Gray Baby Syndrome
Gray baby syndrome (also termed Gray or Grey syndrome) is a rare but serious side effect that occurs in newborn infants (especially premature babies) following the accumulation of antibiotic chloramphenicol.
Signs and symptoms
Toxic levels of chloramphenicol after 2–9 days result in: loss of appetite, vomiting, ashen gray color of the skin, Hypotension (low blood pressure), Cyanosis (blue discolouration of lips and skin), Hypothermia, Cardiovascular collapse, hypotonia, abdominal distension, irregular respiration and increased blood lactate.
Pathophysiology
Two pathophysiologic mechanisms are thought to play a role in the development of gray baby syndrome after exposure to the anti-microbial drug chloramphenicol. This condition is due to a lack of glucuronidation reactions occurring in the baby, thus leading to an accumulation of toxic chloramphenicol metabolites:
- The UDP-glucuronyl transferase enzyme system of infants, especially premature infants, is immature and incapable of metabolizing the excessive drug load.
- Insufficient renal excretion of the unconjugated drug.
Insufficient metabolism and excretion of chloramphenicol leads to increased blood concentrations of the drug, causing blockade of the electron transport of the liver, myocardium, and skeletal muscles. Since the electron transport is an essential part of cellular respiration, its blockade can result in cell damage. In addition, the presence of chloramphenicol weakens the binding of bilirubin and albumin, so increased levels of the drug can lead to high levels of free bilirubin in the blood, resulting in brain damage or kernicterus.
Diagnosis
Gray baby syndrome should be suspected in a new born with abdominal distension, progressive pallid cyanosis, irregular respirations, and refusal to breastfeed. The cause of gray baby syndrome comes from the mother's use of an antibiotic, chloramphenicol, during pregnancy or breastfeeding. The presentation of symptoms can depend on the level of exposure of the drug to the baby. A broad diagnosis is usually needed for babies who present with cyanosis. Blood work is done to determine the level of serum chloramphenicol. Other tools used to help with diagnosis include CT scans, ultrasound, and electrocardiogram.
Prevention
The condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels, or alternatively, third generation cephalosporins can be effectively substituted for the drug, without the associated toxicity.
If maternal use of chloramphenicol cannot be avoided, close monitoring of the baby's symptoms such as feeding difficulties, and blood work is recommended.
Treatment
Chloramphenicol therapy should be stopped immediately. Exchange transfusion may be required to remove the drug. Sometimes, phenobarbital to induce UDP-glucuronyltransferase enzyme is used.