Postnatal serum insulin-like growth factor I deficiency is associated with retinopathy of prematurity and other complications of premature birth

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 mug/L), 29+/-1.76 mug/L with moderate ROP, and 33+/-1.72 mug/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 mug/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 mug/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 less than or equal to33 mug/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.