Postnatal Serum Insulin-Like Growth Factor I Deficiency Is Associated With Retinopathy of Prematurity and Other Complications of Premature Birth
* Göteborg Pediatric Growth Research Center, Department of Pediatrics, Institute of the Health of Women and Children
Department of Ophthalmology, Institute of Clinical Neuroscience
Research Center for Endocrinology and Metabolism, Department of Internal Medicine, Sahlgrenska Academy at Göteborg University, Göteborg
|| Medical Statistics, Örebro University, Örebro
¶ Biostatistics Branch, Department of Mathematical Statistics, Chalmers University of Technology, Göteborg, Sweden
# Departments of Women’s and Children’s Health
** Ophthalmology, Uppsala University, Uppsala, Sweden
Department of Ophthalmology, Children’s Hospital, Harvard Medical School, Boston, Massachusetts
Objective. Insulin-like growth factor I (IGF-I) is necessary for normal development of retinal blood vessels in mice and humans. Because retinopathy of prematurity (ROP) is initiated by abnormal postnatal retinal development, we hypothesized that prolonged low IGF-I in premature infants might be a risk factor for ROP.
Design. We conducted a prospective, longitudinal study measuring serum IGF-I concentrations weekly in 84 premature infants from birth (postmenstrual ages: 24–32 weeks) until discharge from the hospital. Infants were evaluated for ROP and other morbidity of prematurity: bronchopulmonary dysplasia (BPD), intraventricular hemorrhage (IVH), and necrotizing enterocolitis (NEC).
Results. Low serum IGF-I values correlated with later development of ROP. The mean IGF-I ± SEM level during postmenstrual ages 30–33 weeks was lowest with severe ROP (25 ± 2.41 µg/L), 29 ± 1.76 µg/L with moderate ROP, and 33 ± 1.72 µg/L with no ROP. The duration of low IGF-I also correlated strongly with the severity of ROP. The interval from birth until serum IGF-I levels reached >33 µg/L was 23 ± 2.6 days for no ROP, 44 ± 4.8 days for moderate ROP, and 52 ± 7.5 days for severe ROP. Each adjusted stepwise increase of 5 µg/L in mean IGF-I during postmenstrual ages 30 to 33 weeks decreased the risk of proliferative ROP by 45%. Other complications (NEC, BPD, IVH) were correlated with ROP and with low IGF-I levels. The relative risk for any morbidity (ROP, BPD, IVH, or NEC) was increased 2.2-fold (95% confidence interval: 1.41–3.43) if IGF-I was 
33 µg/L at 33 weeks’ postmenstrual age.
Conclusions. These results indicate that persistent low serum concentrations of IGF-I after premature birth are associated with later development of ROP and other complications of prematurity. IGF-I is at least as strong a determinant of risk for ROP as postmenstrual age at birth and birth weight.
Key Words: preterm birth • retinopathy of prematurity • insulin-like growth factor I • intraventricular hemorrhage • bronchopulmonary dysplasia • necrotizing enterocolitis • vascular endothelial growth factor
Abbreviations: IGF-I, insulin-like growth factor I • VEGF, vascular endothelial growth factor • ROP, retinopathy of prematurity • BPD, bronchopulmonary dysplasia • IVH, intraventricular hemorrhage • NEC, necrotizing enterocolitis • GA, gestational age • BW, birth weight
Received for publication Feb 3, 2003; Accepted May 8, 2003.
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