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.[1]

Not to be confused with Bronze baby syndrome.
Gray baby syndrome
SpecialtyPediatrics 
Diagnostic methodproper history taking, monitoring blood level of the drug.

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.[2]

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:[3]

  1. The UDP-glucuronyl transferase enzyme system of infants, especially premature infants, is immature and incapable of metabolizing the excessive drug load.
  2. 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.[2]

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.[2]

Prevention

The condition can be prevented by using chloramphenicol at the recommended doses and monitoring blood levels,[4][5][6] or alternatively, third generation cephalosporins can be effectively substituted for the drug, without the associated toxicity.[7]

If maternal use of chloramphenicol cannot be avoided, close monitoring of the baby's symptoms such as feeding difficulties, and blood work is recommended.[8]

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.

References
  1. McIntyre J, Choonara I (2004). "Drug toxicity in the neonate". Biol Neonate. 86 (4): 218–21. doi:10.1159/000079656. PMID 15249753.
  2. Ed, Cummings; Ma, Edens (2020). "Gray Baby Syndrome". PubMed. PMID 28846297. Retrieved 2020-07-27.
  3. Brunton, Laurence L.; Lazo, John S.; Parker, Keith, eds. (2005). "Chapter 46. Protein Synthesis Inhibitors and Miscellaneous Antibacterial Agents". Goodman & Gilman's The Pharmacological Basis of Therapeutics (11th ed.). New York: McGraw-Hill. ISBN 0-07-142280-3.
  4. Feder H (1986). "Chloramphenicol: what we have learned in the last decade". South Med J. 79 (9): 1129–34. doi:10.1097/00007611-198609000-00022. PMID 3529436.
  5. Mulhall A, de Louvois J, Hurley R (1 January 1983). "Chloramphenicol toxicity in neonates: its incidence and prevention". British Medical Journal (Clinical research ed.). 287 (6403): 1424–7. doi:10.1136/bmj.287.6403.1424. PMC 1549666. PMID 6416440.
  6. Forster J, Hufschmidt C, Niederhoff H, Künzer W (1985). "[Need for the determination of chloramphenicol levels in the treatment of bacterial-purulent meningitis with chloramphenicol succinate in infants and small children]". Monatsschr Kinderheilkd. 133 (4): 209–13. PMID 4000136.
  7. Aggarwal, R; Sarkar, N; Deorari, AK; Paul, VK (Dec 2001). "Sepsis in the newborn". Indian journal of pediatrics. 68 (12): 1143–1147. doi:10.1007/BF02722932. PMID 11838570.
  8. National Toxicology Program (2011). "Chloramphenicol". Report on Carcinogens: Carcinogen Profiles. 12: 92–94. ISSN 1551-8280. PMID 21850123.

Further reading
  • Krasinski, K; Perkin, R; Rutledge, J (1 September 1982). "Gray Baby Syndrome Revisited". Clinical Pediatrics. 21 (9): 571–572. doi:10.1177/000992288202100910. PMID 7105617.
  • Feigin RD, Cherry JD, Demmler-Harrison GJ, Kaplan SL, eds. (2009). "Ch.248. Antibacterial therapeutic agents". Feigin & Cherry's textbook of pediatric infectious diseases (6th ed.). Philadelphia, PA: Saunders/Elsevier. ISBN 1416040447.
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