An exploratory study of clinical factors associated with IGF-1 and IGFBP-3 in preterm infants – Nature

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.
Advertisement
Pediatric Research (2024)Cite this article
147 Accesses
1 Altmetric
Metrics details
Despite advances in parenteral nutrition, postnatal growth failure in very low birthweight (VLBW) preterm infants is common and associated with chronic health problems. Insulin-like growth factor 1 (IGF-1) is positively associated with improved infant growth, but factors which promote IGF-1 levels in this population have not been clearly identified. The objective of this study was to explore early factors that influence IGF-1 in VLBW preterm infants.
VLBW infants were enrolled into a prospective, randomized controlled nutrition trial (N = 87). Outcome measures included IGF-1 and IGFBP-3 levels measured at 35 weeks PMA. Linear regression analyses tested the relationships between candidate clinical predictors and levels of IGF-1 and IGFBP-3.
Higher protein intake, longer duration of parenteral nutrition, and lower IGFBP-3 levels at 1 week of life were associated with lower IGF-1 levels at 35 weeks PMA. Neither early markers of insulin resistance nor degree of illness were associated with IGF-1 levels at 35 weeks PMA.
Optimization of early nutrient intake, and attention to route of delivery, may have a lasting influence on IGF-1/IGFBP-3, and in turn, long-term health outcomes.
In very low birthweight preterm infants, early protein intake, duration of parenteral nutrition, and insulin-like growth factor binding protein 3 (IGFBP-3) levels at 1 week of life are positively associated with insulin-like growth factor 1 (IGF-1) levels at 35 weeks postmenstrual age.
Data from this study highlight the influence of early nutrition on components of the endocrine axis in preterm infants.
Strategies aimed at early initiation of enteral nutrition, as well as optimizing composition of parenteral nutrition, may bolster hormones involved in promoting preterm infant growth.
This is a preview of subscription content, access via your institution

Subscribe to this journal
Receive 14 print issues and online access
£169.00 per year
only £12.07 per issue
Buy this article
Prices may be subject to local taxes which are calculated during checkout
The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.
T. T. Colaizy, S. B. D., K. M. Mcnelis, B. B. Poindexter. in Avery’s Diseases of the Newborn (Christine A. Gleason, S. E. J. ed.) Ch. 68, 1009-1022 (Elsevier, 2018).
Lee, S. M. et al. Prediction of postnatal growth failure among very low birth weight infants. Sci. Rep. 8, 3729 (2018).
Article  PubMed Central  PubMed  Google Scholar 
Lammertink, F., Vinkers, C. H., Tataranno, M. L. & Benders, M. Premature birth and developmental programming: mechanisms of resilience and vulnerability. Front. Psychiatry 11, 531571 (2020).
Article  PubMed  Google Scholar 
Gonzalez Villamizar, J. D., Haapala, J. L., Scheurer, J. M., Rao, R. & Ramel, S. E. Relationships between early nutrition, illness, and later outcomes among infants born preterm with hyperglycemia. J. Pediatr. 223, 29–33.e22 (2020).
Article  CAS  PubMed  Google Scholar 
Ramel, S. E., Brown, L. D. & Georgieff, M. K. The impact of neonatal illness on nutritional requirements-one size does not fit all. Curr. Pediatr. Rep. 2, 248–254 (2014).
Article  PubMed Central  PubMed  Google Scholar 
Ramel, S. E. et al. The relationship of poor linear growth velocity with neonatal illness and two-year neurodevelopment in preterm infants. Neonatology 102, 19–24 (2012).
Article  PubMed  Google Scholar 
Ramel, S. E., Haapala, J., Super, J., Boys, C. & Demerath, E. W. Nutrition, illness and body composition in very low birth weight preterm infants: implications for nutritional management and neurocognitive outcomes. Nutrients 12, 145 (2020).
Article  PubMed Central  PubMed  Google Scholar 
Kajantie, E. et al. Igf-I, Igf Binding Protein (Igfbp)-3, Phosphoisoforms of Igfbp-1, and postnatal growth in very low birth weight infants. J. Clin. Endocrinol. Metab. 87, 2171–2179 (2002).
Article  CAS  PubMed  Google Scholar 
Hellstrom, A. et al. Insulin-Like Growth Factor 1 has multisystem effects on foetal and preterm infant development. Acta Paediatr. 105, 576–586 (2016).
Article  PubMed Central  PubMed  Google Scholar 
Gillman, M. W. et al. Meeting report on the 3rd International Congress on Developmental Origins of Health and Disease (Dohad). Pediatr. Res 61, 625–629 (2007).
Article  PubMed  Google Scholar 
Mollers, L. S. et al. Metabolic-endocrine disruption due to preterm birth impacts growth, body composition, and neonatal outcome. Pediatr. Res. 91, 1350–1360 (2022).
Patel, L. et al. The contributions of plasma Igf-I, Igfbp-3 and leptin to growth in extremely premature infants during the first two years. Pediatr. Res. 61, 99–104 (2007).
Article  CAS  PubMed  Google Scholar 
Hellstrom, A., Sigurdsson, J., Lofqvist, C., Hellgren, G. & Kistner, A. The Igf system and longitudinal growth in preterm infants in relation to gestational age, birth weight and gender. Growth Horm. IGF Res. 51, 46–57 (2020).
Article  PubMed  Google Scholar 
Nagel, E. M. et al. Enhanced parenteral nutrition is feasible and safe in very low birth weight preterm infants: a randomized trial. Neonatology 120, 242–249 (2023).
Morris, E. E. et al. Randomized trial of early enhanced parenteral nutrition and later neurodevelopment in preterm infants. Nutrients 14, 3890 (2022).
Article  CAS  PubMed Central  PubMed  Google Scholar 
Baron, R. M. & Kenny, D. A. The moderator-mediator variable distinction in social psychological research: conceptual, strategic, and statistical considerations. J. Pers. Soc. Psychol. 51, 1173–1182 (1986).
Article  CAS  PubMed  Google Scholar 
Team, R. C. R: A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, https://www.R-project.org/ (2022).
Fu, T. T. et al. Correlation of Nicu anthropometry in extremely preterm infants with brain development and language scores at early school age. Sci. Rep. 13, 15273 (2023).
Article  CAS  PubMed Central  PubMed  Google Scholar 
Miller, A. N. et al. Linear growth is associated with successful respiratory support weaning in infants with bronchopulmonary dysplasia. J. Perinatol. 42, 544–545 (2022).
Article  Google Scholar 
Geng, T. et al. Birth weight modifies the relation between adulthood levels of insulin-like growth factor-1 and type 2 diabetes: a prospective cohort study. BMJ Open Diabetes Res. Care 9, e001885 (2021).
Article  PubMed Central  PubMed  Google Scholar 
Kantake, M. et al. Igf1 gene is epigenetically activated in preterm infants with intrauterine growth restriction. Clin. Epigenet. 12, 108 (2020).
Article  CAS  Google Scholar 
Hellstrom, W. et al. Postnatal serum Igf-1 levels associate with brain volumes at term in extremely preterm infants. Pediatr. Res. 93, 666–674 (2023).
Chung, J. K. et al. Development and verification of a pharmacokinetic model to optimize physiologic replacement of Rhigf-1/Rhigfbp-3 in preterm infants. Pediatr. Res. 81, 504–510 (2017).
Article  CAS  PubMed  Google Scholar 
Hansen-Pupp, I. et al. Continuous longitudinal infusion of Rhigf-1/Rhigfbp-3 in extremely preterm infants: evaluation of feasibility in a phase Ii study. Growth Horm. IGF Res. 36, 44–51 (2017).
Article  CAS  PubMed  Google Scholar 
Hellstrom, A. et al. Igf-1 as a drug for preterm infants: a step-wise clinical development. Curr. Pharm. Des. 23, 5964–5970 (2017).
Article  PubMed Central  PubMed  Google Scholar 
Ley, D. et al. Rhigf-1/Rhigfbp-3 in preterm infants: a phase 2 randomized controlled trial. J. Pediatr. 206, 56–65.e58 (2019).
Article  CAS  PubMed  Google Scholar 
Yumani, D. F., Lafeber, H. N. & van Weissenbruch, M. M. Dietary proteins and Igf I levels in preterm infants: determinants of growth, body composition, and neurodevelopment. Pediatr. Res. 77, 156–163 (2015).
Article  CAS  PubMed  Google Scholar 
Meyers, J. M., Greecher, C. P., Shaffer, M. L. & Shenberger, J. S. Potential influence of total parenteral nutrition on body composition at discharge in preterm infants. J. Matern. Fetal Neonatal. Med. 26, 1548–1553 (2013).
Article  PubMed  Google Scholar 
Hansen-Pupp, I. et al. Influence of insulin-like growth factor I and nutrition during phases of postnatal growth in very preterm infants. Pediatr. Res. 69, 448–453 (2011).
Article  CAS  Google Scholar 
Engstrom, E., Niklasson, A., Wikland, K. A., Ewald, U. & Hellstrom, A. The role of maternal factors, postnatal nutrition, weight gain, and gender in regulation of serum Igf-I among preterm infants. Pediatr. Res. 57, 605–610 (2005).
Article  PubMed  Google Scholar 
Lafeber, H. N., van de Lagemaat, M., Rotteveel, J. & van Weissenbruch, M. Timing of nutritional interventions in very-low-birth-weight infants: optimal neurodevelopment compared with the onset of the metabolic syndrome. Am. J. Clin. Nutr. 98, 556S–560S (2013).
Article  CAS  PubMed  Google Scholar 
Smith, W. J., Underwood, L. E. & Clemmons, D. R. Effects of caloric or protein restriction on insulin-like growth Factor-I (Igf-I) and Igf-binding proteins in children and adults. J. Clin. Endocrinol. Metab. 80, 443–449 (1995).
CAS  PubMed  Google Scholar 
Smith, W. J., Underwood, L. E., Keyes, L. & Clemmons, D. R. Use of insulin-like growth Factor I (Igf-I) and Igf-Binding protein measurements to monitor feeding of premature infants. J. Clin. Endocrinol. Metab. 82, 3982–3988 (1997).
CAS  PubMed  Google Scholar 
Counts, D. R., Gwirtsman, H., Carlsson, L. M., Lesem, M. & Cutler, G. B. Jr. The effect of anorexia nervosa and refeeding on growth hormone-binding protein, the Insulin-Like Growth Factors (Igfs), and the Igf-Binding proteins. J. Clin. Endocrinol. Metab. 75, 762–767 (1992).
CAS  PubMed  Google Scholar 
Reynolds, C. M., Gray, C., Li, M., Segovia, S. A. & Vickers, M. H. Early life nutrition and energy balance disorders in offspring in later life. Nutrients 7, 8090–8111 (2015).
Article  CAS  PubMed Central  PubMed  Google Scholar 
Reynolds, C. M., Perry, J. K. & Vickers, M. H. Manipulation of the growth hormone-insulin-Like Growth Factor (Gh-Igf) axis: a treatment strategy to reverse the effects of early life developmental programming. Int J. Mol. Sci. 18, 1729 (2017).
Article  PubMed Central  PubMed  Google Scholar 
Eguchi, K. et al. Insulin-Like growth factor binding protein-3 suppresses osteoblast differentiation via bone morphogenetic Protein-2. Biochem. Biophys. Res. Commun. 507, 465–470 (2018).
Article  CAS  PubMed  Google Scholar 
Bloomfield, F. H. et al. Early amino acids in extremely preterm infants and neurodisability at 2 years. N. Engl. J. Med. 387, 1661–1672 (2022).
Article  CAS  PubMed  Google Scholar 
Hansen-Pupp, I. et al. Postnatal decrease in circulating insulin-like growth factor-I and low brain volumes in very preterm infants. J. Clin. Endocrinol. Metab. 96, 1129–1135 (2011).
Article  CAS  PubMed  Google Scholar 
Hansen-Pupp, I. et al. Circulatory insulin-like growth factor-i and brain volumes in relation to neurodevelopmental outcome in very preterm infants. Pediatr. Res. 74, 564–569 (2013).
Download references
We would like to thank Scott Lunos, MS for his involvement in the revision of this manuscript. We would like to thank Jennifer Super, RD for her involvement in consultation regarding nutritional aspects of this work. We are also grateful to the participants and their parents for taking part in this study.
University of Minnesota Department of Pediatrics “R Award” to S.E.R.; M.E.P. was supported by NIH/NICHD grant K12HD055887, E.M.N. was supported by NIH/NIDDK grant T32DK083250 and NIH/NICHD grant K99HD108276.
Division of Neonatology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
Megan E. Paulsen, Juan David Gonzalez Villamizar & Sara E. Ramel
Masonic Institute for the Developing Brain, University of Minnesota, Minneapolis, MN, USA
Megan E. Paulsen & Sara E. Ramel
Biostatistical Design and Analysis Center, Clinical Translational Science Institute, University of Minnesota, Minneapolis, MN, USA
Nicholas Marka
University of Minnesota School of Public Health, Minneapolis, MN, USA
Emily M. Nagel
Division of Endocrinology, Department of Pediatrics, University of Minnesota Medical School, Minneapolis, MN, USA
Brandon M. Nathan
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
You can also search for this author in PubMed Google Scholar
S.E.R. conceived and designed the study. E.M.N., J.D.G.V. and M.E.P. performed data acquisition. N.M. analyzed data. All authors interpreted data. M.E.P. and N.M. drafted the manuscript, tables, and figures. All authors critically revised the manuscript, approve submission of manuscript for publication, and agree to be accountable for all aspects of the work.
Correspondence to Megan E. Paulsen.
The authors declare no competing interests.
Parents of patients were required to provide informed consent to participate in this study.
Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
Reprints and permissions
Paulsen, M.E., Marka, N., Nagel, E.M. et al. An exploratory study of clinical factors associated with IGF-1 and IGFBP-3 in preterm infants. Pediatr Res (2024). https://doi.org/10.1038/s41390-023-02970-y
Download citation
Received: 04 May 2023
Revised: 17 October 2023
Accepted: 26 November 2023
Published: 08 January 2024
DOI: https://doi.org/10.1038/s41390-023-02970-y
Anyone you share the following link with will be able to read this content:
Sorry, a shareable link is not currently available for this article.

Provided by the Springer Nature SharedIt content-sharing initiative

Advertisement
Pediatric Research (Pediatr Res) ISSN 1530-0447 (online) ISSN 0031-3998 (print)
© 2024 Springer Nature Limited

source

About The Author

admin

See author's posts