Although the metabolic syndrome has been described in adulthood, our study showed that risk factors for the development of type 2 diabetes mellitus and cardiovascular disease are already present during childhood in short prepubertal children born SGA, suggesting a pretype 2 diabetes mellitus phenotype.

Three years of GH treatment in short children born SGA results in a normalization of height during childhood. Also, bone maturation increased proportionately to the height gain. At start, mean values of BMD and BMAD were significantly reduced but normalized during GH treatment. We did not find an indication to treat very short SGA children (H SDS < or = -3.00) with a higher GH dose. We rather suggest to start GH treatment at an early age in order to achieve a normal height before puberty starts.

All children with meningococcal sepsis showed signs of euthyroid sick syndrome. Alterations in peripheral thyroid hormone metabolism related inversely to the duration of disease and seemed to be enacted by profound induction of type 3 deiodinase rather than by down-regulation of type 1. Lower TT4 levels were related to increased turnover of TBG by elastase. Dopamine was found to suppress only TSH secretion, not other thyroid hormone levels, on PICU admission. Both the TT3/rT3 ratio and TT4 levels were predictive for mortality, but were not superior to IL-6.

Parents of short children born SGA often report that their children have a serious lack of appetite and a low food intake. In this study we investigated food intake, by using a standardized 7-day food questionnaire, in 88 short SGA children before start of GH treatment. The intake was compared with the recommended daily intake (RDI) of age-matched children. We also compared the food intake of GH-treated children (n = 62) with randomized controls (n = 26) after 1 year of GH treatment. In addition, we evaluated the effect of food intake and GH treatment on body composition and serum levels of IGF-I, IGFBP-3 and leptin. Our study shows that caloric intake, fat and carbohydrate intake of short SGA children aged 5.9 (1.6) years was significantly lower compared to the RDI for age-matched children. One year of GH treatment resulted in a significant increase of caloric, fat, carbohydrate and protein intake compared to baseline. Compared to randomized controls, caloric, carbohydrate and protein intake increased significantly after 1 year of GH treatment. Short SGA children had significantly lower SDS scores for LBM, fat mass, skinfold (SF) and BMI compared to age-matched references. They also had significantly lower serum IGF-I, IGFBP-3 and leptin levels. GH treatment resulted in a significant increase of height, LBM, BMI, IGF-I and IGFBP-3 SDS and a significant decrease of SF SDS and leptin SDS. In conclusion, our study shows that short SGA children have indeed a lower food intake than age-matched controls. During GH treatment the food intake increased significantly compared to baseline in contrast to the randomized control group.

Seventy-five small for gestational age (SGA) children were studied in a randomized, double-blind, dose-response GH trial with either 1 or 2 mg GH/m(2).d. Mean (SD) age at the start of GH therapy was 7.3 (2.2) yr. Data were compared with Dutch reference data. In SGA boys, mean (SD) age at onset of puberty was 12.0 (1.0) and 11.6 (0.7) yr, and in SGA girls it was 10.9 (1.1) and 10.6 (1.2) yr when treated with 1 and 2 mg GH/m(2).d, respectively. SGA boys treated with the lower GH dose started puberty later than the appropriate for gestational age (AGA) controls; for the other GH-dosage groups there was no significant difference in age at onset of puberty compared to AGA controls. The age at menarche and the interval between breast stage M2 and menarche were not significantly different for GH-treated SGA girls compared to their peers. The duration of puberty and pubertal height gain of GH-treated SGA boys and girls were not significantly different between the two GH-dosage groups and were comparable with untreated short children born SGA. In conclusion, long-term GH therapy in short SGA children has no influence on the age at onset and progression of puberty compared to AGA controls, regardless of treatment with a dose of 1 or 2 mg GH/m(2).d. Duration of puberty and pubertal height gain were not significantly different between the GH-dosage groups.

It has been suggested that the programming of the endocrine axes occurs during critical phases of fetal development and will be affected by intrauterine growth retardation. As a result, children born small for gestational age (SGA) might have several hormonal disturbances. In later life, one of the questions that might arise is: Do short children born SGA have higher serum dehydroepiandrosterone sulfate (DHEAS) levels than their peers? Therefore, we compared serum DHEAS levels of 181 short prepubertal children aged 3-9 yr born SGA [birth length (SD score) below -2 for gestational age] with a control group of 170 prepubertal age-matched, normal-statured children born appropriate for gestational age (birth length between -2 and +2 SD score). Because relatively high serum DHEAS levels at a young age might result in a premature pubarche, we investigated the incidence of premature pubarche. We also investigated the association between serum DHEAS levels and bone maturation. In addition, we analyzed whether 1 yr of GH treatment with 1 and 2 mg/m(2).d ( approximately 0.035 and 0.070 mg/kg.d, respectively) had an effect on serum DHEAS levels of prepubertal short SGA children. Serum DHEAS levels of the SGA group were comparable with those of age-matched appropriate for gestational age controls. The incidence of premature pubarche was comparable with that of the normal population. There was a weak negative correlation between serum DHEAS levels and bone maturation after the age of 7 yr. After 1 yr of GH treatment, the increase of serum DHEAS levels was the same for both GH dosage groups and the untreated group. In conclusion, this study shows that small size at birth, which might be a feature of fetal growth restriction, has no effect on serum DHEAS levels before the age of 9 yr. The incidence of premature pubarche is comparable with the normal population. Finally, 1 yr of GH treatment has no effect on serum DHEAS levels.

Untreated short SGA children have normal body proportions with the exception of HC, which is relatively large in many of these children. SGA(L+W) children still had a smaller HC at the age of 5.9 years compared with SGA(L) children. Three years of GH treatment induced a proportionate growth resulting in a normalization of height and other anthropometric measurements, including HC, in contrast to untreated SGA control subjects.

Twelve years of growth hormone (GH) therapy of short children born small for gestational age (SGA) have demonstrated that GH is an effective and well-tolerated therapy. Most children will reach a normal adult height (AH). AH of 55 SGA adolescents was comparable for those treated with a GH dose of 1 or 2 mg/m² (∼0.033 or 0.066 mg/kg) per day, mean (SD) AH SDS being –1.2 (0.7) and –0.8 (0.7), respectively. GH therapy had no influence on the age at onset, the progression of puberty, duration of puberty and pubertal height gain. GH therapy induced higher fasting and glucose-stimulated insulin levels after 1 and 6 years, but 6 months after GH stop, all levels returned to normal. At baseline mean systolic blood pressure was significantly increased, but both systolic and diastolic blood pressure decreased significantly during 6 years of GH and remained so after GH stop. GH therapy demonstrated a beneficial effect on serum lipid profiles, body composition, bone mineral density and head growth. Treatment with 2 mg GH/m² per day induced mean serum IGF-I levels of +2 SDS, whereas IGF-I levels remained within the normal range with 1 mg GH/m² per day. In conclusion, long-term GH therapy of short SGA children with 1 mg/m² per day appears to be effective and safe. Since the future consequences of high serum IGF-I levels during long-term GH therapy with 2 mg/m² per day are as yet unknown, it seems safer to treat short prepubertal SGA children with a GH dose of 1 mg/m² per day when children are to be treated continuously for many years.