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  • Clinical Research Article
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Inflammation induces stunting by lowering bone mass via GH/IGF-1 inhibition in very preterm infants

Pediatric Research volume 94, pages 1136–1144 (2023)Cite this article

Abstract

Background

Sustained systemic inflammatory response (SIR) was associated with poor postnatal growth in very preterm infants (VPI). We hypothesize that VPI with sustained SIR will exhibit linear growth retardation related to lower bone mass accrual mediated by GH/IGF-1 axis inhibition at term corrected age (CA).

Methods

C-reactive protein (CRP), procalcitonin (PCT), growth hormone (GH), insulin-like growth factor 1 (IGF-1), calcium, phosphorus, alkaline phosphatase, anthropometric, nutritional, neonatal and maternal data were collected prospectively in 23 infants <32 weeks gestational age. Body composition using dual-energy X-ray absorptiometry was performed at term CA. Analysis was undertaken with multiple linear regression models.

Results

At term CA 11 infants with sustained SIR compared with 12 infants without sustained SIR present significantly lower IGF-1, length z-score (LZS), bone mineral content (BMC) and lean mass (LM), and higher GH and fat mass (FM). LZS was associated significantly with PCT, BMC with IGF-1, FM and LM with CRP, GH with bronchopulmonary dysplasia and CRP, and IGF-1 with invasive mechanical ventilation, CRP and PCT.

Conclusions

In addition to the known effect on linear growth failure, sustained SIR induces lower bone mass accrual related to higher GH and lower IGF-1 levels in VPI.

Impact

  • Very preterm infants (VPI) with sustained systemic inflammatory response (SIR) compared with VPI without SIR present stunting, lower bone mass, higher GH and lower IGF-1 levels at term corrected age.

  • SIR may help to explain the influence of non-nutritional factors on growth and body composition in VPI.

  • SIR induces postnatal stunting related to lower bone mass accrual via GH/IGF-1 axis inhibition in VPI.

  • VPI with SIR need special attention to minimize inflammatory stress, which could result in improved postnatal growth.

  • Research on inflammatory-endocrine interactions involved in the pathophysiology of postnatal stunting is needed as a basis for new interventional approaches.

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Fig. 1: Flowchart of sample size.
Fig. 2: Explanatory model of the effect of inflammation on the regulation of the growth hormone/insulin-like growth factor 1 axis.

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Data availability

The datasets generated during the present study are available to others upon reasonable request via email to the corresponding author.

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Acknowledgements

The authors thank Nicholas Basily for editing the English language of this manuscript.

Funding

This study was supported by the Agencia Nacional de Promoción Científica y Tecnológica (FONCYT) grant PICT 2019-3062.

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Authors and Affiliations

  1. Department of Pediatrics and Neonatology, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina

    Eduardo Cuestas, Macarena Hillman, Silvia Galetto & Alina Rizzotti

  2. Department of Clinical Biochemistry, Hospital Privado Universitario de Córdoba, Instituto Universitario de Ciencias Biomédicas de Córdoba, Córdoba, Argentina

    María Isabel Gaido

  3. Department of Radiology, Instituto Conci–Carpinella, Córdoba, Argentina

    Viviana Sobh & Lucrecia Torres Damico

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  1. Eduardo Cuestas
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Contributions

E.C. conceptualized and designed the study, coordinated and supervised data collection, carried out the final data analyses, drafted the manuscript, and reviewed and revised the final manuscript. M.H., S.G., M.I.G., V.S. and A.R. designed the data collection instruments, manually collected data, carried out the initial analyses, and reviewed and revised the manuscript for important intellectual content. All authors have approved the final manuscript as submitted.

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Correspondence to Eduardo Cuestas.

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The authors declare no competing interests.

Ethics approval and consent to participate

The study was approved by the Institutional Review Board at Hospital Privado Universitario de Córdoba, and the infants’ parents gave written informed consent (HP 4-308). This study used anonymized and deidentified data, fulfilling local data protection regulations.

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Cuestas, E., Hillman, M., Galetto, S. et al. Inflammation induces stunting by lowering bone mass via GH/IGF-1 inhibition in very preterm infants. Pediatr Res 94, 1136–1144 (2023). https://doi.org/10.1038/s41390-023-02559-5

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