Open Access Open Badges Research article

Addition of host genetic variants in a prediction rule for post meningitis hearing loss in childhood: a model updating study

Marieke S Sanders12, Rogier CJ de Jonge13*, Caroline B Terwee4, Martijn W Heymans4, Irene Koomen5, Sander Ouburg2, Lodewijk Spanjaard6, Servaas A Morré27 and A Marceline van Furth1

Author Affiliations

1 Department of Pediatric Infectious Diseases - Immunology, and Rheumatology, VU University Medical Center, Amsterdam, The Netherlands

2 Department of Medical Microbiology, Laboratory for Immunogenetics, VU University Medical Center, Amsterdam, The Netherlands

3 Department of Neonatology, Erasmus MC - Sophia Children’s Hospital, Room Sp-3434, PO-box 2040, Rotterdam, 3000 CB The Netherlands

4 Department of Epidemiology and Biostatistics and the EMGO Institute for Health and Care Research, VU University Medical Center, Amsterdam, The Netherlands

5 Department of Pediatrics, Westfriesgasthuis, Hoorn, The Netherlands

6 Department of Medical Microbiology, Netherlands Reference Laboratory for Bacterial Meningitis, Academic Medical Center, Amsterdam, The Netherlands

7 Department of Genetics and Cell Biology, Institute for Public Health Genomics, Research Schools GROW and CAPHRI, Faculty of Health, Medicine & Life Sciences, University of Maastricht, Maastricht, The Netherlands

For all author emails, please log on.

BMC Infectious Diseases 2013, 13:340  doi:10.1186/1471-2334-13-340

Published: 23 July 2013



Sensorineural hearing loss is the most common sequela in survivors of bacterial meningitis (BM). In the past we developed a validated prediction model to identify children at risk for post-meningitis hearing loss. It is known that host genetic variations, besides clinical factors, contribute to severity and outcome of BM. In this study it was determined whether host genetic risk factors improve the predictive abilities of an existing model regarding hearing loss after childhood BM.


Four hundred and seventy-one Dutch Caucasian childhood BM were genotyped for 11 single nucleotide polymorphisms (SNPs) in seven different genes involved in pathogen recognition. Genetic data were added to the original clinical prediction model and performance of new models was compared to the original model by likelihood ratio tests and the area under the curve (AUC) of the receiver operating characteristic curves.


Addition of TLR9-1237 SNPs and the combination of TLR2 + 2477 and TLR4 + 896 SNPs improved the clinical prediction model, but not significantly (increase of AUC’s from 0.856 to 0.861 and from 0.856 to 0.875 (p = 0.570 and 0.335, respectively). Other SNPs analysed were not linked to hearing loss.


Although addition of genetic risk factors did not significantly improve the clinical prediction model for post-meningitis hearing loss, AUC’s of the pre-existing model remain high after addition of genetic factors. Future studies should evaluate whether more combinations of SNPs in larger cohorts has an additional value to the existing prediction model for post meningitis hearing loss.

Genetics; SNP; Risk; Prediction; Bacterial meningitis; Hearing loss; Child