title: Mitochondrial mutation m.1555A>G as a risk factor for failed newborn hearing screening in a large cohort of preterm infants.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Paediatrics, University of Lübeck, University Hospital of Schleswig Holstein, Ratzeburger Allee 160, G-23538 Lübeck, Germany. wolfgang.goepel@uksh.de.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Göpel
authors.forename: Sandra
authors.initials: S
authors.lastname: Berkowski
authors.forename: Michael
authors.initials: M
authors.lastname: Preuss
authors.forename: Andreas
authors.initials: A
authors.lastname: Ziegler
authors.forename: Helmut
authors.initials: H
authors.lastname: Küster
authors.forename: Ursula
authors.initials: U
authors.lastname: Felderhoff-Müser
authors.forename: Ludwig
authors.initials: L
authors.lastname: Gortner
authors.forename: Michael
authors.initials: M
authors.lastname: Mögel
authors.forename: Christoph
authors.initials: C
authors.lastname: Härtel
authors.forename: Egbert
authors.initials: E
authors.lastname: Herting
mesh_terms: D000617:Aminoglycosides / Q000008:administration & dosage / Q000009:adverse effects; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects; D015331:Cohort Studies; D004272:DNA, Mitochondrial / Q000235:genetics*; D005260:Female; D034381:Hearing Loss / Q000175:diagnosis* / Q000235:genetics; D006320:Hearing Tests; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D019102:Infant, Very Low Birth Weight; D008297:Male; D009154:Mutation; D015997:Neonatal Screening; D012307:Risk Factors
chemical_list: D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D004272:DNA, Mitochondrial