Economic Burden of Congenital Cytomegalovirus Disease on Families in the United States
Round 1
Reviewer 1 Report
Comments and Suggestions for AuthorsThe manuscript addresses an important and understudied topic by examining the economic burden associated with congenital cytomegalovirus (cCMV), and the authors provide valuable descriptive evidence on family-level consequences. However, the current version requires substantial strengthening before it can meet the standards of a high-quality journal. The study is primarily descriptive, based on a cross-sectional web-based survey design involving caregivers, children, and siblings, with the stated objective of assessing family spillover effects and economic impacts. The following major concerns should be addressed.
- A major concern is that the manuscript’s novelty and theoretical contribution are not sufficiently established. Although estimating family spillover effects of cCMV is valuable, the manuscript does not clearly articulate what conceptual advancement it provides beyond existing cost-of-illness studies and economic burden frameworks. The authors should strengthen the contribution by positioning the study within broader theories of family spillover effects, caregiver burden, health economics, and societal costs of childhood disabilities. Recent literature has emphasized that environmental, social, and health outcomes should be examined through multidimensional pathways rather than isolated outcomes; for example, “Environmental Degradation in South Asia: Implications for Child Health and the Role of Institutional Quality and Globalization” demonstrates the importance of linking health consequences with broader socioeconomic mechanisms. Similarly, “Synergistic Impacts of Technological Advancement and Environmental Hazards on Social Change and Human Well-Being in South Asia” highlights the importance of understanding how external shocks translate into household and social consequences. The authors should clarify how their findings extend existing economic burden research and why this study provides new theoretical insights rather than only additional descriptive estimates.
- The literature review requires significant improvement because the current framing does not sufficiently identify the unresolved research gap. The manuscript acknowledges that family-level impacts of cCMV remain understudied, but the discussion should be expanded by critically comparing previous studies, explaining methodological limitations in existing evidence, and demonstrating why a comprehensive assessment of caregivers, affected children, and siblings is necessary. The authors should incorporate more recent interdisciplinary studies examining health disparities, socioeconomic vulnerability, and household consequences of health shocks. For example, “Navigating the Landscape of Child Health Insurance Coverage in Punjab, Pakistan: A Socioeconomic Perspective” provides an example of how socioeconomic characteristics shape access, vulnerability, and health-related outcomes, while “The Role of Environmental Concern in Shaping Support for Green Business Practices: Evidence from the World Values Survey” illustrates how individual-level perceptions and social factors can influence behavioral responses. Although these studies are not directly focused on cCMV, they provide useful perspectives on integrating socioeconomic dimensions into health-related analyses.
- The theoretical framework and hypothesis development are insufficiently developed. The manuscript mainly presents empirical objectives but does not establish a clear theoretical model explaining why cCMV generates economic costs, caregiver productivity losses, and family spillover effects. A stronger framework should explain the causal chain from disease severity and caregiving demands to medical expenditures, labor market consequences, psychological burden, and family welfare outcomes. The authors should consider incorporating established frameworks such as the family spillover model, human capital theory, and caregiver burden theory. Studies such as “Balancing Well-Being and Environment: The Moderating Role of Governance in Sustainable Development Amid Environmental Degradation” demonstrate the value of developing a theoretical mechanism explaining how external conditions influence well-being outcomes rather than only reporting associations.
- A major methodological concern relates to the representativeness and generalizability of the sample. The study relies on a convenience sample recruited through advocacy networks and online communities, which may introduce substantial selection bias because families experiencing greater burdens may be more likely to participate. The manuscript itself indicates that participants were recruited through the National Cytomegalovirus Foundation database, newsletters, social media groups, and community alliances. The authors should provide stronger justification for sample representativeness, compare participant characteristics with available epidemiological information, discuss potential non-response bias, and conduct sensitivity analyses where possible. The limitations section should also be expanded to explain how recruitment channels may affect estimates of economic burden.
- The measurement strategy requires additional clarification and validation. The manuscript combines multiple instruments and newly developed survey questions to estimate costs and health outcomes, but insufficient attention is given to measurement consistency, comparability, and potential reporting bias. The study uses different health utility instruments depending on age groups, including EQ-5D-5L, IQI, HuPS, and HUI measures. While this approach may be necessary, the authors should explain more clearly how differences across instruments were addressed and whether estimates are directly comparable. Furthermore, caregiver-reported diagnoses, costs, and productivity losses may suffer from recall bias and perception bias. The authors should provide additional robustness checks, validation procedures, or sensitivity analyses to evaluate the reliability of reported economic outcomes.
- The empirical analysis would benefit from a more rigorous analytical strategy. The manuscript mainly reports descriptive statistics, and no formal hypothesis testing or inferential modeling is conducted. While descriptive evidence is useful for estimating economic burden, a high-impact journal would expect deeper analytical investigation into the determinants of variation in costs and health outcomes. The authors should consider multivariate regression models examining how disease severity, demographic characteristics, insurance status, socioeconomic conditions, and caregiving intensity influence economic burden. Such analysis would move the manuscript beyond reporting average costs and provide more meaningful implications for policymakers.
- The treatment of heterogeneity requires substantial improvement. The manuscript stratifies some outcomes by cCMV severity, but the mechanisms underlying differences across severity groups are not fully explored. The authors should investigate whether economic consequences differ systematically by caregiver characteristics, household income, employment status, insurance coverage, child age, and disease severity. A more detailed heterogeneity analysis would substantially strengthen the manuscript’s contribution.
- The discussion section requires deeper interpretation and stronger connection with policy implications. At present, the implications appear largely focused on acknowledging the existence of economic burden, but the manuscript should explain how findings translate into healthcare policy, family support programs, early screening strategies, insurance coverage decisions, and economic evaluation frameworks. The authors should avoid presenting costs merely as descriptive figures and instead discuss how these estimates can inform resource allocation and prevention strategies.
- The manuscript would also benefit from a more comprehensive discussion of limitations and future research directions. Although the authors acknowledge several limitations, including the cross-sectional design and survey-based approach, they should more explicitly discuss the inability to establish causal relationships, possible recall errors, limited external validity, and the absence of longitudinal evidence. Future research should examine how economic burden evolves over time as children age, whether interventions reduce caregiver costs, and how healthcare systems influence family outcomes.
Author Response
From the authors: Please find out point-by-point responses to your comments copied here and attached as a separate document for convenience.
Reviewer #1
Comments to the Author
The manuscript addresses an important and understudied topic by examining the economic burden associated with congenital cytomegalovirus (cCMV), and the authors provide valuable descriptive evidence on family-level consequences. However, the current version requires substantial strengthening before it can meet the standards of a high-quality journal. The study is primarily descriptive, based on a cross-sectional web-based survey design involving caregivers, children, and siblings, with the stated objective of assessing family spillover effects and economic impacts. The following major concerns should be addressed.
Comment 1: A major concern is that the manuscript’s novelty and theoretical contribution are not sufficiently established. Although estimating family spillover effects of cCMV is valuable, the manuscript does not clearly articulate what conceptual advancement it provides beyond existing cost-of-illness studies and economic burden frameworks. The authors should strengthen the contribution by positioning the study within broader theories of family spillover effects, caregiver burden, health economics, and societal costs of childhood disabilities. Recent literature has emphasized that environmental, social, and health outcomes should be examined through multidimensional pathways rather than isolated outcomes; for example, “Environmental Degradation in South Asia: Implications for Child Health and the Role of Institutional Quality and Globalization” demonstrates the importance of linking health consequences with broader socioeconomic mechanisms. Similarly, “Synergistic Impacts of Technological Advancement and Environmental Hazards on Social Change and Human Well-Being in South Asia” highlights the importance of understanding how external shocks translate into household and social consequences. The authors should clarify how their findings extend existing economic burden research and why this study provides new theoretical insights rather than only additional descriptive estimates.
Response 1: This was pragmatic research designed to inform specific evidence gaps critical for future health economic modelling assessments of CMV prevention strategies. As stated in the Introduction, there is a paucity of data on the family spillover effects of children with cCMV disease in the US and global population; while many studies have examined the short-term costs of cCMV, few have quantified the economic and health status family spillover effects of caring for a child with cCMV, which are critical to inform the full economic and societal impact of the disease. As stated in the Discussion, to our knowledge, this is the first US study to estimate the financial family spillover associated with childhood cCMV, contributing critical evidence toward a more comprehensive understanding of the economic burden of cCMV on families and society. Indeed, as you mention in your introductory comments, “this manuscript addresses an important and understudied topic…”
It is important to note that this work was not designed as a theoretical piece nor to provide insights into broader socioeconomic mechanisms. The literature you mention above is wholly unrelated to the key topics covered in this manuscript, including cCMV, family spillover effects, or caregiver burden, and thus would be inappropriate to include in our focused and cohesive review of the literature. In response to your comment, we have strengthened the Introduction by explicitly noting that “The conceptual framework for assessing lifetime economic burden of cCMV in the US by Lucas et al. (2019) guided our approach.”
Comment 2: The literature review requires significant improvement because the current framing does not sufficiently identify the unresolved research gap. The manuscript acknowledges that family-level impacts of cCMV remain understudied, but the discussion should be expanded by critically comparing previous studies, explaining methodological limitations in existing evidence, and demonstrating why a comprehensive assessment of caregivers, affected children, and siblings is necessary. The authors should incorporate more recent interdisciplinary studies examining health disparities, socioeconomic vulnerability, and household consequences of health shocks. For example, “Navigating the Landscape of Child Health Insurance Coverage in Punjab, Pakistan: A Socioeconomic Perspective” provides an example of how socioeconomic characteristics shape access, vulnerability, and health-related outcomes, while “The Role of Environmental Concern in Shaping Support for Green Business Practices: Evidence from the World Values Survey” illustrates how individual-level perceptions and social factors can influence behavioral responses. Although these studies are not directly focused on cCMV, they provide useful perspectives on integrating socioeconomic dimensions into health-related analyses.
Response 2: Please see our response to comment 1.
Comment 3: The theoretical framework and hypothesis development are insufficiently developed. The manuscript mainly presents empirical objectives but does not establish a clear theoretical model explaining why cCMV generates economic costs, caregiver productivity losses, and family spillover effects. A stronger framework should explain the causal chain from disease severity and caregiving demands to medical expenditures, labor market consequences, psychological burden, and family welfare outcomes. The authors should consider incorporating established frameworks such as the family spillover model, human capital theory, and caregiver burden theory. Studies such as “Balancing Well-Being and Environment: The Moderating Role of Governance in Sustainable Development Amid Environmental Degradation” demonstrate the value of developing a theoretical mechanism explaining how external conditions influence well-being outcomes rather than only reporting associations.
Response 3: Please see our response to comment 1.
Comment 4: A major methodological concern relates to the representativeness and generalizability of the sample. The study relies on a convenience sample recruited through advocacy networks and online communities, which may introduce substantial selection bias because families experiencing greater burdens may be more likely to participate. The manuscript itself indicates that participants were recruited through the National Cytomegalovirus Foundation database, newsletters, social media groups, and community alliances. The authors should provide stronger justification for sample representativeness, compare participant characteristics with available epidemiological information, discuss potential non-response bias, and conduct sensitivity analyses where possible. The limitations section should also be expanded to explain how recruitment channels may affect estimates of economic burden.
Response 4: We agree that the representativeness and generalizability of the sample may be limited to the families of children with moderate or severe cCMV disease as our study relies on a convenience sample recruited through advocacy channels. However, given that cCMV is underdiagnosed, not nationally reportable in the US, and substantially less recognized than other causes of childhood disability, there are limited representative data on the epidemiology and sociodemographic characteristics of this disease population. Of note, eligible families in our study resided in 44 of 50 states, demonstrating geographic diversity. We have expanded the verbiage in the limitations section to say: “The survey was administered in English language only and relied on a convenience sample of families who elected to participate, with 90% of caregivers identifying as female, White, or having a college-level education, raising the possibility of selection and responder bias, thus limiting generalizability.”
Comment 5: The measurement strategy requires additional clarification and validation. The manuscript combines multiple instruments and newly developed survey questions to estimate costs and health outcomes, but insufficient attention is given to measurement consistency, comparability, and potential reporting bias. The study uses different health utility instruments depending on age groups, including EQ-5D-5L, IQI, HuPS, and HUI measures. While this approach may be necessary, the authors should explain more clearly how differences across instruments were addressed and whether estimates are directly comparable. Furthermore, caregiver-reported diagnoses, costs, and productivity losses may suffer from recall bias and perception bias. The authors should provide additional robustness checks, validation procedures, or sensitivity analyses to evaluate the reliability of reported economic outcomes.
Response 5: We reviewed the literature closely and used validated, age-appropriate survey instruments where available. We also conducted cognitive debriefing interviews to refine all newly developed survey instruments and included careful eligibility requirements to minimize recall bias and perception bias (e.g., eligible caregivers only provided primary care to the child with cCMV and did not provide care for another individual with disabilities or medical needs). Furthermore, we have included the full survey questionnaires in the S materials in order to provide clarity and transparency, as well as providing detailed scores stratified by age / health utility instrument and cCMV symptom severity at birth (Supplemental Table 4). For example, we note in the Discussion that “The HUI was selected for its sensitivity to domains central to cCMV morbidity, particularly hearing loss, while the HuPS was used for younger children and harmonized with the HUI3 to enable continuous, commensurate utility measurement beginning at age 2 years.” Additionally, the verbiage in the limitation section currently says: “The wide age range of participants necessitated the use of multiple utility instruments and modes of administration, which may not be fully comparable despite efforts to harmonize measures.”
Comment 6: The empirical analysis would benefit from a more rigorous analytical strategy. The manuscript mainly reports descriptive statistics, and no formal hypothesis testing or inferential modeling is conducted. While descriptive evidence is useful for estimating economic burden, a high-impact journal would expect deeper analytical investigation into the determinants of variation in costs and health outcomes. The authors should consider multivariate regression models examining how disease severity, demographic characteristics, insurance status, socioeconomic conditions, and caregiving intensity influence economic burden. Such analysis would move the manuscript beyond reporting average costs and provide more meaningful implications for policymakers.
Response 6: Thank you for the feedback. As noted in the Methods, the a priori objectives of this study were descriptive; no power calculations or formal statistical hypothesis testing was performed. Furthermore, descriptive / unadjusted data are generally preferred for health economic modelling inputs. However, we agree that multivariable models examining how disease severity, demographic characteristics, insurance status, socioeconomic conditions, and caregiving intensity influence economic burden of cCMV is an interesting line of inquiry – in fact our team has recently published other complementary studies on this topic – e.g., Diaz-Decaro et al. (2025) https://doi.org/10.1016/j.clinthera.2025.03.006 and Buck et al (2025) https://doi.org/10.1080/03007995.2025.2554734. We have added the following verbiage to the Discussion: “Future research should utilize multivariable analyses to explore how factors such as cCMV symptom severity at birth and future sequalae, child demographic characteristics and socioeconomic conditions, and caregiver and household attributes influence family spillover effects associated with cCMV.”
Comment 7: The treatment of heterogeneity requires substantial improvement. The manuscript stratifies some outcomes by cCMV severity, but the mechanisms underlying differences across severity groups are not fully explored. The authors should investigate whether economic consequences differ systematically by caregiver characteristics, household income, employment status, insurance coverage, child age, and disease severity. A more detailed heterogeneity analysis would substantially strengthen the manuscript’s contribution.
Response 7: Thank you for the feedback, we agree that this would be an interesting future line of inquiry; however, it was not the objective of the current study. Please see our response to comment 6.
Comment 8: The discussion section requires deeper interpretation and stronger connection with policy implications. At present, the implications appear largely focused on acknowledging the existence of economic burden, but the manuscript should explain how findings translate into healthcare policy, family support programs, early screening strategies, insurance coverage decisions, and economic evaluation frameworks. The authors should avoid presenting costs merely as descriptive figures and instead discuss how these estimates can inform resource allocation and prevention strategies.
Response 8: Thanks for your feedback. Again, this research was a first step designed to inform specific evidence gaps critical for future health economic modelling assessments of CMV prevention strategies. We clearly state as much in the Discussion: “Incorporating family spillover effects into economic evaluations is therefore essential for accurately estimating the societal value of cCMV prevention and intervention strategies, including vaccines, maternal antiviral therapies, and newborn screening programs. By quantifying health state utilities and indirect costs across affected children and family members, this study provides critical input parameters for cost-effectiveness models and national cost-of-illness estimates, thereby strengthening the evidence base needed to inform policy decisions and prioritize investments in cCMV prevention and care.”
Comment 9: The manuscript would also benefit from a more comprehensive discussion of limitations and future research directions. Although the authors acknowledge several limitations, including the cross-sectional design and survey-based approach, they should more explicitly discuss the inability to establish causal relationships, possible recall errors, limited external validity, and the absence of longitudinal evidence. Future research should examine how economic burden evolves over time as children age, whether interventions reduce caregiver costs, and how healthcare systems influence family outcomes.
Response 9: Thank you for your comment. We have added the following paragraph on future research directions to the Discussion: “Future research in this area should utilize multivariable analyses to explore how predictors such as cCMV symptom severity at birth and future sequalae, child demographic characteristics and socioeconomic conditions, and caregiver / household attributes influence family spillover effects associated with cCMV. Additionally, as universal newborn screening (NBS) programs for cCMV expand in the US (e.g., Minnesota implemented statewide universal NBS in February 2023 and Connecticut implemented statewide universal NBS in July 2025), increasing numbers of infants are being diagnosed before symptoms emerge. Among the many opportunities for research that these innovative programs will create, longitudinal data collection on the economic burden of cCMV will be critical and allow examination of how costs evolve over time as children age, as well as whether interventions and modifiable healthcare practices reduce caregiver costs and improve family outcomes.”
We have also expanded the verbiage in the limitations section to say: “Moreover, because data were collected at a single timepoint per child and the sample skewed toward younger ages, long-term trajectories and lifetime costs of cCMV were not fully captured, and we were unable to establish causal relationships.”
Author Response File: 
Author Response.pdf
Reviewer 2 Report
Comments and Suggestions for AuthorsCongratulations on this important research.
I only have minor comments for your consideration at this time:
Introduction
Sentence at Line 39 is confusing for the reader. Consider rephrasing to - something like: Maternal CMV infection can result in adverse prebirth impacts (eg miscarriage) and babies born with CMV can experience life-long impacts including………….
Line 45 is also a little unclear. What is described is the severity of symptoms/sequale not the severity of congenital CMV as stated. Consider rephasing.
In the background it would be helpful to let readers outside of the US know what costs are usually covered by government or insurance? Are allied health costs mostly covered meaning that what you are reporting here constitutes the remaining costs? Or do families need to cover the total costs of allied health services? What is the situation for families who do not have health insurance - are their out-of -pocket costs potentially much greater or not? Also be good to know whether house adaptions and bathroom and mobility equipment etc are usually covered by government/insurance or not in the US - this would place some of the results in a clearer context for readers outside of the US.
Otherwise the introduction is great – provides background, highlights the knowledge gap and why it is important.
Materials and methods
Figure 1. It is a little unclear why Method 1 is on the left of the figure – and not included with the other Methods 2,3,4 in the blue boxes?
Line 164/5 see above comment re Severity of symptoms/sequelae rather than severity of cCMV.
Results
See line 179 as per comment above.
Table 1. Would it be possible to put the headings for each variable justified to the Left, or bolded or have the row shaded. This would make the Table easier to read.
Most respondents were white – was this expected? Consider commenting on this in the discussion perhaps?
The cost of home adaptions seem low at $4,713 – is this mostly subsidised by government or other agencies in the US? Were most children ambulant? A hoist or bathroom adaptions or adaptions to access the house e.g. a ramp etc is usually considerable – perhaps these costs are included elsewhere or subsidised by government/other agencies?
Table 2. Same comment re making the variable headings easier to read. Table 2 is actually very difficult to follow. It’s unclear as to what the TOTALs are tallying and where variables begin and end. Some variables have a TOTAL row and other’s do not. But very difficult to discern why.
It would be good to understand more about the children’s clinical presentation i.e. their functional limitations – but perhaps this is not available? A child with isolated mild unilateral hearing impairment versus a child with bilateral spastic cerebral palsy would have different costs. I note this is somewhat discussed in paragraph starting line 261 and in section 3.5. Similarly younger children with greater impacts may not require use of wheeled mobility aids/hoists etc as yet as their family are still able to manually lift them.
It would be good to note the involvement of people with lived experience of CMV as authors/research partners in the strengths of this study. Good example for other researchers working in this space.
Author Response
From the authors: Please find out point-by-point responses to your comments copied here and attached as a separate document for convenience.
Reviewer #2
Comments to the Author
Comment 1: Congratulations on this important research. I only have minor comments for your consideration at this time:
Response 1: Thank you for the positive feedback!
Introduction
Comment 2: Sentence at Line 39 is confusing for the reader. Consider rephrasing to - something like: Maternal CMV infection can result in adverse prebirth impacts (eg miscarriage) and babies born with CMV can experience life-long impacts including………….
Response 2: Thank you for the suggestion, we have rephrased to say “Maternal CMV infection can result in adverse prebirth impacts (e.g., miscarriage) and babies born with CMV can experience life-long impacts including…”
Comment 3: Line 45 is also a little unclear. What is described is the severity of symptoms/sequale not the severity of congenital CMV as stated. Consider rephasing.
Response 3: Thank you for the suggestion, we have rephrased to say “The severity of symptoms associated with cCMV at birth can be categorized as…”
Comment 4: In the background it would be helpful to let readers outside of the US know what costs are usually covered by government or insurance? Are allied health costs mostly covered meaning that what you are reporting here constitutes the remaining costs? Or do families need to cover the total costs of allied health services? What is the situation for families who do not have health insurance - are their out-of -pocket costs potentially much greater or not? Also be good to know whether house adaptions and bathroom and mobility equipment etc are usually covered by government/insurance or not in the US - this would place some of the results in a clearer context for readers outside of the US.
Response 4: Healthcare coverage in the US for a child with cCMV depends mostly on insurance type (private, public / Medicaid-eligible, or no insurance). Most states have pathways that let a child with a significant disability qualify for Medicaid based on the child's income / assets only (disregarding parental income entirely), but this varies significantly by state. Private insurance coverage is also not one size fits all, with benefits varying based on the specific plan. In general, allied health is close to comprehensively covered, but families frequently do end up paying meaningful out-of-pocket costs for care that exceed visit caps, plus copays and deductibles. Durable medical equipment such as hearing aids and communication devices are generally covered when documented as medically necessary, but house adaptions such as wheelchair ramps and bathroom accessibility renovations are typically excluded. The main way families get help with the latter is through Medicaid Home and Community-Based Services waivers, which are separate, state-specific programs, often with a lifetime cap and significant waitlists. Otherwise, families often patch together nonprofit grants, tax-deductible medical-expense treatment for the modification costs, or just pay out-of-pocket.
We have added health insurance coverage to Table 1 for context and the following verbiage to the Discussion to address this: “Of note, healthcare coverage in the US for a child with cCMV depends mostly on insurance type (e.g., private, public / Medicaid-eligible, no insurance), but this is also impacted by the state of residence as well as the specific private insurance plan. Allied health is close to comprehensively covered, but families frequently end up paying meaningful out-of-pocket costs for care that exceed visit caps, plus copays and deductibles. Durable medical equipment such as hearing aids and communication devices are generally covered, but house adaptions such as wheelchair ramps and bathroom accessibility renovations are typically excluded.”
Comment 5: Otherwise the introduction is great – provides background, highlights the knowledge gap and why it is important.
Response 5: Thank you again!
Materials and methods
Comment 6: Figure 1. It is a little unclear why Method 1 is on the left of the figure – and not included with the other Methods 2,3,4 in the blue boxes?
Response 6: Method 1 was our initial / primary source of recruitment, and we only transitioned to using Methods 2-4 if we hadn’t met our enrollment target after pre-specified periods of recruitment time: 4 weeks for Method 2, 12 weeks for Method 3, and 14 weeks for Method 4. As such, Method 1 precedes the other Methods and so we felt that it would be most intuitive to keep it separate and on the left side of the figure.
Comment 7: Line 164/5 see above comment re Severity of symptoms/sequelae rather than severity of cCMV.
Response 7: We have rephrased to say “Stratification by Severity of Symptoms Associated with cCMV at Birth”
Results
Comment 8: See line 179 as per comment above.
Response 8: We have rephrased to say “cCMV symptom severity at birth was…”
Comment 9: Table 1. Would it be possible to put the headings for each variable justified to the Left, or bolded or have the row shaded. This would make the Table easier to read.
Response 9: Thank you for the suggestion – the headers were actually supposed to be bolded but the tables were reformatted by the journal. We have bolded them again.
Comment 10: Most respondents were white – was this expected? Consider commenting on this in the discussion perhaps?
Response 10: Given that cCMV is underdiagnosed, not nationally reportable in the US, and substantially less recognized than other causes of childhood disability, we did not have specific expectations regarding the racial / ethnic composition of the cohort. However, since 90% of caregivers identified as female, White, or had a college-level education, we have added this detail to the limitations section.
Comment 11: The cost of home adaptions seems low at $4,713 – is this mostly subsidised by government or other agencies in the US? Were most children ambulant? A hoist or bathroom adaptions or adaptions to access the house e.g. a ramp etc is usually considerable – perhaps these costs are included elsewhere or subsidised by government/other agencies?
Response 11: $4,713 is actually the mean total out-of-pocket costs for home adaptation as well as specialized schooling costs; the mean out-of-pocket costs of home modifications alone was $1,805. Almost half the cohort had a child with cCMV that was preschool age or younger, which likely limited the costs in this age group (as you note in your comment below), and the standard deviation was quite large ($7,103) compared to the mean, also suggesting a positively skewed distribution where most families reported no costs (the median was $0). This is supported by data showing home adaptation costs for families of children aged 5-7 and 8-17 were higher (mean: $2,389; standard deviation: $7,716 and mean: $3,715; standard deviation: $10,558, respectively) than for younger children. Overall, this implies that relatively few families reported out-of-pocket costs for home adaptation, but when reported, the costs were substantial. The current study focused on family out-of-pocket costs and did not collect any specific information regarding subsidies by the US government or other agencies; the former has now been emphasized in the Introduction and the following verbiage has been added to the limitations section: “The survey also focused on out-of-pocket costs and did not collect any information regarding subsidies by the US government or other agencies.”
Comment 12: Table 2. Same comment re making the variable headings easier to read. Table 2 is actually very difficult to follow. It’s unclear as to what the TOTALs are tallying and where variables begin and end. Some variables have a TOTAL row and other’s do not. But very difficult to discern why.
Response12: Thank you for the suggestion – similar to Table 1, the headers were actually supposed to be bolded but the tables were reformatted by the journal. We have bolded them again and reformatted / reorganized the rows to make this table easier to read.
Comment 13: It would be good to understand more about the children’s clinical presentation i.e. their functional limitations – but perhaps this is not available? A child with isolated mild unilateral hearing impairment versus a child with bilateral spastic cerebral palsy would have different costs. I note this is somewhat discussed in paragraph starting line 261 and in section 3.5. Similarly younger children with greater impacts may not require use of wheeled mobility aids/hoists etc as yet as their family are still able to manually lift them.
Response 13: Section 3.5 (and Supplemental Table 2) describe how caregiver-reported information about disease symptom severity at birth was used to assign an exploratory severity category based on the definitions reported by Rawlinson et al. (2017). We also collected caregiver-reported information about current symptoms and sequelae at the time of the survey; this information was used to assign a current severity category based on preliminary latent classes from then unpublished research by one of the co-authors (MHP; now published in Pollick et al. [2026] https://doi.org/10.1038/s41390-025-04327-z); however, this objective was very exploratory and was not included in the current manuscript.
Comment 14: It would be good to note the involvement of people with lived experience of CMV as authors/research partners in the strengths of this study. Good example for other researchers working in this space.
Response 14: Thank you for acknowledging this; verbiage has been added to the Discussion: “A final strength of this research on family spillover effects was the involvement of a mother of a child with cCMV (MHP) in terms of having lived experience with this disease.”
Author Response File: Author Response.pdf
Round 2
Reviewer 1 Report
Comments and Suggestions for AuthorsI appreciate the authors’ careful and constructive efforts in revising the manuscript. The comments and suggestions provided during the review process have been satisfactorily addressed, and the manuscript has improved considerably in terms of organization, clarity, and overall presentation. The revised version is substantially stronger and well prepared for publication. Therefore, I am pleased to recommend the manuscript for acceptance.
