++
Utilizing an ABC (Airway, Breathing, Circulation) algorithm of
evaluation permits a rapid and systematic consideration of the most
common causes of cyanosis in the newborn period (Table
49-2). It is important to recognize that cyanosis
is more difficult to recognize at lower hemoglobin values due to
the altered concentration of deoxygenated hemoglobin as shown in eTable 49.1.
+++
Airway: Upper
and Lower Airway Disease
++
Abnormalities of the airway will generally present shortly after
birth.4,5 Choanal atresia occurs in about 1 in
5000 infants, with unilateral disease being more common. Choanal atresia
should be suspected when an infant’s distress is more obvious
in a quiet state and improves during crying. It can be confirmed by
the inability to pass a suction catheter through the nares into
oropharynx, as well as by computer tomography scanning. Placement of
an oral airway should provide immediate improvement. Other associated
anomalies are very common; in particular, CHARGE sequence (coloboma, heart disease, atresia
of choana, retarded growth and development, genitourinary
anomalies, ear/hearing anomalies) should
be considered.
++
Micrognathia, retrognathia, or the Pierre Robin sequence generally
presents early in life and will be obvious on physical examination. The
airway obstruction from the posterior tongue is more pronounced
in supine position. When present, a cleft palate does not cause respiratory
distress unless feeding difficulties are severe. These infants may
require tracheostomy for several years until the mandible grows
enough to maintain the tongue in a more anterior position.
++
Laryngomalacia is a congenital abnormality of the larynx and
is the most common cause of inspiratory stridor in infants. While
it may be noted immediately after birth, it commonly presents at
several weeks of age. Airway symptoms typically worsen with crying,
feeding, and respiratory infections. Gastroesophageal reflux is
a common association. Subglottic stenosis may occur as a congenital malformation
or be acquired after prior airway manipulation. Infants present
with stridor, respiratory distress, or obstructive apnea.
++
Vocal cord paralysis may occur in association with birth or surgical
trauma and is another common cause of stridor in the newborn. It is
typically unilateral, causing a hoarse cry and minimal respiratory
symptoms. In contrast, bilateral vocal cord paralysis can cause
severe respiratory distress, and a tracheostomy may be required.
In these cases, central nervous system anomalies such as the Arnold-Chiari malformation
should be considered.
++
Other conditions may cause intrinsic or extrinsic compression
of the trachea. Tracheal stenosis is characterized by inspiratory
and expiratory stridor, respiratory distress, wheezing, and persistent
cough. Symptoms typically worsen after an upper airway
infection. The diagnosis is confirmed by direct bronchoscopic visualization.
Tracheal stenosis is often associated with complete tracheal rings which may
require extensive surgical repair in case of multiple rings or long-segment
stenosis. A number of conditions may produce extrinsic airway compression. Abnormal
development of the great vessels (eg, vascular ring) can compress
or deviate the trachea, causing airway obstruction. An anomalous
distal origin of the innominate artery from the aortic arch is the
most common cause, but other anomalies include double aortic arch
or an aberrant right subclavian artery. Specialized cardiac computerized
tomography or magnetic resonance imaging studies are helpful in
accurately defining the anatomy. Neck or mediastinal masses such
as teratomas and cystic hygromas represent large lesions that can
cause extrinsic compression of the trachea; these are typically associated
with visible neck masses. Subglottic hemangiomas should be considered
in infants who have skin hemangiomas. Because hemangiomas typically
increase in size over the first 6 to 12 months of life, symptoms
often emerge after an initially benign history. The trachea
can also be compressed by masses such as teratomas, cystic hygromas,
or hemangiomas.
+++
Breathing: Lung Disease
++
Respiratory distress syndrome (RDS; see also Chapter 54), also known as hyaline membrane disease, occurs almost
exclusively in premature infants. The cause of RDS is surfactant deficiency,
which results in decreased lung compliance and functional residual
capacity and increased dead space. Rates of RDS are related inversely
to the gestational age of the infant, but it affects about 40% of
infants with birth weights of 501 to 1500 g and about 20% with
birth weights of 1251 to 1500 g. Other factors that increase the
risk for RDS include maternal diabetes, male gender, and delivery by
cesarean section. While the incidence and severity of RDS decreases
in more mature infants, it is important to remember that a significant
percentage of late preterm infants (defined as 34 0/7 to
36 6/7 weeks’ gestation) will develop RDS.6 Infants
will present visible respiratory distress (tachypnea, grunting, nasal
flaring, subcostal and intercostal retractions) associated with
their cyanosis. A chest radiograph will show poor lung expansion
association with a homogenous “ground-glass” appearance
and air bronchograms (which are produced by air-filled bronchi superimposed on
collapsed alveoli).
++
Neonatal pneumonia (see Chapter 50) is most
commonly acquired at the time of birth and usually causes diffuse
rather than lobar infiltrates. The initial radiograph is frequently indistinguishable
from the ground-glass appearance of RDS, although pleural effusions are
more characteristic of pneumonia. Bacterial pneumonia is most common,
and frequent pathogens include group B β-hemolytic
streptococci (GBS) and gram-negative enteric bacilli (Escherichia
coli, Klebsiella, Enterobacter). Important elements of
the maternal history will include colonization with group B β-hemolytic
streptococci with or without adequate intrapartum prophylaxis (more
than 2 doses of penicillin prior to delivery) as well as a history
of prolonged rupture of membranes (> 18 hours) or a history of maternal
fever or chorioamnionitis. Herpes simplex and cytomegalovirus are
viral causes of neonatal pneumonia but typically present as components
of disseminated infections. Congenital chlamydia infections can
cause pneumonia that presents between 2 and 8 weeks of age, typically
with upper respiratory symptoms associated with a cough and apnea.
++
Approximately 13% of all live births are associated
with meconium stained fluid, although only 5% of these
infants develop meconium aspiration syndrome. The traditional belief
was that aspiration occurs with the first breath after birth, leading
to the practice of aggressive suctioning protocols. More recent
data suggest that in utero aspiration may be responsible for the
most severely affected infants. Meconium aspiration can injure the
lung through multiple mechanisms, including mechanical obstruction
of the airways, chemical pneumonitis, inactivation of surfactant,
and vasoconstriction of pulmonary vessels, all of which
prevent adequate ventilation and oxygenation in the immediate postnatal
period. Air trapping substantially increases the risk of pneumothorax.
Infants tend to present shortly after birth with a variable degree
of respiratory distress and hypoxemia; the latter is often in proportion
to the severity of pulmonary hypertension. The chest radiograph
typically reveals coarse, patchy infiltrates with hyperinflation
of the lung fields, although the severity of radiographic findings does
not correlate well with the clinical disease.
++
Congenital lung abnormalities are rare but important causes of
respiratory distress in the newborn.5 In
many cases, infants are initially asymptomatic, with respiratory
distress developing over time. Careful review of the chest X-ray
should reveal most of these lesions. Congenital diaphragmatic
hernia is a relatively common birth defect, occurring
in approximately 1 per 3000 births. Due to its frequent association
with significant pulmonary hypoplasia and pulmonary hypertension,
infants with congenital diaphragmatic hernia typically present shortly
after birth with respiratory distress. Congenital cystic adenomatoid
malformations (CCAM) are extremely rare lung abnormalities composed
of cystic lung tissue with communication to the bronchial tree. In some
cases, medical imaging is needed to differentiate this lesion from
a congenital diaphragmatic hernia. Pulmonary sequestration is a
rare condition characterized by nonfunctioning primitive lung tissue
that does not communicate with the tracheobronchial tree and receives
vascular supply from the systemic circulation (thoracic or abdominal
aorta). Sequestrations may occasionally present in the neonatal
period with signs of congestive heart failure due to the “runoff” circulation
but more commonly present later in life with recurrent infections. Congenital
lobar emphysema (CLE) is an overinflated, hyperplastic area of the
lung surrounded by otherwise normal lung tissue. These are most
common in the upper lobes. Symptoms are progressive but are occasionally
evident at birth. Surgical excision is usually curative, although
overinflation of remaining lung areas can occur.
++
It is important to remember that respiratory failure and cyanosis
may occur secondary to neurological or other organ dysfunction.
For instance, birth injury associated with neurological depression
or hypoxic-ischemic encephalopathy is commonly associated with hypoventilation. Phrenic
nerve injury may cause diaphragmatic paresis. In addition, excessive
oral secretions and inadequate swallowing may obstruct the airway
and cause respiratory distress. Hypoglycemia may cause central nervous
system depression and secondary respiratory distress; this is most
commonly seen in small-for-gestational-age infants, large-for-gestational-age
infants, infants of diabetic mothers, infants with birth asphyxia,
or in rare cases due to primary hyperinsulinism (eg, nesidioblastosis
or Beckwith-Wiedemann syndrome). Abdominal distension may compress
the thorax and interfere with normal respiration. This may be seen
as a result of gastrointestinal pathology (obstruction) or large
intra-abdominal mass effect (renal/genitourinary masses,
severe ascites). Finally, later preterm or even term infants may present
with apneic episodes as a cause of cyanosis.
+++
Circulation:
Cardiac and Circulatory Causes
++
Polycythemia can cause pulmonary hypertension due to increased
viscosity of the blood interfering with pulmonary perfusion. This
may be seen in infants of diabetic mothers, in the presence of delayed
clamping of the umbilical cord or chronic fetal hypoxia (eg, placental
insufficiency, preeclampsia), in recipient twins of twin-to-twin
transfusion syndrome, and in conditions such as trisomy 21.
++
Abnormalities of the hemoglobin molecule itself may interfere
with the normal chemical combination of hemoglobin with oxygen,
but these are very rare in neonates. The most common cause is methemoglobinemia,
which results from the oxidation of hemoglobin molecules from the
normal ferrous to ferric state. Infants are more susceptible to
methemoglobinemia because fetal hemoglobin is more easily oxidized
than is adult hemoglobin and because levels of methemoglobin reductase
are relatively low in infants. Methemoglobinemia may result from
exposure to oxidants (eg, nitrites, sulfonamides, prilocaine, metoclopropamide)
or, rarely, from congenital deficiency of methemoglobin reductase.
The characteristic clinical scenario is a blue-gray-appearing infant
without respiratory distress who has decreased oxygen saturation
but normal arterial oxygen tension.
++
Severe cyanosis is a prominent feature of congenital heart disease
associated with separate circulations and poor mixing (e.g. aortopulmonary
transposition) or complete mixing but diminished pulmonary blood
flow.7 In the case of complete mixing (eg, tricuspid
or aortic atresia), arterial oxygen saturation is a function of
the relative amounts of pulmonary and systemic blood flow and the
relative oxygenation in the pulmonary and systemic venous return.
Hence, hypoxemia can result from markedly diminished pulmonary blood flow;
however, hypoxemia can also result from exuberant pulmonary blood
flow with pulmonary edema and poor systemic blood flow, which reduces
the oxygenation of systemic venous return. Thus, cardiac disease
associated with complete mixing may be associated with a variable
degree of cyanosis. In any of these conditions in which pulmonary blood
flow is dependent on blood directed to the lungs through a patent
ductus arteriosus, cyanosis can worsen at the time of ductus closure
and tends to improve rapidly after the ductus is reopened following
initiation of prostaglandin E1 (PGE1).
++
The systemic and pulmonary circulations are normally in series
with each other, but in complete transposition, the circulations
are in parallel. Therefore, deoxygenated systemic venous blood returns
to the right atrium, enters the right ventricle, and exits through
the aorta. Infants with transposition of the great arteries are
dependent on communication between the pulmonary and systemic circuits
for mixing. If the ventricular septum is intact, life-threatening
cyanosis will develop when the foramen ovale and ductus arteriosus
close in the hours or days after birth. While a patent ductus arteriosus
will improve atrial mixing to a variable degree, adequate interatrial
communication is needed for adequate mixing and oxygenation. Infants
with a large ventricular septal defect may present after the first
few days of life because there is more potential for mixing as other
shunts close.
++
Persistent pulmonary hypertension of newborn (PPHN) describes
the failure of the normal circulatory transition that occurs after birth3 and
is characterized by marked pulmonary hypertension that causes hypoxemia
and right-to-left extrapulmonary shunting of blood through fetal
channels (foramen ovale and ductus arteriosus). The combination
of inadequate pulmonary perfusion and extrapulmonary shunting leads
to severe, refractory hypoxemia. PPHN often complicates parenchymal
lung diseases such as meconium aspiration syndrome in newborn infants,
because pulmonary vessels readily constrict in response to alveolar
hypoxia. However, PPHN can also occur as an idiopathic
condition in the absence of underlying parenchymal
disease. In these cases, the syndrome is believed to be the result
of an abnormally remodeled vasculature that develops in utero in
response to prolonged fetal stress, hypoxia, and/or pulmonary
hypertension. PPHN is commonly associated with lung hypoplasia,
as seen in congenital diaphragmatic hernia.