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Assessment of catabolic state in infants with the use of urinary titin N-fragment



Urinary titin N-fragment levels have been used to assess the catabolic state, and we used this biomarker to evaluate the catabolic state of infants.


We retrospectively measured urinary titin N-fragment levels of urinary samples. The primary outcome was its changes according to postmenstrual age. The secondary outcomes included differences between gestational age, longitudinal change after birth, influence on growth, and relationship with blood tests.


This study included 219 patients with 414 measurements. Urinary titin N-fragment exponentially declined with postmenstrual age. These values were 12.5 (7.1–19.6), 8.1 (5.1–13.0), 12.8 (6.0–21.3), 26.4 (16.4–52.0), and 81.9 (63.3–106.4) pmol/mg creatinine in full, late, moderate, very, and extremely preterm infants, respectively (p < 0.01). After birth, urinary levels of titin N-fragment exponentially declined, and the maximum level within a week was associated with the time to return to birth weight in preterm infants (ρ = 0.39, p < 0.01). This was correlated with creatine kinase in full-term infants (ρ = 0.58, p < 0.01) and with blood urea nitrogen in preterm infants (ρ = 0.50, p < 0.01).


The catabolic state was increased during the early course of the postmenstrual age and early preterm infants.


  • Catabolic state in infants, especially in preterm infants, was expected to be increased, but no study has clearly verified this.

  • In this retrospective study of 219 patients with 414 urinary titin measurements, the catabolic state was exponentially elevated during the early postmenstrual age.

  • The use of the urinary titin N-fragment clarified catabolic state was prominently increased in very and extremely preterm infants.

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Fig. 1: Urinary levels of titin N-fragment during postmenstrual age.
Fig. 2: Urinary levels of titin N-fragment in full-term and preterm infants.
Fig. 3: Longitudinal change in urinary levels of titin N-fragment after birth.
Fig. 4: Relationship between urinary titin N-fragment and the time to return to birth weight.


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We would like to thank Yoshihiro Okayama (Clinical Research Center for Development Therapeutics, Tokushima University Hospital) for his support in the statistical aspect. We would also like to thank those who supported the muscle atrophy zero-project, which aims to prevent muscle atrophy in patients.

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Authors and Affiliations



S.F. and N.N. equally contributed to conception and design, acquisition of data, analysis, interpretation of data, and drafting of the manuscript as first authors. K.F. and K.S. equally contributed to all aspects of this study as second authors. T.S., K.O., K.H., and R.T. performed laboratory testing and analysis of data. M.U., R.N., and H.A. were involved in the acquisition of the data and drafting of the manuscript. J.O., H.S., and K.I. supervised all aspects of this study. M.M. supervised and contributed equally to all aspects of this study including drafting the article and revising it critically for important intellectual content as a corresponding author. All authors read and approved the final version to be published.

Corresponding author

Correspondence to Nobuto Nakanishi.

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Titin N-Fragment Assay Kit was partly provided from Immuno-Biological Laboratories Co. Ltd. (Gunma, Japan). This study was partly supported by a crowdfunding project entitled the Muscle Atrophy Zero Project, using the platform “Otsucle” This study was partially supported by JSPS KAKENHI Grant Number JP20K17899.

Competing interests

M.M. discloses being employed by Kobe Gakuin University, which received funding from KNC Laboratories Inc., Kobe, Japan. M.M. further discloses being a scientific adviser for the Daiichi-Sankyo Co., Tokyo, Japan, and JCR Pharma Co., Ashiya, Japan. The remaining authors declare no competing interests.

Consent statement

Ethics approval was obtained from the Institutional Review Board of Kobe University (#B200211) and Tokushima University (#1425). Opt-out and opt-in informed consent at the Kobe University and Tokushima University, respectively, was obtained for this study. Written informed consent was obtained from all parents for the use of their personal medical data in research.

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Fukushima, S., Nakanishi, N., Fujioka, K. et al. Assessment of catabolic state in infants with the use of urinary titin N-fragment. Pediatr Res 91, 1748–1753 (2022).

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