Kathryn Beardsall1, Sophie Vanhaesebrouck2, Jan Frystyk3, Amanda L Ogilvy-Stuart4, Christine Vanhole2, Mirjam van Weissenbruch5, Paula Midgley6, Marta Thio7, Luc Cornette8, Bryan Gill8, Iviano Ossuetta9, Isabel Iglesias7, Claire Theyskens10, Miranda de Jong5, Jag S Ahluwalia4, Francis de Zegher2, David B Dunger11. 1. Department of Pediatrics, University of Cambridge, Addenbrooke's Hospital NHS Trust, Hills Road, Cambridge, United Kingdom; Neonatal Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. Electronic address: kb274@cam.ac.uk. 2. Department of Woman and Child, University of Leuven, Leuven, Belgium. 3. Medical Research Laboratory, Department of Clinical Medicine, Faculty of Health, Aarhus University and Department of Internal Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. 4. Neonatal Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom. 5. VU University Medical Center, Amsterdam, The Netherlands. 6. Simpson Center for Reproductive Health, Royal Infirmary of Edinburgh, Edinburgh, Scotland. 7. Hospital Universitari Sant Joan de Déu, Esplugues, Barcelona, Spain. 8. Leeds General Infirmary, Leeds, United Kingdom. 9. Luton and Dunstable Hospital, Bedfordshire, United Kingdom. 10. ZOL Genk, Genk, Belgium. 11. Department of Pediatrics, University of Cambridge, Addenbrooke's Hospital NHS Trust, Hills Road, Cambridge, United Kingdom.
Abstract
OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 μg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.
OBJECTIVES: Insulin regulates the secretion of insulin-like growth factor I (IGF-I) in the newborn, and low levels of IGF-I have been linked to neonatal morbidity. As part of the Neonatal Insulin Replacement Therapy in Europe Trial, we investigated the impact of early insulin treatment on IGF-I levels and their relationship with morbidity and growth. STUDY DESIGN: Prospective cohort analyses of data collected as part of an international randomized controlled trial. Blood samples (days 1, 3, 7, and 28), were taken for IGF-I bioassay from 283 very low birth weight infants (<1500 g). RESULTS: Early insulin treatment led to a late increase in IGF-I levels between day 7 and 28 (P = .028). In the first week of life IGF-I levels were lower in infants with early hyperglycemia; mean difference -0.10 μg/L (95% CI -0.19, -0.02, P = .02). Lower levels of IGF-I at day 28 were independently associated with an increased risk of chronic lung disease, OR 3.23 (95% CI, 1.09-9.10), and greater IGF-I levels were independently associated with better weight gain, 0.10 kg (95% CI, 0.03-0.33, P = .02). CONCLUSIONS: Early intervention with insulin is related to increased IGF-I levels at 28 days. Low IGF-I levels are associated with hyperglycemia, increased morbidity, and reduced growth. Increasing IGF-I levels may improve outcomes of very low birth weight infants.
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