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Long-term administration of sirolimus does not affect the physical development of children with tuberous sclerosis complex

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Abstract

Purpose

There was no evidence whether the mammalian/mechanistic target of rapamycin pathway hyperactivation and long-term use of mTOR inhibitors have any effects on the physical development of children. The aim was to evaluate these effects by comparing the physical development of children with TSC and normal children.

Methods

A total of 120 eligible children were enrolled. They were administered sirolimus and followed for at least 12 months. Height, weight, BMI and lipid metabolism index were collected during treatment. Pearson’s chi-square and Fisher’s exact test were used for comparison of proportions of patients exhibiting normal and abnormal physical growth before and after 1 year of treatment. Logistic regression was used to evaluate the influence of age, sex and abnormal lipid metabolism on the increased BMIs of TSC patients after treatment.

Results

Most of the enrolled TSC children were in the normal height, weight and BMI ranges at baseline (91.7%, 95.8% and 78.3%, respectively). Most remained in the normal height, weight and BMI ranges after 1 year of sirolimus treatment (94.2%, 95% and 76.7%, respectively). There was no significant difference in the proportion of physical development before and after treatment (p > 0.05). Thirty-eight (38/106, 35.8%) patients had increased BMIs after 1 year of treatment, but there was no significant correlation between age, sex and lipid metabolism and increased BMI.

Conclusions

Overactivation of the mTOR pathway and long-term administration of sirolimus does not affect the physical development of children with TSC.

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Availability of data and material

The data that support the findings of this study are available from the corresponding author, upon reasonable request.

Code availability

None.

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Funding

The National Key Research and Development Program of China funded this project (2016YFC1000707).

Author information

Author notes

  1. Jian Chen and Wen He contributed equally to this study.

Authors and Affiliations

  1. Faculty of Pediatrics, Department of Pediatrics, The First Medical Center of Chinese, Chinese PLA General Hospital, PLA General Hospital, 28 Fuxing road, Haidian district, Beijing, 100853, China

    Jian Chen, Wen He, Yang-Yang Wang, Meng-Na Zhang, Qian Lu, Qiu-Hong Wang, Bin Wang & Li-Ping Zou

  2. Center for Brain Disorders Research, Capital Medical University, Beijing Institute for Brain Disorders, Beijing, China

    Xiao-Mei Luo & Li-Ping Zou

Authors
  1. Jian Chen
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  2. Wen He
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Contributions

Jian Chen and Wen He designed the study and performed its implementation and drafting of the manuscript. Yang-Yang Wang, Meng-Na Zhang, Qian Lu and Qiu-Hong Wang designed the study’s analytical strategy and performed the analyses and preparation of the text. Xiao-Mei Luo and Bin Wang provided pertinent advice. All the authors read and approved the final manuscript.

Corresponding author

Correspondence to Li-Ping Zou.

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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. The study was approved by the Ethics Committee of the Chinese PLA General Hospital (No. S2013-028–01) and the Chinese Clinical Trial Registry No. was CHICTR-OCH-13003763.

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Informed written consents were obtained from the parents of the patients.

Conflict of interest

The authors declare that they have no competing interests.

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Chen, J., He, W., Wang, YY. et al. Long-term administration of sirolimus does not affect the physical development of children with tuberous sclerosis complex. Childs Nerv Syst 38, 947–952 (2022). https://doi.org/10.1007/s00381-022-05446-2

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  • DOI: https://doi.org/10.1007/s00381-022-05446-2

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