Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants

William Hellström; Lisa M Hortensius; Chatarina Löfqvist; Gunnel Hellgren; Maria Luisa Tataranno; David Ley; Manon J N L Benders; Ann Hellström; Isabella M Björkman-Burtscher; Rolf A Heckemann; Karin Sävman

doi:10.1038/s41390-022-02134-4

Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants

Pediatr Res. 2023 Feb;93(3):666-674. doi: 10.1038/s41390-022-02134-4. Epub 2022 Jun 9.

Authors

William Hellström¹, Lisa M Hortensius^{2

3}, Chatarina Löfqvist^{4

5}, Gunnel Hellgren^{4

6}, Maria Luisa Tataranno^{2

3}, David Ley⁷, Manon J N L Benders^{2

3}, Ann Hellström⁴, Isabella M Björkman-Burtscher⁸, Rolf A Heckemann⁹, Karin Sävman^{10

11}

Affiliations

¹ Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. william.hellstrom@gu.se.
² Department of Neonatology, Wilhelmina Children's Hospital, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
³ University Medical Center Utrecht Brain Center, Utrecht University, Utrecht, The Netherlands.
⁴ Section for Ophthalmology, Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁵ Institute of Health Care Science, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁶ Institute of Biomedicine, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
⁷ Department of Pediatrics, Institute of Clinical Sciences, Skåne University Hospital Lund, Lund, Skåne, Sweden.
⁸ Department of Radiology, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg and Sahlgrenska University Hospital, Gothenburg, Sweden.
⁹ Department of Medical Radiation Sciences, Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹⁰ Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
¹¹ Region Västra Götaland, Department of Neonatology, The Queen Silvia Children's Hospital, Sahlgrenska University Hospital, Gothenburg, Sweden.

Abstract

Background: Growth factors important for normal brain development are low in preterm infants. This study investigated the link between growth factors and preterm brain volumes at term.

Material/methods: Infants born <28 weeks gestational age (GA) were included. Endogenous levels of insulin-like growth factor (IGF)-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor (expressed as area under the curve [AUC] for serum samples from postnatal days 1, 7, 14, and 28) were utilized in a multivariable linear regression model. Brain volumes were determined by magnetic resonance imaging (MRI) at term equivalent age.

Results: In total, 49 infants (median [range] GA 25.4 [22.9-27.9] weeks) were included following MRI segmentation quality assessment and AUC calculation. IGF-1 levels were independently positively associated with the total brain (p < 0.001, β = 0.90), white matter (p = 0.007, β = 0.33), cortical gray matter (p = 0.002, β = 0.43), deep gray matter (p = 0.008, β = 0.05), and cerebellar (p = 0.006, β = 0.08) volume adjusted for GA at birth and postmenstrual age at MRI. No associations were seen for other growth factors.

Conclusions: Endogenous exposure to IGF-1 during the first 4 weeks of life was associated with total and regional brain volumes at term. Optimizing levels of IGF-1 might improve brain growth in extremely preterm infants.

Impact: High serum levels of insulin-like growth factor (IGF)-1 during the first month of life were independently associated with increased total brain volume, white matter, gray matter, and cerebellar volume at term equivalent age in extremely preterm infants. IGF-1 is a critical regulator of neurodevelopment and postnatal levels are low in preterm infants. The effects of IGF-1 levels on brain development in extremely preterm infants are not fully understood. Optimizing levels of IGF-1 may benefit early brain growth in extremely preterm infants. The effects of systemically administered IGF-1/IGFBP3 in extremely preterm infants are now being investigated in a randomized controlled trial (Clinicaltrials.gov: NCT03253263).

Publication types

Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Brain
Gestational Age
Gray Matter / metabolism
Humans
Infant
Infant, Extremely Premature*
Infant, Newborn
Insulin-Like Growth Factor I* / metabolism
Magnetic Resonance Imaging / methods
Vascular Endothelial Growth Factor A / metabolism

Substances

Insulin-Like Growth Factor I
Vascular Endothelial Growth Factor A

Associated data

ClinicalTrials.gov/NCT03253263