Respiratory Distress in the Newborn

Respiratory distress is common, affecting up to 7% of all term newborns, (1) and is increasingly common in even modest prematurity. Preventive and therapeutic measures for some of the most common underlying causes are well studied and when implemented can reduce the burden of disease. (2)(3)(4)(5)(6)(7)(8) Failure to readily recognize symptoms and treat the underlying cause of respiratory distress in the newborn can lead to short- and long-term complications, including chronic lung disease, respiratory failure, and even death.After completing this article, the reader should be able to:Respiratory distress is one of the most common reasons an infant is admitted to the neonatal intensive care unit. (1) Fifteen percent of term infants and 29% of late preterm infants admitted to the neonatal intensive care unit develop significant respiratory morbidity; this is even higher for infants born before 34 weeks’ gestation. (2) Certain risk factors increase the likelihood of neonatal respiratory disease. These factors include prematurity, meconium-stained amniotic fluid (MSAF), caesarian section delivery, gestational diabetes, maternal chorioamnionitis, or prenatal ultrasonographic findings, such as oligohydramnios or structural lung abnormalities. (2)(9)(10)(11)(12)(13)(14) However, predicting which infants will become symptomatic is not always possible before birth. Regardless of the cause, if not recognized and managed quickly, respiratory distress can escalate to respiratory failure and cardiopulmonary arrest. Therefore, it is imperative that any health care practitioner caring for newborn infants can readily recognize the signs and symptoms of respiratory distress, differentiate various causes, and initiate management strategies to prevent significant complications or death.Respiratory distress in the newborn is recognized as one or more signs of increased work of breathing, such as tachypnea, nasal flaring, chest retractions, or grunting. (1)(15) Normally, the newborn’s respiratory rate is 30 to 60 breaths per minute. Tachypnea is defined as a respiratory rate greater than 60 breaths per minute. (15) Tachypnea is a compensatory mechanism for hypercarbia, hypoxemia, or acidosis (both metabolic and respiratory), (16) making it a common but nonspecific finding in a large variety of respiratory, cardiovascular, metabolic, or systemic diseases. Pulmonary disease may incite tachypnea, especially in neonates. The natural elastic property of the lungs is to deflate. When balanced by the outward recoil of the chest wall, functional residual capacity (FRC) occurs at the end of expiration to prevent alveoli from collapsing. The newborn chest wall, composed primarily of cartilage, is more pliable, predisposing neonatal lungs to pulmonary atelectasis and decreased FRC. (16)(17)(18) Pulmonary compliance refers to a given change in volume (ΔVolume) for every given change in pressure (ΔPressure), essentially the ability of the alveoli to fill with air under a set pressure. If lung compliance is decreased, such as with transient tachypnea of the newborn (TTN), respiratory distress syndrome (RDS), pneumonia, or pulmonary edema, there is a decrease in tidal volume. To achieve sufficient minute ventilation, the respiratory rate must increase. Hypoxemia further increases tachypnea. (16)(18) Therefore, affected newborns present with marked tachypnea. Because tachypnea is a nonspecific symptom, additional clinical findings aid in narrowing the cause to a respiratory disorder.Increased work of breathing results from mismatched pulmonary mechanics from increased airway resistance (ΔPressure/Volumetric Flow), decreased lung compliance (ΔVolume/ ΔPressure), or both. Airway resistance increases when there is obstruction of air flow. The critical importance of airway radius is indicated in the equation R = V(8lη/πr(4)), where R is resistance, V is flow, l is length, η is viscosity, and r is radius. (19) If the airway radius is halved, resistance increases 16-fold. Nasal flaring is a compensatory symptom that increases upper airway diameter and reduces resistance and work of breathing. Retractions, evident by the use of accessory muscles in the neck, rib cage, sternum, or abdomen, occur when lung compliance is poor or airway resistance is high. Noisy breathing may indicate increased airway resistance, and the type of noise auscultated may help localize airway obstruction (Table 1). Stertor is a sonorous snoring sound heard over extrathoracic airways that indicates nasopharyngeal obstruction. Stridor is a high-pitched, monophonic breath sound that indicates obstruction at the larynx, glottis, or subglottic area. Wheezing may also be high pitched but is typically polyphonic, is heard on expiration, and indicates tracheobronchial obstruction. Grunting is an expiratory sound caused by sudden closure of the glottis during expiration in an attempt to maintain FRC and prevent alveolar atelectasis. Because lung compliance is worse at very low or very high FRC, achieving and maintaining physiologic FRC is essential in the management of respiratory disorders with poor compliance, such as RDS or TTN. On the other end of the spectrum, meconium aspiration syndrome (MAS) is an example of lower airway obstruction with air trapping. These newborns often have high lung volumes, which adversely affects their lung compliance. Regardless of the cause, it is vital to recognize symptoms and act quickly. If the newborn cannot sustain the extra work of breathing to meet its respiratory needs, respiratory failure follows. This failure may manifest as impaired oxygenation (cyanosis) or ventilation (respiratory acidosis). Without prompt intervention, respiratory arrest is imminent.The causes of respiratory distress in a newborn are diverse and multisystemic. Pulmonary causes may be related to alterations during normal lung development or transition to extrauterine life. Normal lung development occurs in 5 phases (20) (Table 2). Respiratory disease may result from developmental abnormalities that occur before or after birth. Early developmental malformations include tracheoesophageal fistula, bronchopulmonary sequestration (abnormal mass of pulmonary tissue not connected to the tracheobronchial tree), and bronchogenic cysts (abnormal branching of the tracheobronchial tree). Later in gestation, parenchymal lung malformations, including congenital cystic adenomatoid malformation or pulmonary hypoplasia from congenital diaphragmatic hernia or severe oligohydramnios, may develop. More common respiratory diseases, such as TTN, RDS, neonatal pneumonia, MAS, and persistent pulmonary hypertension of the newborn (PPHN), result from complications during the prenatal to postnatal transition period. Although mature alveoli are present at 36 weeks’ gestation, a great deal of alveolar septation and microvascular maturation occur postnatally. The lungs are not fully developed until ages 2 to 5 years. (20)(21) Therefore, developmental lung disease can also occur after birth. Bronchopulmonary dysplasia (BPD), for example, is a significant lung disease that complicates prematurity due to arrested alveolarization in developing lungs exposed to mechanical ventilation, oxygen, and other inflammatory mediators before normal development is complete. As defined by an ongoing oxygen requirement at 36 weeks’ adjusted gestational age, BPD affects up to 32% of premature infants and 50% of very low-birth-weight infants. (22)The underlying cause of respiratory distress in a newborn varies and does not always lie within the lungs (15) (Table 3). Thus, after initial resuscitation and stabilization, it is important to use a detailed history, physical examination, and radiographic and laboratory findings to determine a more specific diagnosis and appropriately tailor management. A thorough history may guide in identifying risk factors associated with common causes of neonatal respiratory distress (Table 4). A detailed physical examination should focus beyond the lungs to identify nonpulmonary causes, such as airway obstruction, abnormalities of the chest wall, cardiovascular disease, or neuromuscular disease, that may initially present as respiratory distress in a newborn. Radiographic findings can identify diaphragmatic paralysis, congenital pulmonary malformations, and intrathoracic space–occupying lesions, such as pneumothorax, mediastinal mass, and congenital diaphragmatic hernia, that can compromise lung expansion. Significant tachypnea without increased work of breathing should prompt additional laboratory investigation to identify metabolic acidosis or sepsis. Hypoglycemia, hypomagnesemia, and hematologic abnormalities may result in a depressed ventilatory drive or impaired oxygen transport to the peripheral tissues, so laboratory evaluation should also be considered with these clinical findings. Hypermagnesemia may contribute to respiratory distress and affect a newborn’s capacity to respond to resuscitation due to hypotonia and a depressed respiratory drive or even apnea.Cardiovascular disease may be difficult to distinguish from pulmonary causes of respiratory distress (Table 5). Most congenital heart defects present with cyanosis, tachypnea, or respiratory distress from cardiac failure. Timing may be an important clue to differentiation because very few congenital heart defects present immediately after birth; more often they present several hours to days after delivery as the ductus arteriosus closes. (2) Table 5 aids in this differentiation.Pulmonary hypertension should be considered in any infant with respiratory distress and cyanosis. This condition results when there is a failure to transition from in utero to postnatal pulmonary circulation after delivery. Pulmonary vascular resistance remains high, resulting in cyanosis from impaired pulmonary blood flow and right-to-left shunting of blood across the foramen ovale and ductus arteriosus. Shunting further contributes to systemic hypoxemia and metabolic acidemia—both of which contribute to ongoing increased pulmonary vascular resistance. PPHN may be primary or secondary to respiratory disease, particularly congenital diaphragmatic hernia, MAS, or RDS. When PPHN occurs without concurrent pulmonary disease, differentiating from cyanotic heart disease is difficult. The response to ventilation with 100% oxygen (hyperoxia test) can help distinguish the 2 conditions. In some neonates with PPHN, the Pao2 will increase to above 100 mm Hg, whereas it will not increase above 45 mm Hg in infants with cyanotic heart defects that have circulatory mixing. (5)(23)Four case scenarios are highlighted to help in identifying the most common causes of respiratory distress in the newborn followed by discussion about the pathophysiology, risk factors, prevention, and management strategies for each disorder.A 3.2-kg female infant is delivered by caesarean section at 38 weeks’ gestational age without a trial of labor. Her Apgar scores are 9 and 9 at 1 and 5 minutes, respectively. She develops tachypnea and subcostal retractions with nasal flaring at 1 hour of life. Temperature is 97.9°F (36.6°C), pulse is 165 beats per minute, and respiratory rate is 74 breaths per minute. Aside from increased work of breathing, her physical examination findings are normal. The chest radiograph is shown in Figure 1. She requires supplemental oxygen via nasal cannula with a fraction of inspired oxygen (Fio2) of 0.3 for 36 hours. She then weans to room air. Her respiratory rate is 35 breaths per minute, and she has no increased work of breathing.TTN, also known as retained fetal lung fluid syndrome, presents with early respiratory distress in term and late-preterm infants. TTN is a frequent cause of respiratory distress in newborns and is caused by impaired fetal lung fluid clearance. Normally in utero, the fetal airspaces and air sacs are fluid filled. For effective gas exchange to occur after birth, this fluid must be cleared from the alveolar airspaces. Late in gestation and before birth, the chloride and fluid-secreting channels in the lung epithelium are reversed so that fluid absorption predominates and fluid is removed from the lungs. This process is enhanced by labor, so that delivery before labor onset increases the risk of retained fetal lung fluid. (20) Factors that increase the clearance of lung fluid include antenatal corticosteroids, fetal thorax compression with uterine contractions, and a release of fetal adrenaline in labor, which enhances uptake of lung fluids. (24)Infants with TTN usually present with tachypnea and increased work of breathing, which persists for 24 to 72 hours. Chest radiographs reveal excess diffuse parenchymal infiltrates due to fluid in the interstitium, fluid in the interlobar fissure, and occasionally pleural effusions (Figure 1). Management is supportive. Infants may require supplemental oxygen, and frequently the distending forces of continuous positive airway pressure (CPAP) are necessary to assist in maintaining alveolar integrity and driving fluid into circulation. Blood gases often reveal a mild respiratory acidosis and hypoxemia. The course of TTN is self-limited and does not usually require mechanical ventilation.Preventive measures may include avoiding elective caesarean section before the onset of labor in infants younger than 39 weeks’ gestation. This is because the most common risk factors for TTN include delivery before 39 weeks’ gestation, (1)(2)(3)(9)(25)(26) precipitous delivery, fetal distress, maternal sedation, and maternal diabetes. Although it is well known that premature infants have a higher risk of respiratory problems, the consequences of early-term delivery (37–38 weeks’ gestation) are underrecognized. Early-term infants have an increased risk of requiring respiratory support, mechanical ventilation, and neonatal service; delivery by caesarean section in this population is common and further increases risk. (25) In addition, a single course of antenatal of at hours before an elective term caesarean delivery respiratory infants. On the of and a about elective delivery before onset of labor at than 39 weeks’ gestation and to be of the increased risk of respiratory in late preterm and early-term infant is born by delivery at 39 weeks’ gestational age after of for hours. Apgar scores are and at 1 and 5 minutes, respectively. requires an of in the delivery is and has are Temperature is pulse is beats per minute, and respiratory rate is breaths per minute. given and tachypnea and requires and ventilation for increased work of breathing, respiratory and oxygen requirement during the hours. The chest radiograph is shown in Figure in the newborn may be or in Infants may amniotic via at the of birth, or (20) is the most common of neonatal and is at birth. is the most common that affects term infants. occurs when the is to the The most common are and of the and the pulmonary and physiologic the newborn at higher risk of The respiratory and the decreased of pulmonary result in decreased clearance of from the respiratory also have and which is even more in the premature factors for include of maternal and prematurity. (1) Infants present with increased work of breathing and oxygen Chest often diffuse parenchymal infiltrates with air or effusions may also be In to infants and neonatal is of a blood and fluid and is for any symptomatic the newborn with or a of and an are the initial For infants have in a neonatal intensive care unit for more than such as and require Infants develop in the or at are to have caused by respiratory respiratory and and and and Infants with caused by present in the newborn of with a but no or may also be present to days after Chest diffuse and a blood with a of or without requires systemic and Regardless of the newborns with require care in to infants will require not supplemental oxygen but also and mechanical measures include and for cardiovascular PPHN is a common of neonatal the of of neonatal and its complications on maternal and of newborns at high risk after delivery. caring for newborns should be able to recognize infants and has must also which infants require additional and after birth. have by the for and and by the of and the of and for management of infants. Infants require additional include born to are or with a history of affected by or with an but delivered at than weeks’ gestation, with of hours or or with The for these is followed by to every at hours before may be for are at low risk for For should be and if is of should be is for with In to are in clinical and may be by but are not for of maternal and the of has decreased from per to 0.3 case per However, and to occur with as the Most of the term infants affected are born to without or with an but or and not during labor. are born to hours before delivery or for increase the burden of disease. it is imperative to appropriately any newborn with the risk factors after birth. to any infant develops signs or symptoms of requires a evaluation blood and fluid and If maternal is but the infant has no signs or symptoms of disease, a evaluation and blood with for at is not require a evaluation and for but is not necessary clinical infants should be for hours. to these will decrease the of neonatal and for early and that may prevent complications, such as PPHN or is delivered via delivery because of preterm labor at weeks’ gestation. Apgar scores are and at 1 and 5 minutes, respectively. The infant is cyanotic and requires immediately after delivery. has subcostal retractions, and nasal decreased air in the lung Temperature is pulse is beats per minute, and respiratory rate is breaths per minute. requires an of chest radiograph is shown in Figure also known as disease, is a common cause of respiratory disease in the premature RDS is also in infants have in RDS is caused by a of alveolar which increases in resulting in and low lung as diffuse infiltrates on radiograph (Figure 1). Pulmonary a in the of RDS and contributes to the development of air lung fluid is to in the decreased of channels in the lung and a in the 2 days after in premature infants. Infants typically on onset of by the after with RDS typically present within the several hours of often immediately after delivery. infants have marked respiratory distress with tachypnea, nasal flaring, and Grunting occurs when an infant to maintain an FRC in the of lungs by As the infant the expiratory this glottis, there is a and increased residual volume that the airway and also an expiratory Infants with RDS have cyanosis and require supplemental of RDS may respond to the distending of but more severe require and of into the lungs. there are no that if and when to of in the 2 hours of for all premature infants younger than 30 weeks’ gestation. with ventilation (CPAP) and and for infants require more than to oxygen to maintain an greater than mm In a management it is important to the of antenatal corticosteroids, the clinical radiographic findings, and the oxygen course of RDS is self-limited and typically by age to days in with the and as the infant to (20) of mechanical ventilation before this is and should with to lung Infants not with should be for the of a ductus arteriosus or other congenital heart disease. The infant initially with of and should also be for (20) On it is to initiate in the newborn with RDS because may present in the and findings on chest radiographs can be from premature will lower the of RDS. However, to prevent premature have with the rate of premature of all in To infants will clinical the use of maternal antenatal of reduce the of RDS, and in infants age to weeks’ gestation. female infant is delivered via caesarean section at weeks’ gestational age because of large for gestational age The amniotic fluid is with She is and cyanotic at with respiratory Apgar scores are 2 and at 1 and 5 minutes, respectively. Temperature is pulse is beats per minute, and respiratory rate is breaths per minute. examination findings are significant for marked increased work of breathing with nasal flaring, subcostal and retractions, a and in lung Her chest radiograph is shown in Figure occurs when the meconium before birth. Infants born are at risk for aspiration of meconium in utero or immediately after birth. infant is born and develops respiratory distress after delivery, which cannot be to cause, is as is composed of amniotic and is present in the as early as weeks’ gestation but is not present in the lower until 34 weeks’ is in infants younger than weeks’ gestation. In the or acidosis may result in a and of the resulting in meconium in may occur in utero or immediately after as the is to the newborn and as it The of meconium is to The causes airway and a with release of As meconium the obstruction which results in air and The chest radiograph initially with diffuse parenchymal In lungs become with of atelectasis and alveolar (Figure 1). is by the in resulting in so radiographs may of RDS with low lung Although air may occur with other respiratory of the pneumothorax, and PPHN are common in (Figure is at strategies to the oxygen is and and mechanical ventilation may also be considered in severe with is common and reduces the for oxygenation and the risk of Because results in a alveolar are not by pulmonary blood severe hypoxemia may result and further increases pulmonary vascular resistance. PPHN by and right-to-left shunting at the ductus arteriosus. is a pulmonary without systemic is often with ventilation in severe of to maintain oxygenation and ventilation and reduce the for of is because meconium is a for pulmonary compromise is common after As as 50% of affected infants are as airway disease during their of and persistent pulmonary is in as as years. of the significant associated with MAS, measures are and nasopharyngeal on the meconium-stained infant after delivery of the but before delivery of the and initially to be an effective However, a trial in that this does not prevent or decrease the for mechanical ventilation or of on the is no immediately after also a for all meconium-stained infants until a large trial that and infants born no and increased the rate of This finding has by a change in in of the depressed infant as defined by a low heart rate beats per poor and no respiratory and the breathing infant is not of all are Although the of has decreased during the to of these will develop infants weeks’ gestation) developed However, a that of labor at weeks’ gestation reduces the risk of and without the risk of caesarean Therefore, not to beyond weeks’ gestation. In addition, in fetal heart rate have for that may help prevent in utero aspiration of or of into the amniotic has as a to decrease the of Although is for the with oligohydramnios, does not indicate a risk of to severe or to readily recognize respiratory distress in the newborn and physiologic abnormalities associated with each of the various causes will guide management. Although the measures is early and of the common neonatal respiratory will decrease short- and long-term complications and related of infants.