloon in sick VLBW infants,37 whereas others have demonstrated that the dynamic method is very reliable even in the presence of chest wall distortion.38 We measured dynamic respiratory mechanics without an esophageal balloon as this method is less invasive, is less affected by chest wall distortion, and has been used successfully by us and other investigators.11,18,22,36,39 Crs increased significantly by 74% from baseline in the high-dose treatment group and by 66% in the low-dose treatment group. Avery et al35 reported a 64% increase in dynamic lung compliance after 48 to 72 hours of dexamethasone treatment in 14 preterm infants (2–6 weeks of age). Other investigators have reported comparable results.7,36 The improvement in Crs is probably secondary to the mobilization of pulmonary fluid coupled with decreased microvascular permeability and decreased pulmonary inflammation.3–8 This improvement in respiratory mechanics translated into a significant decrease in MAP and oxygen supplementation in both the low- and high-dose dexamethasone regimens. Thus, under the conditions of our study, the clinical effects of both regimens on dynamic compliance, oxygenation, and ventilation are comparable and both are effective.
The short-term outcome of dexamethasone treatment was comparable in our study between the low-dose and high-dose dexamethasone groups. There was no significant difference on survival, days of mechanical ventilation, retreatment with dexamethasone, or survival without CLD. In this preliminary study, there was no significant difference between the 2 groups in the development of CLD, when evaluated by oxygen requirement at 36 weeks’ postconceptional age. The short-term clinical complications observed during dexamethasone treatment were also comparable. There was no significant difference between the low- and high-dose treatment groups in the incidence of proven sepsis, necrotizing enterocolitis, retinopathy of prematurity, spontaneous gastrointestinal perforation, or pneumothorax. However, the current study was not designed to detect these differences as the primary outcome measures were dynamic respiratory mechanics, MAP, and Fio2. It is possible that this study lacks the power to detect differences in other outcome variables. A larger study will need to be done to conclude on the short- and long-term clinical outcomes and complications of the 2 different dose regimens of dexamethasone in VLBW infants. In addition, new studies using low-dose glucocorticoid therapy or physiologic replacement40 should include long-term follow-up of the pulmonary and neurodevelopmental outcome of treated VLBW infants before recommendations can be made on the use of postnatal steroids.
We found that both dose regimens of moderately early dexamethasone have comparable beneficial effects on dynamic pulmonary mechanics, oxygenation, and ventilation in VLBW infants who are at risk for CLD. Significant increases in Crs are present in both the low-dose and high-dose dexamethasone groups on days 2, 5, and 7 of dexamethasone therapy. MAP and Fio2 are significantly decreased during dexamethasone therapy in both groups of infants. We speculate that the lower dose of dexamethasone while being as effective as the higher dose of dexamethasone in improving pulmonary mechanics and gas exchange may minimize short- and long-term side effects of systemic steroids. However, postnatal steroids should be used with caution when it becomes essential while treating ventilator-dependent VLBW infants. We speculate that with increased use of a single course of antenatal steroids and with surfactant therapy, only a very small number of ventilator-dependent VLBW infants who are at high risk for CLD should require low-dose glucocorticoid therapy (moderately early) after 7 days of age. An additional study with long-term follow-up of patients treated with moderately early dexamethasone is under way to determine further clinical outcome and potential long-term side effects of dexamethasone therapy.
PROTEASE INHIBITORS AND REDUCED MORTALITY IN CHILDREN WITH HIV-1
“In a cohort of 1028 children and adolescents infected with human immunodeficiency virus type 1 (HIV-1), the use of combination therapy including protease inhibitors increased from 7% in 1996 to 73% in 1999. Over the 4-year period, mortality declined from 5.3% to 0.7%. This analysis was adjusted for multiple potentially confounding variables; the authors estimate that the use of combination therapy including protease inhibitors in HIV-1-infected children reduces the risk of death by 67%.”
Gortmaker SL, Hughes M, Cervia J, et al. Effect of combination therapy including protease inhibitors on mortality among children and adolescents infected with HIV-1. N Engl J Med. 2001;345:1522–1528
Noted by JFL, MD
We extend our appreciation to Alan H. Jobe, MD, PhD, for suggestions and critical review of the manuscript. We also thank the staff of the Newborn Intensive Care Unit for their cooperation during the study.
- Received April 10, 2001.
- Accepted September 21, 2001.
- Reprint requests to (M.D.) LAC–USC Medical Center, Women’s and Children’s Hospital, 1240 North Mission Rd, L-919, Los Angeles, CA 90033. E-mail:
- ↵Groneck P, Gotze-Speer B, Oppermann M, Eiffert H, Speer CP. Association of pulmonary inflammation and increased microvascular permeability during the development of bronchopulmonary dysplasia: a sequential analysis of inflammatory mediators in respiratory fluids of high-risk preterm neonates. Pediatrics.1994;93 :712– 718
- ↵Durand M, Sardesai S, McEvoy C. Effects of early dexamethasone therapy on pulmonary mechanics and chronic lung disease in very low birth weight infants: a randomized, controlled trial. Pediatrics.1995;95 :584– 590
- ↵Halliday HL, Ehrenkranz RA. Moderately early (7–14 days) postnatal corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). In: The Cochrane Library, 4, 2000. Oxford: Update Software
- ↵Bhuta T, Ohlsson A. Systematic review and meta-analysis of early postnatal dexamethasone for prevention of chronic lung disease. Arch Dis Child Fetal Neonatal Ed.1998;79 :F26– F33
- ↵Kugelman A, Durand M, Garg M. Pulmonary effect of inhaled furosemide in ventilated infants with severe bronchopulmonary dysplasia. Pediatrics.1997;99 :71– 75
- ↵McEvoy C, Sardesai S, Macri C, Paul R, Durand M. Neonatal pulmonary mechanics and oxygenation after prophylactic amnioinfusion in labor: a randomized clinical trial. Pediatrics.1995;95 :688– 692
- ↵Halliday HL, Ehrenkranz RA. Early postnatal (<96 hours) corticosteroids for preventing chronic lung disease in preterm infants (Cochrane Review). In: The Cochrane Library, 4, 2000. Oxford: Update Software
- ↵Yeh TF, Lin YJ, Huang CC, et al. Early dexamethasone therapy in preterm infants: a follow-up study. Pediatrics. 1998;101(5). Available at: http://www.pediatrics.org/cgi/content/full/101/5/e7
- ↵O’Shea TM, Kothadia JM, Klinepeter KL, et al. Randomized placebo-controlled trial of a 42-day tapering course of dexamethasone to reduce the duration of ventilator dependency in very low birth weight infants: outcome of study participants at 1-year adjusted age. Pediatrics.1999;104 :15– 21
- ↵Avery GB, Fletcher AB, Kaplan M, Brudno DS. Controlled trial of dexamethasone in respirator-dependent infants with bronchopulmonary dysplasia. Pediatrics.1985;75 :106– 111
- ↵Thomson A, Elliott J, Silverman M. Pulmonary compliance in sick low birth weight infants: how reliable is the measurement of oesophageal pressure? Arch Dis Child.1983;58 :891– 896
- ↵Watterberg KL, Gerdes JS, Gifford KL, Lin H-M. Prophylaxis against early adrenal insufficiency to prevent chronic lung disease in premature infants. Pediatrics.1999;104 :1258– 1263
- Copyright © 2002 by the American Academy of Pediatrics