Abstract

Neonates administered ethanol-containing medicines are potentially at risk of dose-dependent injury through exposure to ethanol and its metabolite, acetaldehyde. Here, we determine blood ethanol and acetaldehyde concentrations in 49 preterm infants (median birth weight = 1190 g) dosed with iron or furosemide, medicines that contain different amounts of ethanol, and in 11 control group infants (median birth weight = 1920 g) who were not on any medications. Median ethanol concentrations in neonates administered iron or furosemide were 0.33 (range = 0–4.92) mg/L, 0.39 (range = 0–72.77) mg/L and in control group infants were 0.15 (range = 0.03–5.4) mg/L. Median acetaldehyde concentrations in neonates administered iron or furosemide were 0.16 (range = 0–8.89) mg/L, 0.21 (range = 0–2.43) mg/L and in control group infants were 0.01 (range = 0–0.14) mg/L. There was no discernible relationship between blood ethanol or acetaldehyde concentrations and time after medication dose.Conclusion: Although infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure. The data suggest the need to account for the effects of acetaldehyde in the benefit-risk analysis of administering ethanol-containing medicines to neonates. What is Known: • Neonates are commonly treated with ethanol-containing medicines, such as iron and furosemide. • However, there is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde. What is New: • In this study, we find low blood ethanol concentrations in neonates administered iron and/or furosemide but markedly elevated blood acetaldehyde concentrations in some infants receiving these medicines. • Our data suggest that ethanol in drugs may cause elevation of blood acetaldehyde, a potentially toxic metabolite.

Highlights

  • Preterm neonates are often chronically treated with oral liquid formulation medicines that contain ethanol as an excipient [12, 13, 20, 22]

  • Conclusion: infants dosed with iron or furosemide had low blood ethanol concentrations, blood acetaldehyde concentrations were consistent with moderate alcohol exposure

  • There is no data on whether this leads to appreciable increases in blood concentrations of ethanol or its metabolite, acetaldehyde

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Summary

Introduction

Preterm neonates are often chronically treated with oral liquid formulation medicines that contain ethanol as an excipient [12, 13, 20, 22]. In this context, ethanol is used as an organic phase co-solvent. Exposure to ethanol in utero is associated with fetal alcohol syndrome [2]. Since pre- and post- natal organ development correlates with age, it follows that neonates born prematurely and exposed to ethanol could be at risk of ‘ex utero fetal alcohol syndrome’. As ethanol effects in adults correlate with blood ethanol concentrations [24], it is likely that adverse effects of ethanol in preterm infants will correlate with blood ethanol concentrations

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