The endocrine consequences for very low birth weight premature infants

The aims of this study were: (1) to determine whether premature and small-for-gestational-age (SGA) children have alterations to the insulin-like growth factor (IGF)-IGF binding protein axis and (2) to evaluate growth in premature children. Three groups of children were evaluated: (i) premature children of 36 weeks gestation, which included AGA and SGA subgroups; and (iii) children born at term and AGA with normal childhood heights and weights. Fasting plasma IGF-I, insulin-like growth factor binding protein-3 (IGFBP-3), and IGF-II (all expressed as microgm/L) were drawn on available subjects. To examine the influence of SGA on the IGF-IGFBP axis, term SGA subjects were compared with term AGA subjects. To examine the influence of prematurity on the IGF-IGFBP axis, preterm SGA subjects were compared with term SGA subjects and preterm AGA subjects were compared with the normal-stature AGA controls. This ensured that groups of very similar stature and nutritional statuses were compared. Auxological data were available for 24 premature children, and biochemical data were available for 77 children, including the premature children. Across the height standard deviation score (SDS) range, premature children did not reach mid-parental height (MPH) SDS and were approximately 0.6 standard deviations (SDs) below the MPH SD (P < 0.0001). Plasma IGF-I and IGFBP-3 levels were higher in term SGA subjects compared with term AGA subjects (P < 0.001, respectively). Conversely, IGF-I and IGFBP-3 values were lower in the premature SGA subgroup compared with the premature AGA subgroup (P < 0.001 for both), and both were also lower in the premature AGA subgroup compared with the normal-statured AGA subgroup (P < 0.001 for both). IGF-II values were higher in the preterm group than in the term group (P < 0.001). In conclusion, very low birth weight (VLBW) children, regardless of whether they were AGA or SGA, have low plasma IGF-I and IGFBP-3 levels in mid-childhood, suggesting partial growth hormone (GH) resistance. Conversely, term SGA children have elevated plasma IGF-I and IGFBP-3 levels. When combined, premature birth plays a more dominant role than SGA on the IGF-IGF binding protein axis.