What is Gray Baby Syndrome?
Chloramphenicol is a man-made antibiotic that was first found in 1947. Originally, it was developed to treat typhoid fever, but its use has decreased because the bacteria that causes typhoid fever, Salmonella typhi, commonly resists this antibiotic. Chloramphenicol has also been historically used to treat kids showing symptoms of a fever and a type of rash called petechial for its ability to effectively handle meningococcal sepsis and rickettsial disease – two kinds of serious infections.
Despite these setbacks, chloramphenicol’s affordable price, wide variety of uses and low risk of causing harmful effects have earned it a place on the World Health Organization’s list of must-have medicines. And as bacteria gradually become resistant to most of our current antibiotics, there’s renewed global interest in reusing chloramphenicol to fight various infections.
However, 12 years after chloramphenicol was discovered, researchers found the first instance of a potentially deadly side effect in newborns, particularly those born prematurely. This condition, known as “gray-baby syndrome,” was observed in babies who were given chloramphenicol (either by mouth or through a vein) within two days after birth and later showed symptoms like a swollen belly, vomiting, being too cold, turning blue, and problems with their heart and blood vessels. These babies’ skin also changed color – first mottled and eventually a gray color, which is why this reaction is called “gray-baby syndrome.”
What Causes Gray Baby Syndrome?
When chloramphenicol, a type of medication, is present in high amounts in the blood, there are usually two primary causes for this. Normally, a healthy liver will break down the chloramphenicol drug (mostly through a process called glucuronidation). But in newborn babies, the liver and kidneys aren’t fully developed yet. The liver might struggle to produce an enzyme called UDP-glucuronyltransferase, which helps break down drugs, and the kidneys might not be able to efficiently get rid of chloramphenicol and its breakdown products. These two factors can result in raised levels of chloramphenicol in a baby’s blood.
High levels of the drug can cause problems because chloramphenicol can push out a substance called unconjugated bilirubin from another substance, albumin. This leads to a condition known as kernicterus, which is a form of brain damage that occurs in newborns with severe jaundice. If left untreated, kernicterus can lead to death.
Risk Factors and Frequency for Gray Baby Syndrome
Premature babies and newborns are the most susceptible to ‘gray-baby syndrome’, a condition resulting from exposure to chloramphenicol, a type of medication. This is mainly due to their kidneys and liver, which are not fully developed and thereby having reduced ability to process this drug. Instances of chloramphenicol causing harm have also been found in children and teenagers. For safety, doctors often adjust the dosage of this drug based on the child’s weight. They use different guidelines for newborns less than 15 days old, infants who are 2 to 4 weeks old, and children who are older than a month.
Signs and Symptoms of Gray Baby Syndrome
Gray-baby syndrome is a condition that can happen due to the overuse of a medication called chloramphenicol. The way this syndrome presents can change based on how much of the drug is in the baby’s system. The best way to know if a baby has been exposed to chloramphenicol is if a caregiver reports its use. Usual signs of the syndrome can include reduced appetite, irritability, and vomiting. This syndrome can also happen if the drug is taken by a pregnant mother because it can pass through the breast milk. The drug is generally not recommended for pregnant or breastfeeding women for these reasons. Physical signs can include a change in mental state, from lethargy (extreme drowsiness) to obtundation (a state less than full alertness), a gray-blue skin color, paleness, and a bloated or tender abdomen.
- Reduced appetite
- Irritability
- Vomiting
- Lethargy or decreased alertness
- Gray-blue skin color
- Paleness
- Bloated or tender abdomen
Testing for Gray Baby Syndrome
If a newborn baby appears unwell and shows signs of turning blue (cyanosis), doctors must consider a wide range of possible causes. These include infections that the baby may have caught around the time of birth (neonatal sepsis), injuries possibly caused by another person (non-accidental trauma), a twisted intestine (midgut volvulus), heart defects they were born with (congenital heart disease), or rare genetic conditions that affect chemical reactions in the body (inborn mistakes of metabolism).
To help understand what might be causing the baby’s symptoms, the doctor will need to carry out several blood tests. The tests can check the baby’s blood sugar (glucose), number and type of blood cells (complete blood count), and levels of various minerals and other chemicals (complete metabolic panel). The doctor may also run tests to look at the levels of gases (blood gas analysis), ammonia, lactic acid and ketones — substances that can build up in the body if there’s a problem with metabolism. Additionally, they may consider tests for troponin and brain natriuretic peptide, natural substances that can indicate heart problems.
If chloramphenicol, an antibiotic, has been given and could be causing toxic side effects, the doctor may measure its level in the baby’s blood.
They might also recommend taking pictures of the inside of the baby’s body using X-rays of the chest and abdomen or CT scans of the head. An ultrasound, which uses sound waves to build up a picture of the body’s interior, might also be needed, especially for the abdomen. An electrocardiogram, a test that measures the electrical activity of the heart may also be useful.
Treatment Options for Gray Baby Syndrome
If a baby has been exposed to too much chloramphenicol, a type of antibiotic, they may experience a condition known as “gray baby syndrome.” This condition requires immediate medical attention and supportive care. Affected babies often have a gray color and may be unstable.
The first step in treatment usually involves stabilizing the baby’s vital signs, such as their heart rate, blood pressure, and oxygen levels. Sometimes, this can involve intubation, which is when a flexible tube is placed into the windpipe to help with breathing. It’s also important to check the baby’s temperature because affected babies are often cold, and they may need to be warmed. Another critical step is to check the baby’s blood sugar levels and correct them if they’re too low.
There are several possible reasons a baby could appear ashen-gray and unstable, including chloramphenicol toxicity, heart conditions, hormonal disorders, metabolic disorders, trauma, seizures, and infections. Therefore, broad-spectrum antibiotics like vancomycin, ampicillin and a third-generation cephalosporin such as ceftriaxone or cefotaxime might be given to help protect against possible infections. Another medication, prostaglandin, might also be given if a heart defect that depends on a specific blood vessel, known as the ductus arteriosus, is suspected.
The main aim of treatment for gray-baby syndrome is to remove the excess chloramphenicol from the baby’s body. This can sometimes be achieved through procedures such as charcoal hemoperfusion (filtering the blood by pumping it through a machine containing activated charcoal) or exchange transfusion (replacing the baby’s blood with fresh donor blood or plasma). Some reports also mention the use of phenobarbital, a medication that can stimulate an enzyme in the body to help break down chloramphenicol.
In some cases, a procedure called cardiopulmonary bypass, which uses a machine to take over the work of the heart and lungs, may be considered. This could include something called extracorporeal membrane oxygenation, which is a type of life support that circulates the baby’s blood through a machine to add oxygen and remove carbon dioxide.
What else can Gray Baby Syndrome be?
There are a number of potential causes to consider when examining a patient for certain symptoms. These could include:
- Adrenal insufficiency hypothyroidism
- Congenital heart diseases
- Chloramphenicol toxicity
- Inborn genetic mistakes of metabolism
- Sepsis
- Seizure
- Trauma
Proper tests and examinations need to be conducted to accurately determine the cause.
What to expect with Gray Baby Syndrome
If the condition is detected early and the medication is stopped right away, the outlook is generally positive. However, if the baby has already developed problems with their organs, the outlook becomes more uncertain.
Possible Complications When Diagnosed with Gray Baby Syndrome
- Bleeding
- Failure of kidney or liver function
- Anemia (low red blood cell count)
- Infections
- Confusions
- Significant weakness
- Issues with vision
- Shock (a severe drop in blood flow)
- Possible death
