Disease-modifying therapies for spinal muscular atrophy: Family experience,ethical considerations,and the role of social determinants of health

Abstract

Objectives:

Spinal muscular atrophy is a progressive neuromuscular condition associated with a complex chronic disease course. An in-depth understanding of the ethical issues and social determinants of health impacting the experiences of families and children living with this condition is critical to improving care delivery. We identified the ethical tensions faced by families caring for children with spinal muscular atrophy as well as the influence of social determinants of health in relation to their perception of novel disease-modifying therapies.

Design:

Qualitative study including semi-structured interviews with caregivers of children with spinal muscular atrophy who received disease-modifying therapies. Interviews were audio recorded, transcribed verbatim, and coded. Thematic analysis was utilized to identify ethically salient themes.

Setting:

The Hospital for Sick Children (Toronto, Canada)

Results:

Fifteen family caregivers of children with spinal muscular atrophy type 1 (n = 5), type 2 (n = 5), and type 3 (n = 5) participated. There were three core themes highlighted including (1) best interests of the child, (2) burden of care and associated moral distress, and (3) parent agency. These experiences were impacted by resources and social determinants of health.

Conclusion:

This study provides important insights into the ethical tensions and relevant social determinants of health impacting the caregiver experience. Understanding the experiences of diverse families will allow more appropriate resource distribution, better counselling and supports for families facing unique psychosocial challenges and treatment burdens, and overall improved delivery of patient and family-centered care.

Keywords

spinal muscular atrophy qualitative nusinersen onasemnogene abeparvovec risdiplam

Introduction

Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder characterized by motor decline, respiratory insufficiency and orthopedic complications.^1–4 Novel disease-modifying therapies have improved life expectancy^5–7 particularly with early treatment afforded by newborn screening programs.⁸ These therapies include (1) onasemnogene abeparvovec, a one-time gene replacement therapy delivered intravenously, (2) nusinersen, an antisense oligonucleotide delivered intrathecally at regular intervals, and (3) risdiplam, a small molecule splicing modifier drug delivered orally.

In this new era, children with SMA and their families face a high burden of morbidity, medical care needs,^9,10 and prognostic uncertainty.¹¹ Decision-making is complex for people with SMA and their caregivers^12–15 as well as practitioners,¹⁶ and heavily influenced by the local clinical setting and resource availability.^17,18 Social determinants of health (e.g., education access and quality, health care and quality, neighborhood and built environment, social and community context, and economic stability as categorized by the Centers for Disease Control and Prevention (CDC))¹⁹ influence how caregivers approach decision-making both as direct and indirect factors. The social determinants of health have significant implications for children living with medical complexity and life-limiting illnesses. Lower socioeconomic status groups are disproportionately impacted by work disruption and the financial burden of caring for a child with medical complexity, more affected by issues of stigma,^20,21 and less likely to access advanced care resources.²² These social considerations are intricately related to the Four Principles of Western biomedical ethics including (1) beneficence - working in the best interest of the child, (2) nonmaleficence (i.e, refraining from or minimizing harm), (3) autonomy - self-determination, and (4) justice, including equity and distributive justice.²³ Better appreciation of the ethical and social factors affecting the care experience of children with SMA can improve the ability of clinicians to deliver family-centered care, address unique challenges faced by families, and participate in decision-making conversations about the type of disease-modifying therapy to initiate.

To our knowledge, no studies to date have examined the personal, psychosocial and systemic factors influencing the care experience of children and families with SMA following the advent of disease-modifying therapies. Using the Four Principles Bioethics framework and the CDC framework for social determinants of health, the aim of this present study was to explore the ethical issues and social determinants of health impacting the care experiences of caregivers for children with SMA receiving disease-modifying therapies within a publicly funded healthcare system.

Methods

A qualitative study was conducted. Research ethics board approval was obtained from The Hospital for Sick Children (1000077616) and written consent was obtained from the caregivers as no children were capable to provide consent themselves. The study was conducted and reported in accordance with the Consolidated Criteria for Reporting Qualitative studies.²⁴

Setting and sampling

The caregivers of children who received onasemnogene abeparvovec, risdiplam, or nusinersen were recruited from the SMA Clinic at The Hospital for Sick Children (Toronto, Canada). The patient population included children who were symptomatic as well as presymptomatic at the time of diagnosis. At the time of study implementation, disease-modifying therapies were offered to all patients who met regional reimbursement criteria. However, many of the children included in this study received disease-modifying therapies through alternative pathways before Health Canada approval was obtained and/or regional reimbursement criteria were established. In Canada, onasemnogene abeparvovec was approved in 2020, nusinersen was approved in 2017, and risdiplam was approved in 2021.

Purposive sampling with maximum variation regarding SMA severity and child's age was used to ensure a wide range of perspectives. Further details on the setting can be found in Xiao et al.²⁵

Data collection

Semi-structured interviews were conducted virtually from January to June 2022. The interview guide involved a semi-structured discussion about experiences with disease-modifying therapies, healthcare delivery, care experiences, and social determinants of health. The interviewer was not known to the caregivers. Demographic and clinical data were collected from the electronic medical record.

Data analysis

Interviews were audio recorded, transcribed verbatim, manually de-identified, and proofread for corrections. Inductive thematic analysis was performed and guided by a narrative bioethics approach that posits that moral insights are made accessible through story-telling.²⁶ The aim of the analysis was to explore ethically salient features of social determinants of health and the core ethical tensions of best practice, disability ethics and moral distress as they pertain to caregiver experience with SMA and novel therapeutics. The authors (LX, RA, DD, MM, SK) independently reviewed the transcripts and three authors (LX, DD, SK) identified recurring codes using NVivo (QSR International, United States). The emerging codes were compared and revised until consensus was achieved amongst authors (LX, RA, DD, MM, SK). Rigor was established through prolonged engagement and peer debriefing. The emerging themes informed the development of a conceptual model for the caregiver experience in the era of disease-modifying therapies. This manuscript focuses on experiences at the level of the individual patient and caregiver whereas experiences at the level of the healthcare system were reported elsewhere.²⁵

Results

Fifteen family caregivers of children with spinal muscular atrophy type 1 (n = 5), type 2 (n = 5), and type 3 (n = 5) participated (see Table 1). Of these children, 14 received nusinersen as their first disease-modifying therapy while one child received risdiplam as their first disease-modifying therapy. Disease-modifying therapies were initiated at a median of 2.0 years (IQR 0.72, 2.6 years) after regulatory approval by Health Canada was issued for the corresponding disease-modifying therapy. There were six children (40%) who had enteral feeding tubes, two children (13%) who required invasive ventilation via tracheostomy, three children (20%) requiring non-invasive ventilation, and six children (40%) receiving mechanical in-exsufflation. For additional demographic characteristics, please refer to Xiao et al.²⁵

Table 1.

Characteristics of children.

	n (%)
Sex
Female	5 (33)
Male	10 (67)
Age at interview (years)
0–1	2 (13)
2–3	4 (27)
4–6	1 (7)
7–10	5 (33)
11+	3 (20)
SMA type
1	5 (33)
2	5 (33)
3	5 (33)
Presence of symptoms when disease-modifying therapy initiated
Symptomatic	13 (86.7)
Presymptomatic	2 (13.3)
Age when first disease-modifying therapy initiated (years), median (IQR)^a	4.9 (0.42, 9.4)
Nusinersen	14 (93)
Onasemnogene Abeparvovec	4 (27)
Risdiplam	2 (13)

SMA: spinal muscular atrophy.

Nusinersen was the first disease-modifying therapy for 14 children; Risdiplam was the first disease-modifying therapy for one child.

Three core themes were identified that highlight the ethical tensions caregivers encounter and the impact of social determinants of health: 1) best interests of the child, 2) burden of care and associated moral distress, and 3) parental agency (see Table 2 and Figure 1).

Figure 1.

Conceptual model for the caregiver experience in the era of disease-modifying therapies.

Table 2.

Illustrative quotations.

Best interests of the child
Treatment impact on disease experience and expectations of outcome	Even though he's not able to walk, I think being able to sit and use his arms to play and interact with people has been a really great thing. (Caregiver 5)
Coping with disability and ableism	Parking is another issue because we always cannot find the accessible parking. You know, there's only four floors of parking right - four levels, and then each level only two assessable parking. How can you accommodate all these children? (Caregiver 12)
Balancing Quality of Life and Life-Sustaining Therapies	I think our goal with care is always just to keep him healthy… I think we've come into occasional problems where my goal is to keep him healthy and happy, but the care team wants to push the medical side a little bit more. (Caregiver 5)
	It's up to him because he's the one who needs to sleep with [non-invasive ventilation]. I cannot force him to. But sometimes he's asking to take it off and he doesn't want to put it back. Like we understand that it's what he needs, but he also needs to sleep and then if he doesn't want it, you cannot make him you know, do that. (Caregiver 14)
	So yeah, the first dose of [nusinersen] was really, really hard. And I couldn't leave the room. For the other doses, I left the room…So I saw, I basically saw everything. And after that, I cried. When they left the room, I really cried like, Oh, my God, how many? Like how many times we have to go through. (Caregiver 1)
Burden of Care and Associated Moral Distress
Caregiver responsibility and guilt	…it's our responsibility… we are parents, and we have to go through it. We cannot run from our responsibilities we have to do this. Both of us, we quit our jobs, we are not doing anything other than taking care of our kids. This is how we manage. (Caregiver 4)
Caregiver responsibility and guilt	This is the way we made her and this is the way we would have to raise her… Sometimes if I feel overwhelmed, I just say to myself, you know, just do what's necessary. (Caregiver 3)
Caregiver burden and identity loss	You're not only a mom, but you're a nurse. You're a caretaker, you're now a physiotherapist. All of the above, really. So it, it puts you into a category where you're not the typical parent. (Caregiver 13)
	The biggest impacts have been not being able to complete university and not being able to return to work, but those are decisions made based on dedicating my life right now to taking care of [child]… I've left my personal life on the side right now to make her the priority to take care of her and focus on her needs. (Caregiver 3)
	Taking care of her, you need to, you know, sacrifice and you need to quit your job. It's something that I didn't think I would do that before. Yeah, and then there's a lot of like, social life, you can't, you can't go out with your friends, you know… So a lot of the times I'm on my own. (Caregiver 12)
	How can I be a wife, a teacher, while also being his mom? (Caregiver 1)
	We were not able to focus very much on our daughter… because our mind is completely around [child with SMA]. (Caregiver 7)
	if I didn't know about SMA, I think I wouldn't pay attention to certain things. I wouldn't constantly check if he's breathing or if he can raise his hand or he's moving. You check neck control. Those are the kind of things, I wouldn't check because for me will come naturally.” (Caregiver 1)
Tension between grief and gratitude	Honestly, it was a death of dreams, but a blessing to be able to take care of her and see her grow and see her slowly meet little inch stones. It's hard because you mourn the fact of her not growing typically, but you're very thankful for the fact that she is alive. And she can talk to me, she can eat, she can laugh, she can play. It's tough mentally. It's very tough…. It's a constant grief that I live with. (Caregiver 13)
Parent agency
Family contexts and social determinants of health	Right now the government doesn't even have a program for SMA. And every time the social worker from [the hospital] tries to help me to get some kind of assistance or help… there is no help available for us. Even if there is a help available, we're not even qualified for it …. So it should be something that the government can jump in and help a family like us because not every family is wealthy. (Caregiver 10)
Family contexts and social determinants of health	All I can hope for is that… I can spend more time with her at least until God decides to you know, make whatever destiny he has for her and God gives me strength when that day comes. (Caregiver 3)
Therapeutic Alliance, Family-Centered Care and Expectations	When I go to [the hospital], honestly, I'm at peace… I know that, okay, he will be taken care of. (Caregiver 1)
	We feel comfortable and safe when we go [to the hospital]. (Caregiver 5)
	They’re basically just like a second family to us, because they know everything about my life. They know everything about [my child]. (Caregiver 10)
Supportive Resources	It was helpful to actually meet someone who faced this - same realities, the same situation. (Caregiver 1)

Best interests of the child

Caring for a child with SMA is complex and involves constant decision-making regarding treatments and care plans. Within the Four Principles framework, caregivers balanced their child's best interests and nonmaleficence by carefully weighing the risks and benefits of treatment courses through consideration of (1) treatment impact on disease experience, expectations of outcome, (2) coping with disability and ableism, and (3) balancing quality of life and life expectancy.

Treatment impact on disease experience and expectations of outcome

Expectations for treatment outcomes varied according to their child's functional status at the time of disease-modifying therapy initiation. Many caregivers also recognized the uncertainty of the future with disease-modifying therapies.

Many parents of presymptomatic children regarded onasemnogene abeparvovec as a potential “cure”, and accordingly had higher expectations for motor function: “So my hope is that he gets to walk. Like he gets to be normal.” (Caregiver 1) Caregiver goals for symptomatic children were more commonly centered around stability of current skills, maintenance of independence, and happiness or ability to communicate rather than desire to achieve advanced milestones like walking. For more severely affected children, the focus shifted toward longevity of life rather than function: “He is surviving.” (Caregiver 4) In cases of severely symptomatic children, many caregivers chose to pursue disease-modifying treatments because of seemingly minor gains of motor function that could significantly impact quality of life, such as finger mobility.

Coping with disability and ableism

Many caregivers described a tension between hoping for improvement and accepting disability. One caregiver commented that it can be very challenging to have such a contrast between cognitive and physical abilities, with their child being unable to do everything the child wishes. Many families also shared examples of accessibility challenges within the hospital and in the community related to accessible parking spots, availability of hoyer lifts, and accessible bathrooms. These experiences highlighted the neighborhood and built environment as a social determinant health indirectly influencing their access to appointments. Although home environmental modifications may be in place to improve mobility, these are not consistently available in the community: “At home we are okay, but when outside it's harder for him and harder for us too.” (Caregiver 2) The use of disease-modifying therapies did not eliminate the need for assistive devices amongst children who started treatments while symptomatic.

Balancing quality of life and life-sustaining therapies

Although disease-modifying therapies were generally viewed positively, some caregivers expressed distress about the process leading up to and receiving therapy administration. When it came to nusinersen therapy, the scheduling, preparation, general anesthesia, and pain related to injections were all sources of concern; “always the injection before and after is very stressful.” (Caregiver 12) Many caregivers also found sleep studies to be quite burdensome and non-invasive respiratory supports were often challenging due to child intolerance.

Considering the burdens associated with life-sustaining and disease-modifying therapies, the tension between optimizing quality of life while simultaneously maximizing life prolongation varied amongst caregivers. Most caregivers expressed the desire to strive for life prolongation, primarily in the form of obtaining disease-modifying therapies for their children. The minority of families described the importance of maintaining quality of life when considering the use of supportive therapies such as nocturnal non-invasive ventilation within the context of disease-modifying therapies.

Burden of care and associated moral distress

The mental and moral burden of navigating the balance between benefit and harm manifested in: (1) caregiver responsibility and guilt, (2) caregiver burden and identity loss, and (3) the tension between grief and gratitude.

Caregiver responsibility and guilt

Caregivers often described their responsibility to keep their child alive. Despite being tired and feeling overwhelmed, the responsibility to keep their child healthy and alive is both a source of strength and a source of moral conflict, as keeping their child alive may be in tension with the child's best interests relating to quality of life.

For some caregivers, this sense of responsibility was tied to feelings of guilt that they unknowingly passed on the disease-causing gene mutation for SMA. Some parents commented “there is always a part of me that will blame myself for it” (Caregiver 1) or that “we didn’t know we carried it… I would have probably chosen not to have children.” (Caregiver 8) One parent commented that it was comforting to hear from the clinician that it was not their fault when the diagnosis was disclosed.

Fear of guilt was also identified to be a driving factor for accepting life-prolonging care and continuing to care for the child, “so I will not be blamed or feel guilty in the future because I will do my best [for] them.” (Caregiver 4) One parent said they were “thinking about giving up so many times, but again, how can I give up my own son, right?” (Caregiver 10)

Caregiver burden and identity loss

The daily care of a child with SMA receiving disease-modifying therapies is demanding. Caregivers highlighted the burden of being the medical expert for their child, managing medical technology, training homecare nurses, or caring for children continuously without respite in the absence of homecare nurses. Caregivers made personal sacrifices to care for their children with high care needs. They identified feelings of identity loss while sacrificing career goals, social life and even their other roles in the family or marriage. Caregivers recognized the family disruption resulting from caring for a child with a chronic illness due to the burden placed on relationships with family members.

Tension between grief and gratitude

Caregivers’ perspectives of caring for a child with SMA was strongly shaped by the child's symptom severity. In children with advanced disease receiving a disease-modifying therapy, many families commented on feelings of gratitude for disease stability and more time spent with their child. Caregivers of children with less severe disease, or having received treatments earlier, shared the burden of living with constant fear and uncertainty. For some families, the grieving process also involved letting go of what they had expected from parenting, sharing it is “not what I thought parenting would be like.” (Caregiver 5)

Parent agency

Families identified various factors which impacted their ability to access or implement care, including (1) social determinants of health, (2) therapeutic alliance, family-centered care and expectations, and (c) supportive resources. This theme explores the concept of justice and the extent to which inequity may compromise autonomy by narrowing the scope of options available for families.

Family contexts and social determinants of health

Economic instability was identified as a source of stress by some families, affecting family structure and self-identity. Caregivers of children with SMA often faced financial limitations that led to changes in their career trajectories or restricted their educational opportunities, adversely affecting education access and quality. Despite the wide range of household incomes in this cohort, no one considered finances to impact the quality of their care received at the hospital. However, caregivers identified that privately accessing resources, such as therapy or medical devices, was both faster and more convenient. Conversely, many families solely relied on publicly available services and identified limitations in the access to these services.

Caregivers identified work-related privileges as contributing to lower stress, including being able to work from home and having supportive jobs allowing time off work for attending appointments. On the other hand, some caregivers from higher income households identified challenges caring for the child and attending appointments when one or both caregivers worked outside of the home. One caregiver commented that they didn’t qualify for many services because of their high income, even though from their perspective it was not sufficient.

Conversely, caregivers from many lower-income households did not consider finances to be a source of stress or concern. Many families prioritized time spent with the child and adjusted their financial expectations. For example, one low income family commented that “it is tight, but enough to live” (Caregiver 4) and another stated “it's hard but… we know this is our normal life.” (Caregiver 2). Interestingly, this observation reflects that structural health determinants like finances are not directly linked to parental beliefs.

Religion, another aspect of social and community context, was not identified as a significant factor to guide medical decision-making. Nonetheless, many families turn to their faith or find strength from religion, “I'm strong, because of my faith.” (Caregiver 2) Some families described their belief that a higher power was acting through the physicians and therapies, stating “God's given us doctors to help us” (Caregiver 13) and believe that “God was helping children through the provision of disease-modifying therapies.” (Caregiver 10)

Therapeutic alliance, family-centered care and expectations

Health care and quality, a domain of the social determinants of health, had a large influence on the care experience. Caregivers recognized the importance of clear and transparent communication with the healthcare team, a holistic care approach, and excellent care coordination to minimize the burden of multiple hospital visits. Accessibility to the healthcare team was identified as important to families; they valued receiving real-time responses, stating “at any moment, I could ask a question, and they would answer.” (Caregiver 1) With a strong therapeutic alliance, caregivers felt their child was well cared for and identified the hospital as a place of comfort.

While having access to the medical team is important, families also stressed that having medical knowledge is empowering and valued being able to solve problems on their own at home. In part, this was because caregivers commented that they know their medically complex child best, stating “I will be her main caregiver until I need to let go of the reigns a little bit… I feel like I know her needs the best.” (Caregiver 13)

Supportive resources

Social and community context greatly influenced the care experience. The support of friends and family was emphasized by many family caregivers as a source of psychological and physical respite. Informal and formal peer support through online resources like social media and patient non-profit organizations was also highly valued by family caregivers to assist with navigating the healthcare system. One family successfully fundraised for the private purchase of onasemnogene abeparvovec before it was reimbursed by the public healthcare system, although this family ultimately accessed therapy on a compassionate basis from the pharmaceutical company. Similarly, another family was able to advocate for their child to receive onasemnogene abeparvovec in the United States before its approval in Canada. This information sharing enabled families to effectively advocate for their child's unique care needs, particularly for those who were the first to receive disease-modifying therapies, but also for the sharing of experiences and resources.

In contrast, it was apparent that non-English speaking families and immigrant families had limited access to peer support, and potentially less opportunity to advocate on behalf of their children. Many immigrant and non-English speaking families did not comment on connections with non-profit organizations or informal community supports. Many also did not have any family close by who could help share the burden of care.

Discussion

Our study explores how social determinants of health and ethical challenges influence caregivers’ experiences in navigating disease-modifying therapies. Caregivers often acted in accordance with the principles of beneficence and nonmaleficence in striving to prolong life and improve its quality. However, tensions arose when life-prolonging therapies such as non-invasive ventilation also imposed physical or emotional burdens. In the era of disease-modifying therapies, the autonomy of caregivers was also modified by inequities related to the social determinants of health. Individuals with more social capital were better able to advocate for therapy access, highlighting disparities in healthcare navigation even in a publicly funded healthcare system.

An important novel finding in this study is the significant impact of disease-modifying therapies on the caregiver experience. Families receiving novel therapeutics carry a sense of qualified hope; while there are feelings of gratitude and optimism, these feelings coexist with fear and uncertainty about the future. Families balance the happiness of having more time to spend with a child who would have otherwise had a much poorer prognosis, together with grieving for the life their child would never have. These experiences were shared amongst caregivers of children who were treated symptomatically as well as presymptomatically. Even in families of presymptomatic children, the burden of living in fear of deterioration is high. The unique experiences of presymptomatic children treated with disease-modifying therapies warrants further research.

The caregivers’ perspectives regarding treatment benefit should be considered as it may differ from the perception of the medical team. Many caregivers valued seemingly small milestones and skills that improve function, independence, and quality of life.²⁷ These expectations and values were influenced by the disease severity of the child at the time of disease-modifying therapy initiation. A recent study by Landfeldt et al. demonstrated a detrimental impact of SMA on health-related quality of life in the era of disease-modifying therapies, with substantial variability across SMA types over time.²⁸ Other studies in the SMA population have demonstrated a high overall rating of quality of life that does not correlate with severity of physical limitations or motor scores²⁹ but is impacted by functional abilities such as washing and transferring.³⁰ In adult cohorts, increased disease severity has been associated with better reported emotional function and quality of life,^31,32 suggesting the factors influencing quality of life are complex and should be carefully re-evaluated as circumstances evolve. These findings highlight the importance of shared decision-making and open and honest communication between practitioners and people with lived experience.^33,34 Our study also identified a complex interaction between the acceptance of disability with the desire for a cure and “normalcy,” particularly for younger children treated while presymptomatic. The role of our systemic infrastructure and societal views on ableism are important to consider, as well as how we conduct conversations regarding treatment options and the emphasis placed on “cure” being the goal for children with disabilities.³⁵

The desire for acting in the best interests of the child was met with the tension of a high burden of care and identity loss in the caregivers, consistent with previous studies.^36,37 Many caregivers have made significant personal compromises including giving up careers and education, sacrificing social life, and having a significant change in family structure.³⁸ Caregivers are uniquely vulnerable to the impact of the social determinants of health and family contexts, which further impact their ability to care for their child with medical complexity.³⁹ Not only are Non-English speaking and immigrant families disproportionately affected by financial hardships, but they are also less likely to have robust peer support systems. A recent study highlighted the lack of psychological support for caregivers to children with SMA in the era of disease-modifying therapies.⁴⁰ These concerns highlight the importance of more supportive infrastructure for caregivers and children living with SMA that may address inequities and relieve caregiver burden. This is particularly relevant for a publicly funded healthcare system where supportive resources can maximize the benefits afforded by disease-modifying therapies.

Although we were able to capture a diverse set of perspectives with our broad inclusion criteria, we had limited ability to draw strong comparisons based on SMA type or severity and demographic characteristics. Additionally, certain unique groups were not well represented such as those diagnosed by newborn screening, those who declined therapy, or those who were treated when symptomatic as compared to presympomatic. The semi-structured nature of the interview format also limited the opportunity to expand upon salient themes. Finally, these findings are based on interviews with caregivers from the Canadian healthcare system, which limits the generalizability of the results to other contexts including low-middle income countries.

Conclusions

The findings of this study provide important insights into the ethical tensions and social determinants of health impacting the care experience of patients with SMA since the advent of novel therapeutics. Understanding the experiences of families from different backgrounds receiving various treatments for their child with SMA will allow more appropriate distribution of targeted resources, better counselling and supports for families facing unique psychosocial challenges and treatment burdens, and overall improved delivery of patient and family-centered care.

Footnotes

Abbreviations

Acknowledgements

We would like to thank the patients and families involved in this research.

Ethcal considerations

Research ethics board approval was obtained from The Hospital for Sick Children (1000077616).

Consent to participate

Written consent was obtained from the caregivers as the children were not capable to consent themselves.

Author contributions

Lena Xiao conceptualized and designed the study, analyzed the data, and critically reviewed and revised the manuscript.

Djurdja Djordjevic analyzed the data, drafted the initial manuscript, and revised the manuscript.

Reshma Amin conceptualized and designed the study, analyzed the data, and critically reviewed and revised the manuscript.

Melissa McCradden and Ms Sohee Kang analyzed the data and revised the manuscript.

Munazzah Ambreen collected data and critically reviewed and revised the manuscript.

Hernan Gonorazky, Jackie Chiang, Elisa Nigro, Eugenia Law, and Lauren Weinstock critically reviewed and revised the manuscript.

All authors approved the final manuscript as submitted and agree to be accountable for all aspects of the work.

Funding

The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This work was supported by Cure SMA Canada. The funding source was not involved in the design or conduct of the study; collection, management, analysis, or interpretation of the data; preparation, review, or approval of the manuscript; or decision to submit the manuscript for publication.

Declaration of conflicting interest

Dr Amin is a committee member of the American College of Chest Physicians and a pediatrics committee member of the American Thoracic Society. Dr Amin holds research grants from Canadian Institutes of Health Research, Cure SMA Canada, Muscular Dystrophy Canada, VHA Home Healthcare, Boehringer-Ingelheim, Medigas, ProResp, Baxter Corporation Endowment Fund for Home Care, and Ontario Ministry of Health and Long-term Care. Dr Xiao reported receiving research funding from The Hospital for Sick Children Clinician-Scientist Training Program, American Thoracic Society ASPIRE fellowship, Baxter Corporation Endowment Fund for Home Care, International Pediatric Sleep Association, and the Sleep Research Society Foundation during the conduct of the study. The other authors have no conflicts of interest to disclose.

Data availability

Due to the sensitive nature of the research, supporting data is not available.

ORCID iDs

Lena Xiao

Hernan Gonorazky

Jackie Chiang

Reshma Amin

Melissa D McCradden

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