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The response to our article was received with interest. Grosse and Lanzieri raise important points in connection with our recent paper , noting concerns that the paper overestimates the financial cost burden associated with congenital cytomegalovirus (cCMV). These points are contingent on our estimate that at least 50% total costs associated with cCMV stemmed from the cost of autism spectrum disorder (ASD) among individuals with cCMV.
First, Grosse and Lanzieri point out that an association between cCMV and ASD has not been conclusively established, citing a systematic review and meta-analysis by Maeyama et al. (2017) . We agree that there is uncertainty over this association and the prevalence estimates used (along with many of the other estimates), and have emphasised throughout our article that (i) the model is limited by the validity of the inputs, and (ii) more research is required to fully understand the epidemiology, aetiology and prognosis of cCMV. Indeed, Maeyama et al. (2017)  report a significant association between cCMV and ASD, but caution that these calculations are seriously limited by the infrequent number of events in the included studies. As we do, they stress the need for further research to clarify this issue.
Second, Grosse and Lanzieri suggest that the prevalence calculation of ASD attributable to cCMV should have been calculated as the proportion of cCMV individuals with ASD minus the proportion of non-cCMV individuals with AS...
Second, Grosse and Lanzieri suggest that the prevalence calculation of ASD attributable to cCMV should have been calculated as the proportion of cCMV individuals with ASD minus the proportion of non-cCMV individuals with ASD. While we understand the criticism of the calculation of ASD prevalence in cCMV, had we calculated the prevalence in the way suggested here (i.e. making assumptions that the underlying level of ASD in the cCMV population not attributable to the virus would match that observed in the non-cCMV population, and that this should be removed from our estimates) we would be treating ASD differently to the other impairments reported. For all impairments, the estimated number of children with cCMV affected by that impairment was used, not accounting for the level of diagnosis in the general population. We appreciate that where data are robust, the suggested approach would be advisable, but given the scarcity of prevalence studies for some impairments and level of variation in prevalence estimates for others, we sought to simplify assumptions as far as possible.
While our study aimed to estimate the financial burden of cCMV to the UK, we acknowledge, and indeed state in the discussion, that there is a lack of robust evidence for use as inputs into such an analysis. On the basis of the estimates we have imputed from the available data, we believe the true cost of cCMV is likely to be substantial. Our paper emphasises the need for further and more detailed research into both the costs and impairments associated with cCMV to allow greater accuracy in the calculation of cost estimates.
 Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV in the UK. Arch Dis Child 2018 doi: 10.1136/archdischild-2018-316010 [published Online First: 2018/11/26]
 Maeyama K, Tomioka K, Nagase H, et al. Congenital cytomegalovirus infection in children with autism spectrum disorder: systematic review and meta-analysis. J Autism Dev Disord 2018;48(5):1483-91. doi: 10.1007/s10803-017-3412-x [published Online First: 2017/12/01]
Retzler et al. report estimates of the economic cost of congenital cytomegalovirus (cCMV) in the United Kingdom.1 The projected costs of autism spectrum disorder (ASD) among persons with cCMV accounted for at least 50% of the total costs attributed to cCMV. However, an association between cCMV and ASD has not been conclusively established,2 and, in their analysis, Retzler et al. did not take into account the cost of ASD among children without cCMV.
Retzler et al. used published ASD prevalence estimates from a Dutch study of >30,000 children screened for cCMV at 6 years of age using stored dried blood specimens, of whom 133 were CMV-positive. Of 26 children classified with symptomatic cCMV, 2 (7.7%) had ASD, as did 2/107 (1.9%) with asymptomatic cCMV.3 Retzler et al. assumed 11% of children with cCMV are symptomatic, which implies a weighted average ASD prevalence of 2.5% among children with cCMV. Five of 274 (1.8%) matched children without cCMV in the Dutch study also had ASD. If ASD were causally associated with cCMV, which has not been shown, the cost of ASD attributable to cCMV would be the cost difference of ASD among children with and without cCMV. Therefore, the projected cost of cCMV has been overestimated. Moreover, if the reported association of cCMV with ASD turns out to be non-causal, the total cost of cCMV could be half that estimated by Retzler et al.
1. Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV...
1. Retzler J, Hex N, Bartlett C, et al. Economic cost of congenital CMV in the UK. Arch Dis Child 2018 doi: 10.1136/archdischild-2018-316010 [published Online First: 2018/11/26]
2. Maeyama K, Tomioka K, Nagase H, et al. Congenital cytomegalovirus infection in children with autism spectrum disorder: systematic review and meta-analysis. J Autism Dev Disord 2018;48(5):1483-91. doi: 10.1007/s10803-017-3412-x [published Online First: 2017/12/01]
3. Korndewal MJ, Oudesluys-Murphy AM, Kroes ACM, et al. Long-term impairment attributable to congenital cytomegalovirus infection: a retrospective cohort study. Dev Med Child Neurol 2017;59(12):1261-68. doi: 10.1111/dmcn.13556 [published Online First: 2017/10/11]