What Is Gray Baby Syndrome? Causes, Symptoms, And Treatment

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Gray baby syndrome (GBS) is a rare disorder that is caused due to the presence of high levels of chloramphenicol in babies born prematurely. Chloramphenicol is an antibiotic that is used in the treatment of bacterial infections such as meningitisⁱXThe inflammation of the meninges or membranes around the brain and spinal cord due to an infection. , cholera, and typhoid fever. The common symptoms of this disease include graying of the baby’s skin, cardiac issues, and swelling up of the abdomen (also known as abdominal distension). Although the complications caused due to this syndrome can be severe, they can be prevented. Read on to know more about the causes, signs, treatment, diagnosis, and prevention of this syndrome.

Causes Of Gray Baby Syndrome

The primary cause is the accumulation of the antibiotic chloramphenicol in the blood serumⁱXThe liquid part of the blood left after the blood cells and clotting materials are removed. of an infant.  Blood serum levels of chloramphenicol higher than 50mcg/mL is associated with gray baby syndrome. Toxic levels of chloramphenicol may cause a circulatory collapse that leads to mottling (smears of color) of the skin in ashen-gray color (1). This disease is named after the appearance of gray-colored skin in newborn babies.

Gray baby syndrome can be due to the following deficiencies in neonates (1).

• The immature liver may not be able to metabolize the chloramphenicol.
• Newborn’s kidneys are not efficient enough to excrete chloramphenicol and its metabolic products from the body.

A well-functioning liver and kidneys can metabolize and excrete the chloramphenicol. However, it may not be the case in babies. This could be a reason that premature neonates are more vulnerable to gray baby syndrome than healthy and full-term infants.

Note: A research study published by the CDC suggests that newborns getting this syndrome in utero due to maternal exposure to chloramphenicol is extremely low (2).

Risk Factors Of Gray Baby Syndrome

The following risk factors may play a vital role in the development of gray baby syndrome during the neonatal period.

• Reduced liver (hepatic) function
• Reduced kidney (renal) function
• High dose of chloramphenicol
• Longer duration of chloramphenicol treatment
• Maternal use may cause chloramphenicol to reach the baby through breast milk
• Underweight and malnourished children

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Pediatricians decide chloramphenicol dose based on weight. This weight-based dosage may vary among newborns until the first 15 days. There may also be variations in dosage in babies up to four weeks old and those older than a month.

Note: Although there is a lack of quality evidence, NHS reports suggest that chloramphenicol is contraindicated in breastfeeding mothers due to infant toxicity (3). It is also a category C drug that may cause complications in pregnant women (4).

Symptoms Of Gray Baby Syndrome

Gray baby syndrome may occur after two to nine days of chloramphenicol treatment. The onset and severity may vary based on drug levels and hepatorenal functions.

Gray baby syndrome symptoms may include (5) (6):

• Fussiness
• Poor feeding
• Weakness
• Vomiting
• Changes in mental status such as lethargy and less alertness (obtundation)
• Pale appearance (pallor)
• Ashen-gray color of the skin
• Abdominal tenderness
• Abdominal distention
• Hypotension (low blood pressure)
• Cyanosis causing blue lips, blue nails and bluish skin

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• Respiratory distress
• Low body temperature

Seek medical advice if you notice any signs and symptoms of toxicity in newborns due to direct or maternal intake of chloramphenicol antibiotics.

Complications Of Gray Baby Syndrome

The following complications can be associated with chloramphenicol toxicity (1) (7):

• Bleeding
• Liver failure
• Renal failure
• Aplastic anemiaⁱXA rare blood disorder in which the body does not produce enough new blood cells due to bone marrow damage. due to bone marrow toxicity (8)
• Inflammation of the optic nerve (optic neuritis) and vision problems
• Problems with peripheral nerves (Peripheral neuritisⁱXNumbness and tingling in the extremities due to nerve damage. )
• Cardiovascular collapse or shock
• Infection
• Brain damage

Chloramphenicol could displace bilirubin (formed by the breakdown of red blood cells) from albumin (main blood protein). Free or non-albumin bound bilirubin may lead to jaundice (yellow skin and eyes) and permanent brain damage known as kernicterus (1)

Diagnosis Of Gray Baby Syndrome

Diagnosis of the gray baby syndrome can be made from the ashen-gray appearance of the skin along with the history of exposure to chloramphenicol in babies. Neonatologists or pediatricians may also look for signs of toxicity during physical examination.

The following tests are ordered to confirm the diagnosis of the gray baby syndrome (1):

• Blood tests could show the levels of chloramphenicol in the blood. Cardiac biomarkers, arterial blood gasⁱXA test that measures the levels of oxygen and carbon dioxide in the blood to examine the working of the lungs. , metabolic profileⁱXA set of blood tests to check the levels of different blood components and gain information about metabolism and chemical balance. , etc., are based on blood tests to identify or exclude conditions that can be present with neonatal cyanosis.

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• CT scan, abdominal X-rays, or abdominal ultrasound are conducted depending on the symptoms.

• Electrocardiography (ECG) and echocardiography are often done to exclude cardiac causes of circulatory collapse and skin discoloration.

Your doctor may perform these tests to look for neonatal sepsisⁱXBlood infection in babies less than 90 days old. , trauma, volvulusⁱXA condition in which the intestine twists around itself and its mesentery to create a bowel obstruction. , heart diseases, and metabolic syndromes to make a differential diagnosis, since these conditions may also cause cyanosis in babies.

Treatment For Gray Baby Syndrome

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The treatment for gray baby syndrome is intensive support therapy with the withdrawal of chloramphenicol. Babies with problems in the blood and circulatory system receive aggressive resuscitation in intensive care units. They may receive appropriate oxygen therapy, ventilation, and early intubation, depending on the requirement.

If the baby develops hypothermiaⁱXThe inability of the body to produce heat faster than it loses, leading to a severe drop in body temperature. , then they will require rewarming. HypoglycemiaⁱXA condition in which there is an excessive drop in blood sugar levels. will require glucose correction.

The direct removal of antibiotic chloramphenicol molecules from the blood can be achieved by the following treatments (6).

• Activated charcoal hemoperfusion: This is an extracorporeal (outside the body) method to filter the toxin from the body.

• Exchange transfusion: This life-saving procedure involves the replacement of a patient’s blood with fresh donor plasma or blood.

Third-generation cephalosporin and phenobarbital medications are also used for treating gray syndrome (5).

Prognosis Of Gray Baby Syndrome

The prognosis or outcomes are good if the gray baby syndrome is diagnosed earlier, and the chloramphenicol treatment is discontinued. However, if the baby has developed organ failure before diagnosis, then there is a high risk of worse prognosis.

Prevention Of Gray Baby Syndrome

Avoiding chloramphenicol exposure is a way to prevent gray baby syndrome. This can be achieved by practicing the following steps.

• Pediatricians and infectious disease experts try to give other safer antibiotics instead of chloramphenicol to babies.

• Expecting mothers and nursing mothers should go for treatment with newer antibiotics instead of chloramphenicol since it may cause birth defects in unborn babies and neonatal toxicity.

• If required, lower doses of chloramphenicol for a long duration are often prescribed for babies to prevent toxic effects.

Healthy babies and premature infants are carefully monitored for drug levels in the blood if they are treated with chloramphenicol antibiotics.

Long-term therapy with oral or intravenous chloramphenicol may result in gray baby syndrome. You may also seek a healthcare provider’s advice before using chloramphenicol eye drops for bacterial conjunctivitisⁱXbacterial infection causing the inflammation of the membrane that covers the eyelids and the eyeball.  in infants and children since this may also result in toxicity (9). Pediatric drug therapy with chloramphenicol is only considered when it is an absolute requirement.

Infographic: Use Of Chloramphenicol In Lactating Mothers

If you are nursing your newborn, you must be aware of certain crucial factors regarding the use of chloramphenicol during breastfeeding. This infographic shares some critical points about using chloramphenicol while breastfeeding.

Illustration: Momjunction Design Team

Get the high-quality PDF version of this infographic.

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Dr. Wayne HoughMBChB, MMed, FC Paeds

Dr. Wayne Hough is a pediatrician with around six years of experience in the field. He is currently based in the Northern Suburbs of Cape Town in South Africa. Dr. Hough got his medical degree from the University of Stellenbosch. He then worked at the Tygerberg Children's Hospital before completing his pediatric training and qualification from the South African College...more

Dr Bisny T. JosephMedical Doctor

Dr. Bisny T. Joseph is a Georgian Board-certified physician. She has completed her professional graduate degree as a medical doctor from Tbilisi State Medical University, Georgia. She has around 5 years of experience in various sectors of medical affairs as a physician, medical reviewer, medical writer, health coach, and Q&A expert. Her interest in digital medical education and patient education...more

Rohit GarooBSc, MBA

Rohit Garoo is a writer-turned-editor with over 9 years of experience in content writing, editing, and content marketing. He did his bachelors in Science at St. Xavier's College, Hyderabad, and masters in Business Administration at Osmania University. Also, he holds a certificate in Developmental Psychology from The University of Queensland and loves to expand his knowledge through certifications in various...more

Shinta Liz SunnyM.Tech

Shinta is a biotechnologist who is highly intrigued by science and technology. She holds a master's degree in Biotechnology from Karunya Institute of Technology and Sciences and a PG Diploma in cellular and molecular diagnostics from Manipal University. At MomJunction, Shinta writes on mother and child health and wellness. Previously, she worked as a scientist for three years, involved in developing...more