eMedicine Specialties > Pediatrics: Cardiac Disease and Critical Care Medicine > Neonatology

Pulmonary Interstitial Emphysema

Abhay J Bhatt, MD, MBBS, Assistant Professor, Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center
Rita M Ryan, MD, Professor of Pediatrics, Chief, Division of Neonatology, Director, Neonatal-Perinatal Medicine Fellowship Program, University at Buffalo, State University of New York, Women's and Children's Hospital of Buffalo

Updated: Apr 16, 2009

Introduction

Background

Pulmonary interstitial emphysema (PIE) is a collection of gases outside of the normal air passages and inside the connective tissue of the peribronchovascular sheaths, interlobular septa, and visceral pleura secondary to alveolar and terminal bronchiolar rupture. Pulmonary interstitial emphysema is more frequent in premature infants who require mechanical ventilation for severe lung disease. Once pulmonary interstitial emphysema is diagnosed, intensive respiratory management is required to reduce mortality and morbidity.

This radiograph, obtained from a premature infant at 26 weeks' gestation, shows characteristic radiographic changes of pulmonary interstitial emphysema (PIE) of the right lung.

Pathophysiology

Pulmonary interstitial emphysema often occurs in conjunction with respiratory distress syndrome (RDS), but other predisposing etiologic factors include meconium aspiration syndrome (MAS), amniotic fluid aspiration, and infection.

Positive pressure ventilation (PPV) and reduced lung compliance are significant predisposing factors. However, in extremely premature infants, pulmonary interstitial emphysema can occur at low mean airway pressure and probably reflects increased sensitivity of the underdeveloped lung to stretch. Pulmonary interstitial emphysema has been rarely reported in the absence of mechanical ventilation or continuous positive airway pressure. The process of pulmonary interstitial emphysema is initiated when air ruptures from the alveolar airspace and small airways into the perivascular tissue of the lung.

Infants with RDS have an initial increase in interstitial and perivascular fluid that rapidly declines over the first few days of life. This fluid may obstruct the movement of gas from ruptured alveoli or airways to the mediastinum, causing an increase of PIE. Another possible mechanism for entrapment of air in the interstitium is the increased amount of pulmonary connective tissue in the immature lung. The entrapment of air in the interstitium may result in a vicious cycle that causes compression atelectasis of the adjacent lung, which then necessitates a further increase in ventilatory pressure with still more escape of air into the interstitial tissues.

Plenat et al described two topographic varieties of air leak: intrapulmonary pneumatosis and intrapleural pneumatosis.^{[1 ]}. In the intrapulmonary type, which is more common in premature infants, the air remains trapped inside the lung and frequently appears on the surface of the lung, bulging under the pleura in the area of interlobular septa. This phenomenon develops with high frequency on the costal surface and the anterior and inferior edges but can involve all of the pulmonary areas. In the intrapleural variety, which is more common in more mature infants with compliant lungs, the abnormal air pockets are confined to the visceral pleura, often affecting the mediastinal pleura. The air of pulmonary interstitial emphysema may be located inside the pulmonary lymphatic network.^{[2 ]}

The extent of pulmonary interstitial emphysema can vary. It can present as an isolated interstitial bubble, several slits, lesions involving the entire portion of one lung, or diffuse involvement of both lungs. Pulmonary interstitial emphysema does not preferentially localize in any one of the 5 pulmonary lobes.

Pulmonary interstitial emphysema compresses adjacent functional lung tissue and vascular structures and hinders both ventilation and pulmonary blood flow, resulting in impedance of oxygenation, ventilation, and blood pressure. This further compromises the already critically ill infant with a significant increase in mortality and morbidity. Pulmonary interstitial emphysema can completely regress or decompress into adjacent spaces, causing pneumomediastinum, pneumothorax, pneumopericardium, pneumoperitoneum, or subcutaneous emphysema.^{[3 ]}

Frequency

United States

The prevalence of pulmonary interstitial emphysema widely varies with the population studied. In a study by Gaylord et al, pulmonary interstitial emphysema developed in 3% of infants admitted to the neonatal ICU (NICU).^{[4 ]}In a retrospective case-controlled study, 24% (11 of 45) extremely low birth weight infants developed pulmonary interstitial emphysema.^{[5 ]}This study was done in the present era of tocolysis, antenatal steroids, and postnatal surfactant administration; however, all infants included in the study were treated with conventional ventilator in the assist-control mode before the onset of pulmonary interstitial emphysema.

Reported incidence of pulmonary interstitial emphysema in published clinical trials can be useful. In a randomized trial of surfactant replacement therapy at birth, in premature infants born at 25-29 weeks' gestation, Kendig et al reported pulmonary interstitial emphysema in 8 of 31 (26%) control neonates and in 5 of 34 (15%) surfactant-treated neonates.^{[6 ]}Another randomized controlled trial of prophylaxis versus treatment with bovine surfactant in neonates born at less than 30 weeks' gestation included 2 of 62 (3%) early surfactant-treated neonates, 5 of 60 (8%) late surfactant-treated neonates, and 15 of 60 (25%) control neonates with pulmonary interstitial emphysema^{[7 ]}. Kattwinkel et al compared prophylactic surfactant administration versus the early treatment of RDS with calf lung surfactant in neonates born at 29-32 weeks' gestation; 3 of 627 neonates in the prophylaxis group and 3 of 621 neonates in the early treatment group developed pulmonary interstitialemphysema.^{[8 ]}This information suggests a higher incidence of pulmonary interstitial emphysema in more immature infants as well as those with late surfactant therapy.

International

Studies reflecting international frequency demonstrated that 2-3% of all infants in NICUs develop pulmonary interstitial emphysema.^{[9,10 ]}When limiting the population studied to premature infants, this frequency increases to 20-30%, with the highest frequencies occurring in infants weighing fewer than 1000 g.^{[11 ]}In another study of low birth weight infants, the incidence of pulmonary interstitial emphysema was 42% in infants with birth weight of 500-799 g, 29% in those with birth weight of 800-899 g, and 20% in those with birth weight of 900-999 g.^{[12 ]}Minimal information is available about the prevalence of pulmonary interstitial emphysema in the postsurfactant era. In a prospective multicenter trial comparing early high-frequency oscillatory ventilation (HFOV) and conventional ventilation in preterm infants of fewer than 30 weeks' gestation with RDS, 15 of 139 (11%) infants in the high-frequency group and 15 of 134 (11%) infants in the conventional group developed pulmonary interstitialemphysema.^{[9 ]}

Mortality/Morbidity

The mortality rate associated with pulmonary interstitial emphysema is reported to be as high as 53-67%.^{[4,11 ]}Lower mortality rates of 24% and 38% reported in other studies could result from differences in population selection.^{[10,13 ]}Morisot et al reported an 80% mortality rate with pulmonary interstitial emphysema in infants with birth weight of fewer than 1600 g and severe RDS.^{[14 ]}The early appearance of pulmonary interstitial emphysema (<48 h after birth) is associated with increased mortality, but this may reflect the severity of the underlying parenchymal disease.^{[14,10 ]}

In survivors, morbidity is also high. Pulmonary interstitial emphysema can predispose an infant to other air leaks. In a study by Greenough et al, 31 of 41 infants with pulmonary interstitial emphysema developed pneumothorax, compared with 41 of 169 infants without pulmonary interstitial emphysema.^{[13 ]}In addition, 21 of 41 babies with pulmonary interstitial emphysema developed intraventricular hemorrhage (IVH), compared with 39 of 169 among infants without pulmonary interstitial emphysema. Pulmonary interstitial emphysema may not resolve for 2-3 weeks; therefore, it can increase the length of time of mechanical ventilation and the incidence of bronchopulmonary dysplasia. Some infants may develop chronic lobar emphysema, which may require surgical lobectomies.

In a more recent study in the postsurfactant era, 4 of 11 infants with pulmonary interstitial emphysema developed severe IVH (grade 2 or higher) compared with 4 of 34 infants without pulmonary interstitial emphysema. Additionally, pulmonary interstitial emphysema remained significantly associated with death (odds ratio, 14.4; 95% confidence interval [CI], 1-208; P = 0.05).^{[5 ]}

Sex

In a study by Plenat et al, pulmonary interstitial emphysema developed equally in both sexes (21 males, 18 females). Although these data also included cases with intrapleural pneumatosis, no relationship between sex and type of interstitial pneumatosis is noted.^{[1 ]}

Age

Pulmonary interstitial emphysema is more common in infants of lower gestational age. Pulmonary interstitial emphysema usually occurs within the first weeks of life. Development of pulmonary interstitial emphysema within the first 24-48 hours after birth is often associated with extreme prematurity, very low birth weight, perinatal asphyxia, and/or neonatal sepsis and frequently indicates a grave prognosis.

Clinical

History

Pulmonary interstitial emphysema (PIE) is a radiographic and pathologic diagnosis. In most cases, the discovery of pulmonary interstitial emphysema may be preceded by a decline in the baby's clinical condition. Hypotension and difficulty in oxygenation and ventilation can suggest the development of pulmonary interstitial emphysema. Alternatively, the baby can present with the signs of one of the complications of pulmonary interstitial emphysema, such as pneumothorax. Sometimes, pulmonary interstitial emphysema becomes apparent following reexpansion of a collapsed lung after drainage of a pneumothorax.

Physical

No specific signs of pulmonary interstitial emphysema are reported. Overinflation of the chest wall and crepitations on auscultation on the affected side may be present.

Causes

Risk factors include the following:

• Prematurity
• Respiratory distress syndrome (RDS)
• Meconium aspiration syndrome (MAS)
• Amniotic fluid aspiration
• Infection - Neonatal sepsis, pneumonia, or both
• Low Apgar score or need for positive pressure ventilation (PPV) during resuscitation at birth
• Use of high peak airway pressures on mechanical ventilation
• Incorrect positioning of the endotracheal tube in one bronchus

Differential Diagnoses

Other Problems to Be Considered

• The roentgenologic appearance of pulmonary interstitial emphysema (PIE) can be confused with the following:^{[15 ]}
  • Air-bronchogram in respiratory distress syndrome (RDS)
  • Aspiration pneumonia
  • Pulmonary edema
  • Distended airways in patients on a ventilator
• Other differential diagnosis of persistent pulmonary interstitial emphysema includes the following:
  • Congenital cystic adenomatoid malformation
  • Lymphangiectasia
  • Bronchogenic cysts
  • Congenital lobar emphysema
  • Cystic lymphangioma
  • Sequelae of prior infection
  • Diaphragmatic hernia

Workup

Laboratory Studies

• Blood gases should be obtained in patients with pulmonary interstitial emphysema (PIE) to ensure adequate gas exchange.

Imaging Studies

• See Media files 1-3.
  
  

  

  This radiograph, obtained from a 1-day-old premature infant at 24 weeks' gestation, shows bilateral pulmonary interstitial emphysema (PIE). Linear radiolucencies extending up to the lung periphery are visible.

  
  
  

  

  This radiograph, obtained from a premature infant at 26 weeks' gestation, shows characteristic radiographic changes of pulmonary interstitial emphysema (PIE) of the right lung.

  
  
  

  

  This radiograph shows pneumothorax and pulmonary interstitial emphysema (PIE) on the right side. Interstitial air prevents collapse of the underlying lung by a tension pneumothorax. In such cases, extreme caution is required during drainage of a pneumothorax to avoid perforation of the underlying lung.

  
  
• The classic radiologic appearance of pulmonary interstitial emphysema often provides a clear diagnosis. Pulmonary interstitial emphysema is best visualized in the anteroposterior supine projection. Pulmonary interstitial emphysema has two basic radiographic appearances, linear and cystlike radiolucencies, although both types often appear together.
• Linear radiolucencies are coarse and nonbranching, measure from 3-8 mm, and vary in width but rarely exceed 2 mm.
• Small cystlike radiolucencies extend in diameter from 1-4 mm, and, though generally round, they may appear oval or slightly lobulated.
• Disorganized haphazard distribution of pulmonary interstitial emphysema in localized areas is unlike the anatomically organized pattern of the air-bronchogram. The air-bronchogram is a classic radiographic sign of respiratory distress syndrome (RDS), which should not be confused with pulmonary interstitial emphysema. In RDS, long, smooth, branching, linear radiolucencies decrease in caliber from the hilum and frequently disappear at the lung periphery. Pulmonary interstitial emphysema should be suspected when coarse radiolucencies appear in the lung periphery or when the lucencies do not branch in a pattern consistent with the normal bronchial tree.
• In some patients receiving mechanical ventilation, distended airways and alveoli have a somewhat similar appearance to that of pulmonary interstitial emphysema on radiography. Over time, it either progresses to a classic radiographic picture of pulmonary interstitial emphysema or resolves very rapidly as ventilator settings are decreased.
• Pulmonary interstitial emphysema can rarely be misinterpreted as normally aerated lung surrounded by exudate as in an aspiration syndrome or pulmonary edema.^{[15 ]}

Histologic Findings

• The histology of pulmonary interstitial emphysema is well described by Plenat et al.^{[1 ]} The histology demonstrates interstitial slits preferentially located in perivenous topography.
• Sometimes, the peribronchial arterial or arteriolar sheaths are involved. Air dissects through a plane just next to the arterial or arteriolar face, opposite the bronchus, which is pushed into adjoining parenchyma. The bronchoarterial solidarity most often is respected.
• Seldom, air can dissect arterioles and bronchioles and isolate them from the adjacent lobules. On the periphery of interstitial slits, the small vessels are compressed but never ruptured, whereas the collagen fibers are constantly broken and squeezed together.

Treatment

Medical Care

Different treatment modalities have been used to manage pulmonary interstitial emphysema (PIE), with variable success.

• Lateral decubitus positioning^{[16 ]}
  • This conservative approach has been used with success and is most effective in infants with unilateral pulmonary interstitial emphysema. The infant is placed in the lateral decubitus position with the affected lung in a dependent position. This therapy can result in plugging of dependent airways and improved oxygenation of the nondependent lung. The latter allows for overall decreased ventilatory settings. The combination of the above factors helps in resolution of pulmonary interstitial emphysema.
  • In different case studies of lateral decubitus position as a treatment of unilateral pulmonary interstitial emphysema in infants, pulmonary interstitial emphysema resolved in 48 hours to 6 days with minimal recurrence and a low failure rate. Lateral decubitus positioning should be considered as an early first-line therapy in the management of unilateral pulmonary interstitial emphysema. Lateral decubitus positioning has been used successfully for patients with bilateral pulmonary interstitial emphysema when one side is more significantly affected.
• Selective main bronchial intubation and occlusion
  • Many case reports detail successful treatment of severe localized pulmonary interstitial emphysema in infants with selective intubation of the contralateral bronchus to decompress the overdistended lung tissue and to avoid exposing it to high positive inflationary pressures^{[17,18,19 ]}. Selective bronchial intubation of the right main bronchus is not a difficult procedure; the left side may be more difficult. The endotracheal tube of the same diameter as for a regular intubation is inserted 2-4 cm beyond its usual position. It is introduced with the bevel on the end of the tube positioned so that the long part of the tube is toward the bronchus to be intubated. This increases the chance of entering the correct bronchus as the tube is advanced into the airway. Turning the infant's head to the left or right moves the tip of the endotracheal tube to the contralateral side of the trachea and may help in selective tube placement.
  • Weintraub et al have described a method for left selective bronchus intubation using a regular Portex endotracheal tube in which an elliptical hole 1 cm in length has been cut through half the circumference 0.5 cm above the tip of the oblique distal end.^{[19 ]}With the side with the elliptical hole directed to the left lung, left selective bronchus intubation can be easily and repeatedly accomplished. Another method of selective intubation is the use of a small fiberoptic bronchoscope to direct the endotracheal tube tip into the desired bronchus. Selective intubation under fluoroscopy can also be considered.
  • Potential complications of the selective intubation/ventilation include atelectasis in the affected lung, injury to bronchial mucosa with subsequent scarring and stenosis, acute hypoventilation or hypoxemia if ventilating one lung is inadequate, excessive secretions, hyperinflation of the intubated or nonoccluded lung, upper lobe collapse when intubating the right lung, and bradycardia. Despite potential risks, selective bronchial intubation is a desirable alternative to lobectomy in a persistent, severe, localized pulmonary interstitial emphysema causing mediastinal shift and compression atelectasis and not responding to conservative management. This procedure should be attempted before any surgical intervention.
• High-frequency ventilation
  • Keszler et al studied use of high-frequency jet ventilation (HFJV) in 144 newborns with pulmonary interstitial emphysema.^{[20 ]}They concluded that HFJV was safe and more effective than rapid-rate conventional ventilation in the treatment of newborns with pulmonary interstitial emphysema. With HFJV, similar oxygenation and ventilation was obtained at lower peak and mean airway pressures, suggesting that, in infants with pulmonary interstitial emphysema, a reduction in the amount of air leaking into the interstitial spaces would occur.
  • Similar effects can be achieved by use of HFOV.
    • In a study by Clark et al, 27 low birth weight infants who developed PIE and respiratory failure while on conventional ventilation were treated with HFOV.^{[21 ]}Surviving patients showed continued improvement in oxygenation and ventilation at an increasingly lower fraction of inspired oxygen (FiO₂) and proximal airway pressure with resolution of pulmonary interstitial emphysema, whereas nonsurvivors progressively developed chronic respiratory insufficiency with continued pulmonary interstitial emphysema from which recovery was not possible. Overall survival in nonseptic patients was 80%.
    • They found HFOV to be effective in the treatment of pulmonary interstitial emphysema and hypothesized that interstitial air leak is decreased during HFOV because adequate ventilation is provided at lower peak distal airway pressures. Although this mode of ventilation has inherent risks, it can be a very effective tool in experienced hands for the treatment of severe diffuse pulmonary interstitial emphysema. Care must be taken in smaller infants who require a high amplitude to ventilate because the active exhalation during HFOV may cause small airway collapse and exacerbate gas trapping.
• Other treatment modalities
  • Case reports and/or case series describe different approaches for the management of pulmonary interstitial emphysema, including 3-day course of dexamethasone (0.5 mg/kg/d),^{[22 ]}chest physiotherapy with intermittent 100% oxygen in localized and persistent compressive pulmonary interstitial emphysema,^{[23 ]}artificial pneumothorax,^{[24,25 ]}and multiple pleurotomies.^{[26 ]}
  • Despite success claimed by the authors, the efficacy of these treatment modalities from these case reports seems questionable. With advancements in respiratory care, these treatment modalities rarely are used.

Surgical Care

Lobectomy is indicated in a small number of patients with localized pulmonary interstitial emphysema when spontaneous regression is not occurring and medical management has failed.^{[27,28,29 ]}Although clear guidelines for surgical intervention are difficult to establish, it should be reserved for infants in whom the risks of recurring complications outweigh those of surgery. It seems most helpful in infants who develop severe lobar emphysema.

Consultations

All infants with pulmonary interstitial emphysema need to be under the care of a neonatologist. In some cases, pediatric pulmonology and pediatric surgery consultations are appropriate.

Diet

The overall importance of appropriate nutritional management of ill newborns cannot be overstressed. Most of these infants are treated with total parenteral nutrition and require diligent attention.

Follow-up

Further Inpatient Care

• Admission/transfer to a NICU is indicated for patients with pulmonary interstitial emphysema (PIE).
• A thoracentesis set should be readily available due to the possibility of air leak, including pneumothorax and pneumopericardium.

Further Outpatient Care

• Monitoring for physical and psychomotor development in a neonatal follow-up care program or equivalent program is important because most infants with pulmonary interstitial emphysema are premature and are at risk for developmental delay. In addition, pulmonary interstitial emphysema has been associated with increased risks of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), which also increase the risks of developmental delay in these infants.
• Patients with chronic lung disease may need pediatric pulmonology follow-up care.

Deterrence/Prevention

• Surfactant
  • Prophylactic surfactant administration to infants (<30-32 weeks' gestation) judged to be at risk of developing respiratory distress syndrome (RDS) compared with selective use of surfactant in infants with established RDS has been demonstrated to decrease the risk of pulmonary interstitial emphysema.^{[30 ]}
  • Metaanalysis of early surfactant replacement therapy with brief ventilation compared with later, selective surfactant replacement and continued mechanical ventilation suggests a trend towards a decreased incidence of air leak syndromes in premature infants in the early surfactant group. Early surfactant treatment, less invasive ventilatory support, or both could be responsible factors for the observed beneficial trend.^{[31 ]}
  • According to one report, in infants with respiratory distress, multiple doses of animal-derived surfactant extract resulted in greater improvements in oxygenation and ventilatory requirements, a decreased risk of pneumothorax, and a trend toward improved survival.^{[32 ]}
• High-frequency ventilation
  • In a study comparing high-frequency positive pressure ventilation (HFPPV) to conventional ventilation, Pohlandt et al reported a reduction in the risk of pulmonary interstitial emphysema with HFPPV.^{[33 ]}Review of different trials of elective high-frequency oscillatory ventilation (HFOV) versus conventional ventilation for acute pulmonary dysfunction in preterm infants suggests an increase in the incidence of air leak syndromes including but not limited to pulmonary interstitial emphysema in the HFOV group.^{[34 ]}
  • A prospective randomized multicenter study of HFOV versus conventional ventilation in premature infants with RDS showed no difference in the incidence of pulmonary interstitial emphysema.^{[35 ]}Limited data regarding rescue HFOV for pulmonary dysfunction in the preterm infant also showed no difference in the rate of pulmonary interstitial emphysema.^{[36 ]}
  • Cochrane reviews of trials of elective high-frequency jet ventilation (HFJV)versus conventional ventilation for RDS demonstrated no significant difference in the incidence of air leak syndrome in the individual trials or in the overall analysis^{[37 ]}.
  • In summary, current literature suggests that elective or rescue high-frequency ventilation does not prevent the development of pulmonary interstitial emphysema.
• Other considerations
  • Different modes of conventional ventilation: No significant difference in the rate of pulmonary interstitial emphysema was found either in pooled analysis within subgroups or overall pooled analysis of trials comparing volume-targeted versus pressure-limited ventilation in the neonate.^{[38 ]}
  • Avoid use of high peak inspiratory pressure (PIP).
  • Be careful (watch manometer) during manual ventilation.

Complications

• Death
• Respiratory insufficiency
• Other air leaks
  • Pneumomediastinum
  • Pneumothorax
  • Pneumopericardium
  • Pneumoperitoneum
  • Subcutaneous emphysema (rare)
• Massive air embolism
• Chronic lung disease of prematurity
• Intraventricular hemorrhage
• Periventricular leukomalacia

Prognosis

• Long-term follow-up data are scarce.
• Gaylord et al demonstrated a high (54%) incidence of chronic lung disease in survivors of pulmonary interstitial emphysema compared with their nursery's overall incidence of 32%. In addition, 19% of the infants developed chronic lobar emphysema; 50% received surgical lobectomies.^{[4 ]}

Miscellaneous

Medicolegal Pitfalls

• Although the primary risk factor for pulmonary interstitial emphysema, prematurity, is rarely preventable, attention should be given to the use of as little mechanical ventilatory support as is necessary for the patient's very fragile lungs.
• Because pneumothorax is a known complication, anticipatory guidance for this possibility should be provided for all those caring for the infant. Appropriate personnel should be readily available to address this complication.

Multimedia

Media file 1: This radiograph, obtained from a 1-day-old premature infant at 24 weeks' gestation, shows bilateral pulmonary interstitial emphysema (PIE). Linear radiolucencies extending up to the lung periphery are visible.

Media file 2: This radiograph, obtained from a premature infant at 26 weeks' gestation, shows characteristic radiographic changes of pulmonary interstitial emphysema (PIE) of the right lung.

Media file 3: This radiograph shows pneumothorax and pulmonary interstitial emphysema (PIE) on the right side. Interstitial air prevents collapse of the underlying lung by a tension pneumothorax. In such cases, extreme caution is required during drainage of a pneumothorax to avoid perforation of the underlying lung.

References

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38. [Best Evidence] McCallion N, Davis PG, Morley CJ. Volume-targeted versus pressure-limited ventilation in the neonate. Cochrane Database Syst Rev. 2005;CD003666. [Medline].

Keywords

pulmonary interstitial emphysema, PIE, respiratory distress syndrome, RDS, meconium aspiration syndrome, MAS, amniotic fluid aspiration, intrapulmonary pneumatosis, intrapleural pneumatosis, pneumomediastinum, pneumothorax, pneumopericardium, pneumoperitoneum, subcutaneous emphysema, bronchopulmonary dysplasia, chronic lobar emphysema, intraventricular hemorrhage, IVH, prematurity, very low birth weight, perinatal asphyxia, neonatal sepsis, pneumonia, positive pressure ventilation

Contributor Information and Disclosures

Author

Abhay J Bhatt, MD, MBBS, Assistant Professor, Department of Pediatrics, Division of Newborn Medicine, University of Mississippi Medical Center
Abhay J Bhatt, MD, MBBS is a member of the following medical societies: American Academy of Pediatrics
Disclosure: Nothing to disclose.

Coauthor(s)

Rita M Ryan, MD, Professor of Pediatrics, Chief, Division of Neonatology, Director, Neonatal-Perinatal Medicine Fellowship Program, University at Buffalo, State University of New York, Women's and Children's Hospital of Buffalo
Rita M Ryan, MD is a member of the following medical societies: American Academy of Pediatrics, American Thoracic Society, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Medical Editor

Steven M Donn, MD, Professor of Pediatrics, Director, Neonatal-Perinatal Medicine, Department of Pediatrics, University of Michigan Health System
Steven M Donn, MD is a member of the following medical societies: American Pediatric Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

Brian S Carter, MD, FAAP, Professor of Pediatrics (Neonatology), Vanderbilt University School of Medicine; Co-director, Pediatric Advance Comfort Team, Monroe Carell Jr Children's Hospital at Vanderbilt
Brian S Carter, MD, FAAP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Hospice and Palliative Medicine, American Academy of Pediatrics, American Society for Bioethics and Humanities, American Society of Law Medicine and Ethics, National Hospice and Palliative Care Organization, and Southern Society for Pediatric Research
Disclosure: Nothing to disclose.

CME Editor

Carol L Wagner, MD, Professor of Pediatrics, Medical University of South Carolina
Carol L Wagner, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American Medical Women's Association, American Public Health Association, American Society for Bone and Mineral Research, American Society for Clinical Nutrition, Massachusetts Medical Society, National Perinatal Association, and Society for Pediatric Research
Disclosure: Nothing to disclose.

Chief Editor

Ted Rosenkrantz, MD, Professor, Departments of Pediatrics and Obstetrics/Gynecology, Division of Neonatal-Perinatal Medicine, University of Connecticut School of Medicine
Ted Rosenkrantz, MD is a member of the following medical societies: American Academy of Pediatrics, American Medical Association, American Pediatric Society, Connecticut State Medical Society, Eastern Society for Pediatric Research, and Society for Pediatric Research
Disclosure: Nothing to disclose.

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