Serum leptin in short children born small for gestational age: relationship with the growth response to growth hormone treatment. The Swedish Study Group for Growth Hormone Treatment

Abstract

The product of the obese (ob) gene, leptin, is an adipocyte-derived hormone that is involved in the regulation of appetite and body weight. This study was undertaken in order to describe the basal serum levels of leptin in prepubertal short children born small for gestational age (SGA) and their relationship with growth parameters, before and during growth hormone (GH) treatment. Eighty-nine prepubertal short children (66 boys, 23 girls; height standard deviation score (SDS), ¹5.4 to ¹2.0; age, 2.0 to 12.8 years) born SGA, 12 of whom (9 boys, 3 girls) had signs of Silver-Russell syndrome, were included in the study. Serum leptin concentrations were measured by radioimmunoassay. Leptin levels in the children born SGA were compared with those in a reference group of 109 prepubertal healthy children born at an appropriate size for gestational age (AGA). The mean (S.D.) change in height SDS was 0.11 (0.22) during the year before the start of GH therapy (0.1 IU/kg/day) and increased to 0.82 (0.44) during the first year (P<0.001) and to 1.28 (0.59) during the 2-year period of GH therapy (P<0.001). The children born SGA were significantly leaner than the reference group. An inverse correlation was found between leptin and chronological age in the SGA group (r =¹0.31, P<0.01). The mean serum level of leptin in the children born SGA who were older than 5.5 years of age was 2.8 mg/l which was significantly lower than the mean value of 3.7 mg/l found in the children born AGA of the same age range. The difference remained after adjustment of leptin levels for sex, age, body mass index (BMI) and weight-for-height SDS (WH SDS SDS). Leptin correlated with WH SDS SDS (r =0.32, P<0.001) and BMI (r=0.36, P<0.01) in the reference population, but not in the SGA group. No correlation was found between leptin and spontaneous 24-h GH secretion, insulin-like growth factor (IGF)-I or IGF-binding protein-3 levels, or with fasting insulin or cortisol levels. Leptin levels at the start of GH treatment were correlated with the growth response over both 1 year (r=0.46, P<0.001) and 2 years (r=0.51, P<0.001) of GH therapy. Using multiple regression analysis, models including leptin levels at the start of GH therapy could explain 51% of the variance in the growth response after 1 year and 44% after 2 years of GH treatment.In conclusion, serum leptin levels are reduced in short children born SGA and are inversely correlated with chronological age. Leptin concentrations correlate with the growth response to GH treatment and might be used as a marker for predicting the growth response to GH treatment.

Gestational Pattern of Heme Oxygenase Expression in the Rat

“…These factors have a clear role in fetal growth as they are found at lower levels in pregnancies complicated by intrauterine growth restriction (20,35). Although this is merely an association, we speculate that HO may play a role in intrauterine growth.…”

Serum markers of GH and insulin action in 12-year-old children born small for gestational age

“…Woods et al reported that short prepubertal SGA children have lower leptin levels than their short control children with normal birth weight (7). According to Boguzewski et al, SGA children, with an age range of 2.0 to 12.8 years, had lower leptin levels than AGA children of the same age range (23).…”

“…In puberty, leptin levels decrease in boys, while the levels continue to increase in girls (22). In SGA children, leptin levels have been reported to be lower than in AGA children (23).…”

Secular Trends in Pubertal Development

“…The long-term impact of foetal growth – such as its association with cardiovascular diseases – has been observed and attracted much attention in recent years [51, 52, 53]. It has been known that infants born small- for-gestational age had much lower levels of neonatal and childhood serum leptin, insulin-like growth factor-I and insulin-like growth factor binding protein-3 [54, 55, 56, 57, 58]. We can thus speculate that this subnormal neonatal hormone profile at birth may have a long-term imprinting effect on the postnatal timing of puberty, although the mechanism for this is unclear.…”