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Postnatal serum IGF-1 levels associate with brain volumes at term in extremely preterm infants
William Hellström1, Lisa M Hortensius2,3, Chatarina Löfqvist4,5
1Department of Pediatrics, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden. william.hellstrom@gu.se.
Insights
Insulin-like growth factor 1 (IGF-1) levels in the first month of life are linked to brain development in preterm infants. Higher IGF-1 is associated with larger brain volumes, suggesting potential benefits for optimizing growth.
Area of Science:
- Neonatal neuroscience
- Pediatric endocrinology
- Developmental biology
Background:
- Growth factors are crucial for brain development but are often low in preterm infants.
- This study examines the relationship between specific growth factors and brain volume in extremely preterm infants.
Purpose of the Study:
- To investigate the association between endogenous growth factor levels and brain volumes at term-equivalent age in infants born before 28 weeks gestational age.
- To determine if insulin-like growth factor 1 (IGF-1) and other growth factors correlate with total and regional brain volumes.
Main Methods:
- Serum samples from 49 extremely preterm infants (gestational age <28 weeks) were collected on postnatal days 1, 7, 14, and 28.
- Endogenous levels of IGF-1, brain-derived growth factor, vascular endothelial growth factor, and platelet-derived growth factor were quantified using area under the curve (AUC).
- Brain volumes (total, white matter, gray matter, cerebellum) were measured using MRI at term-equivalent age and analyzed via multivariable linear regression.
Main Results:
- Higher IGF-1 levels were independently associated with larger total brain volume (p<0.001), white matter (p=0.007), cortical gray matter (p=0.002), deep gray matter (p=0.008), and cerebellar volume (p=0.006).
- No significant associations were found for other investigated growth factors.
- These findings were adjusted for gestational age at birth and postmenstrual age at MRI.
Conclusions:
- Early postnatal exposure to IGF-1 is positively associated with brain growth in extremely preterm infants.
- Optimizing IGF-1 levels may be a potential strategy to enhance brain development in this vulnerable population.
- Further research, including clinical trials, is ongoing to explore the therapeutic potential of IGF-1.
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).
