The Preterm Infant, Ototoxic Drugs, and the NICU

This update steps a little outside of speech-language pathology’s typical scope, but it is still something that affects us and our clients.

In 2007 the American Academy of Pediatrics suggested that all infants with increased risk for hearing loss receive hearing screening between 24 and 30 months of age.  One significant risk factor is the use of ototoxic drugs, particularly with premature neonates.  The development of the cochlea occurs relatively late during gestation, as demonstrated by higher frequencies (1000 – 3000 Hz) only being detectable within the womb after about 33 weeks.  When born prematurely, the infant may be exposed to the hearing world before they’re ready; the NICU is noisy and confusing, with sounds from a plethora or machines and people reaching peaks of 120 dBA.  Expectedly, the exposure to such intense sound even occasionally can have long-lasting effects on hearing.

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The immune system of premature infants is also not at peak efficiency.  Common in NICU infants is a body-wide septic infection, for which one or a series of broad-spectrum antibiotics will be used.  Aminoglycosides — most commonly the affordable gentamicin — are commonly used for their efficacy against Gram-negative bacteria.  Unfortunately, one of the side-effects of this drug type is toxicity to the auditory nerve.  Animal studies have suggested that children are significantly more prone than adults to ototoxicity of aminoglycosides.

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Although the results in the literature prevent definite conclusions — largely due to variations in dosage, noise levels, and duration — the pairing of noise and ototoxic drugs potentiates the risk to early hearing loss.  Loud noise may in fact directly increase the effects of aminoglycosides:  Louder noises cause mechanoelectrical transduction (MET) to take place in hair cells, opening the cell to the expected electrolyte and also the unexpected ototoxic drug.  The effect is further increased by certain mitochondial mutations, though the prevalence of this in premature infants is not well known.

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The implications and recommendations accumulated from the references below are as follows:

• Create a quieter NICU environment by using silent alarms, sound-level checks, private bed suites, and more.
• Genetic testing to determine elevated risk to aminoglycoside ototoxicity.
• Expand the research in aminoglycoside use and safety.
• Advise regular hearing screening in the first few years of life.

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More information on ototoxicity: http://www.asha.org/public/hearing/Ototoxic-Medications/

Recommended resources:

White RD. Designing environments for developmental care. Clin Perinatol 2011; 38:745–749.

White RD. The newborn intensive care unit environment of care: how we got here, where we’re headed, and why. Semin Perinatol 2011; 35:2–7.

Refs:

Joint Committee on infant hearing. Year 2007 position statement: principles and guidelines for early hearing detection and intervention programs. Pediatrics. 2007;120:898–921.

So, T. Y. (2009). Use of Ototoxic Medications in Neonates—The Need for Follow-Up Hearing Test. The Journal of Pediatric Pharmacology and Therapeutics: JPPT, 14(4), 200.

Zimmerman, E., & Lahav, A. (2012). Ototoxicity in preterm infants: effects of genetics, aminoglycosides, and loud environmental noise. Journal of Perinatology, 33(1), 3-8.