Response to: CK-MM screening using neonatal dried blood spots may be inadequate at detecting all dystrophin mutation carriers
We thank Mehri and Finsterer for their valuable comments on our article “Neonatal screening for Duchenne muscular dystrophy in eastern China: a closed prospective study” published in the journal Translational Pediatrics (1,2). We address each of your questions in detail below.
Our study adopted the creatine kinase MM isoenzyme (CK-MM) assay for neonatal screening. In clinical practice, most parents decline muscle biopsy for their infants, so we did not perform this procedure to distinguish Duchenne muscular dystrophy (DMD) from Becker muscular dystrophy (BMD) among our confirmed cases. Still, our pediatric neurology team routinely carries out muscle biopsy for patients with ambiguous genetic results. According to our hospital’s pathology records, roughly 30 children received dystrophy-related muscle biopsies in 2025, while over 300 patients were clinically diagnosed with dystrophinopathy.
Admittedly, CK-MM testing may miss rare cases where myocardial damage occurs first rather than skeletal muscle lesions. This clinical phenotype has a low incidence rate; these patients typically develop symptoms only in adulthood, and early identification via newborn screening also raises ethical concerns. In our cohort, all infants with elevated CK-MM were recalled for follow-up tests, including total CK and CK-MB. None of these children showed normal total CK alongside markedly increased CK-MB.
We apologize for the ambiguous wording in the “Results” section regarding sampling time points. As stated in our Methods, dried blood spots (DBS) were collected from newborns within 72 hours after birth and adequate breastfeeding. In our cohort, 48.8% of samples were collected on postnatal day 3 and 42.4% on postnatal day 4; all of these specimens complied with the 72-hour collection criterion. Less than 10% of all DBS samples were collected beyond the recommended time window due to individual clinical circumstances.
As supported by previous neonatal cohort studies, elevated CK-MM in initial DBS samples is mainly attributed to birth trauma from vaginal delivery, forceps or vacuum-assisted extraction (3). Such injury selectively raises skeletal muscle-derived CK-MM, whereas total serum CK may remain normal in the early postpartum period. Another key factor is the time gap: the follow-up venous blood tests were conducted more than one week after the initial DBS screening. By the time of re-examination, the transient CK-MM elevation caused by delivery injury had already returned to baseline, which explains the inconsistent results between the two tests. No seizures or rhabdomyolysis were observed in these infants during follow-up.
We agree that excluding female newborns from the analysis is a clear limitation of this work. A number of female carriers can develop clinical symptoms and pose hereditary risks. Multiple studies have found that CK-MM levels are slightly higher in male newborns than in females (4,5). Accordingly, several screening programs have adopted gender-specific CK-MM cutoffs. For instance, Brigham and Women’s Hospital used 1,080 ng/mL for full-term male infants and 958 ng/mL for females (6). Given the distinct reference ranges between genders, we will carry out dedicated research on female newborns if research funding becomes available.
Acknowledgments
None.
Footnote
Provenance and Peer Review: This article was commissioned by the editorial office, Translational Pediatrics. The article did not undergo external peer review.
Funding: None.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-2026-0574/coif). The authors have no conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
References
- Qian G, Yang R, Huang X, et al. Neonatal screening for Duchenne muscular dystrophy in eastern China: a closed prospective study. Transl Pediatr 2026;15:72. [Crossref] [PubMed]
- Mehri S, Finsterer J. CK-MM screening using neonatal dried blood spots may be inadequate at detecting all dystrophin mutation carriers. Transl Pediatr 2026; [Crossref]
- Amato M, Nagel R, Hüppi P. Creatine-kinase MM in the perinatal period. Klin Padiatr 1991;203:389-94. [Crossref] [PubMed]
- Maloney B, Park S, Sowizral M, et al. Factors influencing creatine kinase-MM concentrations in newborns and implications for newborn screening for Duchenne muscular dystrophy. Clin Biochem 2023;118:110614. [Crossref] [PubMed]
- Neal RC, Ferdinand KC, Ycas J, et al. Relationship of ethnic origin, gender, and age to blood creatine kinase levels. Am J Med 2009;122:73-8. [Crossref] [PubMed]
- Parad RB, Sheldon Y, Bhattacharjee A. Implementation of Hospital-Based Supplemental Duchenne Muscular Dystrophy Newborn Screening (sDMDNBS): A Pathway to Broadening Adoption. Int J Neonatal Screen 2021;7:77. [Crossref] [PubMed]
