Analysis The Relationship Between Growth Response During Growth Hormone Treatment In Short Children Born With Intrauterine Growth Retardation And Serum Level Of Insulin-like Growth Factor-1 And IGF-binding Protein-3

Objective Intrauterine growth retadation (IUGR) refers to a newborn with a birth weight below-2 SD or 10th percentile for gestational age, also called small for gestational age (SGA). About 3%-10% of the newborns were born with IUGR. Most children born with IUGR show catch-up growth to a normal height during the first 2 yr of life, but approximately 10%-15% of them remain short with a height below-2SD scores, and have an increased risk of being short as adults. Recent decades, the incidence of IUGR is increasing worldwide. IUGR and its related studies have become a research hotspot. Our study is to evaluate the effect of growth hormone(GH) treatment in short children born with IUGR and to explore the relationship between pre-treatment serum level of insulin-like growth factor-1 (IGF-1), insulin-like growth factor binding protein-3(IGFBP-3) and growth response after GH treatment. Method To collect 50 cases of short pre-puberty children born with IUGR received growth hormone treatment at least one year in our hospital during June 2003～May 2008. The inclusion criteria were:1. children with IUGR/SGA without Russell-Silver Syndrome (RSS). IUGR was defined as birth weight less than 2SD below the mean for gestational age.2. Height below-2SDS.3. growth velocity(GV)≤4cm/year.4. Bone age delay 2 years to chronological age.5. Head magnetic resonance image (MRI) except intracranial tumor.6. Children with thyroid dysfunction, chronic liver or kidney diseases, obesity, malnutrition and diabetes and female children with Turner syndrome and other chromosomal diseases were excluded from study. Before GH treatment, we should record their height, weight and calculate growth velocity, et al. And growth hormone stimulation test should be taken among these children by professional endocrine pediatrician. The growth hormone we used is recombinant growth hormone,0.15IU/kg/d, for at least 12 months. To compare the differences of growth velocity, height and height SDS before and after GH treatment; analyze the relevance of pre-treatment serum level of IGF-1, IGFBP-3 and growth response after GH treatment; according to their GH secretory status, they were divided into two subgroups, growth hormone deficiency (GHD) subgroup and non-GHD subgroup, comparing the differences of growth response after GH treatment between GHD subgroup and non-GHD subgroup. Result 1. The growth velocity, height and height SDS of short children born with IUGR significantly improved after GH treatment. Before growth hormone treatment, their growth velocity 3.29400±0.65040cm/y, height 117.12400±19.21902cm, height SDS-2.97100±1.14299SDS versus after GH treatment, their growth velocity 11.234±1.3338cm/yr(P<0.01), height 128.35800±19.01057cm(P<0.01), height SDS-1.78860±1.21531SDS(P<0.01), respectively. Short children born with IUGR have very good growth response during GH treatment.2. Pre-treatment serum level of IGF-1,IGFBP-3 both have negative relevance with growth velocity after GH treatment, r=-0.589,-0.342 (P<0.05), respectively.3. Comparing the differences of growth response after GH treatment, there was no significant differences between GHD subgroup and non-GHD subgroup (P>0.01). Height gain in GHD subgroup is 11.7091±1.31761cm, height SDS gain 1.0850±0.39744; Height gain in non-GHD subgroup is 10.8607±1.24494cm, height SDS gain 1.2589±0.666763. The growth response is similar between both subgroups during GH treatment. Conclusion 1. There is significant difference before and after GH treatment in growth velocity, height and height SDS. Good growth response in growth velocity, height and height SDS among short children born with IUGR during GH treatment shows that GH can effectively improve the height of short children born with IUGR.2. Pre-treatment serum level of IGF-1, IGFBP-3 both has negative relevance with growth velocity after GH treatment. The negative relevance of pre-treatment serum level of IGF-1,IGFBP-3 with growth velocity after GH treatment, indicating that the lower pre-treatment serum IGF-1, IGFBP-3 level, the greater increase of growth velocity, height and height SDS of patients, the better clinical effect of GH treatment. Pre-treatment serum level of IGF-1,IGFBP-3 can be considered as makers predicting the growth response of GH treatment in short children born with IUGR.3. The growth response between GHD subgroup and non-GHD subgroup has no significant differences, which shows that the decision to treat a short IUGR child with GH therapy should not be based upon the GH response to a provocative test.