Faktori rizika za razvoj metaboličkih, endokrinih i kardiovaskularnih poremećaja kod dece koja su rođena mala za gestacionu starost
Doktorand
Stanković, Sandra M.Mentor
Živić, SašaČlanovi komisije
Golubović, EmilijaZdravković, Dragan
Šaranac, Ljiljana
Radović-Janošević, Dragana
Metapodaci
Prikaz svih podataka o disertacijiSažetak
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
betwe...en 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.