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JAMA Pediatr
JAMA Pediatr
JAMA Pediatrics
2168-6203
2168-6211
American Medical Association

39008286
10.1001/jamapediatrics.2024.1911
pld240023
Research
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Research Letter
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Newborn Screening and Birth Prevalence for Spinal Muscular Atrophy in the US
Newborn Screening and Birth Prevalence for Spinal Muscular Atrophy
Letters
Belter Lisa MPH 1
Taylor Jennifer L. PhD 2
Jorgensen Erica BS 1
Glascock Jacqueline PhD 1
Whitmire Sarah M. MS 1
Tingey Jessica J. MPhil 1
Schroth Mary MD 1
1 Cure SMA, Elk Grove Village, Illinois
2 American College of Medical Genetics and Genomics, Bethesda, Maryland
Article Information

Accepted for Publication: April 24, 2024.

Published Online: July 15, 2024. doi:10.1001/jamapediatrics.2024.1911

Open Access: This is an open access article distributed under the terms of the CC-BY-NC-ND License. © 2024 Belter L et al. JAMA Pediatrics.

Corresponding Author: Lisa Belter, MPH, Cure SMA, 925 Busse Rd, Elk Grove Village, IL 60007 (lisa.belter@curesma.org).
Author Contributions: Ms Belter and Dr Schroth had full access to all of the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Belter, Taylor, Glascock, Whitmire, Tingey, Schroth.

Acquisition, analysis, or interpretation of data: Belter, Jorgensen, Schroth.

Drafting of the manuscript: Belter, Tingey.

Critical review of the manuscript for important intellectual content: Belter, Taylor, Jorgensen, Glascock, Whitmire, Schroth.

Statistical analysis: Belter, Whitmire.

Obtained funding: Schroth.

Administrative, technical, or material support: Taylor, Jorgensen, Glascock, Tingey, Schroth.

Supervision: Belter, Glascock, Schroth.

Conflict of Interest Disclosures: Ms Belter reported receiving salary support from Cure SMA Real World Evidence Collaboration during the conduct of the study. Dr Taylor reported receiving salary support from the Eunice Kennedy Shriver National Institute of Child Health and Human Development during the conduct of the study. Mrs Jorgensen reported receiving salary support from Cure SMA Real World Evidence Collaboration during the conduct of the study. Ms Whitmire reported receiving salary support from Cure SMA Real World Evidence Collaboration during the conduct of the study. Ms. Tingey reported receiving salary support from Cure SMA Real World Evidence Collaboration during the conduct of the study. Dr Schroth reported receiving salary support from Cure SMA Real World Evidence Collaboration during the conduct of the study. No other disclosures were reported.

Funding/Support: This study was funded by the Cure SMA Real World Evidence Collaboration, which includes Cure SMA, Biogen, Genentech/Roche, and Novartis Gene Therapies.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, or approval of the manuscript; and decision to submit the manuscript for publication. The funder had the opportunity to review the manuscript and provided no feedback.

Data Sharing Statement: See Supplement 2.

Additional Contributions: Mary Curry, ND, Vice President of Clinical Research and Care at Cure SMA, critically reviewed and revised the manuscript. Dr Curry was not financially compensated for her contributions.

Additional Information: The Cure SMA Real World Evidence Collaboration was established in 2021 to leverage the experience, expertise, and resources of pharmaceutical and biotechnology companies and nonprofit organizations involved in development of SMA therapeutics to guide the future direction of real-world evidence collection and use in SMA. Current members include Biogen, Genentech/Roche, and Novartis Gene Therapies.

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Copyright 2024 Belter L et al. JAMA Pediatrics.
https://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the CC-BY-NC-ND License.
jamapediatr-e241911.pdf

This cross-sectional study describes the collection and use of state-provided data on newborn screening for spinal muscular atrophy.
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pmcSpinal muscular atrophy (SMA) is an autosomal recessive disease resulting in progressive motor neuron death, muscle denervation, and weakness.1 Rapid, widespread implementation of newborn screening (NBS) for SMA in the US since 2018 has facilitated the collection of precise SMA data, including birth prevalence.2 Cure SMA, a US-based patient advocacy organization supporting people with SMA, partnered with state public health laboratories (PHLs) to collect data on infants who were screened for SMA and confirmed to have SMA diagnosis. This study estimated the birth prevalence of SMA and evaluated the distribution of SMN2 copy number in US newborns with SMA.

Methods

Data on SMA NBS were obtained from state PHLs via public health department websites, direct sharing with Cure SMA, or an online survey (eAppendix in Supplement 1) hosted by Cure SMA between October and December 2021. Cure SMA notified state PHL staff of its plan to publish SMA NBS outcomes and asked for permission to include state-level SMA birth prevalence data in publications. The WCG IRB Connexus deemed this cross-sectional study exempt from review and informed consent because it met the consent waiver requirements. We followed the STROBE reporting guideline.

National birth prevalence of SMA was calculated by dividing the number of babies identified by newborn screening with confirmed SMA diagnosis divided by the total number of infants screened from states that provided applicable data (Figure). False-positive screening results were not included. Wilson score method was used to calculate 95% CIs. State-level birth prevalence rates were shown if the number of SMA-positive cases was more than 5.

Figure. Data Collection for Estimating Birth Prevalence of Spinal Muscular Atrophy (SMA)

NBS indicates newborn screening.

State PHL data for SMN2 copy numbers for infants with confirmed SMA-positive results were aggregated. All data from PHLs were provided in aggregate. Data analysis was performed using Stata version 14.1 (StataCorp LLC).

Results

Data generated between January 27, 2018, and December 31, 2022, were collected from 41 state PHLs of the 48 states conducting SMA NBS. Thirty of 48 states provided data for 6 244 825 infants, of whom 425 had a confirmed SMA diagnosis. The overall SMA birth prevalence was approximately 1 in 14 694 (95% CI, 0.00006-0.00007) (Table).

Table. State-Level Data Used to Estimate US Spinal Muscular Atrophy Birth Prevalence

State	Permanent screening start date	Reporting period start date	Reporting period end date	Test unit	No. of tests performed or infants screened	No. of positive test results	Birth prevalence, 1 in (95% CI)	
Alabamaa	February 14, 2022	February 14, 2022	August 31, 2022	Tests	32 408	<5	NA	
Alaskaa,b,c	July 1, 2022	July 1, 2022	October 31, 2022	Infants	3117	<5	NA	
Arizonaa,c	January 1, 2022	January 1, 2022	June 30, 2022	Infants	36 914	<5	NA	
Arkansasa	March 23, 2020	March 23, 2020	October 31, 2022	Tests	86 619	<5	NA	
Californiaa,b,c	June 24, 2020	DNR	DNR	Infants	DNR	DNR	DNR	
Coloradoa	January 20, 2020	January 20, 2020	October 31, 2022	Tests	176 511	15	NA	
Connecticutd	January 1, 2020	DNR	DNR	OOS	OOS	OOS	OOS	
Delawarea,c	January 1, 2020	January 1, 2020	September 30, 2022	Infants	30 586	<5	NA	
Floridaa,c	April 27, 2020	April 27, 2020	December 31, 2022	Infants	580 580	40	14 515 (0.00005-0.00009)	
Georgiab	April 1, 2020	DNR	DNR	Unknown	OOS	OOS	OOS	
Idahob	February 1, 2022	DNR	DNR	Unknown	OOS	OOS	OOS	
Illinoisa,c	June 29, 2020	June 29, 2020	June 30, 2022	Infants	256 699	14	18 336 (0.00003-0.00009)	
Indianaa,c	July 1, 2018	July 1, 2018	October 26, 2022	Infants	347 329	21	16 539 (0.00004-0.00009)	
Iowaa,c	September 8, 2021	September 15, 2021	October 26, 2022	Infants	40 434	5	8087 (0.00005-0.00029)	
Kansasa	February 1, 2020	February 1, 2020	December 31, 2022	Tests	123 968	7	NA	
Kentuckya,c	August 13, 2019	August 13, 2019	December 31, 2022	Infants	165 233	17	9720 (0.00006-0.00016)	
Louisianae	January 20, 2022	DNR	DNR	Unknown	DNR	DNR	NA	
Mainea,b,c	April 1, 2021	DNR	DNR	Infants	DNR	DNR	DNR	
Marylanda,b,c	June 17, 2019	DNR	DNR	Infants	DNR	DNR	DNR	
Massachusettsc,f	NA	January 27, 2018	October 27, 2022	Infants	290 465	13	22 343 (0.00003-0.00008)	
Michiganc,e	March 9, 2020	November 4, 2019	November 31, 2021	Infants	207 858	21	9898 (0.00007-0.00015)	
Minnesotaa,c	March 1, 2018	March 18, 2018	September 30, 2022	Infants	293 322	27	10 864 (0.00006-0.00013)	
Mississippib	November 1, 2019	DNR	DNR	Unknown	DNR	DNR	DNR	
Missouria	October 1, 2019	January 2, 2019	October 31, 2022	Tests	265 807	20	NA	
Montanab	March 1, 2021	DNR	DNR	Unknown	DNR	DNR	DNR	
Nebraskaa,c	November 14, 2020	November 14, 2020	December 31, 2021	Infants	43 031	<5	NA	
New Hampshirec,e	December 26, 2019	January 1, 2020	December 31, 2020	Infants	11 829	<5	NA	
New Jerseya,c	February 1, 2022	January 31, 2022	November 30, 2022	Infants	84 006	<5	NA	
New Mexicob	June 1, 2022	DNR	DNR	Unknown	DNR	DNR	DNR	
New Yorka,c	October 1, 2018	October 1, 2018	October 31, 2022	Infants	873 314	43	20 310 (0.00004-0.00007)	
North Carolinaa,d	May 1, 2021	January 5, 2021	October 31, 2022	Unknown	186 945	<10	NA	
North Dakotaa,b,c	September 1, 2021	July 1, 2020	December 31, 2022	Infants	30 404	<5	NA	
Ohioa,b,c,f	October 24, 2022	DNR	DNR	Infants	DNR	DNR	DNR	
Oklahomaa	March 16, 2021	March 1, 2021	November 30, 2022	Tests	76 141	8	NA	
Oregona,c	June 1, 2022	June 1, 2022	October 31, 2022	Infants	17 569	<5	NA	
Pennsylvaniaa,c	March 1, 2019	March 1, 2019	September 30, 2022	Infants	478 654	41	11 674 (0.00006-0.00012)	
Rhode Islanda,c	July 1, 2020	July 1, 2020	February 28, 2022	Infants	17 858	<5	NA	
South Carolinab	September 26, 2022	DNR	DNR	Unknown	DNR	DNR	DNR	
South Dakotaa,b,c	September 1, 2021	DNR	DNR	Infants	DNR	DNR	DNR	
Tennesseea,b,c	February 1, 2020	DNR	DNR	Infants	DNR	DNR	DNR	
Texasa	June 1, 2021	June 1, 2021	May 31, 2022	Tests	748 541	27	NA	
Utaha,b,c	January 29, 2018	DNR	DNR	Infants	DNR	DNR	DNR	
Vermonta,c	May 1, 2019	May 1, 2019	November 7, 2022	Infants	17 860	<5	NA	
Virginiab	March 16, 2022	DNR	DNR	Unknown	DNR	DNR	DNR	
Washingtona,b,c	August 7, 2020	DNR	DNR	Infants	DNR	DNR	DNR	
West Virginiaa,b,c	November 20, 2019	November 18, 2019	March 31, 2020	Infants	28 644	<5	NA	
Wisconsina,c	October 15, 2019	October 15, 2019	September 14, 2022	Infants	176 841	15	11 789 (0.00005-0.00014)	
Wyominga	January 20, 2020	January 20, 2020	October 31, 2022	Tests	15 309	<5	NA	
National SMA birth prevalence	NA	NA	NA	NA	6 244 825	425	1 in 14 694 (0.00006-0.00007)	
Abbreviations: DNR, did not respond; OOS, opted out of sharing; NA, not applicable; SMA, spinal muscular atrophy.

a Data shared directly with Cure SMA.

b Did not respond to request to share state-level data.

c Data used to calculate national SMA birth prevalence rate.

d Opted out of sharing state-level data.

e Data shared through state public health department websites.

f Data from pilot screening program.

Twenty-one states provided SMN2 copy number for infants with confirmed SMA. Proportions of SMN2 copy number among 240 infants were 5% with 1 copy, 49% with 2 copies, 33% with 3 copies, and 13% with 4 or more copies.

Discussion

The overall SMA birth prevalence according to the largest collection of SMA NBS data on US infants is lower than the historic global SMA birth prevalence estimate of approximately 1 in 10 000.3,4,5 In 2017, the American College of Obstetricians and Gynecologists joined the American College of Medical Genetics and Genomics in recommending carrier screening for SMA to all individuals considering their reproduction options.6 This change in care practice informs reproductive choices and may be a factor in the current birth prevalence. Additionally, approximately 5% of SMA cases have a single-nucleotide variant in SMN1 that is not detected by NBS and is not factored into the birth prevalence estimate.5

The first study limitation is that data were collected at different time points after statewide SMA NBS implementation. Thus, data may be more accurately described as minimum birth prevalence rates, as states reporting smaller data intervals may show more variability in birth prevalence estimates than states reporting 1 year or more of data. Second, varying data collection time points impeded the ability to report the proportion of births covered in this analysis. Third, birth prevalence calculation was limited to data from states reporting the number of infants screened.

These findings indicate that approximately 1 in 14 694 newborns in the US have SMA. Such information may be used to anticipate health care resource use for SMA and to plan future research in SMA care and treatment.

Supplement 1. eAppendix. Cure SMA Quarterly Request: SMA Newborn Screening Information

Supplement 2. Data Sharing Statement
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References

1 Arnold WD, Kassar D, Kissel JT. Spinal muscular atrophy: diagnosis and management in a new therapeutic era. Muscle Nerve. 2015;51 (2 ):157-167. doi:10.1002/mus.24497 25346245
2 Cure SMA. Newborn screening for SMA. 2022. Accessed September 9, 2023. https://www.curesma.org/newborn-screening-for-sma/
3 Sugarman EA, Nagan N, Zhu H, . Pan-ethnic carrier screening and prenatal diagnosis for spinal muscular atrophy: clinical laboratory analysis of >72,400 specimens. Eur J Hum Genet. 2012;20 (1 ):27-32. doi:10.1038/ejhg.2011.134 21811307
4 Verhaart IEC, Robertson A, Leary R, . A multi-source approach to determine SMA incidence and research ready population. J Neurol. 2017;264 (7 ):1465-1473. doi:10.1007/s00415-017-8549-1 28634652
5 Prior TW, Nagan N, Sugarman EA, Batish SD, Braastad C. Technical standards and guidelines for spinal muscular atrophy testing. Genet Med. 2011;13 (7 ):686-694. doi:10.1097/GIM.0b013e318220d523 21673580
6 American College of Obstetricians and Gynecologists. Committee opinion No. 691: carrier screening for genetic conditions. Obstet Gynecol. 2017;129 (3 ):e41-e55. doi:10.1097/AOG.0000000000001952 28225426
