Clinical Study Of RhGH On Short Children Born Small For Gestational Age And Preterm

Background and ObjectiveShort stature is one of the most common disorders in the endocrine field of children.Among all adult short stature cases,the proportion less than the gestational age(SGA)is about 20%-22%.After the birth of most SGA,there will be a catch-up growth(CUG)period.About 10%-15%of SGA cannot achieve catch-up growth,which is manifested as short stature in childhood or short stature in adults.Over the past two decades,the birth rate of premature babies has been on the rise in most countries around the world.Short stature is common in premature babies,and most of them will experience a catch-up growth(CUG)process after birth to make up for the defect of body length at birth.Premature babies who don't experience catch-up growth tend to be shorter than their predicted adult height.Preterm infants with small for gestational age(SGA)and infants with extremely low birth weight(ELBW)were more likely to exhibit no catch-up growth and were more likely to be short in adolescence and even adulthood.The application of recombinant human growth hormone(rhGH)in pediatric therapy has been more than 30 years,and it has effectively improved the height of children with short stature.This study included two parts:to investigate the therapeutic effect of different doses of rhGH on SGA short stature children in the low age group(2-4 years old),and to evaluate the safety of different doses of rhGH.To study the therapeutic effect of rhGH on short stature children born in preterm,to observe the therapeutic response of children born in SGA preterm and AGA preterm to rhGH,and to observe the growth-promoting effect of rhGH on short children born in different birth and gestational ages.to provide certain clinical basis for rhGH treatment of shortchildren born in small for gestational age and premature.Part One Different doses of rhGH therapy in young children born small for gestational ageObjectiveThe rhGH has been recommended for treatment of short children born small for gestational age for more than ten years,effectively improving the growth rate and height of children without catch-up growth.However,the rhGH dose recommended in the national and regional guidelines varies somewhat.In relevant clinical studies at home and abroad,the observed objects are basically school-age or adolescent children,and most of them focus on the comparison of therapeutic effects of high-dose rhGH and low-dose rhGH treatment.Currently,there are few clinical studies on the therapeutic effects of different doses of rhGH on SGA in low age group(2-4 years old).In this study,retrospective analysis was conducted to observe the curative effect and possible adverse reactions of early treatment of SGA short stature with different dose of rhGH in full-term SGA children aged 2-4 years...The rhGH has been recommended for treatment of short children born small for gestational age for more than ten years,effectively improving the growth rate and height of children without catch-up growth.However,the rhGH dose recommended in the national and regional guidelines varies somewhat.In relevant clinical studies at home and abroad,the observed objects are basically school-age or adolescent children,and most of them focus on the comparison of therapeutic effects of high-dose((0.2-0.22)U/kg/d)rhGH and low-dose((0.1-0.12)U/kg/d)rhGH treatment.Currently,there are few clinical studies on the therapeutic effects of different doses of rhGH on SGA in low age group(2-4 years old).In this study,retrospective analysis was conducted to observe the curative effect and possible adverse reactions of early treatment of SGA short stature with different dose of rhGH in full-term SGA children aged 2-4 years.Methods1.subjects:this study was conducted at the Department of pediatric endocrinology of Shandong Provincial Hospital Affiliated to Shandong University between March 2014 and June 2018.A total of 73 children born full-term SGA with short stature who met the criteria were included in the study.According to different doses of rhGH treatment,it was divided into two groups:medium dose group(dose of rhGH was 0.15u/kg/d)and High dose group(dose of rhGH was 0.2u/kg/d).The treatment lasted for 3 years.2.Methods:Height and weight were measured regularly before and after treatment,body mass index(BMI)was calculated,and Height Velocity(HV)was calculated before and after treatment.Height standard deviation score(HtSDS)and Weight standard deviation score(WtSDS)before and after treatment were calculated.IGF-1,fasting blood glucose,HbAlc and thyroid function were measured every 3 months.Bone age X-ray was reexamined every six months.Results1.The mean HV of medium GH dose group and high GH dose group were respectively increased after treatment,there were significant differences in both two groups(P<0.05).HV increased most significantly in the two groups is at 12 months,respectively.However,there was no significant difference between the two groups after treatment(P>0.05).2.HtSDS in both groups increased significantly after treatment compared with that before treatment.After 3 years of treatment with GH,HtSDS increased from-3.4 ± 0.52 and-3.5 ±0.43 before treatment to-1.78 ± 0.32 and-1.75 ±0.23 after treatment.with HSDS at 3 years,respectively,compared with before treatment,and there were significant differences between the two groups(P<0.05).There was no significant difference in HtSDS between the two groups within 3 years after treatment and between the two groups(P>0.05).3.HtSDS in both groups increased significantly after treatment compared with that before treatment.4.There was no significant change in BMI between the two groups before and after treatment.After treatment,there was a slight increase of BA/CA compared with that before treatment in the two groups,but there was no statistical significance(P>0.05).5.After treatment,IGF-1 level in both groups was significantly higher than that before treatment,and the difference before and after treatment was significant(P<0.05).The level of 1GF-1 in both groups reached the highest value at 36 months of treatment,with an average value of 235.45 ug/L and 232.37 ug/L,respectively.6.The levels of FPG,HbAlc,TSH,FT3 and FT4 in the two groups were within the normal range before and after treatment,and there was no significant difference between the two groups before and after treatment(P>0.05).Conclusions1.Medium dose of GH(0.15Ukg/d)and high dose of GH(0.2Ukgd)early treatment can significantly promote the growth of SGA children,and there is no difference in the growth-promoting effect of the two doses of GH2.No abnormal glucose metabolism and thyroid function,nor other serious adverse reactions,were found in low-age SGA children treated with medium and high doses of rhGH.Part Two Clinical Research of rhGH on short children born pretermObjectiveAccording to the statistics of the World Health Organization(WHO),about 14.9 million premature babies are born globally every year,accounting for 11.1%of the total number of live births in the World,among which the vast majority(84%)are MPT.Preterm birth is a worldwide problem,no matter developed countries or poor and backward countries and regions,the incidence of preterm birth is high.Premature infants are prone to a variety of short-term and long-term complications,such as bronchopulmonary dysplasia,necrotizing enterocolitis,cerebral palsy,impaired vision and hearing,and growth disorders.At present,there are few clinical studies related to rhGH in the treatment of short children born preterm.The purpose of this study was to explore the growth-promoting effect of rhGH on short children born premature,so as to provide certain clinical reference basis for improving the height of short children born preterm.MethodsSubjects:this study was conducted at the Department of pediatric endocrinology of Shandong Provincial Hospital Affiliated to Shandong University between March 2014 and June 2018.A total of 52 children born preterm with short stature who met the criteria were included in the study.According to the relationship between birth weight and gestational age,it was divided into two groups:SGA PT group:a total of 30 cases,including 17 males and 13 females,with an average gestational age of 33.2±0.34weeks at birth and an average age of 4.35±0.32 years at the beginning of rhGH treatment.AGA PT group:22 cases,including 10 males and 12 females,with mean gestational age of 33.5±0.42 weeks at birth,rhGH initiation,and mean age of 4.61±0.22 years at treatment.According to the gestational age at birth,30 children born small for gestational age and preterm were divided into three groups:late preterm SGA group(LPT SGA group):a total of 10 cases,including 6 males and 4 females,with an average gestational age of 35.3±0.21 weeks at birth and an average age of 4.45±0.32 years at the beginning of rhGH treatment.Moderate preterm SGA group(MPT SGAgroup):a total of 12 cases,including 7 males and 5 females,with an average gestational age of 33.1±0.17 weeks at birth and an average age of 4.26±0.28 years at the beginning of rhGH treatment.very preterm SGA group(VPT SGA group):a total of 8 cases,including 4 males and 4 females,with an average gestational age of 30.2±0.23 weeks at birth and an average age of 4.29±0.15 years at the beginning of rhGH treatment.The treatment lasted for 3 years.2.Methods:height and weight were measured for all children,and HV,BMI,HtSDS and WtSDS were calculated.For the specific measurement equipment and method,please refer to the first part of the study.All examination procedures are completed by endocrine professionals.All children completed GH stimulation test,IGF-1,FPG and HbAlc were measured,and bone age was measured every six months.ResultsObservation of rhGH treatment for children in SGA PT group and AGA PT group1.In the first,second and third year of GH treatment,HV in both groups was significantly higher than that before the treatment(P<0.01).In SGA PT group,HV in the first and second year of treatment was significantly higher than that in AGA PT group(P<0.05).2.After treatment,height SDS and weight SDS are significantly higher than that before treatment in both groups(P<0.05).Comparison between the two groups showed that HtSDS in SGA PT group was significantly higher than that in AGA PT group at frest 2 years in treatment(P<0.05);there was no significant difference at the third year(P>0.05);WtSDS in SGA PT group was significantly higher than that in AGA PT group at the first year after treatment(P<0.05),and there was no significant difference at second and third years.3.the bone age of the two groups increased slightly after treatment,but still lower than the chronological age by the third year of treatment.There was no significant difference(P>0.05).4.After treatment,the IGF-1 level in the two groups was significantly higher than that before treatment(P<0.05),the FPG and HbAlc levels were within the normal range.RhGH therapy on LPT SGA group,MPT SGA group and VPT SGA group1.children in the three groups all achieved rapid growth after GH treatment,and there were significant differences in HV of the three groups after and before treatment(P<0.01).There was no significant difference in HV between each group at 1,2 and 3 years after treatment.2.There were significant differences in height SDS between the VPT SGA group at the first and second year after treatment and before treatment(P<0.05),and no significant differences in height SDS between the third year and before treatment.There was no significant difference between LPT SGA group and MPT SGA group before and after the treatment of height SDS.3.there was no significant difference in weight SDS and bone age between the three groups before and after treatment.4.at the first,second and third year of treatmentI,IGF-1 levels of children in the three groups were significantly different from those before treatment(P<0.05).During treatment,FPG and HbAlc were at normal levels in the three groups.Conclusions:1.For children born at preterm in short stature aged 2-6 years,rhGH treatment can achieve good growth effects without serious complications.2.The growth-promoting effect of rhGH on children born preterm with SGA is superior to that with AGA.3.There was no difference in the therapeutic effect of rhGH in children born preterm with different gestational age.