http://repub.eur.nl/res/aut/3484/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/33781/ 2011-04-01T00:00:00Z Background Fetal growth restriction is thought to negatively influence reproductive function in later life. Serum anti-Mllerian hormone (AMH) is a marker of the primordial follicle pool. The objectives of this study were to evaluate the effect of being born small for gestational age (SGA) on serum AMH levels and to investigate the effect of growth hormone (GH) treatment on serum AMH levels in short SGA girls.Methods Serum AMH levels were investigated in 246 prepubertal girls aged 310 years: 119 untreated short SGA and 127 healthy controls. Associations between AMH levels and clinical characteristics were analysed using multiple regression analyses. In addition, we investigated the effect of GH treatment on serum AMH levels in short SGA girls.Results Serum AMH levels were similar in short SGA and healthy control girls (P 0.95). In short SGA girls, AMH levels were not significantly influenced by birth weight standard deviation score (SDS), birth length SDS and gestational age, even after adjustment for age, height SDS and body mass index (BMI) SDS at sampling, socio-economic status and maternal smoking during gestation. Serum AMH levels did not change during 4 years of GH treatment in short SGA girls (P 0.43). Conclusions Serum AMH levels in prepubertal short SGA girls are similar to healthy controls, indicating that the follicle pool is not compromised due to SGA birth. GH treatment has no effect on AMH levels in short SGA girls. http://repub.eur.nl/res/pub/14510/ 2008-12-01T00:00:00Z Background/Aims: Some studies reported an impaired gonadal function in males born small for gestational age (SGA). We investigated Sertoli cell function by measuring serum inhibin B and antimullerian hormone (AMH) levels in prepubertal boys and young men born SGA in comparison with age-matched controls born appropriate for gestational age (AGA). Methods: Inhibin B and AMH levels were determined in 73 prepubertal short SGA boys and in 72 age-matched AGA boys. In addition, 25 SGA boys were re-examined after 2 years of growth hormone (GH) treatment. Furthermore, inhibin B, AMH, testosterone, LH and FSH were studied in three groups of young men: 21 SGA men treated with GH, 15 SGA men with spontaneous catch-up growth and 25 young men born AGA. Results: Prepubertal short SGA boys and AGA boys had similar inhibin B (87.3 and 78.2 ng/ml) and AMH levels (75.6 and 63.6 μg/l, respectively). GH treatment did not result in different inhibin B and AMH levels. In young SGA men, inhibin B, testosterone, LH and FSH levels were similar compared to young AGA men. AMH levels were higher in the young SGA men (p = 0.03). Conclusions: Being born SGA does not impair Sertoli cell function. Young men born SGA have a normal hypothalamic-pituitary- testis axis. http://repub.eur.nl/res/pub/7256/ 2006-01-25T00:00:00Z Wij hebben verschillende onderzoeken gedaan naar kinderen met een laag geboorte lengte of gewicht voor de zwangerschapsduur (SGA=Small for Gestational Age) en een kleine lengte waarvoor behandeling met groeihormoon (GH). Aan mijn promtieonderzoek hebben de kinderen van de 1e en 2e Nederlandse GH- trial deel genomen. Deze studies zijn gestart tussen 1991-2001. Beide studies gebruiken dezelfde inclusie en exclusie criteria. Kort samengevat gaat het om kinderen die een geboortelengte of geboorte gewicht hadden kleiner dan -2.0 SDS en op moment van inclusie een lengte kleiner dan -2 SDS en een leeftijd tussen de 3.0 en 7.9 jaar. Het zijn gezonde kinderen zonder syndromen of andere chronische afwijkingen die hun lengte zouden kunnen hebben beïnvloed. In de 1e studie werden de kinderen met een enkelvoudige of dubbele dosis GH behandeld. In de 2e studie werd 2/3 van de kinderen behandeld met GH en 1/3 bleef 3 jaar onbehandeld en startte daarna met GH. Eerdere resu! ltaten van deze studies zijn beschreven in de proefschriften van W. de Waal, T. Sas and N. Arends. In eerste instantie hebben we gekeken naar het effect van SGA op de orgaan ontwikkeling. We hebben onderzoek gedaan naar de adrenarche in SGA kinderen met een kleine lengte in vergelijking met AGA kinderen. Tevens is er gekeken in de SGA groep wat de incidentie van premature pubarche is. We hebben onderzocht wat het effect is van foetale groei op het aantal ovariële follikels bij SGA meisjes in vergelijking met AGA meisjes. Onderzocht is wat het effect is van foetale groei op de testes ontwikkeling bij SGA jongens in vergelijking met AGA jongens. Tevens hebben we onderzocht wat het effect is van GH op de adrenarche, ovaria en testis functie. We hebben de puberteitontwikkeling onderzocht van GH behandelde SGA kinderen door middel van het bepalen van de leeftijd en lengte waarop de puberteit start, de progressie van de puberteit en de lengte winst tijdens de puberteit. Er is onderzocht of SGA kinderen een verminderde voedingsintake hebben in vergelijking met gezonde Nederlan! dse kinderen. Tevens hebben we de voedingsintake in combinatie met body compositie en serum IGF-I, IGFBP3 en leptine van GH behandelde kinderen vergeleken met onbehandelde SGA kinderen. Tenslotte hebben we onderzocht wat het effect is van GH op de kwaliteit van leven in vergelijking met onbehandelde SGA kinderen. http://repub.eur.nl/res/pub/13881/ 2005-10-01T00:00:00Z CONTEXT AND OBJECTIVES: The objective of this study was to elucidate the influence of disease severity, deiodination, sulfation, thyroid hormone binding, and dopamine use on thyroid function in euthyroid sick syndrome. SETTING: The study was performed at a university-affiliated pediatric intensive care unit (PICU). DESIGN: This was an observational cohort study. PATIENTS: Sixty-nine children with meningococcal sepsis were studied. MAIN OUTCOME MEASURES: Differences in thyroid function among nonsurvivors, shock survivors, and sepsis survivors on PICU admission were the main outcome measures. RESULTS: The main study group consisted of 45 non-dopamine-treated children. All children had decreased total T3 (TT3)/rT3 ratios without elevated TSH. T4 sulfate levels were decreased in 88%. Nonsurvivors had paradoxically higher TT3/rT3 ratios than shock survivors (0.71 vs. 0.30); this ratio also correlated with shorter duration of disease (r = -0.43). TT4 and T4-binding globulin (TBG) levels declined with increasing disease severity. TBG levels correlated inversely with elastase levels (r = -0.46). Only TSH levels were significantly lower in 24 dopamine-treated children compared with non-dopamine-treated children (0.65 vs. 0.84), whereas other thyroid hormones did not significantly differ. Both higher TT3/rT3 ratios and lower TT4 levels were predictive for mortality, but this disappeared when IL-6 was entered into the regression model. CONCLUSIONS: 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. http://repub.eur.nl/res/pub/13491/ 2004-09-01T00:00:00Z OBJECTIVE: Although short children who were born small for gestational age (SGA) seem to have normal body proportions, objective data both before and during growth hormone (GH) treatment are very limited. Therefore, we investigated in a large group of short children who were born SGA the effects of GH treatment versus no treatment on head circumference (HC) and body proportions. Furthermore, we studied differences in linear growth and HC between SGA children who were born with a low birth length and birth weight (SGA(L+W)) and SGA children who were born with a low birth length only (SGA(L)). METHODS: An open-labeled, GH-controlled, multicenter study was conducted for 3 years. Non-GH-deficient short SGA children (n = 87), with a mean age (standard deviation) of 5.9 (1.5) years, were randomized to either a GH group (n = 61), receiving GH in a dose of 33 microg/kg/day, or an untreated control group (n = 26). Height; weight; HC; sitting height; armspan; and hand, tibial, and foot size were measured and expressed as standard deviation score (SDS) adjusting for gender and age. RESULTS: At baseline, all anthropometric measurements, except HC SDS, were significantly lower compared with -2 SDS. During GH treatment, all anthropometric measurements normalized in accordance to the normalization of height SDS. At the start of the study, mean HC SDS was significantly lower in SGA(L+W) children compared with SGA(L) children. It is interesting that most (14 of 16) children with an HC SDS less than -2.00 had been born SGA(L+W). During GH treatment, the 3-year increase in height, HC, and other anthropometric measurements was comparable between SGA(L+W) and SGA(L) children. In both SGA(L+W) and SGA(L) control subjects, no changes in SDSs of height, HC, and other anthropometric measurements were found during the 3-year follow-up period. CONCLUSIONS: 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. http://repub.eur.nl/res/pub/10313/ 2004-01-01T00:00:00Z 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. http://repub.eur.nl/res/pub/10274/ 2003-01-01T00:00:00Z 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.