Early growth, retinopathy of prematurity and insulin-like growth factors in preterm infants

Abstract: Aims:Paper I: To perform measurements of the lower leg length (LLL) in preterm infants, compare and evaluate handling error and precision of two instruments, and estimate the time required to show growth.Paper II-IV: To investigate whether low postnatal levels of serum IGF-I are associated with abnormal retinal vessel development. Study factors associated with postnatal serum concentrations of IGF-I and of IGFBP-3 in preterm infants. Characterise longitudinal growth and the influence on growth by IGF-I, IGF-II and IGFBP-3 in preterm infants from birth until 40 weeks postmenstrual age (PMA).Material and methods:Paper I: The LLL of 35 preterm infants born in Göteborg 1999, with a median PMA of 29 weeks were measured according to LLL with a mini-knemometer and a simple calliper on 409 different occasions.Papers II-IV: A prospective, longitudinal study measuring IGF-I, IGF-I, IGFBP-3 and growth in preterm infants, PMA <32 weeks (Paper II, n=84, Paper III, n=76, Paper IV, n=73). The infants were evaluated for ROP. Results:Paper I: There was no significant difference in precision between the two instruments. The handling error was 0.36 mm for the simple calliper and 0.59 mm for the mini-knemometer. With a growth velocity of 0.5 mm/day and a handling error of 0.36 mm, growth can be shown after two days.Paper II: A long duration of low serum levels of IGF-I correlated with development of ROP. The mean level of serum IGF-I during weeks 30-33 PMA was lowest in infants with severe ROP. Paper III: Postnatal development of serum IGF-I and IGFBP-3 was associated with postmenstrual age (p<0.001), weight gain (SDS) (p<0.001) and enteral intake of protein (p<0.001). Male gender was associated with lower IGF-I levels (p<0.001). Paper IV: 27% of the infants were born SGA and remained small. All infants demonstrated a period of severe growth restriction for weight, length and head circumference (HC), followed by a period of catch-up growth from about 32 weeks PMA. At 40 weeks PMA 50% were below 2SD in weight and length while the HC were equal to the reference. Conclusions:Paper I: The simple calliper was well suited for weekly measurements of LLL and growth was possible to detect within a week. Paper II-IV: The IGF-I and IGFBP-3 levels seem to be as strong a determinant for developing ROP as GA and low BW. The levels of circulating IGF-I are associated with the degree of prematurity, BW, weight gain and enteral intake of protein. Preterm infants are at a high risk of extra uterine growth restriction while the head circumference demonstrated an early catch-up growth.Future studies may reveal if enhanced nutrition or other intervention in preterm infants will restore serum IGF-I levels to intrauterine levels or if IGF-I supplementation is needed in order to decrease the morbidity and optimise growth in these vulnerable infants.