Age-period-cohort modelling of type 1 diabetes incidence rates among children included in the EURODIAB 25-year follow-up study.

AIMS: Specific patterns in incidence may reveal environmental explanations for type 1 diabetes incidence. We aimed to study type 1 diabetes incidence in European childhood populations to assess whether an increase could be attributed to either period or cohort effects. METHODS: Nineteen EURODIAB centres provided single year incidence data for ages 0-14 in the 25-year period 1989-2013. Case counts and person years were classified by age, period and cohort (APC) in 1-year classes. APC Poisson regression models of rates were fitted using restricted cubic splines for age, period and cohort per centre and sex. Joint models were fitted for all centres and sexes, to find a parsimonious model. RESULTS: A total of 57,487 cases were included. In ten and seven of the 19 centres the APC models showed evidence of nonlinear cohort effects or period effects, respectively, in one or both sexes and indications of sex-specific age effects. Models showed a positive linear increase ranging from approximately 0.6 to 6.6%/year. Centres with low incidence rates showed the highest overall increase. A final joint model showed incidence peak at age 11.6 and 12.6 for girls and boys, respectively, and the rate-ratio was according to sex below 1 in ages 5-12. CONCLUSION: There was reasonable evidence for similar age-specific type 1 diabetes incidence rates across the EURODIAB population and peaks at a younger age for girls than boys. Cohort effects showed nonlinearity but varied between centres and the model did not contribute convincingly to identification of environmental causes of the increase.

Alterations of oral microbiota and impact on the gut microbiome in type 1 diabetes mellitus revealed by integrated multi-omic analyses.

BACKGROUND: Alterations to the gut microbiome have been linked to multiple chronic diseases. However, the drivers of such changes remain largely unknown. The oral cavity acts as a major route of exposure to exogenous factors including pathogens, and processes therein may affect the communities in the subsequent compartments of the gastrointestinal tract. Here, we perform strain-resolved, integrated meta-genomic, transcriptomic, and proteomic analyses of paired saliva and stool samples collected from 35 individuals from eight families with multiple cases of type 1 diabetes mellitus (T1DM). RESULTS: We identified distinct oral microbiota mostly reflecting competition between streptococcal species. More specifically, we found a decreased abundance of the commensal Streptococcus salivarius in the oral cavity of T1DM individuals, which is linked to its apparent competition with the pathobiont Streptococcus mutans. The decrease in S. salivarius in the oral cavity was also associated with its decrease in the gut as well as higher abundances in facultative anaerobes including Enterobacteria. In addition, we found evidence of gut inflammation in T1DM as reflected in the expression profiles of the Enterobacteria as well as in the human gut proteome. Finally, we were able to follow transmitted strain-variants from the oral cavity to the gut at the individual omic levels, highlighting not only the transfer, but also the activity of the transmitted taxa along the gastrointestinal tract. CONCLUSIONS: Alterations of the oral microbiome in the context of T1DM impact the microbial communities in the lower gut, in particular through the reduction of "mouth-to-gut" transfer of Streptococcus salivarius. Our results indicate that the observed oral-cavity-driven gut microbiome changes may contribute towards the inflammatory processes involved in T1DM. Through the integration of multi-omic analyses, we resolve strain-variant "mouth-to-gut" transfer in a disease context. Video Abstract.

Management of type 1 diabetes.

Late diagnosis and lack of access to insulin contribute most to the mortality of people with type 1 diabetes. The presence of this chronic noncommunicable disease is not bound by borders or even continents. Without treatment, it is fatal, while with treatment and good control, it is possible to prevent acute complications (hyperglycemia and hypoglycemia) and to reduce severe late complications (cardiovascular and cerebrovascular, kidney failure and blindness). Access to equipment and supplies for diagnosis and to essential drugs for hospitals and later families at an affordable price is critical to mortality and morbidity in Africa. Intensive training of professionals in the field and in hospitals to recognize and treat this disease is necessary. These factors, together with intensive education of patients and their families, can reduce the mortality and morbidity of diabetes. Adequate management of diabetes, an important noncommunicable disease, will contribute to meeting the Sustainable Developments Goals and reducing infant mortality.

Subtraction of subcutaneous fat to improve the prediction of visceral adiposity: exploring a new anthropometric track in overweight and obese youth.

BACKGROUND: The efficiency of traditional anthropometric measurements such as body mass index (BMI) or waist circumference (Waist C) used to replace biomedical imaging for assessing visceral adipose tissue (VAT) is still highly controversial in youth. HYPOTHESIS AND OBJECTIVES: We evaluated the most accurate model predicting VAT in overweight/obese youth, using various anthropometric measurements and their correlation with different body fat compartments, especially by testing, for the first time in youth, the hypothesis that subtracting the anthropometric measurement the most highly correlated with subcutaneous abdominal adipose tissue (SAAT) and less correlated possible with VAT from an anthropometric abdominal measurement highly correlated with visceral and total abdominal adipose tissue (TAAT), predicts VAT with higher accuracy. SUBJECTS AND METHODS: VAT and SAAT data resulted from magnetic resonance imaging (MRI) analysis performed on 181 boys and girls (7-17 y) from Diabetes & Endocrinology Care Paediatrics Clinic in Luxembourg. Height, weight, abdominal diameters, waist, hip, and thigh circumferences were measured with a view to developing the anthropometric VAT predictive algorithms. RESULTS: In girls, subtracting proximal thigh circumference (Proximal Thigh C), the most closely correlated anthropometric measurement with SAAT, from Waist C, the most closely correlated anthropometric measurement with VAT was instrumental in improving VAT prediction, in comparison with the most accurate single VAT anthropometric surrogate. [Formula: see text] Residual analysis showed a negligible estimation error (5 cm2 ). In boys, Waist C was the best VAT predictor. CONCLUSIONS: Subtraction of abdominal subcutaneous fat is important to predict VAT in overweight/obese girls.

Seasonality at the clinical onset of type 1 diabetes-Lessons from the SWEET database.

BACKGROUND: Seasonality at the clinical onset of type 1 diabetes (T1D) has been suggested by different studies, however, the results are conflicting. This study aimed to evaluate the presence of seasonality at clinical onset of T1D based on the SWEET database comprising data from 32 different countries. METHODS: The study cohort included 23 603 patients (52% males) recorded in the international multicenter SWEET database (48 centers), with T1D onset ≤20 years, year of onset between 1980 and 2015, gender, year and month of birth and T1D-diagnosis documented. Data were stratified according to four age groups (<5, 5-<10, 10-<15, 15-20 years) at T1D onset, the latitude of European center (Northern ≥50°N and Southern Europe <50°N) and the year of onset ≤ or >2009. RESULTS: Analysis by month revealed significant seasonality with January being the month with the highest and June with the lowest percentage of incident cases (P < .001). Winter, early spring and late autumn months had higher percentage of incident cases compared with late spring and summer months. Stratification by age showed similar seasonality patterns in all four age groups (P ≤ .003 each), but not in children <24 months of age. There was no gender or latitude effect on seasonality pattern, however, the pattern differed by the year of onset (P < .001). Seasonality of diagnosis conformed to a sinusoidal model for all cases, females and males, age groups, northern and southern European countries. CONCLUSIONS: Seasonality at T1D clinical onset is documented by the large SWEET database with no gender or latitude (Europe only) effect except from the year of manifestation.

Classifying insulin regimens--difficulties and proposal for comprehensive new definitions.

Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1 diabetes there is little distinctiveness about concepts and the nomenclature is confusing. Even among experts similar terms are used for different strategies. The aim of our review--based on the experiences of the Hvidoere Study Group (HSG)--is to propose comprehensive definitions for current insulin regimens reflecting current diabetes management in childhood and adolescence. The HSG--founded in 1994--is an international group representing 24 highly experienced pediatric diabetes centers, from Europe, Japan, North America and Australia. Different benchmarking studies of the HSG revealed a broad variety of insulin regimens applied in each center, respectively. Furthermore, the understanding of insulin regimens has been persistently different between the centers since more than 20 yr. Not even the terms 'conventional' and 'intensified therapy' were used consistently among all members. Besides the concepts 'conventional' and 'intensified', several other terms for the characterization of insulin regimens are in use: Basal Bolus Concept (BBC), multiple daily injections (MDI), and flexible insulin therapy (FIT) are most frequently used, although none of these expressions is clearly or consistently defined. The proposed new classification for insulin management will be comprehensive, simple, and catchy. Currently available terms were included. This classification may offer the opportunity to compare therapeutic strategies without the currently existing confusion on the insulin regimen.

Seasonal variation in month of diagnosis in children with type 1 diabetes registered in 23 European centers during 1989-2008: little short-term influence of sunshine hours or average temperature.

BACKGROUND: The month of diagnosis in childhood type 1 diabetes shows seasonal variation. OBJECTIVE: We describe the pattern and investigate if year-to-year irregularities are associated with meteorological factors using data from 50 000 children diagnosed under the age of 15 yr in 23 population-based European registries during 1989-2008. METHODS: Tests for seasonal variation in monthly counts aggregated over the 20 yr period were performed. Time series regression was used to investigate if sunshine hour and average temperature data were predictive of the 240 monthly diagnosis counts after taking account of seasonality and long term trends. RESULTS: Significant sinusoidal pattern was evident in all but two small centers with peaks in November to February and relative amplitudes ranging from ± 11 to ± 38% (median ± 17%). However, most centers showed significant departures from a sinusoidal pattern. Pooling results over centers, there was significant seasonal variation in each age-group at diagnosis, with least seasonal variation in those under 5 yr. Boys showed greater seasonal variation than girls, particularly those aged 10-14 yr. There were no differences in seasonal pattern between four 5-yr sub-periods. Departures from the sinusoidal trend in monthly diagnoses in the period were significantly associated with deviations from the norm in average temperature (0.8% reduction in diagnoses per 1 °C excess) but not with sunshine hours. CONCLUSIONS: Seasonality was consistently apparent throughout the period in all age-groups and both sexes, but girls and the under 5 s showed less marked variation. Neither sunshine hour nor average temperature data contributed in any substantial way to explaining departures from the sinusoidal pattern.

Does the body adiposity index (BAI) apply to paediatric populations?

OBJECTIVE: Validation of body adiposity index (BAI) in a paediatrics sample; and to develop, if necessary, a valid BAI for paediatrics (i.e. BAIp). METHODS: A total of 1615 children (52% boys) aged 5-12 years underwent anthropometry. Their body composition was assessed using a foot-to-foot bioimpedance. The validity of BAI = (Hip circumference/Height(1.5)) - 18 was tested by combining correlation and agreement statistics. Then, the sample was split into two sub-samples for the construction of BAIp. A regression was used to compute the prediction equation for BAIp-based percentage of body fat (%BF). RESULTS: The initial BAI over-estimated the %BF of children by 49% (29.6 ± 4.2% versus 19.8 ± 6.8%; p < 0.0001). The original methodology led to a BAIp = (Hip circumference/Height(0.8)) - 38 in children. When compared to BAI, BAIp showed both better correlation (r = 0.57; p < 0.01 versus r = 0.74; p < 0.0001) and agreement (ICC = 0.34; [95% CI = -0.19-0.65] versus ICC = 0.83; [95% CI = 0.81-0.84]). However, there were some systematic biases between the two values of %BF as exemplified by the large 95% limit of agreement [-9.1%; 8.8%] obtained. CONCLUSION: BAI over-estimates the %BF in children. In contrast, BAIp appears as a new index for children's body fatness, with acceptable accuracy. In its current form, this index is valid only for large-scale studies.

Level of physical activity among children and adolescents in Europe: a review of physical activity assessed objectively by accelerometry.

This study explored the proportion of European youth who are sufficiently active according to physical activity (PA) recommendations, based exclusively on objective assessment through accelerometers. A systematic electronic search of studies published up to March 2012 was conducted. PubMed was used to identify accelerometry-assessed PA studies that involved European youth. Within the 131 European studies, only 35 clearly reported the proportion of youth meeting the PA recommendations. Different thresholds lying between 1000 and 4000 counts/min (cpm) were used to define moderate-to-vigorous PA (MVPA). Overall, up to 100% of youth may be sufficiently active when using a threshold of approximately >1000-1500 cpm. With the most cited cut-off point (i.e. >2000 cpm), up to 87% of European youth might be considered physically active with reference to the current recommendations. Alternatively, with a cut-off point >3000 cpm, no more than 3-5% of them appeared to achieve these recommendations. The large discrepancy in outcomes released by accelerometer data is mainly due to the variety of cut-off points for MVPA among youth, hindering the definition of a clear goal towards PA promotion in Europe. Standardization of methods is urgently required.

Does biological maturity actually confound gender-related differences in physical activity in preadolescence?

AIM: To examine: (i) if maturity-related gender differences in moderate-to-vigorous physical activity (MVPA) depend on how maturity status is defined and measured; and (ii) the influence of maturity level on compliance with PA recommendations. METHODS: The study involved 253 children (139 boys) aged 9.9 ± 0.9 years, with mean stature and weight of 1.39 ± 0.08 m and 35.8 ± 8.8 kg respectively. Their PA was evaluated using an Actigraph accelerometer (Model 7164). Maturity was assessed using the estimated age at peak height velocity (APHV) and a standardized APHV by gender (i.e. centred APHV). RESULTS: Boys engaged in significantly more MVPA than girls (P < 0.0001). There was a significant correlation between the centred APHV and MVPA in boys (r = 0.20; P = 0.016), but not in girls (r = 0.13; P = 0.155). An ancova controlling for the estimated APHV showed no significant interactions between gender and APHV, and the main effect of gender on MVPA was negated. Conversely, there was a significant main effect of APHV on MVPA (F 1,249 = 6.12; P = 0.014; η p (2) = 0.024). Only 9.1% of children met the PA recommendations, including 14.4% of boys and 2.6% of girls (P < 0.01). This observation also applies in both pre-APHV (12.7% of boys vs. 2.4% of girls, P < 0.001) and post-APHV children (23.8% of boys vs. 3.4% of girls, P < 0.0001). No differences in PA guidelines were observed between pre-APHV and post-APHV children. CONCLUSIONS: Among prepubescent children, the influence of biological maturity on gender differences in PA may be a function of how maturity status is determined. The most physically active prepubescent children were those who were on time according to APHV.

Trends in childhood type 1 diabetes incidence in Europe during 1989-2008: evidence of non-uniformity over time in rates of increase.

AIMS/HYPOTHESIS: The aim of the study was to describe 20-year incidence trends for childhood type 1 diabetes in 23 EURODIAB centres and compare rates of increase in the first (1989-1998) and second (1999-2008) halves of the period. METHODS: All registers operate in geographically defined regions and are based on a clinical diagnosis. Completeness of registration is assessed by capture-recapture methodology. Twenty-three centres in 19 countries registered 49,969 new cases of type 1 diabetes in individuals diagnosed before their 15th birthday during the period studied. RESULTS: Ascertainment exceeded 90% in most registers. During the 20-year period, all but one register showed statistically significant changes in incidence, with rates universally increasing. When estimated separately for the first and second halves of the period, the median rates of increase were similar: 3.4% per annum and 3.3% per annum, respectively. However, rates of increase differed significantly between the first half and the second half for nine of the 21 registers with adequate coverage of both periods; five registers showed significantly higher rates of increase in the first half, and four significantly higher rates in the second half. CONCLUSIONS/INTERPRETATION: The incidence rate of childhood type 1 diabetes continues to rise across Europe by an average of approximately 3-4% per annum, but the increase is not necessarily uniform, showing periods of less rapid and more rapid increase in incidence in some registers. This pattern of change suggests that important risk exposures differ over time in different European countries. Further time trend analysis and comparison of the patterns in defined regions is warranted.

Paediatric screening for hypercholesterolaemia in Europe.

Different screening strategies are currently recommended to identify children with (familial) hypercholesterolaemia in order to initiate early lipid management. However, these strategies are characterised to date by low adherence by the medical community and limited compliance by parents and children. In a literature review, the authors assess which children should undergo screening and which children are in effect identified through the currently recommended strategies. Furthermore, the authors discuss the different screening tools and strategies currently used in Europe and what is known about the negative aspects of screening. The authors conclude that currently recommended selective screening strategies, which are mainly based on family history, lack precision and that a large percentage of affected children who are at increased risk of future coronary artery disease are not being identified. The authors propose universal screening of children between 1 and 9 years of age, a strategy likely to be most effective in terms of sensitivity and specificity for the identification of children with familial hypercholesterolaemia. However, this concept has yet to be proven in clinical practice.

Management of familial hypercholesterolemia in children and young adults: consensus paper developed by a panel of lipidologists, cardiologists, paediatricians, nutritionists, gastroenterologists, general practitioners and a patient organization.

UNLABELLED: Since heterozygous familial hypercholesterolemia (HeFH) is a disease that exposes the individual from birth onwards to severe hypercholesterolemia with the development of early cardiovascular disease, a clear consensus on the management of this disease in young patients is necessary. In Belgium, a panel of paediatricians, specialists in (adult) lipid management, general practitioners and representatives of the FH patient organization agreed on the following common recommendations. 1. Screening for HeFH should be performed only in children older than 2 years when HeFH has been identified or is suspected (based on a genetic test or clinical criteria) in one parent.2. The diagnostic procedure includes, as a first step, the establishment of a clear diagnosis of HeFH in one of the parents. If this precondition is satisfied, a low-density-lipoprotein cholesterol (LDL-C) levelabove 3.5 mmol/L (135 mg/dL) in the suspected child is predictive for differentiating affected from non-affected children. 3. A low saturated fat and low cholesterol diet should be started after 2 years, under the supervision of a dietician or nutritionist.4. The pharmacological treatment, using statins as first line drugs, should usually be started after 10 years if LDL-C levels remain above 5 mmol/L (190 mg/dL), or above 4 mmol/L (160 mg/dL) in the presence of a causative mutation, a family history of early cardiovascular disease or severe risk factors. The objective is to reduce LDL-C by at least 30% between 10 and 14 years and, thereafter, to reach LDL-C levels of less than 3.4 mmol/L (130 mg/dL). CONCLUSION: The aim of this consensus statement is to achieve more consistent management in the identification and treatment of children with HeFH in Belgium.

Birthweight and the risk of childhood-onset type 1 diabetes: a meta-analysis of observational studies using individual patient data.

AIMS/HYPOTHESIS: We investigated whether children who are heavier at birth have an increased risk of type 1 diabetes. METHODS: Relevant studies published before February 2009 were identified from literature searches using MEDLINE, Web of Science and EMBASE. Authors of all studies containing relevant data were contacted and asked to provide individual patient data or conduct pre-specified analyses. Risk estimates of type 1 diabetes by category of birthweight were calculated for each study, before and after adjustment for potential confounders.Meta-analysis techniques were then used to derive combined ORs and investigate heterogeneity between studies. RESULTS: Data were available for 29 predominantly European studies (five cohort, 24 case-control studies), including 12,807 cases of type 1 diabetes. Overall, studies consistently demonstrated that children with birthweight from 3.5 to 4 kg had an increased risk of diabetes of 6% (OR 1.06 [95% CI 1.01-1.11]; p=0.02) and children with birthweight over 4 kg had an increased risk of 10% (OR 1.10 [95% CI 1.04-1.19]; p=0.003), compared with children weighing 3.0 to 3.5 kg at birth. This corresponded to a linear increase in diabetes risk of 3% per 500 g increase in birthweight (OR 1.03 [95% CI 1.00-1.06]; p=0.03). Adjustments for potential confounders such as gestational age, maternal age, birth order, Caesarean section, breastfeeding and maternal diabetes had little effect on these findings. CONCLUSIONS/INTERPRETATION: Children who are heavier at birth have a significant and consistent, but relatively small increase in risk of type 1 diabetes.

Target setting in intensive insulin management is associated with metabolic control: the Hvidoere childhood diabetes study group centre differences study 2005.

OBJECTIVE: To evaluate glycaemic targets set by diabetes teams, their perception by adolescents and parents, and their influence on metabolic control. METHODS: Clinical data and questionnaires were completed by adolescents, parents/carers and diabetes teams in 21 international centres. HbA1c was measured centrally. RESULTS: A total of 2062 adolescents completed questionnaires (age 14.4 +/- 2.3 yr; diabetes duration 6.1 +/- 3.5 yr). Mean HbA 1c = 8.2 +/- 1.4% with significant differences between centres (F = 12.3; p < 0.001) range from 7.4 to 9.1%. There was a significant correlation between parent (r = 0.20) and adolescent (r = 0.21) reports of their perceived ideal HbA1c and their actual HbA1c result (p < 0.001), and a stronger association between parents' (r = 0.39) and adolescents' (r = 0.4) reports of the HbA1c they would be happy with and their actual HbA1c result. There were significant differences between centres on parent and adolescent reports of ideal and happy with HbA1c (8.1 < F > 17.4;p < 0.001). A lower target HbA1c and greater consistency between members of teams within centres were associated with lower centre HbA1c (F = 16.0; df = 15; p < 0.001). CONCLUSIONS: Clear and consistent setting of glycaemic targets by diabetes teams is strongly associated with HbA1c outcome in adolescents. Target setting appears to play a significant role in explaining the differences in metabolic outcomes between centres.

Associations between physical activity, sedentary behavior, and glycemic control in a large cohort of adolescents with type 1 diabetes: the Hvidoere Study Group on Childhood Diabetes.

BACKGROUND: The Hvidoere Study Group on Childhood Diabetes has demonstrated persistent differences in metabolic outcomes between pediatric diabetes centers. These differences cannot be accounted for by differences in demographic, medical, or treatment variables. Therefore, we sought to explore whether differences in physical activity or sedentary behavior could explain the variation in metabolic outcomes between centers. METHODS: An observational cross-sectional international study in 21 centers, with demographic and clinical data obtained by questionnaire from participants. Hemoglobin A1c (HbA1c) levels were assayed in one central laboratory. All individuals with diabetes aged 11-18 yr (49.4% female), with duration of diabetes of at least 1 yr, were invited to participate. Individuals completed a self-reported measure of quality of life (Diabetes Quality of Life - Short Form [DQOL-SF]), with well-being and leisure time activity assessed using measures developed by Health Behaviour in School Children WHO Project. RESULTS: Older participants (p < 0.001) and females (p < 0.001) reported less physical activity. Physical activity was associated with positive health perception (p < 0.001) but not with glycemic control, body mass index, frequency of hypoglycemia, or diabetic ketoacidosis. The more time spent on the computer (r = 0.06; p < 0.05) and less time spent doing school homework (r = -0.09; p < 0.001) were associated with higher HbA1c. Between centers, there were significant differences in reported physical activity (p < 0.001) and sedentary behavior (p < 0.001), but these differences did not account for center differences in metabolic control. CONCLUSIONS: Physical activity is strongly associated with psychological well-being but has weak associations with metabolic control. Leisure time activity is associated with individual differences in HbA1c but not with intercenter differences.

Establishing glycaemic control with continuous subcutaneous insulin infusion in children and adolescents with type 1 diabetes: experience of the PedPump Study in 17 countries.

AIMS/HYPOTHESIS: To assess the use of paediatric continuous subcutaneous infusion (CSII) under real-life conditions by analysing data recorded for up to 90 days and relating them to outcome. METHODS: Pump programming data from patients aged 0-18 years treated with CSII in 30 centres from 16 European countries and Israel were recorded during routine clinical visits. HbA(1c) was measured centrally. RESULTS: A total of 1,041 patients (age: 11.8 +/- 4.2 years; diabetes duration: 6.0 +/- 3.6 years; average CSII duration: 2.0 +/- 1.3 years; HbA(1c): 8.0 +/- 1.3% [means +/- SD]) participated. Glycaemic control was better in preschool (n = 142; 7.5 +/- 0.9%) and pre-adolescent (6-11 years, n = 321; 7.7 +/- 1.0%) children than in adolescent patients (12-18 years, n = 578; 8.3 +/- 1.4%). There was a significant negative correlation between HbA(1c) and daily bolus number, but not between HbA(1c) and total daily insulin dose. The use of <6.7 daily boluses was a significant predictor of an HbA(1c) level >7.5%. The incidence of severe hypoglycaemia and ketoacidosis was 6.63 and 6.26 events per 100 patient-years, respectively. CONCLUSIONS/INTERPRETATION: This large paediatric survey of CSII shows that glycaemic targets can be frequently achieved, particularly in young children, and the incidence of acute complications is low. Adequate substitution of basal and prandial insulin is associated with a better HbA(1c).

Concerns, expectations and perception regarding stature, physical appearance and psychosocial functioning before and during high-dose growth hormone treatment of short pre-pubertal children born small for gestational age.

BACKGROUND/AIMS: Few data are available about parental concerns and psychosocial functioning of young children born small for gestational age (SGA) treated with growth hormone (GH). The present study focused on the perception of short stature and the concerns and expectations of the parents regarding GH treatment. METHODS: Forty prepubertal short SGA children, randomized into a GH-treated and a GH-untreated group, and their parents were evaluated by a questionnaire and a semi-structured interview at start and after 2 years of follow-up. RESULTS: Before start, 85% of the parents were concerned about short stature, 76% expected an increase in adult height of > or =10 cm and 81% expected a positive impact on well-being. Half of the parents expressed fears regarding GH treatment. After 2 years, more parents of treated children reported obvious growth and physical changes, and fewer parents reported teasing because of short stature. An improvement of well-being was reported by half of the parents of treated and untreated children. Fears about GH treatment disappeared almost completely. CONCLUSION: The perspective of GH treatment induced major adult height expectations. In treated children, the physical effects of GH treatment became obvious, teasing because of short stature decreased and initial concerns about short stature and GH therapy decreased.