Pharmacoepidemiology of Drug Exposure in Intubated and Non-Intubated Preterm Infants With Severe Bronchopulmonary Dysplasia.

Background: Infants with severe bronchopulmonary dysplasia (BPD) are commonly treated with off-label drugs due to lack of approved therapies. To prioritize drugs for rigorous efficacy and safety testing, it is important to describe exposure patterns in this population. Objective: Our objective was to compare rates of drug exposure between preterm infants with severe bronchopulmonary dysplasia based on respiratory support status at or beyond 36 weeks post-menstrual age. Methods: A cross-sectional cohort study was performed on October 29, 2019. Preterm infants with severe BPD were eligible and details of respiratory support and drug therapy were recorded. Wilcoxon paired signed rank test was used to compare continuous variables between the invasive and non-invasive groups. Fisher's exact test was used to compare binary variables by respiratory support status. Results: 187 infants were eligible for the study at 16 sites. Diuretics were the drug class that most subjects were receiving on the day of study comprising 54% of the entire cohort, followed by inhaled steroids (47%) and short-acting bronchodilators (42%). Infants who were invasively ventilated (verses on non-invasive support) were significantly more likely to be receiving diuretics (p 0.013), short-acting bronchodilators (p < 0.01), long-acting bronchodilators (p < 0.01), systemic steroids (p < 0.01), systemic pulmonary hypertension drugs (p < 0.01), and inhaled nitric oxide (p < 0.01). Conclusion: Infant with severe BPD, especially those who remain on invasive ventilation at 36 weeks, are routinely exposed to multiple drug classes despite insufficient pharmacokinetic, safety, and efficacy evaluations. This study helps prioritize sub-populations, drugs and drug classes for future study.

The impact of neurally adjusted ventilatory assist mode on respiratory severity score and energy expenditure in infants: a randomized crossover trial.

OBJECTIVE: Examine respiratory severity scores (RSS) (mean airway pressure × fraction of inspired oxygen) and resting energy expenditure (REE) on neurally adjusted ventilatory assist (NAVA) compared with synchronized intermittent mandatory ventilation with pressure controlled and supported breath (SIMV (PC)PS). STUDY DESIGN: A randomized, crossover trial in a level IV neonatal intensive care unit. Twenty-four patients were ventilated with NAVA or SIMV (PC) PS for 12 h and then crossed over to the alternative mode for 12 h. The primary outcome (RSS) and additional secondary respiratory outcomes were analyzed. RESULTS: RSS and measured REE were not different between modes. On NAVA, peak inspiratory pressures were lower (17.8 vs 19.9 cmH2O (P<0.05)) without higher oxygen requirements. Respiratory rates were higher on NAVA (52 vs 39 (P<0.05)), estimated work of breathing (WOB) (0.01 vs 0.04 J l-1 (P<0.05)) was improved. CONCLUSION: NAVA mode can be safe without increase in RSS or REE. Although respiratory rates were higher, this was offset by lower peak inspiratory pressures and WOB during NAVA.

Barriers to enrollment in a randomized controlled trial of hydrocortisone for cardiovascular insufficiency in term and late preterm newborn infants.

OBJECTIVE: To analyze reasons for low enrollment in a randomized controlled trial (RCT) of the effect of hydrocortisone for cardiovascular insufficiency on survival without neurodevelopmental impairment (NDI) in term/late preterm newborns. STUDY DESIGN: The original study was a multicenter RCT. Eligibility: ⩾34 weeks' gestation, <72 h old, mechanically ventilated, receiving inotrope. Primary outcome was NDI at 2 years; infants with diagnoses at high risk for NDI were excluded. This paper presents an analysis of reasons for low patient enrollment. RESULTS: Two hundred and fifty-seven of the 932 otherwise eligible infants received inotropes; however, 207 (81%) had exclusionary diagnoses. Only 12 infants were randomized over 10 months; therefore, the study was terminated. Contributing factors included few eligible infants after exclusions, open-label steroid therapy and a narrow enrollment window. CONCLUSION: Despite an observational study to estimate the population, very few infants were enrolled. Successful RCTs of emergent therapy may require fewer exclusions, a short-term primary outcome, waiver of consent and/or other alternatives.

Inter-center variation in death or tracheostomy placement in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the presence and sources of inter-center variation (ICV) in the risk of death or tracheostomy placement (D/T) among infants with severe bronchopulmonary dysplasia (sBPD)Study design:We analyzed the Children's Hospitals Neonatal Database between 2010 and 2013 to identify referred infants born <32 weeks' gestation with sBPD. The association between center and the primary outcome of D/T was analyzed by multivariable modeling. Hypothesized diagnoses/practices were included to determine if these explained any observed ICV in D/T. RESULTS: D/T occurred in 280 (20%) of 1383 eligible infants from 21 centers. ICV was significant for D/T (range 2-46% by center, P<0.001) and tracheostomy placement (n=187, range 2-37%, P<0.001), but not death (n=93, range 0-19%, P=0.08). This association persisted in multivariable analysis (adjusted center-specific odds ratios for D/T varied 5.5-fold, P=0.009). CONCLUSIONS: ICV in D/T is apparent among infants with sBPD. These results highlight that the indications for tracheostomy (and subsequent chronic ventilation) remain uncertain.

A comparison of 7-day versus 10-day course of low-dose dexamethasone for chronically ventilated preterm infants.

OBJECTIVE: The objective of the study was to compare the effect of two different dexamethasone regimens on respiratory outcomes of ventilator-dependent preterm infants. STUDY DESIGN: Retrospective study of ventilated preterm infants <29 weeks gestational age treated with either 7-day or 10-day dexamethasone course. Primary outcome was days to successful extubation. Other outcomes included rate of successful extubation and need for repeat steroid therapy. RESULTS: Fifty-nine infants were identified; 32 (54%) received 7 days of dexamethasone and 27 (46%) received 10 days of dexamethasone. Both groups had comparable baseline demographics and clinical characteristics. Mean time to successful extubation was similar between the two groups (5.1±2.7 days in 7-day group and 6.0±3.7 days in 10-day group, P=0.42). Successful extubation by end of treatment (56% versus 67%, P=0.44) and need for repeat steroid therapy (47% versus 33%, P=0.43) were also similar. CONCLUSION: 7-day and 10-day course of dexamethasone have comparable efficacy in facilitating extubation of ventilator-dependent preterm infants.

Inhaled nitric oxide usage in preterm infants in the NICHD Neonatal Research Network: inter-site variation and propensity evaluation.

OBJECTIVE: The use of inhaled nitric oxide (iNO) in preterm infants remains controversial. In October 2010, a National Institutes of Health consensus development conference cautioned against use of iNO in preterm infants. This study aims (1) to determine the prevalence and variability in use of iNO in the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NICHD NRN) before and after the consensus conference and (2) separately, to examine associations between iNO use and severe bronchopulmonary dysplasia (BPD) or death. STUDY DESIGN: The NICHD NRN Generic Database collects data including iNO use on very preterm infants. A total of 13 centers contributed data across the time period 2008 to 2011. Infants exposed or not to iNO were compared using logistic regression, which included factors related to risk as well as their likelihood of being exposed to iNO. RESULT: A total of 4885 infants were assessed between 2008 and 2011; 128 (2.6%) received iNO before day 7, 140 (2.9%) between day 7 and 28, and 47 (1.0%) at >28 days. Center-specific iNO use during 2008 to 2010 ranged from 21.9 to 0.4%; 12 of 13 sites reduced usage and overall NRN iNO usage decreased from 4.6 to 1.6% (P<0.001) in 2011. The use of iNO started between day 7 and day 14 was more prevalent among younger infants with more severe courses in week 1 and associated with increased risk of severe BPD or death (odds ratio 2.24; 95% confidence interval 1.23 to 4.07). CONCLUSION: The variability and total use of iNO decreased in 2011 compared with 2008 to 2010. iNO administration started at ⩾ day 7 was associated with more severe outcomes compared with infants without iNO exposure.

Predicting death or tracheostomy placement in infants with severe bronchopulmonary dysplasia.

OBJECTIVE: To estimate the risk of death or tracheostomy placement (D/T) in infants with severe bronchopulmonary dysplasia (sBPD) born < 32 weeks' gestation referred to regional neonatal intensive care units. STUDY DESIGN: We conducted a retrospective cohort study in infants born < 32 weeks' gestation with sBPD in 2010-2011, using the Children's Hospital Neonatal Database. sBPD was defined as the need for FiO2 ⩾ 0.3, nasal cannula support >2 l min(-1) or positive pressure at 36 weeks' post menstrual age. The primary outcome was D/T before discharge. Predictors associated with D/T in bivariable analyses (P < 0.2) were used to develop a multivariable logistic regression equation using 80% of the cohort. This equation was validated in the remaining 20% of infants. RESULT: Of 793 eligible patients, the mean gestational age was 26 weeks' and the median age at referral was 6.4 weeks. D/T occurred in 20% of infants. Multivariable analysis showed that later gestational age at birth, later age at referral along with pulmonary management as the primary reason for referral, mechanical ventilation at the time of referral, clinically diagnosed pulmonary hypertension, systemic corticosteroids after referral and occurrence of a bloodstream infection after referral were each associated with D/T. The model performed well with validation (area under curve 0.86, goodness-of-fit χ(2), P = 0.66). CONCLUSION: Seven clinical variables predicted D/T in this large, contemporary cohort with sBPD. These results can be used to inform clinicians who counsel families of affected infants and to assist in the design of future prospective trials.

Impact of intercurrent respiratory infections on lung health in infants born <29 weeks with bronchopulmonary dysplasia.

OBJECTIVE: Assess the impact of intercurrent respiratory infections in infants <29 weeks gestational age (GA). STUDY DESIGN: A retrospective cohort study of 111 infants born <29 weeks GA, controlling for bronchopulmonary dysplasia (BPD) severity and assessing pulmonary health over the first year of life through oxygen, diuretic and inhaled steroid use. RESULT: Regression analysis showed viral infections increased oxygen use (odds ratio (OR) of 15.5 (confidence interval (CI)=3.4, 71.3)). The trend test showed increasing numbers of viral infections were associated with increased oxygen (OR (95% CI)=6.4 (2.3 to 17.4), P=0.0003), diuretic (OR (95% CI)=2.4 (1.1to 5.2), P=0.02) and inhaled steroid use (OR (95% CI)=2.2 (1.003 to 5.2), P=0.049), whereas bacterial infections were not. CONCLUSION: Viral infections caused more long-term pulmonary morbidity/mortality than bacterial infections on premature lung health, even when controlling for BPD.

Infants born at <29 weeks: pulmonary outcomes from a hybrid perinatal system.

OBJECTIVE: To assess pulmonary outcomes of infants <29 weeks gestational age (GA), delivered at level I, II and III facilities, to identify potentially modifiable factors affecting bronchopulmonary dysplasia (BPD) severity and to assess the external generalizability of the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) BPD Outcome Estimator. STUDY DESIGN: Outcomes for infants <29 weeks GA born during (2008-2010) and delivered either at an inborn level III center or in a level II or III metropolitan area hospital with transfer to a level IV center, or delivered in a distant level I or II center and then transported to a level IV center were assessed. BPD severity was compared with the NICHD Neonatal BPD Outcome Estimator. RESULT: Of 158 infants who comprised the cohort, 28 (17.8%) had no BPD, 39 (24.2%) had mild BPD, 45 (28.7%) had moderate BPD, 31 (19.7%) had severe BPD and 15 (9.6%) died at ≤36 weeks post menstrual age. Site of birth did not predict severe BPD or death. Receiver operator characteristic curves showed fair predictability for none/mild and severe BPD. CONCLUSION: BPD severity was not dependent on site of birth. The NICHD BPD outcome estimator provides fair prediction for extreme outcomes.

Sildenafil citrate, bronchopulmonary dysplasia and disordered pulmonary gas exchange: any benefits?

OBJECTIVE: The objective of this study is to determine the effects that sildenafil citrate has on gas exchange in infants with bronchopulmonary dysplasia (BPD)-associated pulmonary hypertension (PH). STUDY DESIGN: A retrospective review was performed from 2005 to 2009. Infants treated with sildenafil citrate for greater than 48 h were included. Standard patient data was collected, including echocardiogram, inspired oxygen and systemic blood pressure, before and during administration of sildenafil citrate. RESULT: Sildenafil citrate was used in 21 preterm infants with BPD-associated PH. A significant reduction in estimated right ventricular peak systolic pressure was seen after initiation of sildenafil citrate, with the majority of infants showing no improvement in gas exchange at 48 h of treatment. Four infants died during treatment. CONCLUSION: Sildenafil citrate reduced estimated pulmonary artery pressures, but this reduction was not reflected in improved gas exchange within the first 48 h.

Pilot trial of late booster doses of surfactant for ventilated premature infants.

OBJECTIVE: Many premature infants at risk for bronchopulmonary dysplasia experience episodes of surfactant dysfunction with reduced surfactant protein B (SP-B). In this study, we investigated the safety and responses to booster doses of surfactant. STUDY DESIGN: A total of 87 infants, 500 to 1250 g birth weight, who were ventilated at 7 to 10 days received 2 or 3 doses of Infasurf (Calfactant, Forest Pharmaceuticals, St Louis, MO, USA) within a 1-week period. RESULT: For 184 doses, occurrence rates of transient bradycardia (13) and plugged endotracheal tube (5) were low, and no other adverse effects were noted. Treatment transiently improved the respiratory severity score (FiO(2) × mean airway pressure), SP-B content (+75%) and surface properties of isolated surfactant. Levels of eight proinflammatory cytokines in tracheal aspirate were interrelated and unchanged from baseline after surfactant treatment. CONCLUSION: Booster doses of surfactant for premature infants with lung disease are safe and transiently improve respiratory status as well as composition and function of endogenous surfactant.

Inhaled nitric oxide in premature infants: effect on tracheal aspirate and plasma nitric oxide metabolites.

OBJECTIVE: Inhaled nitric oxide (iNO) is a potential new therapy for prevention of bronchopulmonary dysplasia and brain injury in premature infants. This study examined dose-related effects of iNO on NO metabolites as evidence of NO delivery. STUDY DESIGN: A subset of 102 premature infants in the NO CLD trial, receiving 24 days of iNO (20 p.p.m. decreasing to 2 p.p.m.) or placebo, were analyzed. Tracheal aspirate (TA) and plasma samples collected at enrollment and at intervals during study gas were analyzed for NO metabolites. RESULT: iNO treatment increased NO metabolites in TA at 20 and 10 p.p.m. (1.7- to 2.3-fold vs control) and in plasma at 20, 10, and 5 p.p.m. (1.6- to 2.3-fold). In post hoc analysis, treated infants with lower metabolite levels at entry had an improved clinical outcome. CONCLUSION: iNO causes dose-related increases in NO metabolites in the circulation as well as lung fluid, as evidenced by TA analysis, showing NO delivery to these compartments.

Hypoxic respiratory failure: etiology and outcomes at one referral center 2000 through 2005.

OBJECTIVE: We calculated in a referral population of term and near-term infants with hypoxic respiratory failure (HRF) as a primary presenting problem the overall survival rate, the need for extracorporeal membrane oxygenation (ECMO) and the incidence of apparently irreversible disorders. STUDY DESIGN: All infants >or=36-week gestation admitted at 25. A total of 32 infants received ECMO, including all four who died, two with histologic evidence of pulmonary malformations and two with septic shock. CONCLUSION: Term or near-term infants with isolated HRF are likely to survive, given the low incidence of pulmonary disorders not supportable by inhaled nitric oxide or ECMO.

Safety and efficacy of nitric oxide in chronic lung disease.

BACKGROUND: Therapies for neonatal chronic lung disease (CLD) of prematurity have had limited success. AIMS: To determine whether inhaled nitric oxide (INO) administered to very low birthweight infants with developing CLD might improve oxygenation without adverse effects. METHODS: Subjects were 10-30 days of age, birth weight < 1250 g, with developing or established CLD, and requiring mechanical ventilation with mean airway pressure > or = 7 cm H2O and FIO2 . or = 0.40. We monitored changes in oxygenation and FIO2 requirement during treatment with INO (initial dose 20 ppm). Tracheal aspirate samples obtained before, during, and after treatment were analysed for interleukin 1beta (IL-1beta), IL-8, 8-epi-prostaglandin F2alpha (8-epi-PGF2alpha), laminin, and endothelin 1 (ET-1) to assess any potential effects of INO on markers of inflammation peroxidation, basement membrane injury, or vasoactivity. RESULTS: Thirty three patients met entry criteria. Mean gestational age was 25 (SD 2) weeks; birth weight was 736 (190 g); age of study infants was 19 (6) days (range 9-29). Mean FIO2 decreased from baseline (0.75) to 0.58 at 72 hours. Duration of therapy was seven days. Tracheal aspirate concentrations of IL-1beta, IL-8, 8-epi-PGF2alpha, ET-1, and laminin were unchanged between baseline and 48 hours of INO, and 48 hours after discontinuation of INO. No new cases of, nor extension of, intraventricular haemorrhage occurred. Four infants died. CONCLUSION: INO (< or = 20 ppm) improved oxygenation in most infants with early CLD, without inducing changes in markers of inflammatory or oxidative injury.

Monocyte chemoattractant protein-1 and its receptor CCR-2 in piglet lungs exposed to inhaled nitric oxide and hyperoxia.

Monocyte chemoattractant protein-1 (MCP-1), acting through its C-C chemokine receptor 2 (CCR-2), has important roles in inflammation, angiogenesis, and wound repair. The individual and combined effects of inhaled nitric oxide (NO) and hyperoxia on lung MCP-1 and CCR-2 in relation to lung leukocyte dynamics are unknown. Because MCP-1 gene is up-regulated by oxidants, we hypothesized that inhaled NO with hyperoxia will increase MCP-1 production and CCR-2 expression more than either gas alone. We randomly assigned young piglets to breathe room air (RA), RA+50 ppm NO (RA+NO), O(2), or O(2)+NO for 1 or 5 d before sacrifice. Lungs were lavaged and tissues preserved for hybridization studies, Western blotting, histology, and immunohistochemistry. The results show that lung MCP-1 production and alveolar macrophage count were significantly elevated in the 5-d O(2) and O(2)+NO groups relative to the RA group (p < or = 0.05). In contrast, lung CCR-2 abundance was diminished in the O(2) group (p

High-dose inhaled nitric oxide and hyperoxia increases lung collagen accumulation in piglets.

Nitric oxide (NO), a pro-oxidant gas, is used with hyperoxia (O(2)) to treat neonatal pulmonary hypertension and recently bronchopulmonary dysplasia, but great concerns remain regarding NO's potential toxicity. Based on reports that exposure to oxidant gases results in pulmonary extracellular matrix injury associated with elevated lavage fluid levels of extracellular matrix components, we hypothesized that inhaled NO with or without hyperoxia will have the same effect. We measured alveolar septal width, lung collagen content, lavage fluid hydroxyproline, hyaluronan and laminin levels in neonatal piglets after 5 days' exposure to room air (RA), RA + 50 ppm NO (RA + NO), O(2) (FiO(2) > 0.96) or O(2) + NO. Matrix metalloproteinase (MMP) activity and MMP-2 mRNA were also measured. In recovery experiments, we measured lung collagen content in piglets exposed to RA + NO or O(2) + NO and then allowed to recover for 3 days. The results show that lung collagen increased 4-fold in the RA + NO piglets, the O(2) and O(2) + NO groups had only a 2-fold elevation relative to RA controls. Unlike the RA + NO piglets, the O(2) and O(2) + NO groups had more than 20-fold elevation in lung lavage fluid hydroxyproline compared to the RA group. O(2) and O(2) + NO also had increased lung MMP activity, extravascular water, and lavage fluid proteins. MMP-2 mRNA levels were unchanged. After 3 days' recovery in room air, the RA + NO groups' lung collagen had declined from 4-fold to 2-fold above the RA group values. The O(2) + NO group did not decline. Alveolar septal width increased significantly only in the O(2) and O(2) + NO groups. We conclude that 5 days' exposure to NO does not result in pulmonary matrix degradation but instead significantly increases lung collagen content. This effect appears potentially reversible. In contrast, hyperoxia exposure with or without NO results in pulmonary matrix degradation and increased lung collagen content. The observation that NO increased lung collagen content represents a new finding and suggests NO could potentially induce pulmonary fibrosis.

Independent and combined effects of prolonged inhaled nitric oxide and oxygen on lung inflammation in newborn piglets.

Clinical use of nitric oxide (NO) is usually in conjunction with high oxygen concentrations, the effects of which may include lung neutrophil accumulation, apoptosis and upregulation of antioxidant enzyme activity. To define the effects of NO on neutrophils from young piglets and its relationship to lung neutrophil dynamics during hyperoxia we exposed thirty piglets to room air (RA), RA+NO (50 ppm NO), O2 (FiO2> or =0.96) or O2+NO for 5 days. Ten additional animals breathed RA+NO or O2+NO, then recovered in RA for 3 days before sacrifice. Neutrophil CD18 and intracellular oxidant production were measured by flow cytometry. Lung apoptosis were assessed by TUNEL assay. Lung myeloperoxidase, SOD and catalase were measured biochemically. When compared to RA group, there was significant reduction in neutrophil CD18 and intracellular oxidant production in the RA+NO group, but lung MPO was unchanged. The O2 and O2+NO groups did not differ in CD18 expression or in intracellular oxidant production, but had significant increase in lung myeloperoxidase compared to the RA group. Apoptosis increased significantly only in the O2+NO group. The O2 group showed significantly increased lung SOD and catalase activity compared to the RA group, whereas the RA+NO and O2+NO groups did not. We conclude that inhaled NO at 50 ppm decreases neutrophil CD18 expression as well as intracellular oxidant production. However, this effect does not impact lung neutrophil accumulation during concurrent hyperoxia. The combination of NO and O2 exposure produces an increase in lung apoptosis. Finally, NO may prevent upregulation of SOD and catalase activity during hyperoxia, potentially increasing injury.

Lung elastic tissue maturation and perturbations during the evolution of chronic lung disease.

BACKGROUND: Infants <30 weeks' gestation have difficulty maintaining adequate functional residual capacity after the first week of life without positive end-expiratory pressure. We hypothesized that this is caused, in part, by increased lung elastic recoil. Our aims were to quantitate parenchymal elastic tissue during normal fetal development and in infants born at 23 to 30 weeks' gestation with prolonged survival at risk for chronic lung disease (CLD). METHODS: The controls were 22 to 42 weeks' gestation (n = 71), received ventilator care, and died within 48 hours of birth, plus 7 term infants who died at 43 to 50 weeks' postconceptional age from nonpulmonary causes. Infants who were 23 to 30 weeks' gestation, at risk for CLD, and who lived 5 to 59 days (n = 44), were separated into groups based on respiratory score (SCORE; The integrated area under the curve of the average daily fraction of inspired oxygen x mean airway pressure (cm H(2)O) over the number of days lived). The SCORE groups, <20, 21 to 69 and 70 to 200, related clinically to mild to severe lung disease. The lungs were tracheally perfused and formalin-fixed and total lung volume (TLV) was measured by water displacement. The paraffin-embedded lung blocks were stained with Miller's elastic stain. The parenchyma and parenchymal elastic tissue were point-counted. The absolute elastic tissue was calculated by multiplying TLV by the parenchymal and elastic fractions. Septal width, alveoli and alveolar duct diameters, and internal surface area (ISA) were also measured. RESULTS: In the controls, the volume density of parenchymal elastic tissue and absolute quantity of elastic tissue increased progressively from 22 to 50 weeks. In infants with CLD and SCORE >/=20, the volume density and absolute quantity of elastic tissue increased significantly. Mean absolute elastic tissue in the 20 to 69 group was 0.76 +/- 0.20 cm(3) greater than in the <20 group (0.46 +/- 0.10 cm(3)) who were similar to the controls, and the 70 to 200 group was 1.32 +/- 0.56 cm(3) greater than the 20 to 69 group. Elastic tissue for infants at risk for CLD, as a percent of predicted for same-age controls, rose linearly with increasing SCORE (r = 0.73; r(2) = 0.55). Control TLV and ISA were linearly related to age. Thirty-nine of the 44 CLD-risk infants had TLVs greater than controls. However, 77% with SCORE 20 to 200 had ISAs less than or equal to the control 95% confidence interval. Control septal width decreased sharply from 23 to 30 weeks, then gradually decreased to term. All infants with SCORE 70 to 200 and 80% of those with SCORE 20 to 69 had widths more than the control 95% confidence interval. Control alveolar and duct diameters doubled from 23 to 50 weeks and were significantly greater in infants with SCORES 20 to 200. DISCUSSION: Lung elastic tissue maturation is tightly controlled during fetal development. With increasing SCORE, elastic tissue increased >200%, accounting, in part, for the positive end-expiratory pressure needed to maintain end-expiratory lung volume in infants at risk for CLD. Saccule and duct diameters more than doubled, and septa thickened significantly in CLD. We propose the following sequence to be operative in CLD: at birth, the preterm infant (

Effects of surfactant treatment on gas-exchange and clinical course in near-term newborns with RDS.

OBJECTIVE: To determine if there is a relationship between acute improvement in pulmonary gas exchange and surfactant use in near-term (35-39 weeks' gestation) infants with respiratory distress syndrome (RDS). METHODS: We examined retrospectively the records of 54 infants admitted during a 15 month period who were 35 or more weeks of gestation, and who demonstrated all the diagnostic features of RDS. Data analyzed included: birth weight; gestational age; Apgar scores; calculated alveolar to arterial oxygen gradient (AaDO2) and oxygenation index (0I); hours of life at intubation; surfactant administration; complications with surfactant administration; use of inotropic medications. RESULTS: A total of 30 of infants were treated with intubation and surfactant administration. Mean FiO2 at the time of surfactant administration was 0.96. The AaDO2 decreased from 64.0 +/- 14.8 kPa to 41.8 +/- 22.5 kPa by 6 hrs (p < 0.0001). There was no relationship between age at treatment (6-89 hr) and response to treatment as measured by changes in AaDO2, FiO2, or oxygenation index (OI). CONCLUSIONS: Near-term infants with severe RDS often respond to exogenous surfactant, suggesting a functional deficiency of endogenous surfactant at a "late" stage in their disease process. We speculate that delayed treatment may still be effective in these patients.