571CHAPTER 51 Neonatal Pulmonary Disease should be done even before radiographic confirmation if the in fant is severely compromised An unstable or recurrent pneumotho rax may require a thoracotomy tu[.]
CHAPTER 51 Neonatal Pulmonary Disease should be done even before radiographic confirmation if the infant is severely compromised An unstable or recurrent pneumothorax may require a thoracotomy tube Cardiac tamponade resulting from a pneumopericardium may be suggested by distant heart tones and hypotensive shock with a normal-appearing electrocardiogram tracing (electromechanical dissociation) Pneumomediastinum often is asymptomatic and rarely benefits from drainage, even in the presence of clinical signs PIE occurs predominantly in preterm infants and often leads to a vicious cycle of increasing ventilator delivery pressures to open alveoli compressed by extrinsic air, which, in turn, leads to more extravasation of air and further collapse Both high-frequency oscillatory ventilation (HFOV) and high-frequency jet ventilation (HFJV) can provide adequate gas exchange using extremely low tidal volumes and a supraphysiologic rate in neonates with acute pulmonary dysfunction, and they may reduce the potential risk of air leak syndrome in neonates.24 However, there is no conclusive evidence that HFOV or HFJV reduces the incidence of air leaks in neonates.25,26 Pulmonary Hemorrhage Pulmonary hemorrhage (PH) in the newborn is a life-threatening condition that has an incidence of to 12 per 1000 live births and 50 per 1000 high-risk infants.27 Common risk factors for PH include prematurity, intrauterine growth restriction, and patent ductus arteriosus (PDA) with systemic steal and asphyxia In most cases, what is called pulmonary hemorrhage is actually the most severe manifestation of pulmonary edema rather than anatomic vascular disruption This conclusion is validated by determining measures of the hematocrit of hemorrhagic fluid suctioned from the airway The hemorrhagic fluid hematocrit generally will be 15% to 20% lower than venous hematocrit in the same patient at the time Finding whole blood in the airway is rare and usually results from trauma from mechanical injury Most infants with PH will have more than one risk factor In the neonate, the factors most commonly associated with hemorrhagic pulmonary edema are those that increase pulmonary blood flow, such as a left-to-right shunt through a PDA Sudden improvement in lung compliance after surfactant therapy, with resultant decrease in pulmonary vascular resistance producing increased left-to-right shunting, may lead to PH The diagnosis is made when the appearance of bloody secretions within an endotracheal tube coincides with acute respiratory deterioration that requires increased oxygen and ventilator support The chest radiograph is nonspecific and may show fluffy opacities, focal ground-glass opacities, or appear as a complete whiteout of the lung fields The goal of management is to stop hemorrhaging while maintaining adequate gas exchange Increasing positive end-expiratory pressure (PEEP) reduces alveolar flooding and can improve oxygenation and left ventricular function Although the airway must be kept clear, frequent suctioning not only may be traumatic but also can aggravate the condition by reducing PEEP High mean airway pressures, which can be safely achieved with high-frequency ventilation (HFV), can be effective in massive pulmonary hemorrhage, yielding rapid improvement in oxygenation Administration of endotracheal or nebulized epinephrine or iced saline solution via the endotracheal tube has been advocated in the past but has questionable efficacy, and epinephrine may worsen the condition by elevating pulmonary vascular pressure Additional therapies that may be beneficial in specific instances include reversal 571 of any coagulopathy or thrombocytopenia, and surfactant.28–30 The rationale for surfactant therapy is that red blood cell products— including hemoglobin, proteins, and lipids—can inactivate the infant’s pulmonary surfactant.31 Even with aggressive management, mortality from hemorrhagic pulmonary edema may exceed 25% The Trial of Indomethacin Prophylaxis in Preterm infants (TIPP) study (post-hoc analysis) showed that risks of death or survival with neurosensory impairment were doubled after serious PH Approximately 60% of preterm infants who survive PH developed bronchopulmonary dysplasia An increased incidence of cerebral palsy (odds ratio [OR], 2.86) and cognitive delay (OR, 2.4) has been reported.32 PH is also associated with an increased risk of seizures and periventricular leukomalacia in survivors at 18 months of age.33 Pneumonia Neonatal pneumonia is a common cause of significant morbidity and mortality In developed countries, term infants have an incidence of less than 1%, whereas the incidence in preterm and sick infants may approach 10%.34 The World Health Organization (WHO) estimated that approximately 800,000 infants die annually from neonatal respiratory infections, most being pneumonia.35 Neonatal pneumonia can be congenital (acquired before labor and rupture of amniotic membrane via hematogenous or ascending infection or by aspiration), intrapartum (acquired during labor via ascending or hematogenous infection), or postnatal (acquired after birth) The lungs represent the most commonly affected organ in neonates with sepsis Bacterial or viral infection in the neonate may begin in utero by transplacental passage or, more commonly, by ascending infection from the maternal genital tract or by hematogenous spread Prolonged rupture of membranes (.18 hours) increases the risk of an ascending infection, although some organisms may invade through intact membranes Cervical bacterial colonization with group B streptococci (GBS) or primary herpes viral cervical infection during pregnancy increases the risk of transmitting those diseases Cesarean delivery is not necessarily protective because fetuses may swallow contaminated amniotic fluid or aspirate organisms in utero Infection occurring during the perinatal period may not present clinically for several days Consequently, congenitally acquired infections may be indistinguishable from infections postnatally acquired (i.e., nosocomial) As a result, organisms that cause perinatal pneumonias are typically those found in the genital tract of the mother and include streptococci (groups A, B, and D), gram-negative rods (e.g., Escherichia coli and Klebsiella species), Listeria monocytogenes, ureaplasma, genital Haemophilus influenzae, and herpesvirus Less commonly, maternal viral infections (e.g., adenovirus, enteroviruses, or varicella) can be vertically transmitted to the fetus Although the incidence of GBS pneumonia has decreased dramatically due to maternal screening and intrapartum treatment, GBS remains a common bacterial cause of neonatal pneumonia However, in very-low-birthweight preterm infants, E coli now dominates Pneumonia may develop as a nosocomial infection in neonates, particularly in those who require mechanical ventilation for other critical illnesses Although reported rates vary widely, in part because of the lack of a diagnostic standard in this population, some authors have suggested that the incidence of ventilatorassociated pneumonia (VAP) may be as high as 30% in selected NICU populations If a VAP is suspected, typical nosocomial 572 S E C T I O N V Pediatric Critical Care: Pulmonary pathogens such as Staphylococcus, Klebsiella, and Pseudomonas species, and the pathogens previously listed for congenital pneumonias should be considered as possible causes Ureaplasma urealyticum and U parvum have frequently been recovered from endotracheal aspirates shortly after birth in very-low-birthweight infants and have been associated with various adverse pulmonary outcomes, including bronchopulmonary dysplasia Diagnosis of congenital pneumonia may be challenging because clinical and radiographic signs may be nonspecific Although congenital infections are generally introduced through the respiratory tract, signs are rarely limited to those of pneumonia; the neonate is particularly prone to rapid dissemination of either bacterial or viral infections and typically has signs of sepsis or meningitis in addition to respiratory distress The chest radiograph initially may appear normal, except for slight streakiness or hyperinflation, or the lung fields may be sufficiently opaque to be confused with surfactant-deficient RDS Meconium aspiration with resultant severe chemical pneumonitis may be indistinguishable radiographically from bacterial pneumonia Heart failure or obstructed anomalous pulmonary venous drainage also can present with a clinical and radiographic picture similar to pneumonia/sepsis Congenitally acquired pneumonia/sepsis can be a rapidly fatal disease, especially in the case of GBS or herpetic viral infections, for which mortality rates as high as 50% have been reported Therefore, a high degree of suspicion is warranted Antibiotics are routinely used in neonates with suspected pneumonia or sepsis Antiviral therapy should be considered if the infant has systemic signs such as shock or disseminated intravascular coagulation or is not responding to initial therapy Meconium Aspiration Syndrome Passage of meconium in utero is a sign of fetal distress (acute or chronic) and occurs because of relaxation of the fetal anal sphincter Moderate distress occurring during labor results in passage of meconium in the final stages of delivery (terminal meconium), whereas more severe or chronic distress results in earlier passage, with resultant staining of the amniotic fluid and fetus Meconium staining is a significant marker of fetal distress and occurs in 10% to 20% of all deliveries, but meconium aspiration syndrome (MAS) occurs in only 4% to 5% of these; MAS is most common in postmature infants.36–38 Intrauterine meconium passage is a maturational phenomenon and is rarely observed in fetuses younger than 34 weeks’ gestation Meconium is a lipid- and protein-rich substance containing desquamated cells from the gastrointestinal (GI) tract, skin, lanugo hair, bile salts, pancreatic enzymes, and mucopolysaccharides and is highly irritating to mucous membranes of the distal airways, resulting in a chemical pneumonitis Dissolved meconium may travel down the respiratory tree and inactivate pulmonary surfactant Meconium induces a potent inflammatory response, and MAS is associated with alterations in the pulmonary vasculature, including remodeling and thickening of the vessel muscle walls This process results in pulmonary vascular hyperreactivity, vasoconstriction, and high resistance and pressure Activation of the complement cascade leads to inflammation and constriction of pulmonary veins As the proinflammatory cytokine profile improves, so does pulmonary function More particulate meconium will remain trapped in small airways, which can lead to a ball-valve type of gas trapping In most cases, the meconium is gradually removed from the respiratory tract through phagocytosis, and normal pulmonary function returns in to days In more severe cases, MAS may lead to respiratory failure, and even death, despite aggressive intervention Infants with meconium aspiration are typically postmature and exhibit elongated nails; peeling skin; and staining of the umbilical cord, skin, and nails Respiratory distress develops shortly after birth The infant’s respirations initially may be depressed if meconium passage occurred in response to a recent intrauterine asphyxia episode Gas trapping may lead to a barrel-shaped appearance of the chest, and respiratory distress may be severe Chest radiographs often show characteristic patchy densities, hyperinflation, and areas of collapse Air leaks are especially common Routine airway suctioning on the perineum or routine endotracheal suctioning for all meconium-stained newborns is no longer recommended The American Academy of Pediatrics (AAP) and American Heart Association Neonatal Resuscitation Program currently recommends gentle clearing of the mouth and nose if necessary and initiation of positive pressure ventilation within the first minute of life in nonbreathing or ineffectively breathing newborns, although this may require further clarification.39 Supplemental oxygen to maintain arterial oxygen saturation, endotracheal suctioning to clear remaining meconium, and ventilatory strategies aimed to minimize gas trapping have been mainstays of management HFV may help to prevent the development of air leaks Antibiotics are commonly used because distinguishing the clinical and radiographic picture from sepsis is difficult and because damage to the airways may predispose to subsequent bacterial infection A systematic review of four clinical trials in term and near-term infants concluded that surfactant administration significantly reduced the need for extracorporeal membrane oxygenation (ECMO), although overall mortality was not affected.40,41 Nevertheless, surfactant replacement therapy is sometimes combined with other therapies, including HFV and inhaled nitric oxide The latter has become a mainstay of therapy for hypoxic respiratory failure, especially when pulmonary hypertension is a feature of MAS or other pneumonias Because intrauterine meconium passage and MAS are frequently associated with a hypoxic event, long-term neurologic outcome remains guarded A cycle of hypoxia, meconium aspiration, and pulmonary hypertension may be established in utero Mortality in the depressed newborn with MAS is as high as 7%, with an incidence of hypoxic-ischemic encephalopathy of 20% and occurrence of air leak syndromes in 11% of affected infants.42 Meconium aspiration during the perinatal period may be associated with an increased risk of reactive airway disease in early childhood.43 Immature Respiratory Control Immature respiratory control in preterm infants remains a major contributor to neonatal respiratory disease Cardiorespiratory and neural maturation may contribute to both respiratory and neurodevelopmental morbidity and often prolongs hospitalization Biological Maturational Considerations The neural circuitry that generates respiratory rhythm and governs inspiratory and expiratory motor patterns is distributed throughout the pons and medulla The medulla contains a specialized region known as the pre-Bötzinger complex, which contains neurons that exhibit intrinsic pacemaker activity capable of producing rhythmic respiratory motor output without sensory feedback Although a fundamental feature of this network is that CHAPTER 51 Neonatal Pulmonary Disease it enables breathing to occur automatically, this systematic central rhythmicity may fail in preterm infants.44 Meanwhile, central and peripheral sensory inputs from multiple sources allow adjustments to the patterns of inspiratory and expiratory activity in response to changing metabolic conditions For example, inhibitory sensory inputs from the upper airway may be particularly prominent in early postnatal life to serve a protective function, although this may trigger potentially clinically significant apnea Excitatory and inhibitory neurotransmitters and neuromodulators mediate the rhythmogenic synaptic communications between neurons of the medulla Glutamate is the major neurotransmitter mediating excitatory synaptic input to brainstem respiratory neurons gAminobutyric acid and glycine are the two primary inhibitory neurotransmitters in the network Responsiveness to carbon dioxide (CO2) is the major chemical driver of respiratory neural output This is apparent in fetal life, where breathing movements increase under hypercapnic conditions in animal models As in later life, CO2/hydrogen ion (H1) responsiveness is predominantly based in the brainstem, although peripheral chemoreceptors contribute to the ventilatory response and respond more rapidly The reduced ventilatory response to CO2 in small preterm infants, especially those with apnea, is primarily the result of decreased central chemosensitivity However, mechanical factors—such as poor respiratory function and an unstable, compliant chest wall—may contribute.45 It is difficult to distinguish the neural from mechanical factors that contribute to respiratory failure in this population.46 Preterm infants respond to a fall in inspired oxygen concentration with a transient increase in ventilation over approximately minute followed by a return to baseline or even depression of ventilation The characteristic response to low oxygen in infants appears to result from initial peripheral chemoreceptor stimulation followed by overriding depression of the respiratory center as a result of hypoxemia Such hypoxic respiratory depression may be useful in the hypoxic intrauterine environment, where respiratory activity is intermittent and not contributing to gas exchange The nonsustained response to low inspired oxygen concentration may, however, be a disadvantage postnatally It may play an important role in the origin of neonatal apnea and offers a physiologic rationale for the decrease in incidence of apnea observed when a slightly increased concentration of inspired oxygen is administered to apneic infants who have a low baseline oxygen saturation Apnea of Prematurity During early postnatal life apneic events are ubiquitous; they can vary widely in duration and are often accompanied by bradycardia and/or intermittent hypoxemia.47 Accordingly, AAP guidelines have historically defined clinical apnea of prematurity as a respiratory pause of 20 seconds or shorter if accompanied by hypoxemia (,80%) and/or bradycardia (,80 beats/min).48 It should be noted that even short respiratory pauses, approximating 10 seconds or less, may be associated with desaturation and/or bradycardia Apnea is categorized as (1) central, with loss of central respiratory drive, resulting in complete cessation of flow and absence of respiratory effort; (2) obstructive, with absence of flow in the presence of respiratory efforts; and (3) mixed, with both central and obstructive components Unfortunately, standard impedance monitoring, which reflects chest wall motion, may fail to differentiate obstructed versus unobstructed inspiratory efforts Simultaneous monitoring of heart rate and oxygen saturation ensures that such events are not missed 573 There is increasing interest in the potential role of apnea with accompanying intermittent hypoxia (and reoxygenation) or later morbidities, both respiratory and neurodevelopmental Intermittent hypoxia (IH) is almost always preceded by a respiratory pause, and often occurs rapidly (,10 s) after cessation of airflow.47 Factors that can influence the initiation, duration, and severity of IH include baseline oxygen saturation,49 oxygen uptake from the alveoli, pulmonary oxygen stores, total blood oxygencarrying capacity, the slope of the hemoglobin oxygen dissociation curve, and metabolic oxygen consumption.50 In extremely preterm infants, IH events are pervasive and transient during early postnatal life, with a relatively low incidence during the first week of life, followed by a rapid increase during the second and third weeks and a plateau or decrease thereafter.51 A secondary analysis of infants enrolled in the Canadian Oxygen Trial52 has shown an association between increased time spent less than 80% during IH events and a greater probability of death or disability, cognitive or language delay, severe retinopathy of prematurity, and motor impairment at 18 months of age53 that was limited to IH events of minute or longer in duration Therapeutic Options Caffeine and CPAP are the mainstay of therapy used to treat apnea and IH Caffeine and other methylxanthines have been prescribed in preterm infants for over 40 years54,55 and have been shown to reduce apnea and the need for ventilation.56 The largest trial of caffeine (Caffeine for Apnea of Prematurity Trial) randomly assigned 2006 infants with birthweights between 500 and 1250 g to caffeine or placebo in the first 10 days of life.57 Although apnea of prematurity was not measured in this clinical trial, caffeine administration was associated with a reduction in duration of positive-pressure support, oxygen supplementation, and the incidence of bronchopulmonary dysplasia Caffeine significantly improved survival without neurodevelopmental disability at 18 to 21 months; it also improved developmental coordination disorders and motor deficits at school age.58 There are various pharmacologic effects of caffeine in apnea of prematurity Most important, it stimulates the respiratory center in the brainstem and increases sensitivity to CO2.59 Mechanisms of action include blockade of adenosine A1 and A2A receptor subtypes, resulting in excitation of respiration neural output.60,61 Caffeine has also been shown to enhance peripheral chemoreceptor activation.62 A loading dose of caffeine showed a rapid (within minutes) and a prolonged (2 hours) increase in diaphragmatic activity that was associated with an increase in tidal volume.63 Last, exposed prenatally to lipopolysaccharide endotoxin, neonatal rodents had improved lung resistance and cytokine profiles after caffeine treatment.64 Optimal strategies of caffeine therapy have yet to be determined, although common practice entails a caffeine citrate loading dose of 20 mg/kg followed by to 10 mg/kg per day.57,65–66 Nasal CPAP is safe and effective and has a prominent role in treatment for apnea of prematurity CPAP is a noninvasive form of applying a constant distending pressure level during inhalation and exhalation It supports infants who are spontaneously breathing but who have airway instability, pulmonary edema, and atelectasis.67 CPAP enhances functional residual capacity, reduces work of breathing, and decreases mixed and obstructive apnea.68–70 There is considerable controversy regarding the best mode of CPAP delivery This is further complicated by the various lowand high-flow cannulae that are widely used for CPAP delivery 574 S E C T I O N V Pediatric Critical Care: Pulmonary despite limited comparative studies Refinement of techniques to both delivery of CPAP and effective synchronized noninvasive ventilation may be the answer Pulmonary Malformations The placenta is the organ of gas exchange in utero; thus, fetal viability does not depend on a functioning lung Not surprisingly, substantial abnormalities of the lung can exist antenatally with little or no clinical indication until delivery of the neonate, when the lung must assume the function of gas exchange Pulmonary Hypoplasia Both static and dynamic expansions of the fetal lung are important determinants of normal fetal lung development Static lung expansion occurs as a result of fetal lung liquid production Epithelial cells within the lung actively secrete fluid into the lung lumen, distending the future airspaces Inadequate production or excessive drainage of fetal lung liquid leads to pulmonary hypoplasia Dynamic lung expansion occurs during fetal breathing movements, which are rhythmic and occur with increasing frequency during the latter part of gestation Absent or abnormal fetal breathing also results in pulmonary hypoplasia Hypoplastic lungs are small in volume and deoxyribonucleic acid content relative to body size They have reduced numbers of alveoli (mean alveolar count [MAC]), bronchioles, and arterioles per unit mass Although its pathophysiologic origins are not well understood, pulmonary hypoplasia can result from impairment of normal fetal lung expansion It generally occurs in conjunction with one of the following conditions: (1) a space-occupying lesion within a hemithorax, such as a diaphragmatic hernia; (2) an inadequate thoracic cage, as occurs in some types of osteochondrogenesislike asphyxiating thoracic dystrophy or achondrogenesis; (3) a deficiency of amniotic fluid (oligohydramnios) due to leakage (preterm rupture of fetal membranes) or underproduction (renal dysplasia); (4) inadequate vascular supply to the developing lung; (5) an absence of fetal breathing movements; or (6) chromosomal anomalies, such as trisomy 13 or 18 If the insult occurs before the pseudoglandular stage of lung development (7–17 weeks), the degree of hypoplasia is severe Pulmonary hypoplasia may occur in the absence of any of these conditions, but such cases of primary isolated pulmonary hypoplasia are rare Infants with pulmonary hypoplasia generally show signs of respiratory failure in the immediate newborn period Reduced lung volume impairs ventilation and leads to hypercarbia Decreased surface area for gas exchange (due to a reduced number of alveoli) leads to hypoxemia A decreased cross-sectional area of the vasculature makes these infants particularly susceptible to pulmonary hypertension, which further exacerbates the hypoxemia The chest radiograph in infants with pulmonary hypoplasia shows low lung volumes but may be otherwise unremarkable The severity of respiratory distress depends on the degree of hypoplasia and presence of associated conditions, such as fetal hydrops or cyanotic heart disease The most common association is renal dysplasia or agenesis In these cases, infants have a history of moderate to severe oligohydramnios and have severe respiratory distress and compression deformities of the face and extremities (Potter sequence) An antenatal sonographic assessment of lung-to-head ratio can be a useful predictor of pulmonary hypoplasia Treatment of infants with pulmonary hypoplasia is supportive Outcome depends on the severity of the hypoplasia and presence of associated lethal anomalies, such as renal agenesis or achondrogenesis The lungs of infants with severe pulmonary hypoplasia may be extremely difficult to ventilate, and pneumothoraces are common because of the need for high distending pressures HFV may be an effective means of ventilating these infants’ lungs, using a combination of high ventilatory rates with extremely low tidal volumes Survival depends on etiology or associated conditions Congenital Diaphragmatic Hernia Congenital diaphragmatic hernia (CDH) occurs in approximately in 2500 to 3000 live births and is the most common cause of pulmonary hypoplasia in the neonate.71,72 At least 750 babies die of CDH in the United States annually, excluding a 15% prenatal termination rate CDH can be associated with other anomalies as part of chromosomal defects, single-gene defects (Denys-Drash syndrome, spondylocostal dysostosis, or neonatal Marfan syndrome), or multiple gene disorders Most cases of CDH are nonsyndromic Failure of the pleuroperitoneal canal to close at to weeks’ gestation results in a diaphragmatic defect that allows GI structures to enter the thoracic cavity as the intestines return from outside the fetus into the abdominal cavity The resulting mass effect in the chest impairs ipsilateral lung growth, characterized by a quantitative reduction in airways and their associated preacinar arteries The defect occurs on the left side in 80% to 85% of cases, because closure of the right pleuroperitoneal membrane normally precedes the left during development Because herniation often occurs before the tenth week of gestation when normal gut rotation occurs, malrotation is common Nongastrointestinal anomalies are found in approximately 25% of cases; the most common involve the cardiovascular system The clinical presentation of CDH depends on the degree of pulmonary hypoplasia present In addition, the abdomen is often scaphoid because of a paucity of abdominal contents As the infant cries and swallows air, the degree of lung compression may worsen, and an infant who appears healthy at delivery may undergo respiratory decompensation within minutes The chest radiograph will show a cystic lesion in the lower lung field, often extending upward along the lateral chest wall Initially, when the intestines remain fluid filled, the radiograph may be similar to that seen with pulmonary sequestrations or fluid-filled cysts As the infant swallows more air, the radiographic findings may be confused with congenital emphysema or even pneumothorax Small or right-sided defects may not present for weeks or even months Indeed, cases have occasionally been incidentally diagnosed during childhood when chest radiographs are obtained for other reasons With the widespread use of antenatal sonography, most cases of CDH are diagnosed before birth, facilitating planned neonatal stabilization In cases in which sonographic findings are equivocal, prenatal magnetic resonance imaging may be particularly useful Initial management focuses on stabilization, including immediate endotracheal intubation and GI decompression Ventilation by bag and mask is avoided to prevent introducing more gas into the GI tract As with pulmonary hypoplasia, the clinical course may be complicated Persistent pulmonary hypertension accompanying CDH may require nitric oxide inhalation therapy or ECMO.73,74 The contralateral nonhypoplastic lung in experimental CDH is functionally immature, implying potential benefit for surfactant therapy However, this maneuver has not been effective in a review of a large national CDH registry.75–77 CHAPTER 51 Neonatal Pulmonary Disease Attempts at intrauterine intervention, either to close the defect or to encourage lung growth through temporary obstruction of fetal lung liquid egress at the trachea, have been disappointing Fetal surgery for CDH has been associated with an unacceptably high incidence of complications, including recurrence of the defect, preterm delivery, and miscarriage.78–80 Fetoscopic tracheal occlusion by clips or removable balloons81 has also been attempted Although early postnatal corrective surgery was advocated in the past, there has been a more recent shift toward delayed repair, in large measure because respiratory function often worsened in the immediate postoperative period Consequently, early aggressive cardiorespiratory stabilization followed by delayed surgical plication is the recommended approach and is associated with improved outcome Surviving children with CDH may have neurodevelopmental disability, hearing loss, feeding difficulties, gastroesophageal reflux, lung disease, scoliosis, and recurrence after repair.82 In patients who required ECMO, 35% had brain abnormalities assessed by computed tomography (CT), and 35% to 45% needed a hearing aid.83–85 Perhaps the most successful advance since the 1990s has been improvement in postnatal treatment to preserve and protect lung parenchyma using gentler ventilatory strategies Congenital Pulmonary Airway Malformation Congenital pulmonary airway malformation (CPAM), previously known as congenital cystic adenomatoid malformation (CCAM), is a relatively infrequent lesion, estimated to occur in in 10,000 pregnancies.86,87 CPAM is a discrete nonfunctioning, intrapulmonary mass characterized by overgrowth of terminal respiratory bronchioles that form cysts ranging from less than mm to more than 10 cm These cysts suppress alveolar growth and can communicate with the tracheobronchial tree, evidenced by air trapping seen after postnatal resuscitation Cysts may also communicate with each other Histologically, the lesions are notable for a preponderance of elastic tissue and for an absence of cartilage The cysts are usually multiple and, in more than 95% of cases, the cystic malformations lie within a single lobe No single lobar predilection exists A contributory gene influencing CPAM development is HOXB588; its expression is maintained at a level typical of early lung development Other growth and maturational factors— including FGF7, KGF, and FGF10—have been implicated CPAMs are often divided into three types, which vary in anatomic and clinical characteristics according to the Stocker classification scheme.89 A revised classification has added two new types, type and type Type is bronchial dysplasia; type is the peripheral form of CPAM.90,91 Type CPAM, which accounts for about half of cases, occurs as a few large (.2 cm) cysts, usually one to four in number, or as a single large cyst surrounded by much smaller satellite cysts Type CPAM, which accounts for about 40% to 45% of cases, consists of multiple small (,2 cm), evenly spaced cysts scattered throughout the affected area Compared with type CPAM, type cysts are associated with a much higher incidence (about 25%) of anomalies in other organs, particularly in the genitourinary tract (e.g., renal dysgenesis) Type CPAM, which accounts for fewer than 10% of cases, occurs as large collections of tiny cysts The affected area can be large, and this type often leads to early cardiovascular compromise, resulting in fetal hydrops or immediate postnatal complications In the alveolo-acinar type of CPAM, small cysts are formed later in development In the bronchial epithelial type, larger cysts are formed early in the pseudoglandular phase of development 575 Depending on the type, CPAM presents during the neonatal period in 50% to 85% of infants, but presentation may be delayed for up to several years Cases are occasionally discovered incidentally Lesions may be detected prenatally during routine sonography The most common presentation of CPAM is respiratory distress that results from obstruction, although infection of the cyst leading to recurrent lobar pneumonias can also occur The elastic walls of the cyst allow easy expansion on inspiration, but the lack of cartilaginous support results in premature closure during exhalation and a ball-valve type of respiratory compromise Chest radiograph findings are variable and depend on the type of CPAM In the neonate, a solid space-occupying mass will appear, becoming air filled over the next several hours or days In types and 2, multiple air-filled cysts may become evident This appearance may be confused with diaphragmatic hernia Placement of a nasogastric tube to determine the location of the stomach and intestines as well as the absence of a scaphoid abdomen helps distinguish between the two entities The multiple small cysts of type CPAM cannot be delineated on a chest radiograph In this case, a CT scan of the chest can be helpful Treatment of symptomatic infants may require noninvasive or positive pressure ventilation Definitive treatment is surgical removal of the affected lobe, which can often be performed thoracoscopically Even if an infant is asymptomatic, surgical resection is recommended by to months of age because of the high risk of expansion or infection if the cysts are left untreated Prognosis depends on the type and extent of the CPAM The large type lesions are more likely to cause immediate respiratory distress and have higher mortality, especially if associated with pulmonary hypoplasia or fetal hydrops The prognosis in type CPAM depends on the presence and nature of associated anomalies.92,93 In addition, malignant transformation of CPAM (mucinous adenocarcinoma) has been reported.94,95 Most cases of CPAM, however, have a good prognosis A CPAM volume ratio may be measured prenatally by sonography An index of length width height 0.52 that exceeds 1.6 at initial diagnosis predicts an increased risk for fetal hydrops.93 Maternal prenatal glucocorticoid treatment increases survival rates and favors the resolution of hydrops in some cases Bronchogenic Cysts Bronchogenic cysts are rare96 and occur as a result of anomalous budding of the ventral or tracheal diverticulum of the foregut during the sixth week of gestation, with subsequent separation from the normally developing bronchi by the sixteenth week of gestation If separation occurs early (,12 weeks), the bronchogenic cyst tends to be located in the mediastinum (the most common type) If separation occurs later, it is more likely to be located in the peripheral pulmonary parenchyma The cyst walls are cartilaginous and receive either systemic or pulmonary blood supply, depending on location.97 Bronchogenic cysts are more common in male infants, usually singular, more commonly right sided, and generally smaller than 10 cm in diameter These lesions generally not communicate with the airway and remain fluid filled, which differentiates them from pulmonary parenchymal cysts Bronchogenic cysts generally not present in the neonatal period unless they are large, expand rapidly, or are located near major airways In these instances, infants may show moderate to severe respiratory distress More commonly, the young child will have recurring episodes of wheezing or infection Treatment may require ventilatory support for infants with respiratory distress ... and initiation of positive pressure ventilation within the first minute of life in nonbreathing or ineffectively breathing newborns, although this may require further clarification.39 Supplemental... feedback Although a fundamental feature of this network is that CHAPTER 51 Neonatal Pulmonary Disease it enables breathing to occur automatically, this systematic central rhythmicity may fail... associated with alterations in the pulmonary vasculature, including remodeling and thickening of the vessel muscle walls This process results in pulmonary vascular hyperreactivity, vasoconstriction,