Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants

BMC Pediatrics

Egbert Herting⁷  Christoph Härtel⁷  Michael Mögel¹  Ludwig Gortner⁶  Ursula Felderhoff-Müser³  Helmut Küster²  Andreas Ziegler⁵  Michael Preuss⁴  Sandra Berkowski⁷  Wolfgang Göpel⁷ 

[1] Department of Paediatrics, University Hospital Carl Gustav Carus, Dresden, Germany;Department of Paediatrics, Georg-August University, Göttingen, Germany;Department of Paediatrics, Essen University Hospital, Essen, Germany;Institute for Medical Biometry and Statistics, University of Lübeck, Lübeck, Germany;Center for Clinical Trials, University of Lübeck, Lübeck, Germany;Department of Paediatrics, University of Homburg, Homburg, Germany;Department of Paediatrics, University of Lübeck, University Hospital of Schleswig Holstein, Ratzeburger Allee 160, G-23538 Lübeck, Germany

关键词: Mutation;    Mitochondrial;    Hearing loss;    Screening;    Newborn;   

Others  :  1137309
DOI  :  10.1186/1471-2431-14-210

 received in 2014-02-25, accepted in 2014-08-15,  发布年份 2014

【 摘 要 】

Background

The mitochondrial m.1555A>G mutation is associated with a high rate of permanent hearing loss, if aminoglycosides are given. Preterm infants have an increased risk of permanent hearing loss and are frequently treated with aminoglycoside antibiotics.

Methods

We genotyped preterm infants with a birth weight below 1500 grams who were prospectively enrolled in a large cohort study for the m.1555A>G mutation. Treatment with aminoglycoside antibiotics in combination with mitochondrial m.1555A>G mutation was tested as a predictor for failed hearing screening at discharge in a multivariate logistic regression analysis.

Results

7056 infants were genotyped and analysed. Low birth weight was the most significant predictor of failed hearing screening (p = 7.3 × 10^-10). 12 infants (0.2%) had the m.1555A>G-mutation. In a multivariable logistic regression analysis, the combination of aminoglycoside treatment with m.1555A>G-carrier status was associated with failed hearing screening (p = 0.0058). However, only 3 out of 10 preterm m.1555A>G-carriers who were exposed to aminoglycosides failed hearing screening. The m.1555A>G-mutation was detected in all mothers of m.1555A>G-positive children, but in none of 2993 maternal DNA-samples of m.1555A>G-negative infants.

Conclusion

Antenatal screening for the m.1555A>G mutation by maternal genotyping of pregnant women with preterm labour might be a reasonable approach to identify infants who are at increased risk for permanent hearing loss. Additional studies are needed to estimate the relevance of cofactors like aminoglycoside plasma levels and birth weight and the amount of preterm m.1555A>G-carriers with permanent hearing loss.

【 授权许可】

   
2014 Göpel et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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