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Insulin, Insulin-Like Growth Factor I (IGF-I), IGF-Binding Protein-1, Growth Hormone, and Feeding in the Newborn

Department of Pediatrics, University of Oxford (A.L.O.-S., S.J.H., C.J.A., A.R.W., D.B.D.), OX3 9DU Oxford; the Department of Surgery, University of Bristol (J.M.P.H.), BSZ 8HW Bristol; the Department of Diabetes and Endocrinology, Radcliffe Infirmary (D.R.M.), OX2 6HE Oxford; and the Department of Medicine, University College London Medical School, Whittington Hospital (V.M.-A., J.S.Y.), N19 3UA London, United Kingdom

Address all correspondence and requests for reprints to: Dr. A. L. Ogilvy-Stuart, Neonatal Unit, The Rosie Hospital, Addenbrooke’s NHS Trust, Robinson Way, Cambridge, United Kingdom CB2 2SW. E-mail: amanda.ogilvy-stuart{at}msexc.addenbrookes.anglox.nhs.uk

The relationship between GH, insulin-like growth factor I (IGF-I), IGF-binding protein-1 (IGFBP-1), and insulin may be critical to the understanding of variation in early growth, especially in the small for gestational age (SGA) baby. To investigate these relationships, we have undertaken 12-h hormone profiles in 26 babies (13 SGA) at a median of 4.5 days of age. GH levels were measured every 10 min; insulin and IGFBP-1 were measured every 20 min. Mean levels of these hormones and IGF-I levels (from a single sample) were related to size at birth. The GH data were analyzed by Pulsar and time series analysis to characterize hormone pulsatility and relationship with feeds.

IGF-I levels correlated with birth weight and length (r² = 0.47; P = 0.004, and r² = 0.5; P = 0.0005, respectively, after allowing for gestation), whereas mean GH levels were negatively related to birth size (r² = -0.18; P = 0.04 and r² = -0.2; P = 0.03 for weight and length, respectively). No direct relationship between mean GH levels and IGF-I was identified. IGF-I levels were higher in appropriate for gestational age (AGA; mean ± SD, 82 ± 61 ng/mL) than in SGA (34 ± 22 ng/mL; P = 0.03) babies. Baseline (mean ± SD, 25.9 ± 11.9), mean (33.9 ± 14.0), and peak (45.0 ± 18.1 µg/L) GH levels were higher in SGA than in AGA babies [17.1 ± 8.2 (P = 0.04), 22.5 ± 10.4 (P = 0.03), and 30.7 ± 15.4 µg/L (P = 0.04), respectively]. Mean IGFBP-1 levels were also higher in SGA than AGA babies (157.4 ± 90.7 vs. 62.7 ± 43.8 ng/mL; P = 0.01). A positive correlation was identified between changes in insulin and coincident pulses of GH (r = 0.147; P < 0.01), whereas there was an inverse relationship between insulin and IGFBP-1, with a lag time 120 min (r = -0.33; P < 0.0001).

In conclusion, these studies indicate that the GH-IGF-I axis is closely related to feeding in the newborn. In SGA babies, low IGF-I and elevated IGFBP-1 reflect the slow growth, but elevated GH and rapid GH pulsatility may be a signal for lipolysis.

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