Faktori rizika za razvoj metaboličkih, endokrinih i kardiovaskularnih poremećaja kod dece koja su rođena mala za gestacionu starost

INTRODUCTION: Children born small for gestational age (SGA) are the target group for the systematic monitoring later in life. These children have 5-7 times higher risk to remain short in adulthood. Also, they are more prone to central obesity, insulin resistance, hypertension and type 2 diabetes, various components of the metabolic syndrome. The incidence of births of SGA children is high and ranges from 2.3 to 10% of live-born infants. OBJECTIVES: The main objective was to detect differences between groups of children born small for gestational age and the control group in the growth and nutritional status, metabolism of carbohydrates (glucose and HgbA1c serum insulin levels, HOMA index and QUICKI), lipid levels (total cholesterol, LDL and HDL cholesterol, triglycerides), determinants of cardiovascular disorders (cIMT, systolic and diastolic blood pressure, CRP) and thyroid function (TSH, FT4). The specific objectives of the research were to determine the relationship between these parameters and predefined risk factors, as well as to demonstrate the effect of treatment with human growth hormone. To clearly define the child small for gestational age in our region we have constructed special neonatal percentile growth curves for the general population, and for Roma infants. METHODS: The study was designed as a clinical observational study. Data were collected prospectively and retrospectively by analyzing the medical records of patients. The study included 159 children treated at the Clinic for children's internal diseases, 97 patients were born as SGA (61.0%), 31 patients with normal weight and length at birth as control group (19.5%) The group of 31 subjects with diabetes mellitus type 1 (19.5%) who were born as SGA were separatly analyzed. The average age of children born as SGA was 13.55 ± 2.81 (10-18) years, while in control group was 13.20 ± 2.59 years. Including criteria for the children in the study were weight and / or length at birth less than P10 for gestational age and sex, singletons and uncomplicated perinatal period. A group of 35 children born as SGA without catch up growth was analyzed prospectively during the first two years of therapy. Pre-prepared questionnaires were used to obtain relevant data from medical history and clinical status of patients was determined. The body mass and height were measured and compared with reference values, body mass index and ponderal index calculated. Serum levels of glucose, total cholesterol, HDL and LDL cholesterol, triglycerides, transaminases, CRP, TSH VIII and FT4, glycosylated hemoglobin A1c and basal insulin were determined. Insulin resistance and sensitivity were calculated by HOMA index (eng.Homeostasis Model Assessment) and QUICK index (eng. Quantitative Insulin Sensitivity Check Index). Ultrasound measurement of intima media thickness of the right and left carotid artery (CIMT) was performed on highresolution ultrasound Acuson X300, according to pre-established standards. Data related to 30321 live births newborns, born from singleton pregnancies in the period from 2006. to 2012. from Nis, Prokuplje and Aleksinac maternity wards were used to construct neonatal growth curves. LMS model was used to construct the percentile and percentile curves. Statistical analysis was done in Microsoft Office Excel 2007, SPSS 16.0, LMS ChartMaker Light version 2.54. Statistical hypothesis was tested at the level of significancy α = 0.05. RESULTS: The majority of the determinations of development of endocrine, metabolic and cardiovascular disorders were different in the examined groups. Low growth, greater waist circumference and higher basal insulinemia were found in the group of children who were born small for gestational age. During the two-year use of growth hormone thrapy, patients had significantly accelerate the growth, while body mass index increase and waist circumference reduction was not statistically significant. GHbA1c significantly increased, but remained within the range of reference values , lowering of total cholesterol and increase of HDL cholesterol were not statistically significant. There were not significant effect of treatment growth hormone on systolic and diastolic blood pressure as well as on progression of atherosclerosis. Hypothyroidism as adverse effect of growth hormone therapy was detected in 11.4% of patients, which is consistent with results from the literature. CONCLUSION: Weight and length at birth is an important indicator of the health status of the children. SGA children were shorter than in the control group more than 1SD, even in those SGA group that shows catch up growth. Females and those with lower genetic potential are at greater risk to remain short. No relationship between socio-economic status and catch up growth was found. Catch up growth in early childhood in SGA children is associated with a bigger waist circumferecnce, while its effect on body mass index is not proven. SGA children are more prone to central obesity and measuring their waist circumference is an important part of the clinical examination. Basal insulin level in SGA was higher than among children in the control group, but without statistical significance. Weight and length, and ponderal index at birth were not associated with the degree of insulin resistance. Bigger waist circumference and higher body mass index are risk factors for the development of insulin resistance. Independent predictor for the occurrence of elevated total cholesterol and LDL cholesterol is smaller weight at birth. During two-year growth hormone therapy patients had significantly accelerated growth, body mass index increased and waist circumference decreased. There was no significant effect on glucose metabolim or lipid profile. IGF-I as a major regulator of longitudinal growth during two years of therapy has increased significantly, but stayed within refernt values. There were no significant effect of growth hormone treatment on systolic and diastolic blood pressure as well as on progression of atherosclerosis. Hypothyroidism as adverse effect of growth hormone therapy was detected in 11.4% of patients. Anthropometric norms for newborn children in South-eastern Serbia were made. Comparing our results with the results 20 years oldre study several differences were observed. Nowdays children are heavier than two decades ago, but the lower limit of normal is lower than in the earlier study. Roma newborns are lighter and shorter than the newborns from general population.