Catch Up Growth Study And Early Growth Hormone Therapy In Children Born Small For Gestational Age

BackgroundBorn small for gestational age(SGA)is defined as birth length and/or weight below an SD score(SDS)of-2(ie,less than third percentile).Most infants born SGA show spontaneous catch-up growth,but about 10%remain small,defined as a height SDS below-2,throughout childhood.Approximately 20%of adults with short stature were born SGA.Catch-up growth usually occurs in the first 2 years and is most pronounced in the first 6 months after birth.A child born SGA who has not shown catch-up growth by 3 years of age is unlikely to do so subsequently and,hence,is likely to remain short into adult life.However,catch-up growth may be more prolonged in preterm infants.Growth hormone(GH)therapy has been shown to be effective in improving height in short children born small for gestational age.Among the patients characteristics found to be related to growth response,young age at start of treatment was related with the better growth response.GH treatment was approved by the US Food and Drug Administration for children born SGA who fail to manifest catch-up growth by the age of 2 years and by the European Agency for the Evaluation of-Medicinal Products for children older than 4 years of age.The consensus statement from the International Societies of Pediatric Endocrinology and the Growth Hormone Research Society proposed that chronological age and height should be taken together for the decision of rhGH treatment:children born SGA with height below-2.5 SDS at the age of 2 years or with height below-2 SDS at the age of 4 years should be eligible for rhGH treatment.Despite the recommendation for rhGH therapy at young ages,a recently review of the impact of rhGH therapy on adult height in short SGA children showed that chronological age at the start of therapy ranged from 7.9 to 10.7years,and some short SGA children only came to medical attention when they were on puberty,with less time for rhGH treatment and the eventual need of postponement of puberty with the addition ofGnRH analogs.Few studies are available on rhGH treatment for young short SGA children,and a greater increase in height velocity was observed in those younger than 4 years of age.The present study was undertaken to evaluate the 3 year growth response to rhGH treatment in very young short children born SGA,with ages at start of rhGH therapy from2 to 4 years as approved by the FDA and after 4 years of age,the European indication,and to abserve the catch-up growth of the full time gestation SGA children in the first three years.ObjectiveThe aim was to analyze the catch-up growth of the full time gestation SGA children of the first three years and the outcome of very young SGA children treated with rhGH and followed for 3 year.The results after 3 year of treatment,compared with an older control group,are shown.Methods1.SGA study group from Shandong maternal and children health care hospital.Inclusion criteria:gestational age of 37-42 weeks,birth weight less than the 10th percentile with infants.Exclusion criteria:Subjects are required to exclude chromos omal disorders,congenital metabolic disease,hypothyroidism,growth hormone defici ency and growth retardation and other endocrine-related diseases,with congenital m al formations and chronic organic diseases.Parents of infants with physical health,un accompanied gestational diabetes during pregnancy.121 SGA children were chosen f or this study.According to their feeding way,theywere assigned into 3groups:breast milk-fedgroup(n=37),full-term child formula-fedgroup(n=56),breast and full-term c hild formula mixed-fedgroup(n=28).Their bodyweight,length and head circumf erence were checked when they were 1 month,2months and every months before 6 nonths,every 2months from 6-12months,every 3months from 12 to 24months,every 6month from 24 to 36 months.2.Patients were selected from Shandong Provincial hospital from 2006.10 to 2014.10 diagnosed as SGA children treated with rhGH.For this study,120 children were selected.Inclusion criteria were as follows:born SGA[birth length and/or weight below-2 standard deviations(SD)for gestational age using our country standards];age between 2 and 6years;standing height below-2SD at screening visit;normal karyotype in girls(for exclusion of Turner syndrome);failure of catch-up growth[height velocity(HV)SDS<0 during the last year],and normal screening laboratory values.Exclusion criteria were chromosomal disorders,genetic syndromes,malformations,maternal history of alcohol or drug addiction,bone dysplasia and any treatment that could affect growth,type 1 or 2 diabetes mellitus,fasting blood glucose>100 mg/dL(5.6 mmol/L),and abnormal 2-h oral glucose tolerance test[OGTT>140 mg/dL(7.8 mmol/L)].They were assigned in two groups by age.One group is older than 2 and less than 4 years and another between 4 and 6 years.A total of 56 patients(30boys)were selected in the 2-4 yrs group and 64 children(34boys)in the 4-6 yrs group.Patients are treated with rhGH 0.15IU/kg/day administered subcutaneously.Height is measured in cm and HV calculated.HSDS and HVSDS(based on the WHO 2006 child standards reference tables)are assessed at baseline and at 3-month intervals throughout the 3 years.X-rays of the left hand and wrist are used to determine BA at baseline and every 6 months thereafter.Fasting plasma glucose and glycated hemoglobin(HbAlc).IGF-1 are measured at baseline,every 3 months thereafter.Results1.Catch-up growth were observed in all 3 groups,most of increase in height and weight Z score occurred very early in life.There were no signifant defference in the 3 defferent feeding way groups.2.Treatment with rhGH was effective;mean HSDS at 2-4 year group was-3.30 at baseline,-2.53 at 1 year and-2.07at 2 year and-11.82 after 3 years of treatment.Respective values for the 4-6 yrs group were-3.4 SDS to-2.2SDS(p<0.05).Increases in both bone age(BA),BA/CA rate increased from 0.71±0.082 to 0.92±0.046 at 2-4 year group,respective values for the 4-6 years group were 0.74±0.092 to 0.93±0.056(p>0.05).Serum IGF-I levels increased significantly after 12 months of treatment with GH(from 111.81 ±34.67 mmol/1 at baseline to 205.93±37.40 mmol/1 at month 12 in group 2-4 yrs and from 118.86±41.33 mmol/1 to 210.52±42.66 mmol/1 in group 4-6 yrs)and increased slowly in the last two years.No child has developed diabetes mellitus during the 3years;no fasting glucose or 2-h oral glucosetolerance test value exceeded the pre-defined limits of 126 or 200 mg/dL,respectively.ConclusionIn conclusion,In this study,Catch-up growth were observed in all 3 groups,most of increase in height and weight Z score occurred very early in life.There were no signifant defference in the 3 defferent feeding way groups.Very young children born SGA without spontaneous catch-up growth presented a significant improvement in height and weight gain during the three years of GH treatment.And short children born SGA were safely and effectively treated with rhGH.