Approach to cyanosis in the newborn

INTRODUCTION — Cyanosis is a common clinical finding in newborn infants. Neonatal cyanosis, particularly central cyanosis, can be associated with significant and potentially life-threatening diseases, including pulmonary, cardiac, metabolic, neurologic, infectious, and hematologic disorders (table 1).

This topic will review the causes of cyanosis in newborn infants and will outline the approach to the evaluation to identify the underlying cause. Other related topics include:

●(See "Overview of neonatal respiratory distress and disorders of transition".)

●(See "Diagnosis and initial management of cyanotic heart disease (CHD) in the newborn".)

●(See "Approach to cyanosis in children".)

PERIPHERAL VERSUS CENTRAL CYANOSIS

●Acrocyanosis – Acrocyanosis is often seen in healthy newborns and refers to peripheral cyanosis around the mouth and the extremities (hands and feet) (picture 1). It is a benign condition caused by vasomotor changes resulting from the transition from fetal to extrauterine life. These vascular changes often result in peripheral vasoconstriction and increased tissue oxygen extraction. (See "Physiologic transition from intrauterine to extrauterine life", section on 'Circulatory changes'.)

Acrocyanosis is differentiated from pathologic causes of peripheral cyanosis (eg, septic shock) by its clinical course. It occurs in otherwise healthy infants immediately after delivery and does not persist beyond 24 to 48 hours after birth.

●Peripheral cyanosis – In peripheral cyanosis, the concentration of deoxygenated hemoglobin on the venous side of the capillary bed is increased due to increased tissue oxygen extraction, whereas the systemic arterial oxygen saturation is normal. Peripheral cyanosis may be associated with peripheral vasoconstriction. It typically affects the distal extremities and sometimes the circumoral or periorbital areas. The extremities may be cool or clammy. In neonates with isolated peripheral cyanosis, the mucus membranes remain pink, which differentiates it from central cyanosis. It can be a benign (eg, acrocyanosis) or pathologic finding. Causes include cold exposure, sepsis, shock, venous obstruction, and polycythemia. Some of these causes may be associated with both central cyanosis and peripheral vasoconstriction. (See 'Causes of peripheral cyanosis' below.)

●Central cyanosis – Central cyanosis refers to reduced oxygen saturation in the arterial circulation. Newborn infants normally have central cyanosis until up to 5 to 10 minutes after birth, as the oxygen saturation rises to 85 to 95 percent by 10 minutes of age [1]. Persistent central cyanosis is always pathologic and should be evaluated and treated promptly.

PATHOPHYSIOLOGY

Mechanisms — Hypoxemia in neonates can occur due to one or more of the following mechanisms:

●Alveolar hypoventilation – Although the primary effect of alveolar hypoventilation is hypercarbia (eg, recurrent apnea), decreased ventilation of the lung can cause hypoxemia and cyanosis. Causes of hypoventilation include central nervous system depression (eg, perinatal asphyxia), airway obstruction (choanal atresia), or neuromuscular disorders (eg, spinal muscular atrophy type 1).

●Ventilation-perfusion mismatch – Normally, areas of decreased ventilation are matched with decreased blood flow. Alterations of this relationship can cause hypoxemia and cyanosis (eg, neonatal pneumonia, pneumothorax).

●Right-to-left shunting – In right-to-left shunting, systemic venous blood bypasses ventilated alveoli and returns to the left side of the heart without being oxygenated, resulting in cyanosis. The site of shunting can be intracardiac (eg, cyanotic congenital heart disease [CHD]), through the ductus arteriosus (eg, persistent pulmonary hypertension), or intrapulmonary (eg, perfusion of non-ventilated areas of the lung). (See "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis" and "Diagnosis and initial management of cyanotic heart disease (CHD) in the newborn".)

●Impaired diffusion – Oxygen must diffuse from the alveoli to the pulmonary capillaries where it binds to hemoglobin (Hgb). Interference with alveolar-arterial diffusion (eg, pulmonary edema) results in reduced oxygen saturation.

In addition, reduced arterial oxygen saturation can be caused by hemoglobinopathies that inadequately transport oxygen or polycythemia. (See "Hemoglobin variants that alter hemoglobin-oxygen affinity".)

A wide range of disorders can cause persistent central cyanosis in newborns. These include cardiac, metabolic, neurologic, infectious, hematologic, and pulmonary disorders (table 1). (See 'Causes of central cyanosis' below.)

Factors that affect cyanosis detection — Cyanosis is generally perceptible in newborns when the deoxy-Hgb level in the capillary bed exceeds 3 g/dL (figure 1). The following factors can affect the detection of cyanosis:

●Hemoglobin concentration – The perception of cyanosis depends upon the absolute concentration of deoxy-Hgb, not the ratio of deoxy- to oxy-Hgb. Cyanosis is visually perceptible when deoxy-Hgb exceeds 3 g/dL, which generally corresponds to an oxygen saturation level <85 percent when the Hgb concentration is 15 g/dL (figure 1). In patients with polycythemia, cyanosis can be detected at a higher oxygen saturation. By contrast, a patient with anemia may not have perceptible cyanosis despite significant hypoxemia. For example, in a patient with a Hgb concentration of 8 g/dL, cyanosis is not perceptible until the oxygen saturation falls below 63 percent.

●Fetal hemoglobin – Fetal hemoglobin (Hgb F) is the predominant form of Hgb in newborn erythrocytes. Hgb F binds oxygen more avidly than adult hemoglobin (Hgb A), which aids in fetal uptake of oxygen from the placenta but results in less oxygen delivery to the tissues. The oxygen dissociation curve for Hgb F is shifted to the left, such that for a given level of arterial oxygen tension (PaO₂), the oxygen saturation is higher in newborns than older infants or adults (figure 2). In other words, for a given oxygen saturation, the PaO₂ value is lower in newborns compared with older patients. For example, an oxygen saturation of 80 percent corresponds to a PaO₂ value of approximately 35 mmHg in newborns versus 45 mmHg in older patients.

●Skin pigmentation – Cyanosis may be less apparent in patients with darker skin pigmentation. For this reason, examination should include the nail beds, tongue, and mucous membranes, which are less affected by pigmentation.

●Other factors – Other physiologic factors common in sick newborns affect the oxygen dissociation curve (figure 2). (See "Hemoglobin variants that alter hemoglobin-oxygen affinity", section on 'Regulation of hemoglobin oxygen affinity'.)

•Factors that increase oxygen affinity of Hgb include metabolic or respiratory alkalosis, cold temperature, and low levels of 2,3 diphosphoglycerate. These factors shift the oxygen dissociation curve to the left, which decreases the concentration of deoxy-Hgb at a given PaO₂ The result is that cyanosis first becomes apparent at a lower PaO₂.

•Factors that decrease oxygen affinity of Hgb include acidosis, fever, and higher levels of Hgb A. These factors shift the oxygen dissociation curve to the right, thereby increasing oxygen delivery to the tissues. This results in a greater concentration of deoxy-Hgb at a given PaO₂ and promotes the appearance of cyanosis at a higher PaO₂.

CAUSES OF PERIPHERAL CYANOSIS — Peripheral cyanosis is due to increased oxygen extraction that generally results from sluggish movement of blood through the capillary circulation. Causes include:

●Cold exposure and benign acrocyanosis (see 'Peripheral versus central cyanosis' above)

●Shock (see "Neonatal shock: Etiology, clinical manifestations, and evaluation")

●Sepsis (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates" and "Clinical features and diagnosis of bacterial sepsis in preterm infants <34 weeks gestation")

●Elevated venous pressure or venous obstruction (eg, venous thrombosis) (see "Neonatal thrombosis: Clinical features and diagnosis")

●Polycythemia (see "Neonatal polycythemia")

CAUSES OF CENTRAL CYANOSIS — Causes of central cyanosis in the newborn can be categorized based on their primary pathophysiology (hypoventilation, ventilation/perfusion mismatch, diffusion impairment, right-to-left shunting and hematologic disorders) (table 1). (See 'Pathophysiology' above.)

Hypoventilatory disorders — Hypoventilation resulting in hypoxemia may be due to airway abnormalities, and neurologic or metabolic disorders.

Airway abnormalities — Cyanosis due to the following conditions results from airway obstruction (table 2) [2]. Most airway abnormalities present shortly after birth.

●Choanal atresia – Bilateral choanal atresia or severe choanal stenosis present with respiratory distress and cyanosis immediately after birth (picture 2A-B). The diagnosis should be suspected in an infant who develops respiratory distress and cyanosis while in a quiet state but becomes pink while crying. Inability to pass a suction catheter through the nose into the oropharynx also strongly suggests choanal atresia or stenosis. The diagnosis is confirmed with nasal endoscopy and/or computed tomography (image 1). (See "Congenital anomalies of the nose", section on 'Choanal atresia'.)

●Micrognathia or retrognathia – Micrognathia or retrognathia that is severe enough to be symptomatic is readily apparent on physical examination. Airway obstruction is caused by the posterior tongue obstructing the retropharyngeal airway, especially when the infant is in a supine position. Airway obstruction is typically less pronounced in the upright or prone positions. (See "Congenital anomalies of the jaw, mouth, oral cavity, and pharynx", section on 'Micrognathia' and "Syndromes with craniofacial abnormalities", section on 'Pierre Robin sequence'.)

●Laryngeal and tracheal abnormalities – Laryngeal and tracheal abnormalities include congenital laryngomalacia, laryngeal clefts, vocal cord paralysis, subglottic stenosis, tracheal stenosis, and vascular rings that cause external compression of the trachea (table 2). These conditions can present soon after birth with airway obstruction, stridor, and cyanosis [3]. Stridor and cyanosis are especially evident while the neonate is crying because the increased negative thoracic pressure causes greater airway obstruction. (See "Congenital anomalies of the larynx", section on 'Laryngomalacia' and "Congenital anomalies of the intrathoracic airways and tracheoesophageal fistula", section on 'Congenital tracheal stenosis' and "Vascular rings and slings".)

Neurologic disorders — Neurologic dysfunction, such as hypoxic ischemic encephalopathy, intracranial hemorrhage, or seizures may cause hypoventilation and apnea resulting in hypoxemia and cyanosis. (See "Clinical features, diagnosis, and treatment of neonatal encephalopathy" and "Germinal matrix and intraventricular hemorrhage (GMH-IVH) in the newborn: Risk factors, clinical features, screening, and diagnosis".)

Metabolic disorders — Metabolic disorders such as severe hypoglycemia may be complicated by apnea leading to intermittent episodes of hypoxemia and cyanosis. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Clinical presentation' and "Inborn errors of metabolism: Epidemiology, pathogenesis, and clinical features", section on 'Clinical manifestations'.)

Pulmonary disorders

Ventilation-perfusion mismatch — Pulmonary disease resulting in ventilation-perfusion mismatch is the most common cause of neonatal cyanosis. Newborn infants who present with cyanosis from lung disease will almost always have some degree of respiratory distress.

Specific causes associated with ventilation-perfusion mismatch, which are discussed in detail separately, include the following:

●Respiratory distress syndrome (RDS) (see "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis")

●Transient tachypnea of the newborn (TTN) (see "Transient tachypnea of the newborn")

●Meconium aspiration syndrome (see "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis")

●Neonatal pneumonia (see "Neonatal pneumonia")

●Air leak syndromes (see "Pulmonary air leak in the newborn")

●Congenital abnormalities of the lung and diaphragm, including congenital diaphragmatic hernia and cystic adenomatoid malformation (see "Congenital diaphragmatic hernia (CDH) in the neonate: Clinical features and diagnosis" and "Congenital pulmonary airway malformation")

Impaired alveolar-arterial diffusion — Pulmonary edema is the major cause of impaired alveolar-arterial diffusion that results in neonatal cyanosis. Pulmonary edema may be associated with both pulmonary and nonpulmonary disease. Examples of nonpulmonary causes of pulmonary edema include:

●Sepsis – In the early stages of sepsis, tachypnea is often a finding due to increased respiratory drive resulting in respiratory alkalosis in response to sepsis-related metabolic acidosis. In the later stages of sepsis, capillary leak may result in pulmonary edema with impaired alveolar-arterial diffusion and ventilation-perfusion mismatch. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Clinical manifestations'.)

●Arteriovenous or venous malformations – Very large arteriovenous or venous malformations (eg, Vein of Galen malformation) may cause high-output cardiac failure and pulmonary edema resulting in respiratory distress and cyanosis. (See "Causes and pathophysiology of high-output heart failure", section on 'Causes and their mechanisms'.)

●Heart failure in neonates with critical congenital heart disease (CHD). (See "Identifying newborns with critical congenital heart disease", section on 'Clinical features'.)

Disorders with right to left shunting — Conditions that result in right to left shunting of deoxygenated blood to the systemic circulation include intracardiac lesions and persistent pulmonary hypertension. Intrapulmonary lesions resulting in impaired ventilation/perfusion of affected alveoli also causes right to left shunting. (See 'Pulmonary disorders' above.)

Cyanotic congenital heart disease — Cyanotic CHD should always be considered as a potential etiology of cyanosis in a newborn infant. Neonates with cyanotic CHD may also develop pulmonary edema due to heart failure resulting in impaired alveolar-arterial diffusion, which contributes to cyanosis. The causes, evaluation, and initial management of cyanotic CHD are discussed separately. (See "Diagnosis and initial management of cyanotic heart disease (CHD) in the newborn".)

Persistent pulmonary hypertension of the newborn — Persistent pulmonary hypertension of the newborn (PPHN) is a condition in which the normal circulatory transition from fetal to newborn circulation fails to occur. In newborns with PPHN, the pulmonary vascular resistance remains abnormally elevated after birth, and right to left shunting of blood persists through the fetal circulatory channels (ductus arteriosus and foramen ovale). This shunting leads to severe hypoxemia and cyanosis. PPHN is most frequently associated with parenchymal lung disease, including meconium aspiration syndrome, neonatal pneumonia, and RDS. As a result, the majority of infants with PPHN will present with respiratory distress and cyanosis. However, idiopathic PPHN may also occur unaccompanied by underlying parenchymal lung disease. PPHN including its pathophysiology, clinical features, diagnosis, and management is discussed separately. (See "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis" and "Persistent pulmonary hypertension of the newborn (PPHN): Management and outcome".)

Hematologic causes

Hemoglobinopathies — Hemoglobinopathies that inadequately transport oxygen can result in cyanosis. These disorders include methemoglobinemia (a genetic disorder in which the iron of heme is oxidized to the ferric state, which is unable to bind oxygen) and other rare variants of hemoglobin with low oxygen affinity. (See "Hemoglobin variants that alter hemoglobin-oxygen affinity" and "Hemoglobin variants that alter hemoglobin-oxygen affinity", section on 'Low oxygen affinity hemoglobin variants: Cyanosis'.)

Polycythemia — Polycythemia is common in newborns and has multiple causes (table 3).

●The most common cause of polycythemia in otherwise healthy term infants is the practice of delaying umbilical cord clamping, which results in increased transfer of placental blood to the infant. (See "Labor and delivery: Management of the normal third stage after vaginal birth", section on 'Delayed cord clamping'.)

●Polycythemia is also a common finding in infants of diabetic mothers. (See "Infants of mothers with diabetes (IMD)", section on 'Polycythemia'.)

●Other causes are summarized in the table (table 3) and discussed separately. (See "Neonatal polycythemia", section on 'Causes'.)

In neonates with polycythemia, cyanosis is readily apparent even at mild levels of hypoxemia (figure 1), as discussed above. (See 'Factors that affect cyanosis detection' above.)

Polycythemia causes cyanosis due to hyperviscosity, which can impair blood flow to critical organs leading to poor tissue perfusion and hypoxemia. In severe cases, hyperviscosity and impaired pulmonary perfusion can contribute to PPHN [4]. (See 'Persistent pulmonary hypertension of the newborn' above.)

RAPID ASSESSMENT AND STABILIZATION — Newborns with persistent central cyanosis after birth should be promptly evaluated and supportive measures should be provided to stabilize the neonate. Neonates who appear cyanotic with respiratory distress and/or poor perfusion warrant prompt initiation of respiratory support, measurement of pulse oximetry, and further cardiorespiratory support while targeting specific etiologies based upon the evaluation.

Additional details of neonatal resuscitation, cardiorespiratory support, and other interventions are provided in separate topic reviews:

●(See "Neonatal resuscitation in the delivery room".)

●(See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn".)

●(See "Neonatal shock: Management".)

●(See "Management and outcome of sepsis in term and late preterm neonates", section on 'Initial empiric therapy'.)

●(See "Diagnosis and initial management of cyanotic heart disease (CHD) in the newborn", section on 'Initial management'.)

CONFIRMING HYPOXEMIA (PULSE OXIMETRY) — Measuring the peripheral oxygen saturation (SpO2) by pulse oximetry confirms the presence of clinically significant hypoxemia. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Pulse oximetry'.)

The SpO2 should be measured in both preductal (right hand) and postductal (either foot) locations. A difference of ≥4 percent between the pre- and postductal SpO2 suggests either a left-sided obstructive congenital heart disease (CHD) defect (eg, critical aortic stenosis, coarctation of the aorta, interrupted aortic arch) or persistent pulmonary hypertension of the newborn (PPHN). However, in infants with PPHN, pre- and postductal saturations may not be different if right-to-left shunting is predominantly through the foramen ovale rather than the ductus. These cases are difficult to differentiate from cyanotic CHD. (See "Diagnosis and initial management of cyanotic heart disease (CHD) in the newborn" and "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis", section on 'Pre- and postductal oxygen saturation'.)

In many birthing centers, all newborns undergo routine pulse oximetry screening prior to discharge from the birth hospitalization. Pulse oximetry screening for critical CHD is summarized in the figure (algorithm 1) and discussed in detail separately. (See "Newborn screening for critical congenital heart disease using pulse oximetry".)

EVALUATION — The goals of evaluation are to determine the underlying cause of cyanosis so that intervention can focus on addressing the specific disorder. Evaluation of the cyanotic infant should systematically assess the infant for abnormalities of the airways, lungs, and heart, as well as other potential abnormalities.

Neonates who are critically ill require immediate cardiorespiratory support to ensure sufficient organ/tissue perfusion and oxygenation. (See 'Rapid assessment and stabilization' above.)

In the stable cyanotic neonate or after stabilizing the critically ill infant, the evaluation is focused on differentiating amongst the possible causes of cyanosis.

History — The history may provide clues to the underlying etiology of neonatal cyanosis and should include a complete assessment of the following:

●Pregnancy and labor – Maternal diabetes may be associated with cyanotic heart disease, neonatal polycythemia, and hypoglycemia. Other important pregnancy and labor historical factors include the following:

•Polyhydramnios is associated with fetal airway, esophageal, and neurological conditions.

•Oligohydramnios is associated with renal defects and pulmonary hypoplasia. (See "Evaluation of congenital anomalies of the kidney and urinary tract (CAKUT)", section on 'Amniotic fluid'.)

•Prolonged rupture of the fetal membranes and peripartum maternal fever may be associated with neonatal sepsis. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Maternal risk factors'.)

•Meconium staining of the amniotic fluid is associated with meconium aspiration syndrome and pulmonary hypertension of the newborn (PPHN). (See "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis", section on 'Pulmonary findings' and "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis", section on 'Clinical manifestations'.)

●Family risk factors including a history of cyanotic congenital heart disease (CHD) (table 4) or underlying hemoglobinopathy. (See "Identifying newborns with critical congenital heart disease", section on 'Risk factors'.)

Physical examination — The physical examination is central to determining the cause of cyanosis. In particular, signs of respiratory distress (eg, tachypnea, inter- and subcostal retractions, nasal flaring, grunting) are suggestive of pulmonary disease, whereas abnormal cardiac findings (eg, abnormal heart sounds, pathologic murmurs) point to a cardiac etiology.

However, some cardiac lesions may have a prominent component of respiratory distress (eg, obstructed total anomalous pulmonary venous return and left-sided obstructive disease); thus, its presence does not rule out congenital heart disease. As a result, both CHD and sepsis should be considered as the underlying diagnosis in any critically ill infant who presents with respiratory distress, cyanosis, poor perfusion and/or shock. Left-sided obstructive lesions in which ductal closure has severely affected systemic blood flow may be indistinguishable from severe sepsis on physical exam and usually requires echocardiographic confirmation of the diagnosis. (See 'Echocardiography' below.)

Respiratory assessment includes:

●Respiratory rate – The respiratory rate should be counted for a full minute to account for variations in rate and rhythm. A normal early rate in the newborn period is 40 to 60 breaths per minute. Neurologic or metabolic causes of cyanosis are usually associated with slow or irregular respirations or intermittent apnea, whereas pulmonary and cardiac disorders are associated with tachypnea.

●Chest wall movement – Neonates with respiratory disorders or airway obstruction may have intercostal, subcostal, or subxiphoid retractions in the highly compliant newborn chest wall.

●Other signs of neonatal respiratory disease include grunting, nasal flaring, and increased use of accessory respiratory muscles.

●Airway assessment – Signs of airway abnormalities include noisy breathing or stridor that may be indicative of laryngomalacia.

Cardiac examination includes:

●Assessment of heart rate, pulses, and perfusion

●Cardiac auscultation to detect any abnormality in the second heart sound or the presence of a heart murmur

●Four-extremity blood pressure (BP) to assist in detection of severe coarctation of the aorta or interrupted aortic arch lesions (see "Clinical manifestations and diagnosis of coarctation of the aorta", section on 'Neonates')

Cardiac findings suggestive of critical CHD are summarized in the table (table 5) and described in detail separately. (See "Identifying newborns with critical congenital heart disease", section on 'Physical examination'.)

Diagnostic tests

Arterial blood gas — Measurement of the peripheral oxygen saturation (SpO2) by pulse oximetry is generally sufficient to confirm hypoxemia and asses the severity. However, direct measurement of the arterial oxygen tension (PaO2) with an arterial blood gas (ABG) provides a more accurate assessment of hypoxemia. ABG analysis is generally warranted in neonates with severe hypoxemia or if the pulse oximetry tracing is unreliable (eg, due to poor perfusion). Clinicians should be aware that the pain associated with an arterial puncture may cause agitation in the newborn, and a resultant decrease in the PaO₂. (See "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Arterial blood gas measurement'.)

Other parameters on the ABG include the arterial carbon dioxide tension (PaCO2) and measurements of acid-base status (pH, base excess, calculated bicarbonate level). An elevated PaCO₂ suggests pulmonary disease. Metabolic acidosis generally indicates poor perfusion, which may be due to inadequate cardiac output or distributive shock. Many blood gas analyzers can also measure a lactate level, which provides additional information about perfusion and oxygen delivery to the tissues.

In methemoglobinemia, which is a rare cause of neonatal cyanosis, the oxygen saturation will be low, but the measured PaO₂ will be normal, which would not be the case in other causes of cyanosis. (See "Methemoglobinemia".)

Historically, hyperoxia testing (ie, measuring the PaO2 before and after administering 100 percent oxygen) was used to help distinguish cyanotic CHD from pulmonary disorders. In the contemporary era, it is generally preferred to proceed directly to echocardiography if there is suspicion of cardiac disease. This is because echocardiography is readily available in most institutions, and it is far more accurate for distinguishing between CHD versus noncardiac causes of cyanosis. In addition, it is well recognized that there are potential harmful effects of exposing neonates to 100 percent oxygen, especially preterm neonates. The hyperoxia test should only be used if reliable echocardiography is not immediately available. The hyperoxia test and its interpretation are summarized in the table (table 6) and discussed in detail separately. (See "Identifying newborns with critical congenital heart disease".)

Other blood tests — Other laboratory studies include:

●Complete blood count (CBC) – This will identify neonates with polycythemia. (See "Neonatal polycythemia", section on 'Laboratory testing'.)

The CBC is generally not useful for establishing or excluding the diagnosis of neonatal sepsis, as discussed separately. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Complete blood count'.)

●Blood glucose – Cyanosis due to apnea and poor perfusion can be seen in neonates with severe hypoglycemia. (See "Pathogenesis, screening, and diagnosis of neonatal hypoglycemia", section on 'Clinical presentation'.)

●Blood culture – Blood culture should be performed in all neonates with clinically significant cyanosis as sepsis is an important potential cause. (See "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Blood culture'.)

Chest radiograph — Chest radiography should be performed in all neonates with clinically significant hypoxemia. The chest radiograph will identify pulmonary disease. It can also demonstrate findings that may suggest CHD; however, the chest radiograph may be normal in some types of CHD.

●Pulmonary disease – In most neonatal pulmonary disorders, the lung fields will be abnormal. Examples include (see "Overview of neonatal respiratory distress and disorders of transition", section on 'Chest imaging'):

•Transient tachypnea of the newborn (TTN) (image 2) (see "Transient tachypnea of the newborn", section on 'Radiographic features')

•Respiratory distress syndrome (RDS) (image 3) (see "Respiratory distress syndrome (RDS) in the newborn: Clinical features and diagnosis", section on 'Chest imaging')

•Pneumonia (see "Neonatal pneumonia", section on 'Diagnostic imaging')

•Meconium aspiration syndrome (image 4) (see "Meconium aspiration syndrome: Pathophysiology, clinical manifestations, and diagnosis", section on 'Diagnosis')

•Congenital diaphragmatic hernia [CDH] (image 5) (see "Congenital diaphragmatic hernia (CDH) in the neonate: Clinical features and diagnosis", section on 'Chest imaging')

•Congenital lobar emphysema (image 6) and congenital pulmonary airway malformation (image 7) (see "Radiographic appearance of developmental anomalies of the lung" and "Congenital lobar emphysema" and "Congenital pulmonary airway malformation")

●Cardiac disease – Findings suggestive of cardiac disease include (table 5) (see "Identifying newborns with critical congenital heart disease"):

•The situs of the heart, stomach, and liver - Abnormal configurations (eg, dextrocardia, right aortic arch, situs inversus) strongly suggest cardiac disease.

•Cardiac size and shape – These may also be abnormal in specific CHD lesions, such as Tetralogy of Fallot ("boot-shaped" heart) (image 8) and transposition of the great arteries ("egg-on-a-string"-shaped heart).

•Pulmonary vascular markings – Increased or decreased pulmonary vascular markings may be seen in cyanotic cardiac lesions (table 5). Decreased pulmonary vascular markings may also be seen in idiopathic pulmonary hypertension of the newborn. (See "Persistent pulmonary hypertension of the newborn (PPHN): Clinical features and diagnosis", section on 'Chest radiograph'.)

Echocardiography — Echocardiography differentiates between cardiac and noncardiac causes of neonatal cyanosis. Echocardiography should be performed if the initial evaluation does not reveal another clear cause for the cyanosis (eg, lung disease) or if there are findings that suggest cardiac disease (eg, differential cyanosis, blood pressure or pulse differential between upper and lower extremities, pathologic murmur, cardiomegaly on chest radiograph). (See "Identifying newborns with critical congenital heart disease".)

SUMMARY AND RECOMMENDATIONS

●Definition – Cyanosis is a bluish discoloration of the tissues that is perceptible when the absolute level of deoxygenated hemoglobin in the capillary bed exceeds 3 g/dL. It is a common clinical finding in newborn infants. (See 'Introduction' above.)

Factors that affect the detection of cyanosis include hemoglobin concentration, the presence of fetal hemoglobin, skin pigmentation, and other physiologic factors that affect the oxygen dissociation curve (eg, acid-base status, temperature of the infant, and levels of 2,3 diphosphoglycerate) (figure 2). (See 'Factors that affect cyanosis detection' above.)

●Peripheral versus central cyanosis

•Peripheral cyanosis – Peripheral cyanosis typically affects the distal extremities and sometimes the circumoral or periorbital areas. It can be a benign (eg, acrocyanosis (picture 1)) or pathologic finding. Causes include cold exposure, sepsis, shock, venous obstruction, and polycythemia. Some of these causes may be associated with both peripheral and central cyanosis. (See 'Causes of peripheral cyanosis' above.)

•Central cyanosis – Central cyanosis refers to reduced oxygen saturation in the arterial circulation. Newborn infants normally have central cyanosis until up to 5 to 10 minutes after birth. Persistent central cyanosis is pathologic and should be evaluated and addressed promptly. (See 'Causes of central cyanosis' above and 'Rapid assessment and stabilization' above.)

●Causes – Neonatal cyanosis can be associated with significant and sometimes life-threatening diseases due to cardiac, pulmonary, metabolic, neurological, infectious, and hematologic disorders (table 1). (See 'Causes of central cyanosis' above.)

●Evaluation – Infants with persistent cyanosis after birth should be promptly evaluated and treated as they are at-risk for potentially life-threatening consequences. The goals of the evaluation are to assess the severity of illness and to determine the underlying cause of cyanosis so that treatment can focus on correcting or managing the specific disorder. (See 'Evaluation' above.)

•Initial stabilization – Neonates who appear cyanotic with respiratory distress and/or poor perfusion warrant prompt initiation of respiratory support and further cardiopulmonary interventions, targeting specific etiologies based upon the evaluation. (See 'Rapid assessment and stabilization' above and "Neonatal resuscitation in the delivery room" and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn".)

•Pulse oximetry – Measuring the peripheral oxygen saturation (SpO2) confirms the presence of clinically significant hypoxemia. The SpO2 should be measured in both preductal (right hand) and postductal (either foot) locations. (See 'Confirming hypoxemia (pulse oximetry)' above and "Respiratory support, oxygen delivery, and oxygen monitoring in the newborn", section on 'Pulse oximetry'.)

•History – The history may identify maternal or perinatal conditions, or family history that provides clues to the underlying cause. (See 'History' above.)

•Examination – Physical examination findings may point to an underlying cause. For example, signs of respiratory distress (tachypnea, retractions, nasal flaring, grunting) suggest likely pulmonary disease, whereas abnormal cardiac findings (abnormal heart sounds, pathologic murmurs) suggest a cardiac etiology. (See 'Physical examination' above and "Identifying newborns with critical congenital heart disease", section on 'Physical examination'.)

•Diagnostic tests – Tests that are helpful in assessing the severity of hypoxemia and differentiating among the various underlying causes of hypoxemia include (see 'Diagnostic tests' above):

-Arterial blood gas (see 'Arterial blood gas' above)

-Complete blood count (see 'Other blood tests' above)

-Blood glucose (see 'Other blood tests' above)

-Blood culture (see "Clinical features, evaluation, and diagnosis of sepsis in term and late preterm neonates", section on 'Blood culture')

-Chest radiograph (see 'Chest radiograph' above)

-Echocardiography (see 'Echocardiography' above)