Links To And Excerpts From PedsCases’ Approach to Cyanosis in a Neonate With Links To Additional Resources

An awesome neonatal online resource is the Iowa Neonatology Handbook:

The Iowa Neonatology Handbook is an ongoing effort by the Division of Neonatology at the University of Iowa Stead Family Children’s Hospital to provide physicians, nurses, and medical students who care for newborn infants a collection of protocols outlining rational approaches to the care of critically ill neonates.

The key to the diagnosis of central cyanosis in the neonate is to always carefully examine the newborn’s tongue and mouth (mucous membranes) and to gently pull down the lower lip to look at the mucous membrane there. The podcast reminds us that:

You should also keep in mind the most common causes of cyanosis in a newborn, which are respiratory
distress syndrome, sepsis, and cyanotic heart disease.

In this post I link to and excerpt from the outstanding PedsCasesApproach to Cyanosis in a Neonate [Link to the podcast] [Link to the transcript], by Michelle Fric Jun 29, 2020:

This podcast presents an approach to cyanosis in neonates. In this episode, listeners will learn how to assess and recognize a cyanotic infant, as well as develop a differential diagnosis and identify immediate investigations and management for the cyanotic infant. This podcast was developed by Michelle Fric, a medical student at the University of Alberta, in collaboration with Dr. Georgeta Apostol, a general pediatrician at the Royal Alexandra Hospital in Edmonton.

Related Content:

And here is the summary from the transcript:


Now that we have developed an approach to a cyanotic newborn, I want to leave you with some key take home points.

1. Checking for cyanosis should always be part of your newborn exam. Central cyanosis persisting after the first 10 minutes of life must always be investigated. Keep in mind, cyanosis is not always obvious, especially in dark-skinned babies. Make sure to look closely in the mouth with a good light. [Gently pull down the lower lip and examine the mucosal color there also as well the tongue.]
2. During the assessment of cyanotic the newborn, it is important to identify the cause of cyanosis on a physiologic basis. It will be helpful to consider if the cyanosis is caused by: cardiac or pulmonary conditions, because these are the most common causes for cyanosis in the newborn and could potentially be lifethreating requiring immediate interventions.                                        2a. Other causes to consider are sepsis, hemoglobin abnormalities, hypoglycemia or metabolic diseases.
3. Remember to check the babies response to supplemental oxygen for the Hyperoxia test.
4. Don’t be afraid to ask for help from your team or consulting services. Cyanosis can indicate a life-threatening pathology. Ensure that the baby is stable before continuing on with the rest of your exam or investigations.

All that follows is excerpted from the PedsCases transcript:

Cyanosis refers to a bluish discoloration of the skin or mucous membranes and is a common finding in newborns. It is a clinical manifestation of the desaturation of arterial or capillary blood and may indicate serious hemodynamic instability. It is important to have an approach to cyanosis, as it can be your only sign of a life-threatening illness.

The goal of this podcast is to develop this approach to a cyanotic newborn with a focus on these can’t miss diagnoses. After listening to this podcast, the learner should be able

1. Define cyanosis
2. Assess and recognize a cyanotic infant
3. Develop a differential diagnosis
4. Identify immediate investigations and management for a cyanotic infant


Cyanosis can be further broken down into peripheral and central cyanosis. It is important to distinguish these as it can help you to formulate a differential diagnosis and
identify cases that are life-threatening.

Peripheral cyanosis affects the distal extremities resulting in blue color of the hands and feet, while the rest of the body remains pinkishand well perfused. This can occur at a normal  systemic oxygen saturation and is commonly seen in healthy newborns for the first 1-2 days of life. This is also referred to
as acrocyanosis and is a generally a benign finding. Peripheral cyanosis is thought to represent venous congestion caused by immature control of vascular tone in neonates and this improves as the neonate matures.

In contrast, central cyanosis affects the entire body, but is most evident in the mucous membranes and tongue. It is caused by an increase in the amount of deoxygenated hemoglobin and is  associated with a low oxygen saturation. Central cyanosis can be normal in newborns for the first 5-10 minutes after birth, but if it persists, it requires immediate evaluation as it is always a manifestation of a serious underlying condition for the neonate.

Clinical Case

Now that we have the basics down, lets start with a case. You are the junior resident on your NICU rotation and you are called to assess a female newborn named Susie who appeared blue immediately after delivery and has not improved over the past thirty minutes.

You start your assessment by ensuring the baby is stable. Her temp is 37.9, she is tachypneic at 110 breaths/min, 85% SaO2 on RA, tachycardic at 177 beats/min, with a mean blood pressure of 61mmHg*.

*Pediatric Vital Signs Reference Chart from PedsCases

*Method of Blood Pressure Measurement in Neonates and Infants: A Systematic Review and Analysis [PubMed Abstract] [Full Text HTML] [Full Text PDF]. J Pediatr. 2020 Jun;221:23-31.e5.

You get a quick history, paying close attention to gestational and delivery history. She was a 3.9kg female born at term after an uncomplicated pregnancy with regular prenatal checks. She was delivered vaginally to a G1P1 mom and labour lasted 22 hours. Mom was GBS negative and has no other health conditions. The nurse tells you that the amniotic fluid was dark in color and APGAR scores were 4 and 6 at 1 and 5 minutes respectively, with little respiratory effort initially.

On exam, she does not appear to have any dysmorphic features. She has blue but moist mucous membranes and her skin is dusky. She has nasal flaring and intercostal retractions. She has normal S1 and S2 with no murmur. She has decreased air entry bilaterally with coarse breath sounds. She has equal femoral pulses bilaterally. Her abdomen is soft with no hepatosplenomegaly. She is moving her limbs symmetrically and her primitive reflexes are in tact. The rest of your exam is unremarkable.


You can break down the pathophysiology of increased deoxygenated hemoglobin
into 5 processes:

1. Hypoventilation – a problem bringing oxygen into the body
2. V/Q mismatch – a problem with lung oxygenation and perfusion
3. Diffusion abnormalities – a problem with the lungs delivering oxygen
4. Right to left shunt – a problem with the heart pumping oxygenated blood to the
5. Inadequate oxygen transport – a problem with hemoglobin carrying the oxygen

Each of these situations can lead to the arterial desaturation of oxygen or hypoxemia, leading to the appearance of cyanosis.

Central cyanosis can be life-threatening and requires urgent evaluation. The differential is broad, and it is helpful to think about it through a systems based approach. Since the
differential is so large, we will focus on major categories:

-Cardiovascular system:

o There are many cyanotic congenital heart lesions, including: Transposition of the great arteries, Tetralogy of Fallot, truncus arteriosus, and tricuspid atresia. Cyanotic heart disease is life threatening and must be identified
early. Cyanosis may be the only clue of a cyanotic heart lesion in an infant who appears to be otherwise well. For more information on cardiac causes, please see the PedsCase podcast on Cyanotic Congenital Heart Disease.
o You should also keep in mind causes of heart failure, which can cause cyanosis. Heart failure can be secondary to sepsis, myocarditis, supraventricular tachycardia, complete heart block, or other cardiac condition
o Persistent pulmonary hypertension may be another cardiovascular cause of cyanosis.

-Conditions related to the respiratory system include:

o Respiratory distress syndrome
o Transient tachypnea of the newborn
o Meconium aspiration
o Diaphragmatic hernia                                                                o You should also keep in mind airway obstructions, which can includechoanal atresia or Pierre Robin Sequence among others.

-Infectious etiologies that cause cyanosis include:

o Pneumonia
o Meningitis
o Or sepsis

-Cyanosis can also be caused by decreased respiratory drive and problems with the nervous system including:

o Maternal sedative drugs (including opioids) causing hypoventilation and apneas in the newborn
o Asphyxia
o Intracranial hemorrhage
o Neuromuscular disease

-Problems with the hematologic system causing cyanosis include:

o Acute or chronic blood loss
o Polycythemia
o Methemoglobinemia, which is a blood disorder with abnormally oxidized hemoglobin which prevents oxygen dissociation to the tissues and can either be hereditary or acquired. Infants are more likely to be affected by acquired forms of methemoglobinemia compared to adults.

Other causes of cyanosis include endocrinology and metabolic concerns, such as:

o Hypoglycemia
o Congenital adrenal hyperplasia
o Inborn errors of metabolism

This may seem like a huge differential. Later, we will discuss some physical exam findings and investigations that can quickly help you narrow it down. You should also keep in mind the most common causes of cyanosis in a newborn, which are respiratory
distress syndrome, sepsis, and cyanotic heart disease.

Peripheral Cyanosis Differential

Peripheral cyanosis can be normal for the first 24 hours of a baby’s life if they appear to be otherwise healthy. However, if the cyanosis persists for more than 24 hours, you should re-assess and investigate for a more serious diagnosis. These other causes of peripheral cyanosis include:

– Cardiogenic shock
– Hypovolemia
– Environmental exposures to air, water

If a baby is born prematurely, they may have benign peripheral cyanosis persisting past the first 24 hours of life. It is still important to rule out the previously mentioned causes of peripheral cyanosis, including sepsis.


When doing your physical exam of a newborn, be sure to include an assessment for cyanosis. First, ensure that the baby is stable by assessing ABCs and a full set of vitals.

Pulse oximetry should be performed in the right hand and either foot. If the O2% is less than 95%, you should administer supplemental oxygen.

Look for signs of respiratory distress, including nasal flaring, chest retractions, tachypnea over 60 breaths/min, stridor, and grunting.

If a cyanotic infant is showing signs of increased work of
breathing, the cause is more likely related to the respiratory system.

A cyanotic neonate could have irregular, weak or absent respirations, which should make you think about central causes of decreased respiratory drive or severe fatigue.

Listen for a murmur or abnormal breath sounds, which can help you differentiate between cardiac and respiratory diseases.

With quick inspection of the newborn, you may identify central cyanosis by checking the lips, [oral] mucous membranes, perioral region, [tongue],and nail beds for bluish discoloration or cyanosis by seeing bluish color of the hands or feet.

However, many cases of cyanosis are not so obvious. It is important to be intentional when looking for cyanosis, as it may be subtle or difficult to detect clinically due to factors such as skin color, exposure to light, or presence of jaundice.

Furthermore, cyanosis may become apparent only during episodes of crying or feeding, when the saturations decrease
further. Ensure you have good lighting and examine the tongue and oral mucosa to prevent missing a cyanotic infant.

To help you differentiate between cardiac and non-cardiac causes, you should perform a hyperoxia test. This compares pulse oximetry with or without an arterial bloodgas before and  after exposure to 100% inspired oxygen for ten minutes. In general, infants with neurologic or pulmonary causes of cyanosis will have a substantial increase in their oxygen saturation after exposure to 100% FiO2, whereas infants with cardiac causes will show negligible change.

You should make sure you complete a full physical exam on the newborn toidentify any other signs that may help with your diagnosis.

If you are taking care of a well newborn, make sure they have their oxygen saturation checked before discharging them home. The Canadian Paediatric Society and Canadian Paediatric Cardiology Association recommend that all newborns should
have pulse oximetry screening before leaving the hospital after birth to enhance detection of critical congenital heart disease. Changes in pulse oximetry may be able to pick up patients with clinically undetectable cyanosis. O2 saturation <90% is abnormal and should be investigated, whereas an O2sat of 90-94% or hand to foot difference >3% is borderline and should be reassessed after an hour and if it’s still < 95% after 2
repeated screens should be investigated.

Investigations & Management

Once again, cyanosis can indicate a life threatening illness. Always go back to your ABCs and make sure the baby is stable.

Signs that the infant needs immediate support include
signs of obstructed airway, poor respiratory effort and fatigue, and circulatory collapse indicated by bradycardia, hypotension, and poor perfusion [for example, prolonged capillary refill].

You may need to consider bag-mask ventilation or intuba[tion.

If you suspect that it may be a cardiac lesion, ensure that the ductus arteriosus stays open by administering prostaglandins.*

*See Protocol for use of prostaglandin E1 from the Iowa Neonatology Handbook [accessed 5-19-2021].

After your thorough history and physical exam, hopefully you have some idea of what system may be the primary cause of your patient’s cyanosis.

Initial bloodwork should include an arterial blood gas to determine the severity of respiratory compromise*, CBC to assess for anemia and sign of infection. Blood culture may be indicated to investigate sepsis. Blood glucose can be checked to determine presence of hypoglycemia.

*I would telephone the neonatologist at the tertiary care transfer center to see if he or she thinks that a venous blood gas would be good enough.

A chest x-ray should be ordered for a cyanotic neonate. Not only does a chest xray help identify lung pathology, but it is also helpful to assess the cardiac silhouette and pulmonary blood flow.

An echocardiogram and ECG should be ordered in the context of a murmur, cardiomegaly on xray, or no improvement with oxygen in order to determine structural heart disease or persistent pulmonary hypertension.

At this point, it would be appropriate to start getting relevant consult services involved, such as cardiology. Once you have your diagnosis, you can initiate definitive management.

Clinical Case

Back to our clinical case… we already know that Susie is showing signs of respiratory distress and cyanosis. Based on what we’ve learned about cyanosis, we know that cardiac and pulmonary causes are the most common and can be life threatening.

We still need to check O2 saturation and get a 4 limb BP.

Initially her O2% was 85% on RA. You give her some supplemental oxygen and monitor her saturations for the hyperoxia test. Her saturations improve to 97% after 10 minutes on 2L of oxygen.

Given the positive response to oxygen, her normal cardiac exam, and abnormal respiratory exam, you are leaning more towards a respiratory cause.

You order a couple investigations, including chest xray, blood gas, CBC, and blood cultures.

Your chest xray images come back quickly but are unreported. The heart appears to be normally shaped and is less than 50% of the mediastinal width. The lungs, however, look abnormal with diffuse patchy areas, no evidence of pneumothorax, and no focal consolidation. Her CBC is within expected range for a newborn and her blood gas shows she is retaining CO2.

Some pertinent positives in your assessment include that she was a term baby, dark stained amniotic fluid, respiratory distress with improvement after supplemental oxygen, and abnormal appearing lungs on CXR.

With [the above] in mind, the top of your differential is meconium aspiration syndrome. You have kept Susie on supplemental oxygen and decided that she is stable without more aggressive forms of respiratory support. You are feeling confident to present to your staff about this interesting case of
neonatal cyanosis!

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