Impact of Nusinersen on the Health-Related Quality of Life and Caregiver Burden in Patients with Spinal Muscular Atrophy with Symptom Onset before the Age of 6 Months

Yun Jeong Lee; Hyunwoo Bae; Young Kyu Shim; Jae So Cho; Jong Hee Chae; Soonhak Kwon

doi:10.26815/acn.2024.00668

Ann Child Neurol > Volume 33(2); 2025 > Article

Lee, Bae, Shim, Cho, Chae, and Kwon: Impact of Nusinersen on the Health-Related Quality of Life and Caregiver Burden in Patients with Spinal Muscular Atrophy with Symptom Onset before the Age of 6 Months

Original article

Annals of Child Neurology 2025;33(2):39-47.

Published online: March 14, 2025

DOI: https://doi.org/10.26815/acn.2024.00668

Impact of Nusinersen on the Health-Related Quality of Life and Caregiver Burden in Patients with Spinal Muscular Atrophy with Symptom Onset before the Age of 6 Months

Yun Jeong Lee, MD¹

, Hyunwoo Bae, MD²

, Young Kyu Shim, MD³

, Jae So Cho, MSc⁴

, Jong Hee Chae, MD^5,⁶

, Soonhak Kwon, MD²

¹Department of Pediatrics, Kyungpook National University Hospital, School of Medicine, Kyungpook National University, Daegu, Korea

²Department of Pediatrics, Kyungpook National University Children’s Hospital, School of Medicine, Kyungpook National University, Daegu, Korea

³Department of Pediatrics, Korea University Ansan Hospital, Seoul, Korea

⁴Department of Pediatrics, Seoul National University Bundang Hospital, Seoul, Korea

⁵Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea

⁶Department of Genomic Medicine, Seoul National University Hospital, Seoul, Korea

Corresponding authors: Soonhak Kwon, MD Department of Pediatrics, Kyungpook National University Children’s Hospital, School of Medicine, Kyungpook National University, 807 Hoguk-ro, Buk-gu, Daegu 41404, Korea
Tel: +82-53-200-5704, Fax: +82-53-425-6683, E-mail: shkwon@knu.ac.kr

Jong Hee Chae, MD Department of Pediatrics, Pediatric Clinical Neuroscience Center, Seoul National University Children's Hospital, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 03080, Korea
Tel: +82-2-2072-3622, Fax: +82-2-743-3455, E-mail: chaeped1@snu.ac.kr

Received July 13, 2024 Revised November 30, 2024 Accepted December 21, 2024

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (https://creativecommons.org/licenses/by-nc/4.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Purpose

This study investigated the impact of nusinersen on health-related quality of life (HRQoL), functional performance, and caregiver burden in patients with infantile-onset spinal muscular atrophy (SMA), addressing a growing interest in disease-modifying treatments.

Methods

A 14-month observational study was conducted to evaluate changes in HRQoL and functional performance using the Pediatric Quality of Life Inventory (PedsQL) Infant Scales and the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT). Caregiver burden was assessed through the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). Motor function was evaluated using the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND). Correlations between CHOP INTEND scores, functional performance, and caregiver burden were analyzed.

Results

Eight patients with infantile-onset SMA and their caregivers participated, with a median treatment initiation age of 4.6 months (range, 1.1 to 15.1). CHOP INTEND scores showed significant improvement (P<0.001), whereas all PedsQL Infant Scale scores declined. Conversely, the PEDI-CAT revealed significant enhancements in daily activities, mobility, and social-cognitive domains (all P<0.001). Caregiver burden lessened across most dimensions (P<0.001), with the exception of the time-related burden (P=0.731). Higher CHOP INTEND scores correlated with improvements in PEDI-CAT domains and a reduction in caregiver burden related to sitting/play and transfer activities.

Conclusion

The study demonstrates the positive effects of nusinersen on functional performance and caregiver burden in patients with infantile-onset SMA. However, discrepancies were observed in HRQoL outcomes, suggesting a need for further research that includes SMA-specific outcome measures to comprehensively assess the treatment's impact on patients' lives.

Keywords: Spinal muscular atrophies of childhood; Nusinersen; Caregiver burden; Quality of life

Introduction

Spinal muscular atrophy (SMA) is a rare autosomal recessive neuromuscular disorder characterized by the degeneration of motor neurons in the spinal cord [1]. It is most commonly caused by a homozygous deletion in the survival motor neuron 1 (SMN1) gene on chromosome 5q13, which results in reduced levels of survival motor neuron (SMN) protein [1]. Humans have a similar gene, SMN2, that also produces the SMN protein. However, due to alternative splicing that excludes exon 7, the SMN2 gene generates a less functional version of the SMN protein. The number of SMN2 copies is strongly correlated with the severity of SMA; more copies can partially compensate for the loss of functional SMN protein, thus influencing the clinical manifestations of the disease [2].

The most common symptoms of SMA are bilateral symmetrical weakness and progressive muscle atrophy, predominantly affecting the lower limbs. SMA is classified into four clinical subtypes based on the age at onset and the severity of symptoms. These range from the most severe, type 1 (infantile-onset), to the least severe, type 4 (adult-onset) [1]. Approximately 50% of infants with SMA present with type 1, characterized by symptom onset at or before 6 months of age and a median life expectancy of less than 2 years without respiratory support [3].

Living with SMA poses significant challenges for patients, their families, and caregivers, stemming from restricted motor, bulbar, and respiratory functions. This condition leads to a reduced quality of life (QoL) for both patients and their caregivers [4,5]. Additionally, parents caring for children with SMA experience considerable burdens related to time, finances, and psychosocial activities [5,6].

Recent advances in SMA treatment, including antisense oligonucleotides [7,8], small molecules [9], and gene therapy [10], have paved the way for changes in the disease trajectory. Nusinersen, an antisense oligonucleotide, modifies the splicing of the SMN2 gene to increase the expression of the full-length SMN protein. This has led to improved motor function and increased survival in SMA patients across various levels of disease severity [7-9]. However, there is a lack of studies focusing on the perspectives of children and caregivers regarding the impact of disease-modifying therapies for SMA on their daily lives [10-15]. Changes in health-related quality of life (HRQoL), activities of daily living, levels of independence, and caregiver burden in response to these interventions need to be addressed. Additionally, the number of validated patient-reported outcome measures for the SMA population is limited [16]. Furthermore, measuring QoL in very young infants with SMA is particularly challenging, as they cannot directly complete an HRQoL instrument. In such cases, proxy reports by parents are necessary.

This study aimed to evaluate the impact of nusinersen treatment on HRQoL and functional performance in patients with infantile-onset SMA and the caregiver burdens reported by their caregivers over time.

Materials and Methods

1. Participants

Patients with infantile-onset SMA were enrolled either before or during treatment with nusinersen at Seoul National University Children’s Hospital and Kyungpook National University Hospital. These patients had confirmed 5q-SMA through genetic testing, either with a homozygous deletion mutation or as a compound heterozygote in SMN1, and exhibited symptoms before 6 months of age. Patients with pre-existing or ongoing medical conditions unrelated to SMA, or those who had received any SMA medication other than nusinersen prior to enrollment or at any point during the study, were excluded. Patients received nusinersen according to the approved regimen in South Korea, which includes loading doses administered on days 0, 14, 28, and 63, followed by maintenance doses every 4 months thereafter. The Research Ethics Committees of Kyungpook National University Hospital (KNUH2020-05-045-001) and Seoul National University Hospital (H-2006-068-1131) approved this research. All parents provided written informed consent prior to their children’s participation.

2. Study design

We assessed the baseline characteristics of patients before treatment, which included age at symptom onset, age at the first administration of nusinersen, sex, number of SMN2 gene copies, motor function assessment results, presence of orthopedic complications, and level of ventilator support. Assessments were conducted at the time of the fourth loading dose and at each maintenance dose thereafter, continuing until the third maintenance dose, approximately 14 months after treatment initiation. Follow-up assessments included evaluations of motor function, motor milestones, caregiver perspectives on the impact of treatment, ventilator and feeding support, orthopedic complications, and adverse events.

3. Motor function assessment

Motor function in patients with SMA was assessed using two established rating scales: the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and the Hammersmith Infant Neuromuscular Examination section 2 motor milestones (HINE-2). This assessment was conducted by two experienced physicians, Jae So Cho and Yun Jeong Lee. The CHOP INTEND, a validated measure of gross motor function for patients with SMA type 1, consists of 16 items and has a scoring range from 0 to 64 [17]. The HINE-2 measures the achievement of motor milestones, including head control, sitting, voluntary grasp, and the ability to kick, roll, crawl, stand, and walk, with scores ranging from 0 to 26 [18]. Higher scores on both the CHOP INTEND and HINE-2 indicate better motor function.

4. HRQoL, functional performance, and caregiver burden

The perspectives of caregivers on patients' HRQoL, functional performance, and caregiver burdens were evaluated. These assessments took place both before the initiation of treatment and at the time of the fourth loading dose and each maintenance dose thereafter. To assess HRQoL, the Pediatric Quality of Life Inventory (PedsQL) Infant Scales were utilized. These scales are specifically designed for infants aged 1 to 24 months and cater to both healthy and ill children. The tool is multidimensional and includes five scales: physical functioning, physical symptoms, emotional functioning, social functioning, and cognitive functioning. The total scale score is derived by summing the scores from all completed items on the PedsQL Infant Scales and dividing by the number of items completed. In this scale, higher scores signify a better HRQoL.

We assessed changes in functional performance and caregiver burdens using two specific tools: the Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) and the Assessment of Caregiver Experience with Neuromuscular Disease (ACEND). The PEDI-CAT is a computer-adaptive caregiver report that assesses daily activities, mobility, social/cognitive function, and responsibility across a broad age range (1 to 21 years). Higher scores on the PEDI-CAT indicate better functional performance. This tool has been particularly noted for its effectiveness in measuring mobility and daily activity skills in SMA types 2 and 3 [19]. In contrast, ACEND is a validated, self-administered instrument that measures the impact of caregiving on parents of children severely affected by neuromuscular diseases, including SMA [20]. ACEND evaluates both the physical impact (such as feeding, grooming, dressing, sitting/play, transfers, and mobility) and the general impact on caregivers (covering aspects like time, emotion, and finance), with higher scores indicating a lower caregiver burden.

5. Statistical analysis

Statistical analysis was performed on data from patients who had received at least five doses of nusinersen, which includes the completion of the first maintenance dose, and whose caregivers had completed the set of questionnaires at least three times. Descriptive statistics were utilized to analyze patient demographics and clinical characteristics. We used generalized estimating equation modeling to evaluate changes over time in the PedsQL Infant Scale, PEDI-CAT, ACEND, CHOP INTEND test, and HINE-2 test scores following nusinersen treatment. This model included variables such as age at symptom onset, sex, and disease duration, and it accounted for within-subject correlation across repeated measurements. Additionally, we performed a correlation analysis between motor function assessments (CHOP INTEND and HINE-2) and scores from patient-reported outcome measures using Pearson correlation coefficients. Correlations were categorized as strong or very strong (coefficients of 0.70 to 1.00), moderate (0.40 to 0.69), and weak (0.10 to 0.39) [21]. Statistical significance was established at a P<0.05. All analyses were conducted using the IBM Statistical Software Package for the Social Sciences (SPSS version 26; IBM Corporation, Armonk, NY, USA).

Results

1. Motor function

This study included eight patients with SMA and their caregivers. The median age at symptom onset was 2.5 months (range, 0.25 to 6.00), and the median age at the initiation of nusinersen treatment was 4.6 months (range, 1.1 to 15.1). The median baseline scores for CHOP INTEND and HINE-2 were 12 (range, 4 to 31) and 1.0 (range, 0 to 6), respectively. Patients received a median of eight nusinersen doses (range, 6 to 15). Seven patients completed the third maintenance dosing assessment. Prior to treatment initiation, ventilator and tube feeding support was necessary for three patients. Detailed baseline characteristics of each patient are presented in Table 1. Notably, both CHOP INTEND and HINE-2 scores showed significant increases from baseline at the time of the third maintenance dosing in all eight patients with SMA type 1. The CHOP INTEND score increased to 26.81±3.97 (mean±standard deviation; P<0.001), and the HINE-2 score improved to 8.82±1.33 (P<0.001) (Fig. 1). During treatment, no additional ventilator or tube feeding support was required by any of the patients.

2. PedsQL Infant Scales and PEDI-CAT analyses

Since the PedsQL Infant Scale is only applicable to patients under 24 months of age, we excluded one patient who began treatment at 15.1 months and was evaluated at 3 years of age from the PedsQL Infant Scale analysis. For the remaining seven caregivers, the mean baseline PedsQL Infant Scale scores were as follows: 61.91±5.19 for physical functioning, 72.30±1.66 for physical symptoms, 73.07±5.68 for emotional functioning, 100.46±1.60 for social functioning, and 67.89±8.89 for cognitive functioning subscales, with an average total score of 73.13±3.43. We observed a significant decline over time in all scales of the PedsQL Infant Scale, including the total scores (Fig. 2). The PEDI-CAT was assessed by eight caregivers, with baseline mean scores of 32.02±0.70 for daily activity, 33.7±0.91 for social-cognitive, and 28.23±1.11 for mobility domains. All domains demonstrated significant improvement over time (P<0.001 for all domains) (Fig. 3).

3. Caregiver burden

ACEND assessments conducted with the eight caregivers generally revealed low mean scores across all seven domains, with the lowest scores observed in the transfer domain. During the treatment, there was a statistically significant reduction in the burden associated with feeding, grooming, dressing, sitting, play, transfers, mobility, emotional aspects, and finances (P<0.001 for all domains). However, the burden related to time did not change from baseline, as demonstrated in Fig. 4 (P=0.731).

4. Correlation between motor function and PEDI-CAT and ACEND scores

In the context of PEDI-CAT results, CHOP INTEND scores showed moderate positive correlations with daily activities (r=0.545, P=0.003) and social-cognitive domains (r=0.692, P<0.001) and a strong positive correlation with the mobility domain (r=0.767, P<0.001) (Table 2). Additionally, daily activities (r=0.787, P<0.001), mobility (r=0.857, P<0.001), and social-cognitive domains (r=0.799, P<0.001) displayed strong positive correlations with HINE-2 scores. CHOP INTEND scores were moderately associated with a reduced burden in sitting/play (r=0.612, P<0.001) and transfer (r=0.610, P<0.001) in the correlation analysis with ACEND. Similarly, HINE-2 scores showed a moderate positive correlation with a reduced burden in sitting/play (r=0.612, P<0.001) and mobility (r=0.588, P<0.001) and a strong correlation with a reduced burden in feeding/grooming/dressing (r=0.750, P<0.001) and transfer (r=0.798, P<0.001).

Discussion

Our study evaluated HRQoL, functional performance, and caregiver burden in infants with SMA, utilizing a variety of patient-reported outcome measures to track changes in these areas during nusinersen treatment. Our findings indicate that the baseline total scores and subscores on the PedsQL Infant Scale, except for the social functioning score, were lower than those reported for healthy controls in previous studies, which ranged between 76.6 and 89.6 [22]. Despite significant improvements in motor outcomes, there was a decline in both the total score and all subscores of the PedsQL Infant Scale during treatment. The PedsQL Infant Scales have been employed in numerous studies to assess HRQoL in chronically ill infants with conditions such as kaposiform hemangioendothelioma, chronic liver disease, and Kawasaki disease [22-25]. Unlike prior studies that compared the HRQoL of ill infants with that of healthy controls, our research focused on the impact of treatment intervention on patients with SMA, specifically examining changes in PedsQL Infant Scale scores. The reasons for the apparent lack of a positive impact of nusinersen on HRQoL in infants with SMA remain uncertain. Our findings suggest that considerable caregiver anxiety, despite improvements in motor function, and potential bias in proxy responses may contribute to this discrepancy. Caregivers often struggle to objectively evaluate their child’s HRQoL, possibly conflating their perceptions with personal emotions [26]. Additionally, our results may have been influenced by parents’ elevated expectations regarding the new treatment’s potential to enhance motor functions to levels comparable to those in healthy infants. This may lead to their dissatisfaction or disappointment with the therapy, which in turn could affect their perceptions of the patients’ HRQoL.

Some studies have suggested a lack of correlation between QoL and functional status in children or adolescents with SMA [27,28]. Despite the deterioration of motor function in SMA types 2 and 3, PedsQL scores have remained stable [27]. Another study indicated that self-reported QoL was higher among patients with SMA type 2 than among those with SMA type 3, even though motor function assessment scores were higher in the SMA type 3 group [28].

The PedsQL Generic Core Scale or Neuromuscular Module, which is commonly used in research on SMA, has demonstrated reliability and validity in pediatric patients with SMA [29,30]. However, there has been limited research on HRQoL using the PedsQL in patients with SMA who are undergoing nusinersen treatment. Notably, a trial involving presymptomatic SMA patients found their PedsQL scores to be comparable to those of healthy controls [15], and children with later-onset SMA who were treated with nusinersen showed a lesser decline in scores on both the PedsQL Generic Core Scale and Neuromuscular Module at 15 months compared to sham controls [10].

The PedsQL Infant Scales are a multidimensional instrument designed to maintain construct consistency across various ages, including items that correspond to the PedsQL Generic Core Scales for ages 2 to 18 years. This tool measures physical, emotional, social, and school/cognitive functioning, allowing for the tracking of generic HRQoL from age 1 month to 18 years across different age groups. However, there is a lack of studies validating the consistency of item measurement in the PedsQL Infant Scale, especially in patients with SMA under 2 years old. SMA manifests at various ages and can vary in type and severity. Although the PedsQL is commonly used in SMA patients, it may not be sensitive enough to fully capture the impact of SMA on QoL. This observation is supported by our previous study, which showed no improvement in the physical health score of the PedsQL Generic Core Scale or in the ‘About My Neuromuscular Disease’ score of the PedsQL Neuromuscular Module for later-onset SMA, despite improvements in motor function assessments [31]. In contrast, for infant-onset SMA, the emotional, social, and school functioning scores on the proxy-reported PedsQL Generic Core Scale showed improvement in the later-onset SMA population [31]. Future research should focus on the ability of PedsQL to detect treatment-related changes or disease progression in SMA, as well as on developing SMA-specific measurement tools [32].

Regarding functional performance, as evaluated using the PEDI-CAT, nusinersen treatment has shown positive impacts across various domains, including daily activities, social-cognitive functions, and mobility. The PEDI-CAT has been validated in SMA groups and has identified differences in functional skills across various types and age groups. However, the mobility and daily activity domains exhibited a floor effect in type I SMA groups [19,33]. The PEDI-CAT offers the potential advantage of a large item bank that encompasses a wide range of ages and abilities. This feature may enhance its ability to detect subtle changes in functional abilities compared to the physical functioning scales used in the PedsQL Infant Scales. This could account for the differing results observed between the PedsQL Infant Scale and the PEDI-CAT.

In contrast to the positive impact observed in the mobility and daily activity domains for patients with infantile-onset SMA, our previous study evaluating PEDI-CAT outcomes in later-onset SMA patients receiving nusinersen treatment did not show meaningful improvements in these areas [31]. These findings suggest that nusinersen treatment has a more pronounced effect on daily activities and mobility in patients with infantile-onset SMA than in those with later-onset SMA. This conclusion is supported by the significant positive correlations between CHOP INTEND and HINE-2 scores and the PEDI-CAT scores in type 1 SMA patients.

Our study observed a significant reduction in caregiver burden across all aspects except for time burden during nusinersen treatment, consistent with previous research that reported a decreased physical impact burden in presymptomatic SMA patients following nusinersen treatment [15]. Additionally, our results showed that reductions in physical impact burden, particularly in activities like sitting/play and transfers, were positively correlated with improvements in motor function, as measured by CHOP INTEND and HINE-2 scores. Therefore, nusinersen treatment can lead to motor function improvements, which in turn, decrease caregiver burden. However, the time burden remained unchanged, as caregivers still had to allocate time for intrathecal injection appointments every 4 months. This finding aligns with another study where caregivers of pediatric patients expressed dissatisfaction due to the time demands associated with treatment and medication administration [34].

This study has several limitations. First, it was conducted with a relatively small sample size, which hindered the performance of subgroup analyses based on patient characteristics such as SMN2 copy number, ventilator support, and orthopedic complications. Second, the inability to measure patient-reported outcomes prior to treatment in some caregivers may limit the generalizability of our findings. Lastly, we were unable to examine baseline demographic factors, such as socioeconomic status, presence of siblings, and place of residence, which could potentially influence HRQoL and caregiver burden.

In conclusion, nusinersen positively affects the functional performance of infants with SMA and reduces the burden on their caregivers. However, the HRQoL as perceived by the caregivers declined over time. The improvement in motor function due to nusinersen primarily reflects changes in functional performance and caregiver burden rather than overall QoL measures. With the emergence of new phenotypes resulting from novel disease-modifying therapies, it is crucial to develop an SMA-specific HRQoL tool that encompasses a wide age range. Such tools would more accurately capture therapeutic responses that are not reflected by traditional motor functional assessments.

Conflicts of interest

Soonhak Kwon is an editor-in-chief emeritus, Jong Hee Chae is an editorial board member, and Jae So Cho is a managing editor of the journal, but they were not involved in the peer reviewer selection, evaluation, or decision process of this article. No other potential conflicts of interest relevant to this article were reported.

Yun Jeong Lee received a grant from Biogen for investigator-initiated clinical research. The funding from Biogen was used for salary payments to clinical evaluators and the purchase of a license for the questionnaire.

Author contribution

Conceptualization: HB, YKS, JSC, JHC, and SK. Data curation: YJL, HB, YKS, and JSC. Formal analysis: YJL, HB, YKS, and JSC. Funding acquisition: YJL. Methodology: YJL and JHC. Project administration: JSC. Visualization: YJL. Writing - original draft: YJL. Writing - review & editing: JHC and SK.

Acknowledgments

Mr. Jung Young-Moon partly supported this paper, and we would like to express our sincere gratitude to him and his son for their support.

Fig. 1.

Changes in (A) Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders (CHOP INTEND) and (B) Hammersmith Infant Neuromuscular Examination section 2 motor milestones (HINE-2) scores over time. SMA, spinal muscular atrophy.

Fig. 2.

Changes in Pediatric Quality of Life Inventory (PedsQL) Infant Scales over time. (A) Physical functioning, (B) physical symptoms, (C) total score, (D) emotional functioning, (E) social functioning, and (F) cognitive functioning. L, loading dose; M, maintenance dose.

Fig. 3.

Changes in Pediatric Evaluation of Disability Inventory Computer Adaptive Test (PEDI-CAT) over time. (A) Daily activity, (B) social-cognitive, and (C) mobility. L, loading dose; M, maintenance dose.

Fig. 4.

Changes in Assessment of Caregiver Experience with Neuromuscular Disease (ACEND) over time. (A) Feeding/grooming/dressing, (B) sitting/play, (C) transfer, (D) mobility, (E) time, (F) emotion, and (G) finance. L, loading dose; M, maintenance dose.

Table 1.

Baseline characteristics of patients with SMA type 1

Patient no.	Age at onset (mo)	Age at treatment (mo)	SMN2 copies	Ventilator support	Tube feeding	Contracture	Baseline CHOP INTEND	Baseline HINE-2	Total dose of nusinersen
1	3	5.2	2				12	1	9
2	2	4.0	2				12	1	8
3	1	2.0	2		+		4	1	7
4	5	9.1	3				30	3	7
5	6	8.5	2				31	6	6
6	6	15.1	2	+	+	+	4	0	15
7	0.5	1.1	2	+			8	0	12
8	0.25	3.2	2	+	+		17	2	8

SMA, spinal muscular atrophy; SMN2, survival motor neuron 2; CHOP INTEND, the Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; HINE-2, Hammersmith Infant Neuromuscular Examination section 2 motor milestones.

Table 2.

Correlations between PEDI-CAT, ACEND, and motor function assessments

Variable	CHOP INTEND score		HINE-2
Variable	Pearson correlation (r)	P value	Pearson correlation (r)	P value
PEDI-CAT domain (n=28)
Daily activity	0.545^a	0.003	0.787^a	<0.001
Mobility	0.762^a	<0.001	0.857^a	<0.001
Social-cognitive	0.692^a	<0.001	0.799^a	<0.001
ACEND domain (n=30)
Feeding/grooming/dressing	0.350	0.079	0.750^a	<0.001
Sitting/play	0.612^a	<0.001	0.612^a	<0.001
Transfer	0.610^a	<0.001	0.798^a	<0.001
Mobility	0.353	0.055	0.588^a	<0.001
Time	-0.091	0.632	0.013	0.944
Emotion	0.103	0.590	0.173	0.360
Finance	0.338	0.067	−0.037	0.848

PEDI-CAT, Pediatric Evaluation of Disability Inventory Computer Adaptive Test; ACEND, Assessment of Caregiver Experience with Neuromuscular Disease; CHOP INTEND, Children’s Hospital of Philadelphia Infant Test of Neuromuscular Disorders; HINE-2, Hammersmith Infant Neuromuscular Examination section 2 motor milestones.

^aStatistical significance at the P<0.05 level.

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