William Hellström1, Lisa M Hortensius2,3, Chatarina Löfqvist4,5, Gunnel Hellgren4,6, Maria Luisa Tataranno2,3, David Ley7, Manon J N L Benders2,3, Ann Hellström4, Isabella M Björkman-Burtscher8, Rolf A Heckemann9, Karin Sävman10,11. 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).
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).
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