Pulmonary function outcomes in bronchopulmonary dysplasia through childhood and into adulthood: implications for primary care.

Bronchopulmonary dysplasia (BPD) results from prematurity and surfactant deficiency with contributing factors from barotrauma, volutrauma, and oxygen toxicity from supportive mechanical ventilation care and infection. These factors result in chronic inflammation with recurring cycles of lung damage and repair that impair alveolarisation and vascularisation in developing infant lungs. With advancement in the understanding of its pathophysiology and resulting therapy, BPD has evolved into a different disorder which has been coined the 'new' BPD. As these patients age, primary care physicians need to understand the impact on pulmonary function. This discussion reviews the pulmonary function outcomes resulting from BPD through later childhood and young adulthood.

Pathogenesis of bronchopulmonary dysplasia.

Bronchopulmonary dysplasia (BPD) refers to a heterogeneous group of lung disorders in infants that is commonly associated with prematurity and surfactant deficiency. BPD results from the complex interplay between impairments in the premature lung such as surfactant deficiency, perinatal insults such as infection, and damage resulting from supportive care of the infant due to barotrauma or volutrauma from mechanical ventilation and oxygen toxicity from supplemental oxygen administration. These factors result in chronic inflammation in the infant lung with recurring cycles of lung damage and repair that may impair alveolarization and vascularization in the developing lungs. As our insight in how to treat BPD improves along with the ability to do so with developing technology and therapies, the underlying pathogenesis will also change. The term 'new' BPD is now commonly used, to describe the changes seen in the post-surfactant era. This discussion reviews the pathogenesis of BPD according to the current medical literature.

Care-by-parent model as a tool for reduction of neonatal opioid withdrawal syndrome in neonates exposed to buprenorphine maintenance therapy in-utero.

Objective: To determine if a structured care-by-parent (CBP) protocol is associated with a reduction in diagnosis of treatment-requiring Neonatal Opioid Withdrawal Syndrome (NOWS).Study design: We performed a pilot retrospective, case control study of pregnant women enrolled in a comprehensive prenatal care program for opioid-dependent patients during which they received buprenorphine for Medication Assisted Treatment (MAT) for Opioid Use Disorder (OUD). Patients who participated in the CBP program actively roomed-in with their infants even after maternal hospital discharge while infants continued to be monitored for development of treatment-requiring NOWS. The primary outcome was the rate of treatment-requiring NOWS in the CBP grouping.Results: Thirty-two (32) cases that were enrolled in the CBP model were compared with 32 matched controls that were not enrolled in this model. There was a significant reduction in the rate of treatment-requiring NOWS among cases compared to the controls (OR = 0.10; p = .001). Neonates undergoing CBP had a decreased length of stay and lower Finnegan scores compared to those who did not undergo CBPConclusion: Among infants born to mothers with OUD in pregnancy, CBP significantly reduces the rate of treatment-requiring NOWS.

Aromatherapy as an adjunctive therapy for neonatal abstinence syndrome: A pilot study.

OBJECTIVE: To determine if aromatherapy added to the current standard of care for opioid withdrawal syndrome decreases hospitali-zation and need for opioid replacement in neonates. DESIGN: Nonblinded, randomized control trial. SETTING: Level 4 neonatal intensive care unit (NICU). PATIENTS AND PARTICIPANTS: Thirty eight patients met inclusion criteria of greater than or equal to 36 weeks of gestation, history of in-trauterine opioid exposure, primary diagnosis of neonatal abstinence syndrome (NAS), and parental permission to participate. INTERVENTIONS: Infants were randomized to either a standard therapy group or a standard therapy plus aromatherapy. MAIN OUTCOME MEASURE(S): Duration of therapy and length of stay. RESULTS: Our pilot study showed that the use of aromatherapy in conjunction with standard therapy reduced the duration of medica-tion treatment by 41 percent and hospital length of stay in the NICU by 36 percent. CONCLUSIONS: The use of aromatherapy appears to help mitigate symptoms of NAS and offers to be a viable treatment modality when used with conventional therapy.

Novel animal model for teaching chest tube placement.

BACKGROUND: The number of procedures available to pediatric residency trainees is few in number and patient size leaves little margin for error. Artificial simulation labs have not been developed for neonatal chest tubes. Use of live animal models is coming under increased scrutiny and is expensive. METHODS: We conducted a simulation skills lab for neonatal chest tube placement using a fryer chicken model. Thirty incoming pediatric interns were prospectively queried on comfort levels of inserting chest tubes prior to and following the simulation lab. RESULTS: On a 5-point Likert scale, comfort levels increased from a median of 1 to 3. All interns reported feeling more comfortable with chest tube placement and all reported having better understanding of the process of chest tube placement following the procedure lab. CONCLUSION: The fryer chicken model is an advantageous, effective model of teaching chest tube placement.

Azithromycin in the extremely low birth weight infant for the prevention of bronchopulmonary dysplasia: a pilot study.

BACKGROUND: Azithromycin reduces the severity of illness in patients with inflammatory lung disease such as cystic fibrosis and diffuse panbronchiolitis. Bronchopulmonary dysplasia (BPD) is a pulmonary disorder which causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis and impaired alveolar development. The purpose of this study was to obtain pilot data on the effectiveness and safety of prophylactic azithromycin in reducing the incidence and severity of BPD in an extremely low birth weight (< or = 1000 grams) population. METHODS: Infants < or = 1000 g birth weight admitted to the University of Kentucky Neonatal Intensive Care Unit (level III, regional referral center) from 9/1/02-6/30/03 were eligible for this pilot study. The pilot study was double-blinded, randomized, and placebo-controlled. Infants were randomized to treatment or placebo within 12 hours of beginning mechanical ventilation (IMV) and within 72 hours of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for the duration of the study. Azithromycin or placebo was continued until the infant no longer required IMV or supplemental oxygen, to a maximum of 6 weeks. Primary endpoints were incidence of BPD as defined by oxygen requirement at 36 weeks gestation, post-natal steroid use, days of IMV, and mortality. Data was analyzed by intention to treat using Chi-square and ANOVA. RESULTS: A total of 43 extremely premature infants were enrolled in this pilot study. Mean gestational age and birth weight were similar between groups. Mortality, incidence of BPD, days of IMV, and other morbidities were not significantly different between groups. Post-natal steroid use was significantly less in the treatment group [31% (6/19)] vs. placebo group [62% (10/16)] (p = 0.05). Duration of mechanical ventilation was significantly less in treatment survivors, with a median of 13 days (1-47 days) vs. 35 days (1-112 days)(p = 0.02). CONCLUSION: Our study suggests that azithromycin prophylaxis in extremely low birth weight infants may effectively reduce post-natal steroid use for infants. Further studies are needed to assess the effects of azithromycin on the incidence of BPD and possible less common side effects, before any recommendations regarding routine clinical use can be made.

Azithromycin protects against hyperoxic lung injury in neonatal rats.

Bronchopulmonary dysplasia (BPD) is a pulmonary disorder that causes significant morbidity and mortality in premature infants. BPD is pathologically characterized by inflammation, fibrosis, and mucosal necrosis, which leads to emphysematous coalescence of alveoli. We tested the hypothesis that azithromycin, a macrolide antibiotic, would decrease the severity of lung injury in an animal model of BPD. Sixty-three rat pups were randomly divided equally into control, hyperoxia, and hyperoxia plus azithromycin groups. The hyperoxia groups were exposed to > 95% oxygen from days of life 4 to 14. On day 14, the animals were processed for lung histology and tissue analysis. Lung morphology was assessed by mean linear intercept, a measure of alveolar size, with larger values corresponding to lungs that are more emphysematous. The degree of lung inflammation was assessed by quantifying interleukin-6 (IL-6) from lung homogenate. Fifty pups survived to day 14 (control = 21, hyperoxia = 11, hyperoxia + azithromycin = 18). Mortality was increased in the hyperoxia group versus the control group (p < .0001). Treatment with azithromycin improved survival in animals subjected to hyperoxia (p < .05). Azithromycin significantly decreased lung damage as determined by the mean linear intercept in the hyperoxia groups (p < .001). Finally, azithromycin-treated pups had lower levels of IL-6 in lung homogenate from the hyperoxia groups (p < .05). Azithromycin treatment resulted in improved survival, less emphysematous change, and decreased IL-6 levels in an animal model of BPD.

Neonatal research and the validity of informed consent obtained in the perinatal period.

BACKGROUND: Consent for participation in clinical research is considered valid if it is informed, understood, and voluntary. In the case of minors, parents give permission for their child to participate in research studies after being presented with all information needed to make an informed decision. Although informed consent is a vital component of clinical research, there is little information evaluating its validity in neonatal intensive-care populations. The objective of this project was to determine the validity of informed consent obtained from parents of infants enrolled in the multicenter randomized research study, neurologic outcomes and pre-emptive analgesia in the neonate (NEOPAIN). DESIGN/METHODS: Parents of infants who survived to discharge and had signed consent for their newborn to participate in the NEOPAIN study at the University of Kentucky were asked 20 open-ended questions to determine their level of understanding about the NEOPAIN study. The NEOPAIN consent form, which had been approved by the University of Kentucky Medical Institutional Review Board (IRB), was used to formulate these questions. Questions addressed the timing of consent, parental understanding of the purpose, benefits, and risks of the study, the voluntary nature of the project, and their willingness to enroll in future studies if the opportunity presented. Answers were scored on a Likert scale, with 1 for no understanding and 5 for complete understanding. RESULTS: Five of 64 parents (7.8%) had no recollection of the NEOPAIN study or of signing consent. Of those who remembered the study, only 67.8% understood the purpose of the study, with a higher proportion of the mothers than fathers knowing the purpose of the study (73.3% vs 57.1%), (p=0.029). Of those who understood the purpose of the study 95% were able to verbalize the benefits, but only 5% understood any potential risks. No parents reported feeling pressured or coerced to sign consent for the project and all parents reported they would enroll their child in additional studies if asked. CONCLUSIONS: Valid consent in the antenatal/perinatal population is difficult, if not impossible, to obtain. To maximize validity of consent in the antenatal/perinatal population every effort should be made to include mothers in the consent process. Additional attention during the consent process should be given to possible risks of the study.

Elevated high-sensitivity C-reactive protein in preterm infants with pulmonary colonization with Ureaplasma.

BACKGROUND: A link between pulmonary Ureaplasma spp. colonization in premature infants and bronchopulmonary dysplasia (BPD) exists and could possibly contribute to systemic inflammation. METHODS: A prospective cohort study was performed from July 2006 to July 2007 where very low birth weight (VLBW) premature infants were screened at birth. Serum and tracheal aspirate samples were collected during the first 28 days of life that represented the early high-sensitivity C-reactive protein (hs-CRP) group, and follow-up samples obtained between 28-42 days of life were the late hs-CRP group. An Enzyme-linked immunosorbent assay (ELISA) for hs-CRP was performed on serum samples while tracheal aspirates underwent polymerase chain reaction (PCR) analysis for Ureaplasma spp. RESULTS: A total of 65 patients were screened. 30 patients completed full analysis, 15 died before early and late hs-CRP samples could be obtained, and 20 had incomplete data due to early discharge or transfer. There was no significant difference between all early and late hs-CRP group levels (mg/L), median [interquartile range] 1.019 [0.242, 5.844] vs. 0.773 [0.143, 8.954] (P=0.3958); however, there was a significant difference when comparing Ureaplasma spp. positivity vs. negativity between both groups, median 2.223 [0.398, 7.099] vs. 0.675 [0.219, 4.038] (P=0.0131) for the early group and median 2.335 [0.359, 14.91] vs. 0.2155 [0.122, 2.296] (P=0.03) for the late group, respectively. CONCLUSIONS: VLBW premature infants colonized with Ureaplasma spp. have an elevated hs-CRP, suggestive of a chronic low-grade systemic inflammatory response.

Use of azithromycin for the prevention of bronchopulmonary dysplasia in preterm infants: a randomized, double-blind, placebo controlled trial.

OBJECTIVE: Since preventive therapies for bronchopulmonary dysplasia (BPD) are limited we treated preterm infants with azithromycin to decrease the incidence of BPD. METHODS: Infants less than 1,250 g birth weight were randomized to azithromycin or placebo within 12 hr of beginning mechanical ventilation and within 72 hr of birth. The treatment group received azithromycin 10 mg/kg/day for 7 days followed by 5 mg/kg/day for a maximum of 6 weeks. Aspirates were collected during the study to assay for Ureaplasma. The primary endpoints were incidence of BPD or mortality. (Clinical Trials Identifier: NCT00319956.) RESULTS: A total of 220 infants were enrolled (n=111 azithromycin, and 109 placebo). Mortality was 18% for the azithromycin group versus 22% for the placebo group (P = 0.45). Incidence of BPD was 76% for the azithromycin group versus 84% for the placebo group (P=0.2). The multiple logistic regression analysis demonstrated an odds ratio of 0.46 decrease in the chance of developing BPD or death for the azithromycin group, but was not statistically significant. The incidence of BPD in the Ureaplasma subgroup was 73% in the azithromycin group versus 94% in the placebo group (P=0.03). Analysis of patients in the Ureaplasma subgroup only, using the exact logistic model demonstrated a decrease in BPD or death in the azithromycin group with an estimated odds ratio of 0.026 (0.001-0.618, 95% confidence interval). CONCLUSIONS: Routine use of azithromycin therapy for the prevention of BPD cannot be recommended. The early treatment of Ureaplasma colonized/infected patients might be beneficial, but a larger multi-centered trial is required to assess this more definitively.