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Key takeaways
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Fetal growth restriction (FGR) is a pregnancy complication in which fetuses have low levels of insulin-like growth factor 1 (IGF-1) and insulin, both important fetal growth hormones.
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This study examined whether fetal infusion of IGF-1 combined with insulin has the potential to enhance placental nutrient delivery, and in turn, promote fetal growth.
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Our investigators found that when fetal insulin levels remained normal, combining infusions of IGF-1 with insulin and dextrose promoted greater body and organ growth than IGF-1 alone.
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These findings challenge past theories that suggested only maternal hormone and nutrient levels, not those of the fetus, were key regulators of nutrient transfer from the placenta to fetus.
Research study background
Perinatal Research Center investigators from Children's Hospital Colorado and the University of Colorado School of Medicine are at the forefront of research on the fundamental mechanisms regulating fetal growth and the complications of placental insufficiency.
Fetal and umbilical cord levels of IGF-1 are directly correlated with birth weight. While previous studies of fetal sheep found that IGF-1 infusion increased the size of some organs, the infusions deeply decreased fetal plasma insulin concentrations which could limit fetal growth potential.
“Fetal growth restriction (FGR), one of our areas of study, affects up to 10% of pregnancies, is a frequent cause of stillbirth and premature birth and can lead to long-term complications. FGR often occurs because the placenta is not delivering enough nutrients to the fetus, resulting in low levels of the important fetal growth hormones insulin-like growth factor 1 (IGF-1) and insulin.”
- JANE STREMMING, MD
This study assessed the impact of fetal infusion of IGF-1 combined with insulin infusion as a potential therapy for FGR. For one week, investigators administered an intravenous infusion of either: IGF-1, IGF-1 with insulin and dextrose (IGF+INS), or vehicle control to normally growing late gestation fetal sheep.
The team found the recipients of IGF+INS were 23% heavier than the control group and had larger hearts, livers and adrenal glands compared to the other groups. The IGF-1-only group had significantly lower final insulin levels than the other groups. Glucose levels were similar across all groups. In addition, the IGF+INS group had lower final oxygen and amino acid levels and demonstrated higher umbilical oxygen uptake and umbilical uptake of several essential amino acids.
This study demonstrated that, under normal insulin and glucose conditions, fetal IGF+INS infusion enhances overall body and organ growth — especially in the heart, liver and adrenal glands — more than IGF-1 infusion alone.
Relevance to future research
These findings are among the first to challenge previous theories that suggested only maternal hormone and nutrient levels, rather than those of the fetus, were the key regulators of nutrient transfer from the placenta to the fetus. Future studies will explore how the mother and fetus communicate with the placenta to optimize nutrient transport and promote healthy growth. Ultimately, researchers hope to develop therapies to improve fetal growth and lifelong health.
Featured researchers
Paul Rozance, MD
Neonatologist
Neonatal Intensive Care Unit
Children's Hospital Colorado
Professor
Pediatrics-Neonatology
University of Colorado School of Medicine
Jane Stremming, MD
Neonatologist
Neonatal Intensive Care Unit
Children's Hospital Colorado
Assistant professor
Pediatrics-Neonatology
University of Colorado School of Medicine
Laura Brown, MD
Neonatologist
Neonatal Intensive Care Unit
Children's Hospital Colorado
Professor
Pediatrics-Neonatology
University of Colorado School of Medicine
