What are the other Names for this Condition? (Also known as/Synonyms)

• Chloramphenicol Toxicity in Neonates
• Chloramphenicol Toxicity in Newborn
• Gray Syndrome from Chloramphenicol Administration in Newborn

What is Gray Syndrome? (Definition/Background Information)

• Gray Syndrome is a potentially fatal complication that develops in newborn infants (usually preterm babies), due to an overdose of the antimicrobial medicine chloramphenicol
• Chloramphenicol is administered intravenously, as a first line of treatment against certain types of meningitis (and other conditions), in a newborn child. However, a large dose might lead to severe toxicity in blood, since the baby’s body lacks a capacity to neutralize the drug, when it is present in large quantities
• Gray Syndrome affecting the newborn causes symptoms, such as pale-blue color, difficulty feeding, cold limbs or body. A blood sample analysis for chloramphenicol, in combination with the classical signs and symptoms, can confirm Gray Syndrome
• Immediate stoppage of chloramphenicol is the first step towards treatment of the condition. The prognosis depends on an early detection of the condition and dosage amounts of the administered drug

Who gets Gray Syndrome? (Age and Sex Distribution)

• Gray Syndrome occurs, almost exclusively during the first few days after the baby’s birth, due to an accidental administration into blood, of high levels of chloramphenicol
• The condition has also been infrequently observed in young infants and children (aged 2 years and below)
• This disorder affects both the male and female child uniformly. There are no gender preferences
• No ethnic or racial predilection is seen

What are the Risk Factors for Gray Syndrome? (Predisposing Factors)

Risk factors for Gray Syndrome include:

• Administration of chloramphenicol to a newborn child (generally during the first 3 days after birth), without careful and regular monitor of chloramphenicol drug levels in blood
• Preterm and malnourished underweight babies are at a higher risk
• Pregnant women receiving chloramphenicol drug-based treatment; particularly, during the last weeks of gestation can affect the unborn baby
• Lactating mothers can pass on this medication through breast milk, to their babies

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases ones chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Gray Syndrome? (Etiology)

• Chloramphenicol is used to treat certain bacterial infections, such as meningitis, in neonates. In the period immediately following birth, the baby’s liver and kidney functioning efficiency is severely limited
• High concentrations of chloramphenicol can neither be completely processed, nor excreted out, of the body system by the newborn child. Hence, chloramphenicol builds up to toxic levels in the bloodstream causing near fatal reactions. For this reason, Gray Syndrome is also known as Chloramphenicol Toxicity in Newborn
• A low birth weight baby, or a baby born preterm, has an even more frail body condition (than a healthy newborn). The drug toxicity side effects in such cases, are severe and life-threatening
• Infrequently, women receive chloramphenicol drug treatment, during their pregnancy for various illnesses, which then gets passed onto their offspring through the placenta; thus accumulating in the fetus
• Nursing mothers, who are under chloramphenicol treatment, can easily pass on the drug to their children

What are the Signs and Symptoms of Gray Syndrome?

The adverse reactions triggered by chloramphenicol in Gray Syndrome include the following signs and symptoms, which are usually noticed from day 2 (to day 9) of starting treatment, with the medicine:

• Reduced oxygen in blood causing blue-colored lips, nails; pale blue-grey body appearance
• Low body temperature (limbs feel cold) and high blood pressure; irregular breathing
• The newborn has feeding difficulties, such as refusal to be breastfed
• Limp body observed with baby showing poor muscle tone
• Vomiting, diarrhea (green, watery stools), and distended abdomen, may be seen

How is Gray Syndrome Diagnosed?

A diagnosis of Gray Syndrome is made by:

• Complete physical exam with a thorough evaluation of medical treatment history of the newborn (and the mother). The chloramphenicol dosage (quantity) administered is indicative and normally provides definitive evidence
• Blood analysis for chloramphenicol levels - blood chloramphenicol levels should be monitored at regular intervals

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Gray Syndrome?

A few complications caused by Gray Syndrome are:

• Improper blood circulation can lead to a cardiovascular collapse; this can cause death, if treatment is delayed
• Bone marrow depression: The body stops creating new platelets and other blood cells, which can cause critical medical problems, such as bleeding and infections.
• Complications caused by other underlying infections or secondary disorders. The impact of infection can be greater, if the baby is born before completion of full gestational term (preterm births), or is undernourished

How is Gray Syndrome Treated?

Early detection with quick aggressive treatment of Gray Syndrome is required; if an over dosage of chloramphenicol is suspected. The treatment measures include:

• Immediate discontinuation of chloramphenicol medication
• Blood transfusion to remove the toxic levels of chloramphenicol in blood. This is achieved through exchange blood transfusions
• Medications to treat any underlying ailments or illnesses, such as infections and bleeding

How can Gray Syndrome be Prevented?

Preventive measures and precautions to be taken for Gray Syndrome include:

• Pregnant women and nursing mothers should not be treated with chloramphenicol
• If the newborn baby can be treated with other alternative medications; then, chloramphenicol should be avoided to the extent possible
• In case chloramphenicol has to be given, then a recommended daily dosage of 15-25 mg/l is considered safe and therapeutic. Any dosage over this, may be unsafe and may lead to Gray Syndrome
• If chloramphenicol drug is administered, then the baby’s blood serum chloramphenicol quantity level has to be constantly monitored. Endeavors shall be made to discontinue the drug, as early as possible

What is the Prognosis of Gray Syndrome? (Outcomes/Resolutions)

Following is the prognosis for Gray Syndrome:

• Early detection and stoppage of chloramphenicol can result in a full recovery. But, even a  slightly delayed detection and the presence of a high levels of the drug chloramphenicol in blood, could be potentially fatal
• The physical condition (healthy or undernourished) of the newborn, and other underlying complications (if any) the child suffers from, may affect the prognosis. The prognosis is usually better in healthy, well-nourished full-term babies, compared to underweight malnourished and preterm babies

Additional and Relevant Useful Information for Gray Syndrome:

• Chloramphenicol is a highly effective drug against a variety of microbial infections, such as typhoid, meningitis, rickets, skin, eye and ear infections, rocky mountain spotted fever, influenza, and other such diseases or disorders
• In certain geographical regions of the world, where access to healthcare resource is severely limited; chloramphenicol is widely used to treat pregnant women and newborn children, as it is relatively cheap. Due to this reason, the mortality rates in such regions due to chloramphenicol toxicity, is higher than in developed countries