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Early Postnatal IGF-1 and IGFBP-1 Blood Levels in Extremely Preterm Infants: Relationships with Indicators of
Alan Leviton1, Elizabeth N Allred1, Raina N Fichorova2
1Department of Neurology, Boston Children's Hospital, Harvard Medical School, Boston, Massachusetts.
Insights
Placenta insufficiency and severe fetal growth restriction are linked to lower insulin-like growth factor 1 (IGF-1) and higher IGF-1-binding protein 1 (IGFBP-1) in newborns. These growth factors correlate with inflammatory and angiogenic proteins.
Area of Science:
- Neonatal Medicine
- Endocrinology
- Perinatal Biology
Background:
- Placental insufficiency and severe fetal growth restriction (sFGR) are critical obstetric complications.
- Insulin-like growth factor 1 (IGF-1) and IGF-1-binding protein 1 (IGFBP-1) play vital roles in fetal development.
- Understanding the relationship between placental function and neonatal growth factors is crucial for predicting outcomes.
Purpose of the Study:
- To investigate the association between indicators of placental insufficiency and neonatal concentrations of IGF-1 and IGFBP-1.
- To determine the relationship between IGF-1 and IGFBP-1 levels and other proteins involved in inflammation, neurotrophic processes, and angiogenesis in neonates.
Main Methods:
- Weekly blood spot samples were collected from a cohort of infants born before 28 weeks of gestation (n≥880).
- Multiplex immunoassays were used to measure concentrations of IGF-1, IGFBP-1, and 25 additional proteins.
- Correlates of high and low concentrations of IGF-1 and IGFBP-1 were analyzed in relation to gestational age and collection day.
Main Results:
- Medically indicated delivery and sFGR were associated with reduced IGF-1 and elevated IGFBP-1 concentrations in the first postnatal day.
- Elevated IGF-1 and IGFBP-1 levels were consistently observed across multiple postnatal days in infants with placental issues.
- High concentrations of IGF-1 and IGFBP-1 correlated with increased levels of inflammatory, neurotrophic, and angiogenic proteins.
Conclusions:
- Impaired placental implantation and sFGR contribute to lower IGF-1 levels in neonates.
- Elevated IGF-1 and particularly IGFBP-1 concentrations are linked to increased systemic inflammation and angiogenic activity in preterm infants.
- These findings highlight the complex interplay between placental health, growth factor signaling, and neonatal systemic responses.
Objective:
To evaluate to what extent indicators of placenta insufficiency are associated with low concentrations of insulin-like growth factor 1 (IGF-1) and IGF-1-binding protein-1 (IGFBP-1) in neonatal blood, and to what extent the concentrations of these growth factors are associated with concentrations of proteins with inflammatory, neurotrophic, or angiogenic properties.
Study Design:
Using multiplex immunoassays, we measured the concentrations of IGF-1 and IGFBP-1, as well as 25 other proteins in blood spots collected weekly from ≥ 880 infants born before the 28th week of gestation, and sought correlates of concentrations in the top and bottom quartiles for gestational age and day the specimen was collected.
Results:
Medically indicated delivery and severe fetal growth restriction (sFGR) were associated with low concentrations of IGF-1 on the first postnatal day and with high concentrations of IGFBP-1 on almost all days. Elevated concentrations of IGF-1 and IGFBP-1 were accompanied by elevated concentrations of many other proteins with inflammatory, neurotrophic, or angiogenic properties.
Conclusion:
Disorders associated with impaired placenta implantation and sFGR appear to account for a relative paucity of IGF-1 on the first postnatal day. Elevated concentrations of IGF-1 and especially IGFBP-1 were associated with same-day elevated concentrations of inflammatory, neurotrophic, and angiogenic proteins.
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