A 2 hour old, 38 week gestation, 3 kg male infant was born to a 25 year old G1P1 A+, VDRL negative, Hepatitis B negative, GBS unscreened, Rubella immune, woman who had an uncomplicated pregnancy, labor and delivery. Apgar scores were 9/9. He was sent to the newborn nursery. He breast fed 1 hour ago without concerns. He now presents with respiratory distress.
Exam: VS T 37, HR 160, RR 80, BP 60/35 (mean 45), oxygen saturation 95% in 2 L/min oxygen via mask. Wt 3kg (50%), Lt 48cm (50%), HC 33.5 cm (50%). He is a term male with obvious respiratory distress and tachypnea. Skin is pale and pink without petechiae, ecchymoses, or lesions. His head is normocephalic with molding. His anterior fontanel is flat. His face is symmetrical with normal palpebral fissures, normal red reflexes, patent nares, normal ears, no clefts, and no neck masses. His chest is symmetric with equal and clear breath sounds. Mild to moderate chest retractions are present. Heart is regular with a normal S1, split S2, and no murmurs. His pulses are normal. His abdomen is soft and round with normal bowel sounds, no masses and no organomegaly. He has normal male genitalia with descended testes. His hips and anus are normal. He has mild hypotonia.
Laboratory results: CBC: WBC 15,000, 8% bands, 50% segs, 40% lymphs, 2% monos, Hct 55%, Plt 250,000. No toxic granulations or vacuoles of the neutrophils are noted. ABG: pH 7.35, PCO2 55 torr, PO2 70 torr, BE -7 in a 30% oxygen hood. CXR: 10 ribs of inflation, streaky linear perihilar densities, and small scattered patchy densities bilaterally.
Over the next several hours, the infant develops progressively more distress and a greater oxygen requirement. He is sent to the newborn special care nursery with worsening tachypnea (RR 90), more retractions and grunting. He is now in 50% O2 by hood.
What is your differential diagnoses? How would you manage this infant?
This chapter will cover the common problems which cause respiratory distress in the newborn within the first week of life. Based on the clinical presentation, onset and gestational age, the most likely diagnosis can be determined.
Respiratory distress is one of the most common presenting problems of newborns. The constellation of signs and symptoms can be the result of pulmonary, cardiac, metabolic, infectious, renal, gastroenterological and neurologic pathologic processes. Newborns with disorders involving any one of these organ systems may present with varying degrees of tachypnea, retractions, grunting, cyanosis, lethargy and tachycardia. Given the similar presentations, the circumstances of the newborn's birth provide important clues to the diagnosis.
Transient tachypnea of the newborn (TTN) is the most common respiratory disorder of the newborn. These infants are usually full term or slightly preterm. They are not at risk for other illnesses. Some infants are delivered by cesarean section; some without labor. The most significant discriminatory findings are the onset of the illness and the degree of distress exhibited by the infant. Typically, the infant becomes tachypneic immediately after birth and has mild respiratory distress. They are neurologically normal. If followed closely, infants remain stable for several hours and/or begin to improve. The chest radiographs reveal hyperinflation with clear lung parenchyma except for perihilar linear densities and fluid in the fissures. There should be no areas of consolidation . The pathophysiological mechanism is the delayed resorption of fetal lung fluid which eventually clears over the next several hours to days. A worsening clinical picture should suggest another diagnosis. Treatment is generally close observation and symptomatic care. Low flow supplemental oxygen may be necessary for several hours.
Meconium in the amniotic fluid occurs in approximately 20% of pregnancies. As a consequence, meconium aspiration is considered to be a relatively common event. Other substances such as blood or amniotic fluid can also be aspirated. Infants with this disorder typically have symptoms similar to infants with TTN, but the presentation may suggest a more severe condition. In addition, while many infants have the onset of symptoms at birth, some infants have an asymptomatic period of several hours before respiratory distress becomes apparent. Infants with aspiration syndromes may require more oxygen, and have greater degrees of tachypnea, retractions and lethargy. The arterial blood gases may reveal more acidosis, hypercapnia and hypoxemia than in infants with TTN. The chest radiographs vary between that of TTN with hyperinflation and perihilar infiltrates to significant heterogeneous lung disease with hyperinflated and hypoinflated areas, patchy and linear infiltrates and atelectasis.
The pathophysiologic mechanism is the obstruction of large and small airways with the aspirated material (meconium, blood, amniotic fluid contents). Pulmonary hypertension may be develop when meconium aspiration occurs in conjunction with varying degrees of in utero asphyxia. Pulmonary hypertension, which often results from hypertrophic pulmonary vascular muscular tissue, is a severe condition characterized by cyanosis from right to left shunting across the atrial septum and patent ductus arteriosus. As the disease process progresses, the symptoms and severity of hypoxemia increase over the subsequent hours. While TTN is in the differential diagnoses initially, this progression should alert the clinician to another diagnosis such as an aspiration syndrome, pulmonary hypertension or infection. Treatment may include supplemental oxygen, mechanical ventilation and specific treatment for pulmonary hypertension, which includes high supplemental oxygen, high frequency mechanical ventilation, inhaled nitric oxide therapy and in the most severe cases, extracorporeal membrane oxygenation therapy (ECMO).
The duration of distress with mild to moderate aspiration syndromes is from several hours to days. Aspiration can occur in utero or during the intrapartum period as well as during the early postpartum period. Since meconium aspiration is the most common problem, much effort has been made over the last 30 years to prevent this disease by reducing intrapartum and postpartum aspiration. Thorough suctioning of the oropharynx with a large bore catheter upon the delivery of the head is typically performed by the obstetrician. The pediatrician, needs to assess the quality of the meconium (thin, moderate or thick) and the state of the newborn before determining what is needed after birth. A large randomized trial has confirmed that aggressive intubation is not necessary for most infants with meconium in the amniotic fluid. The recommendations provided by the NRP (Neonatal Resuscitation Program) are to suction the oropharynx of all infants after the delivery of the head and to intubate and suction the trachea of any infant with meconium in the amniotic fluid, if the infant is depressed (weak. respiratory effort, hypotonia and/or bradycardia).
The sudden onset of significant respiratory distress should raise the possibility of an air leak syndrome. The most common air leak syndromes are pneumomediastinum, pneumothorax and pneumopericardium. In addition to respiratory distress, a severe air leak condition may cause hypotension (due to decreases in cardiac output), muffled heart tones, abdominal distention, asymmetric chest shape and deviation of the cardiac sounds. Chest radiographs are diagnostic with free air in the hemithorax and a visible edge of the collapsed lung. If under tension (i.e., a tension pneumothorax), clinical deterioration will be rapid, the mediastinum will be deviated to the opposite (contralateral) side and the ipsilateral diaphragm will be depressed. The elevation of the thymus with a sail or bat wing sign suggests a pneumomediastinum. The heart is outlined with a halo of air in a pneumopericardium. Hypotension and bradycardia occur rapidly in a tension pneumothorax or pneumopericardium (cardiac dysfunction is due to reduced venous return due to compression of the heart and mediastinal vascular structures). The air leak syndrome known as pulmonary interstitial emphysema (PIE) is usually observed as a consequence of mechanical ventilation in an infant with severe respiratory distress syndrome.
Treatment of significant air leak syndromes requires immediate air evacuation (thoracentesis or pericardiocentesis) with a needle or small catheter, followed by chest or pericardial tube insertion. Pneumomediastinum does not require drainage. In cases other than a bronchopleural fistula, the air leak will usually seal within a few days.
Respiratory distress syndrome (RDS) is the most common disorder of the premature infant. Most infants are less than 34 weeks gestation and the incidence and severity increase with decreasing gestation age. These premature infants have progressively more severe respiratory distress after birth. The classic findings of cyanosis, grunting, nasal flaring, intercostal and subcostal retractions and tachypnea are present. The chest radiograph reveals decreased lung inflation with diffuse symmetrical reticulogranular (ground glass appearance) lung fields and air bronchograms. Oxygen requirements progressively increase over the first few hours after birth. The presence of apnea suggests severe disease accompanied by refractory hypoxemia and acidosis.
While the lung's structural immaturity contributes to the pulmonary dysfunction, the major reason for this disorder is surfactant deficiency. Without surfactant, the surface tension of the alveolar sacs is high, leading to an increased tendency of the alveoli to collapse. Laplace's law describes the behavior of the alveoli without surfactant. This relationship states that as the radius of the air filled alveolus decreases, the pressure within the alveolus increases. This increased pressure requires an equivalent external opposing pressure to keep the alveolus inflated. Without the opposing pressure, the gas under this pressure is forced out of the alveolus. If the alveolus is connected to an adjacent alveolus with a larger radius, air will preferentially inflate the larger alveolus and ultimately collapse the smaller alveolus. This leads to the network of air-filled alveoli juxtaposed to atelectatic alveoli and creates the reticulogranular pattern (ground glass appearance) of the lung. The air bronchograms are created by atelectatic alveoli outlining the adjacent rigidly distended airways. Air filled right and left mainstem bronchi are not visible if they are superimposed over air filled lungs, but when they are superimposed over partially collapsed, fluid filled lungs (as in RDS), the air filled bronchi are visible as air bronchograms. Grunting is the infant's attempt to maintain the pressures and gas volume within the lung by causing expiratory braking using the vocal cords (the glottis is partially closed during exhalation to maintain alveolar distending pressure during exhalation). Surfactant reverses this process. The phospholipids and surfactant related proteins, contained in surfactant, spread along the air liquid interface to decrease alveolar surface tension. Therefore the pressure required to keep the alveoli inflated is lower. Furthermore, the surfactant molecules contribute to the larger alveoli developing a higher surface tension during inspiration and a lower surface tension (as the alveoli deflate) during expiration when the surfactant molecules become more compact along the air liquid interface.
The treatment of RDS generally includes positive pressure ventilation and artificial surfactant replacement. The first purely synthetic surfactant is no longer available. Today, several types of animal based surfactants have been approved for clinical use. After endotracheal intubation, surfactant suspension is administered through the endotracheal (ET) tube and the infant is supported, until extubation is possible, with positive pressure ventilation and continuous positive airway pressure (CPAP) therapy as needed. High frequency ventilation has been shown to improve the short term management of these infants.
Moderately premature infants (29 to 34 weeks gestation) are usually extubated within several days after treatment. However, extremely premature infants (23 to 28 weeks gestation) may continue to require positive pressure respiratory support for several weeks. They are at high risk for bronchopulmonary dysplasia or chronic respiratory insufficiency of the premature. Bronchopulmonary dysplasia is the chronic lung disease consequence of early acute lung disease and/or lung immaturity of the premature infant. Chronic respiratory insufficiency of the premature develops despite early improvement after surfactant therapy and mechanical ventilation.
Infectious pneumonia in newborns is relatively rare. However, premature infants have at least a 10 fold increased incidence of infections when compared to term infants. Mothers with intrapartum fever and prolonged rupture of membranes (>18-24 hours) have a greater risk of transmitting infections to their infants. This risk can be reduced by administering intrapartum antibiotics for mothers with high risk pregnancies or women who are group B Streptococcus (GBS) carriers. However, the use of ampicillin for the GBS infections has increased the incidence of ampicillin resistant coliform infections. The most common bacterial organisms which infect neonates are the GBS, coliforms (E. coli being the most common member of this group), and Listeria monocytogenes. Infected infants present either immediately after birth with respiratory distress or they may present after several hours of an asymptomatic period. The degree of respiratory distress initially may mimic any respiratory disorder. Infants may have fevers or become hypothermic. The symptoms progressively increase in severity and if not treated may lead to shock, DIC and death. Due to the serious consequences associated with delays in treatment for infections, many infants with non-infectious conditions are evaluated and empirically treated with antibiotics for this possibility. The chest radiographs may resemble RDS (with reticulogranular infiltrates and air bronchograms), TTN or aspiration syndromes (with linear or patchy densities). It is unusual to have lobar consolidation from infection in the newborn. A term infant with RDS should be considered to have pneumonia until proven otherwise. The CBC may reveal either a leukocytosis or leukopenia. A left shift with greater than 20% band forms of the total neutrophils is suggestive of infection as are neutrophilic vacuoles and toxic granulation. Platelet counts may be normal or decreased. In severe cases, a coagulopathy with elevated PT and PTT and depressed fibrinogen levels may be present. The gold standard still remains the blood culture or culture of lung and tracheal secretions. Treatment with an aminoglycoside and penicillin is standard to treat for the common organisms. Supportive care may include mechanical ventilation, supplemental oxygen, inotropic agents for hypotension and nitric oxide for infection associated pulmonary hypertension. The mortality from infections has decreased from 50% to 20% with more aggressive intensive care.
Some congenital malformations of the cardiopulmonary system will be addressed here. The first is the infant with cyanotic heart disease. Most infants with transposition of the great arteries, tetralogy of Fallot and hypoplastic right and left heart syndromes, will present in the newborn period. Most infants with cyanotic heart disease typically have a paucity of respiratory distress symptoms except for cyanosis or duskiness. A murmur is usually present, but may be absent. Typically the chest radiograph reveals a normal sized heart or cardiomegaly with clear lung fields and decreased vascular markings (due to diminished pulmonary blood flow). When the infant develops respiratory symptoms, it is usually from severe hypoxemia or acidosis. The infant who is cyanotic with respiratory distress and does not respond to supplemental oxygen (i.e., their oxygen saturation does not improve significantly when given supplemental oxygen). Infants with both cyanosis and respiratory distress may have chest radiographs typical of pulmonary disease. The hyperoxy test (measuring the arterial pO2 while the infant is breathing 100% oxygen) is helpful in distinguishing cyanotic heart disease from severe respiratory disease. The echocardiogram is also diagnostic and will distinguish between cyanotic heart disease and persistent pulmonary hypertension.
Therapy for cyanotic heart disease consists of medical support until definitive surgical repair can take place. In many instances, patency of the ductus arteriosus is necessary to maintain mixing of pulmonary and systemic circulations. This is accomplished with an intravenous infusion of prostaglandin E1 infusions. Later, an artificial shunt is created from the aorta to the pulmonary arteries. Moderate oxygen supplementation to keep oxygen saturations approximately 80% or higher and mild acidosis to maintain a fetal type circulation is attempted to preserve pulmonary function. Multistaged open heart surgery may be necessary for most complex cyanotic heart diseases.
Structural abnormalities of the pulmonary system may also cause respiratory distress. Infants with congenital diaphragmatic hernia frequently present in the immediate newborn period with respiratory distress and refractory cyanosis. The abdomen is scaphoid since the intestines are in the thorax. Bowel sounds are heard over the chest if air enters the intestines from spontaneous breathing or mask valve ventilation. The chest radiograph reveals a bowel gas pattern typically in the left hemithorax with a mediastinal shift to the right. The heart compresses the right lung which may also be hypoinflated or hypoplastic. Surgery to remove the bowel from the thorax and close the diaphragmatic defect is necessary after the infant has been stabilized. High frequency ventilation and nitric oxide therapy are used to treat the bilateral hypoplastic lungs. The hypoplastic lungs develop excessive and abnormal musculature of the pulmonary vessels which lead to pulmonary hypertension. In the most severe cases, extracorporeal membrane oxygenation (ECMO) therapy is used to support the cardiopulmonary failure. However, despite aggressive treatment, approximately 50% of the infants with this condition do not survive. Lung volumes may reach normal values, but there is a persistence of decreased number of alveoli (emphysema). Please refer to the focused chapter on congenital diaphragmatic hernia.
In summary, the term infant with respiratory distress usually has transient tachypnea of the newborn. However, based on the time of onset and the progression and severity of the symptoms, other causes of respiratory distress must be entertained. Premature infants usually have RDS, but must be considered to be at risk for infection. In the case presentation at the beginning of this chapter, the later onset of respiratory distress which increases in severity with time, suggests either aspiration or an infectious process. The unremarkable CBC makes a pneumonia less likely and possibly supports an aspiration syndrome; however the CBC may change with time. Empiric antibiotic therapy is indicated. Management is supportive and supplemental oxygen should be continued. A repeat arterial blood gas is indicated and if the pCO2 is elevate, then consider mechanical ventilation. If the chest radiographs suggest significant atelectasis or a further increase in FiO2 is required, either nasal CPAP (continuous positive airway pressure) or mechanical ventilation with positive pressures may enhance oxygenation.
Simplified summary of some of the major newborn respiratory conditions:
. . . . Clinical factors: Prematurity
. . . . CXR: Ground glass appearance
. . . . Clinical factors: Short labor, C-section delivery
. . . . CXR: Fluid in the fissures, central/perihilar congestion
. . . . Clinical factors: Meconium in amniotic fluid
. . . . CXR: Infiltrates
. . . . Clinical factors: Prolonged rupture of membranes, maternal GBS, prematurity.
. . . . CXR: Infiltrates or hazy lungs (may be identical to RDS).
. . . . Clinical factors: Sudden deterioration, often while on positive pressure ventilation.
. . . . CXR: Collapsed lung, free air in the hemithorax.
Cyanotic congenital heart disease:
. . . . Clinical factors: Heart murmur, persistent hypoxia despite supplemental oxygen.
. . . . CXR: Hypoperfused lungs (lungs appear darker). CXR is often normal.
1. What is the most common cause of respiratory distress in newborns?
2. When is the onset of symptoms for transient tachypnea of the newborn and how might this help distinguish TTN from other disorders?
3. Aspiration syndromes can be caused by what types of materials?
4. The sudden onset of significant respiratory distress and hypotension should suggest what respiratory disorder?
5. Respiratory distress syndrome of the premature infant is caused by what deficiency? What is the radiographic manifestation of this deficiency?
6. What organisms commonly cause newborn pneumonia?
7. What disorder would you consider in a cyanotic infant without respiratory distress?
Newborn radiographs: Available online at: www.hawaii.edu/medicine/pediatrics/neoxray/neoxray.html
1. Hansen T, Corbet A. Pulmonary physiology of the newborn. In: Taeusch WH, Ballard RA (eds). Avery's Diseases of the Newborn, 7th edition. 1998, Philadelphia: WB Saunders Company, pp. 562-575.
2. Gomez M, Hansen T, Corbet A. Principles of Respiratory Monitoring and Therapy. In: Taeusch WH, Ballard RA (eds). Avery's Diseases of the Newborn, 7th edition. 1998, Philadelphia: WB Saunders Company, pp. 585-590.
3. Hansen T, Corbet A. Disorders of the transition. In: Taeusch WH, Ballard RA (eds). Avery's Diseases of the Newborn, 7th edition. 1998, Philadelphia: WB Saunders Company, pp. 602-630.
4. Hansen T, Corbet A. Air block syndromes. In: Taeusch WH, Ballard RA (eds). Avery's Diseases of the Newborn, 7th edition. 1998, Philadelphia: WB Saunders Company, pp. 631-633.
5. Hansen T, Corbet A. Neonatal pneumonias. In: Taeusch WH, Ballard RA, editors. Avery's Diseases of the Newborn. 7th ed. Philadelphia: WB Saunders Company; 1998. p. 648-57.
6. Hansen T, Corbet A, Ballard RA. Disorders of the chest wall and diaphragm. In: Taeusch WH, Ballard RA (eds). Avery's Diseases of the Newborn, 7th edition. 1998, Philadelphia: WB Saunders Company, pp. 685- 692.
7. Long WA, Frantz EG, Henry W, et al. Evaluation of newborns with possible cardiac problems. In: Taeusch WH, Ballard RA (eds). Avery's Diseases of the Newborn, 7th edition. 1998, Philadelphia: WB Saunders Company, pp. 711-734.
8. Soll BJ, Kliegman RM. Respiratory tract disorders. In: Behrman RE, Kliegman RM, Jenson HB (eds). Nelson Textbook of Pediatrics, 16th edition. 2000, Philadelphia: WB Saunders Company, pp. 496-510.
9. Hartman GE. Diaphragmatic hernia. In: Behrman RE, Kliegman RM, Jenson HB (eds). Nelson Textbook of Pediatrics, 16th edition. 2000, Philadelphia: WB Saunders Company, pp. 1231-1233.
10. Initial steps in resuscitation. In: Kattwinkel J (ed). Neonatal Resuscitation Textbook, 4th edition. 2000, Elk Grove Village: American Academy of Pediatrics/American Heart Association, pp. 2.3- 2.9.
11. Possmayer F. Physicochemical aspects of pulmonary surfactant. In: Polin RA, Fox WW (eds). Fetal and Neonatal Physiology, 2nd edition. 1998, Philadelphia: WB Saunders Company, pp.1263-1265.
Answers to questions
2. TTN symptoms occur soon after birth. Later onset of symptoms should suggest other disorders.
3. Meconium, blood, amniotic fluid.
4. Air leaks such as a tension pneumothorax.
5. Surfactant deficiency, which causes some alveoli to collapse next to alveoli which are emphysematous. Some atelectatic alveoli are adjacent to rigid bronchi. These conditions lead to a reticulogranular infiltrate (ground glass) and air bronchogram pattern on the chest radiograph.
6. Group B Streptococcus, gram negative rod organisms (usually E. coli) and Listeria monocytogenes.
7. Cyanotic congenital heart disease.