Anita C S Hokken-Koelega

Erasmus MC, Rotterdam, South Holland, Netherlands

Are you Anita C S Hokken-Koelega?

Claim your profile

Publications (228)943.02 Total impact

  • N E Bakker, K P Wolffenbuttel, L H J Looijenga, A C S Hokken-Koelega
    [Show abstract] [Hide abstract]
    ABSTRACT: Boys with Prader-Willi syndrome (PWS) often have undescended testes. Prospective studies on treatment of cryptorchidism in boys with PWS are lacking. Our aim was to evaluate the effects of human Chorionic Gonadotropin (hCG) treatment on testis position. In those who underwent orchidopexy, biopsy was taken and testis histology studied.
    The Journal of urology. 08/2014;
  • J S Renes, J vanDoorn, A C S Hokken-Koelega
    [Show abstract] [Hide abstract]
    ABSTRACT: Background IGF-I is mainly sequestered in a 150 kD ternary complex with IGFBP-3 and the acid-labile subunit (ALS). Data on complex formation and factors influencing formation have not been established. Dissociation of IGF-I from the ternary complex is in part regulated by proteolysis of IGFBP-3, which reduces its affinity for IGF-I. Short SGA children have lower IGF-I and IGFBP-3 levels compared to healthy peers. Objective To determine complex formation in healthy normal statured children, and assess variables influencing complex formation. Secondly, we determined complex formation in short SGA children Design/methods Complex formation was assessed using (125)I-hIGF-I column chromatography in 70 controls (40 boys), median age 10.6 years, and 40 short SGA children (25 boys), median age 8.6 years. IGFBP-3 was determined by Western immunoblotting. Results (125)I-hIGF-I complex formation showed an age-specific pattern in healthy controls. Variables positively influencing ternary complex formation were higher serum IGF-I levels compared to IGFBP-3 levels (P<0.001), and lower serum IGF-II (P<0.001) and IGFBP-1 levels (P<0.001). In addition, a higher presence of proteolyzed IGFBP-3 negatively influenced 150 kD complex formation (P=0.006). At a young age, healthy children showed considerable IGFBP-3 proteolytic activity which declined with aging (P<0.001). IGFBP-3 proteolytic activity was negatively correlated with IGF-I levels (P<0.001). Compared to healthy controls, short SGA children showed reduced IGF-I levels (-1.3 vs. 0.1 SDS) and increased proteolyzed IGFBP-3 (35.1% vs. 12.2%). Conclusion Age-specific normative values for (125)I-hIGF-I 150 kD ternary complex formation are presented. A decrease in IGF-I, and an increase in IGF-II, IGFBP-1 and IGFBP-3 proteolytic activity associate with reduced (125)I-hIGF-I ternary complex formation. Our results suggest that in conditions were IGF-I levels are low, such as young age and in short SGA children, IGFBP-3 proteolytic activity is increased to ensure IGF-I bioavailability.
    The Journal of clinical endocrinology and metabolism. 06/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Prednisone use and active disease are associated with reduced bone mineral density (BMD) in patients with rheumatoid arthritis (RA). Either or both of these factors may be inevitable during pregnancy in women with RA, but it is unknown whether they variables influence the BMD of the offspring. This study was undertaken to investigate whether medication use or disease activity during pregnancy in RA patients influences the BMD of their prepubertal offspring. Mothers (n = 255) participated in a prospective cohort study of RA and pregnancy, and 108 children of these mothers (ages 5-10 years) were included in this followup study. Information on features known to influence BMD in children, i.e., calcium intake, physical activity, serum 25-hydroxyvitamin D level, sex, height, and weight, was collected. In addition, pre- and postnatal variables known to influence BMD, i.e., gestational age, maternal smoking, birth weight, postnatal rate of growth, and type of feeding, were recorded. Independent variables were prednisone use, sulfasalazine use, and RA disease activity during pregnancy. We found no association of BMD in the children with either prednisone use or RA disease activity during pregnancy, even after correcting for all known associated variables. Sulfasalazine use during pregnancy had a positive effect on the total-body BMD of the offspring (difference in standard deviation score 0.53, P = 0.005). Our findings indicate that neither medication use nor high RA disease activity during pregnancy is associated with decreased BMD in offspring at age ∼7 years. The maternal benefit of medication use for RA during pregnancy outweighs the effect on BMD in the offspring.
    Arthritis & rheumatology (Hoboken, N.J.). 03/2014; 66(3):533-7.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Objective Active rheumatoid arthritis (RA) during pregnancy and the presence of rheumatoid factor (RF) or anti-citrullinated protein antibody (ACPA) are related with a lower birth weight. Prednisone reduces the gestational age. Rapid catch-up in weight for length during the first year of life has been related to worse cardiovascular and metabolic profile in adults. We want to assess the influence of RA disease activity, medication and the presence of RF or ACPA during pregnancy on the growth of the child in the first year of life. Methods Tempo of catch-up in weight during the first year of life was studies. All 180 children were born to mothers with RA. Independent variables were RA disease activity (DAS28), medication and presence of RF or ACPA during pregnancy. Results 31% (52/167) of the children showed catch-up in weight in the first year of whom 90% (47/52) showed rapid catch-up. Elevated DAS28 was associated with rapid catch-up in weight independent of medication or the presence of RF or ACPA during pregnancy (OR, 1.44; 95% CI, 1.07- 1.95; for one point increase in DAS28). Medication had no influence on postnatal growth. Conclusion Elevated RA disease activity during pregnancy should be avoided because it is associated with rapid postnatal catch-up in weight, a risk factor for worse cardiovascular and metabolic profile in adults. Medication during pregnancy, including prednisone, had no effect on growth. Continuation or extension of medication will not only improve maternal health during pregnancy, but could be beneficial for the future health of the unborn child. © 2014 American College of Rheumatology.
    Arthritis & rheumatology (Hoboken, N.J.). 02/2014;
  • [Show abstract] [Hide abstract]
    ABSTRACT: Aims: To determine acid-labile subunit (ALS) levels in short small for gestational age (SGA) children and to assess the relationship between ALS levels and several clinical and laboratory characteristics. Also, to assess whether adding ALS levels to a growth prediction model might improve the long-term growth prediction. Design/Methods: ALS levels were measured in 312 short SGA children at the start of growth hormone (GH) treatment. Results: Median (interquartile range) ALS of all subjects was -0.5 SDS, significantly below the 0 SDS (p < 0.001). In 34 children (11%), ALS levels were ≤-2 SDS. ALS SDS correlated significantly with height SDS (r = 0.24, p < 0.001), weight SDS (r = 0.30, p < 0.001), BMI SDS (r = 0.20, p = 0.001), IGF-I SDS (r = 0.56, p < 0.001) and IGFBP-3 SDS (r = 0.67, p < 0.001). ALS SDS was also positively correlated with fasting insulin (r = 0.41, p < 0.001) and glucose levels (r = 0.33, p < 0.001), and HOMA-IR (r = 0.35, p < 0.001). Baseline ALS levels contributed to the long-term growth prediction of GH treatment (5%, p < 0.001). Conclusion: Short SGA children tend to have lower ALS levels compared to controls, albeit less reduced than IGF-I and IGFBP-3 levels. Our data suggest that ALS may be involved in glucose homeostasis. Determination of ALS levels before the start of GH treatment in short SGA children contributes moderately to a more accurate prediction of the growth response to GH treatment. © 2014 S. Karger AG, Basel.
    Hormone Research in Paediatrics 01/2014; · 1.55 Impact Factor
  • Laura M Breij, Gerthe F Kerkhof, Anita C S Hokken-Koelega
    [Show abstract] [Hide abstract]
    ABSTRACT: Introduction: Non-alcoholic fatty liver disease (NAFLD) is considered the hepatic metabolic syndrome. Some studies demonstrated an association between small size at birth and NAFLD. Rapid catch-up in weight often follows small birth size and has been associated with metabolic syndrome, but its association with NAFLD remained unknown. Patients and Methods: In 268 adults aged 18-24 yrs, BMI, waist circumference, triglyceride, gamma-glutamyltransferase (γ-GT), alkaline phosphatase (ALP), alanine aminotranserase (ALT), and aspartate aminotransferase (AS) levels were determined. Fatty liver index (FLI, 0-100) was calculated. Associations of birth weight SDS and first year gain in weight- and length SDS were determined with FLI and other liver markers. Comparisons were performed between subjects with and without rapid catch-up in weight in the first year of life. Furthermore, a FLI-score (low, intermediate, high risk for NAFLD) was assigned to each participant to determine clinical relevance, and ordinal regression analyses were performed. Results: Gain in weight in the first three months of life was associated with FLI as a continuous variable, whereas low birth weight was not. There were no significant associations with γ-GT, ALT, or AST. Of the subjects with rapid catch-up in weight for length, 27.8% had an intermediate or high FLI at the age of 21 years, compared with 5.3% of subjects with slow catch up. Rapid catch-up was also associated with a higher FLI-score after adjustments (odds ratio:11.7, p-value:0.016). Conclusion: Accelerated gain in weight for length in the first three months of life is associated with a higher risk for NAFLD in early adulthood, whereas small size at birth is not.
    The Journal of Clinical Endocrinology and Metabolism 01/2014; · 6.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Pregnant women suffering from autoimmune disease use glucocorticoids. Glucocorticoids can partly diffuse to the fetus, and may influence the development of the fetal hypothalamic-pituitary-adrenal axis, especially in early stage of pregnancy. The objective was to investigate whether prednisone-exposure in utero influences the cortisol levels of the prepubertal children. Mothers participated in a prospective cohort study on rheumatoid arthritis (RA) and pregnancy. Children were exposed (n=44) or non-exposed (n=65) to prednisone in utero. Salivary cortisol levels were taken from all children during one day: at awakening, 30 minutes after awakening, 1pm and, bedtime. Cortisol levels between groups were also analyzed using area under the curve (AUC), cortisol awakening response (CAR), and slope. The mean age (SD) of the children was 6.98 (1.23). The difference in mean (SD) cortisol level at '1pm' was 5.42 nmol/L (4.08) in the prednisone-exposed and 3.97 nmol/L (4.00) in the non-exposed (p=0.03). Prednisone-exposed children had a higher AUC (β=13.28; p=0.02), even after correction for RA disease activity. No differences were found on CAR, slope or blood pressure. The cortisol levels of the non-exposed were more similar to the age-specific references than the prednisone-exposed. Prednisone use during pregnancy is associated with a higher daytime cortisol level, in the prepubertal offspring, not yet accompanied with clinical outcomes. This conclusion will have no consequences at this moment, but is does raise questions concerning prednisone-exposure in utero and the long-term consequences for the offspring, This article is protected by copyright. All rights reserved.
    Clinical Endocrinology 12/2013; · 3.40 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background: Fetal growth failure has been associated with an increased risk of hypertension, cardiovascular disease and diabetes in adulthood. Exploring the mechanisms underlying this association should improve our understanding of these common adult diseases. Patients and Methods: We investigated 225 SNPs in 10 genes involved in growth and glucose metabolism (GH1, GHR, IGF1, IGF1R, STAT5A, STAT5B, MAPK1, MAPK3, PPARγ and INS) in 1,437 children from the multinational NESTEGG consortium: 345 patients born small for gestational age who remained short (SGA-S), 288 who showed catch-up growth (SGA-Cu), 410 idiopathic short stature (ISS) and 394 controls. We related genotype to pre- and/or postnatal growth parameters, response to growth hormone (if applicable) and blood pressure. Results: We found several clinical associations for GH1, GHR, IGF1, IGF1R, PPARγ and MAPK1. One SNP remained significant after Bonferroni's correction: IGF1R SNP rs4966035's minor allele A was significantly more prevalent among SGA and associated with smaller birth length (p = 0.000378) and birth weight (weaker association), independent of gestational age. Conclusion: IGF1R SNP rs4966035 is significantly associated with birth length, independent of gestational age. This and other associations suggest that polymorphisms in these genes might partly explain the phenotype of short children born SGA and children with ISS. © 2013 S. Karger AG, Basel.
    Hormone Research in Paediatrics 11/2013; · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background:The most important reason for treating children with Prader-Willi syndrome (PWS) with GH is to optimize their body composition.Objectives:The aim of this ongoing study was to determine whether long-term GH treatment can counteract the clinical course of increasing obesity in PWS by maintaining the improved body composition brought during early treatment.Setting:This was a multicenter prospective cohort study.Methods:We have been following 60 prepubertal children for 8 years of continuous GH treatment (1 mg/m(2)/d ≅ 0.035 mg/kg/d) and used the same dual-energy x-ray absorptiometry machine for annual measurements of lean body mass and percent fat.Results:After a significant increase during the first year of GH treatment (P < .0001), lean body mass remained stable for 7 years at a level above baseline (P < .0001). After a significant decrease in the first year, percent fat SD score (SDS) and body mass index SDS remained stable at a level not significantly higher than at baseline (P = 0.06, P = 0.14, resp.). However, body mass index SDSPWS was significantly lower after 8 years of GH treatment than at baseline (P < .0001). After 8 years of treatment, height SDS and head circumference SDS had completely normalized. IGF-1 SDS increased to +2.36 SDS during the first year of treatment (P < .0001) and remained stable since then. GH treatment did not adversely affect glucose homeostasis, serum lipids, blood pressure, and bone maturation.Conclusion:This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.
    The Journal of Clinical Endocrinology and Metabolism 09/2013; · 6.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Background Growth hormone (GH) treatment has become a frequently applied growth promoting therapy in short children born small for gestational age (SGA). In some disorders GH treatment is contraindicated, e.g. chromosomal breakage syndromes. Bloom syndrome is a rare chromosomal breakage syndrome characterized by severe pre- and postnatal growth deficiency, a photosensitive facial erythema, immunodeficiency, mental retardation or learning disabilities, endocrinopathies and a predisposition to develop a wide variety of cancers.Objective We report two patients with Bloom syndrome illustrating the variety in clinical manifestations. They were initially diagnosed with short stature after SGA birth and Silver Russell syndrome and treated with GH.CasesBoth patients presented with pre- and postnatal growth failure, but no clear other characteristic features associated with Bloom syndrome. Photosensitive skin lesions developed only at a pubertal age and were minimal. Also, both children showed normal immunoglobulin levels, normal development and no signs of endocrinopathies at start of GH. Dysmorphic features resembling Silver Russell syndrome were observed in both patients. Remarkably, during GH treatment IGF-I levels increased to values >3.5 SDS, with normal IGFBP-3 levels.Conclusion Short children born SGA comprise a heterogeneous group. Bloom syndrome should be tested for in children with consanguineous parents, dysmorphic features (particularly resembling Silver Russell syndrome), skin abnormalities, and/or IGF-I levels >2.5 SDS during standard GH treatment with normal IGFBP-3 levels.
    The Journal of Clinical Endocrinology and Metabolism 08/2013; · 6.31 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Although severe motor problems in infants with Prader-Willi syndrome (PWS) are striking, motor development has never been studied longitudinally and the results of growth hormone (GH) treatment on motor development are contradictory. The authors studied whether GH treatment can enhance the effect of physical training on motor development in infants with PWS. Twenty-two infants were followed for two years during a randomized controlled trial. The treatment and control groups began GH after baseline or following a control period, respectively. Both groups followed a child-specific physical training program. Motor performance was measured every three months. Multi-level regression analysis revealed that motor development differed significantly between infants (p<.001), and this could be partially explained by baseline motor developmental level (p<.01). GH treatment enhanced the effects of child-specific physical training on both motor developmental rate and motor developmental potential. Moreover, this effect was more pronounced when GH treatment was initiated at a younger age.
    Research in developmental disabilities 07/2013; 34(10):3092-3103. · 4.41 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: In order to evaluate the social cognitive functioning in children with Prader-Willi syndrome (PWS), Theory of Mind (ToM) and symptoms of Autism Spectrum Disorder were evaluated. Sixty-six children with PWS aged 7-17 years were tested using the Theory of Mind test-R and the Diagnostic Interview for Social Communication disorders. We tested the correlation between Total ToM Standard Deviation Score (Total ToM SDS) and genetic subtype of paternal deletion or maternal uniparental disomy, and total IQ, verbal IQ and performal IQ. Prevalence and symptoms of Autism Spectrum Disorder were assessed. Median (interquartile range) of total ToM SDS of those aged 7-17 years was -3.84 (-5.73, -1.57). Their Total ToM SDS correlated with total IQ (β=0.662, p<0.001, adj.R(2)=0.407), in particular with verbal IQ (β=0.502, p=0.001, adj.R(2)=0.409), but not with performal IQ (β=0.241, p>0.05, adj.R(2)=0.259). No difference in Total ToM SDS was found between children with deletion and maternal uniparental disomy (β=-0.143, p>0.05, adj.R(2)=-0.016). Compared to the reference group of healthy children aged 7-12 years, children with PWS in the same age group had a median ToM developmental delay of 4 (3-5) years. One third of children with PWS scored positive for Autism Spectrum Disorder. Most prominent aberrations in Autism Spectrum Disorder were focused on maladaptive behavior. Our findings demonstrate a markedly reduced level of social cognitive functioning, which has consequences for the approach of children with PWS, i.e. adjustment to the child's level of social cognitive functioning.
    Research in developmental disabilities 06/2013; 34(9):2764-2773. · 4.41 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The goal of growth hormone (GH) treatment in a short child is to attain a fast catch-up growth toward the target height (TH) standard deviation score (SDS), followed by a maintenance phase, a proper pubertal height gain, and an adult height close to TH. The short-term response variable of GH treatment, first-year height velocity (HV) (cm/year or change in height SDS), can either be compared with GH response charts for diagnosis, age and gender, or with predicted HV based on prediction models. Three types of prediction models have been described: the Kabi International Growth Hormone Study models, the Gothenburg models and the Cologne model. With these models, 50-80% of the variance could be explained. When used prospectively, individualized dosing reduces the variation in growth response in comparison with a fixed dose per body weight. Insulin-like growth factor-I-based dose titration also led to a decrease in the variation. It is uncertain whether adding biochemical, genetic or proteomic markers may improve the accuracy of the prediction. Prediction models may lead to a more evidence-based approach to determine the GH dose regimen and may reduce the drug costs for GH treatment. There is a need for user-friendly software programs to make prediction models easily available in the clinic.
    Hormone Research in Paediatrics 05/2013; · 1.55 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: STUDY QUESTION: In girls and adolescents with Turner syndrome (TS), is there a correlation between serum AMH levels and karyotype, spontaneous puberty and other biochemical markers of ovarian function, or growth hormone (GH) therapy? SUMMARY ANSWER: Serum anti-Müllerian hormone (AMH) correlates with karyotype, pubertal development, LH, FSH and are measurable in a higher percentage of TS patients under GH therapy. WHAT IS KNOWN ALREADY: Most girls with TS suffer from incomplete sexual development, premature ovarian failure and infertility due to abnormal ovarian folliculogenesis. Serum AMH levels reflect the ovarian reserve in females, even in childhood. STUDY DESIGN, SIZE, DURATION: Cross-sectional study investigating 270 karyotype proven TS patients aged 0-20 years between 2009 and 2010. PARTICIPANTS/MATERIALS, SETTINGS, METHODS: Studies were conducted at three University Children's hospitals in Europe. Main outcome measures were clinical data concerning pubertal development as well as laboratory data including karyotype, serum AMH, LH, FSH, estradiol (E2), inhibin B and IGF. RESULTS AND THE ROLE OF CHANCE: Serum AMH was detectable in 21.9% of all TS girls and correlated strongly with karyotypes. A measurable serum AMH was found in 77% of TS girls with karyotype 45,X/46,XX, in 25% with 'other' karyotypes and in only 10% of 45,X TS girls. A strong relationship was also observed for measurable serum AMH and signs of spontaneous puberty such as breast development [adjusted odds ratio (OR) 19.3; 95% CI 2.1-175.6; P = 0.009] and menarche (crude OR 47.6; 95% CI 4.8-472.9; P = 0.001). Serum AMH correlated negatively with FSH and LH, but did not correlate with E2 and inhibin B. GH therapy increased the odds of having measurable AMH in TS (adjusted OR 4.1; 95% CI 1.9-8.8; P < 0.001). LIMITATIONS, REASONS FOR CAUTION: The cross-sectional design of the study does not allow longitudinal interpretation of the data; for that further studies are needed. High percentage of non-measurable AMH levels in the cohort of TS require categorized analysis. WIDER IMPLICATIONS OF THE FINDINGS: Serum AMH levels are a useful marker of the follicle pool and thus ovarian function in pediatric patients with TS. These findings are in line with the published literature. The finding that GH therapy may affect AMH levels is novel, but must be confirmed by future longitudinal studies.
    Human Reproduction 03/2013; · 4.67 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: The analysis of growth curves of children can be done on either the original scale or in standard deviation scores. The first approach is found in many statistical textbooks, while the second approach is common in endocrinology, for instance in the evaluation of the effect of growth hormone in children that are born small for gestational age that remain small later in childhood. We illustrate here that the second approach may involve more complex modeling and hence a worse model fit.
    Statistical Methods in Medical Research 02/2013; · 2.36 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: BACKGROUND: High rheumatoid arthritis (RA) disease activity during pregnancy is associated with a lower birth weight. Active RA is characterised by high circulating levels of cytokines, which can mediate placental growth and remodelling. OBJECTIVES: To assess the influence of maternal serum cytokine levels on birth weight in RA pregnancy. METHODS: This study is embedded in the PARA Study, a prospective study on RA and pregnancy. In the present study, 161 pregnant women with RA and 32 healthy pregnant women were studied. The main outcome measures were birth weight SD score (birth weight SDS) in relation to maternal serum levels of interleukin-10 (IL-10), interleukin-6 (IL-6) and tumour necrosis factor-α (TNFα) at three different time points: preconception and during the first and third trimester. Single-nucleotide polymorphisms (SNPs) in the corresponding cytokine genes were also studied. RESULTS: During the first trimester, IL-10 was detectable in 16% of patients with RA, IL-6 in 71%, and TNFα in all patients with RA. Mean birth weight SDS of children born to mothers with RA was higher when IL-10 level was high compared with low (difference=0.75; p=0.04), and lower when IL-6 was high compared with low (difference=0.50; p<0.01) in the first trimester. No correlation was seen at the other time points studied or with TNFα. Cytokine levels were not related to their corresponding SNPs. CONCLUSIONS: Maternal IL-10 and IL-6 levels are associated with fetal growth in RA. In the first trimester, high IL-10 levels are associated with higher birth weight SDS, and high IL-6 levels are associated with lower birth weight SDS, even after correction for disease activity.
    Annals of the rheumatic diseases 12/2012; · 8.11 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: What is already known about this subject Parental obesity is a strong risk factor of childhood obesity. High gestational weight gain is associated with childhood body mass index. Previous studies reported inconsistent associations between parental and child anthropometrics. What this study adds Maternal anthropometrics have stronger effects on fetal anthropometrics than paternal anthropometrics. Maternal body mass index has a stronger effect on longitudinally measured childhood body mass index than paternal body mass index. The strongest effect of gestational weight gain on childhood body mass index was seen at the age of 4 years in mothers with normal body mass index. BACKGROUND: There are limited data regarding the associations of both maternal and paternal anthropometrics with longitudinally measured post-natal growth measures in early childhood. OBJECTIVE: To assess the associations of maternal and paternal anthropometrics with growth characteristics and the risk of overweight in pre-school children. STUDY DESIGN: Population-based prospective cohort study from early foetal life onwards in the Netherlands. METHODS: Maternal pre-pregnancy anthropometrics and gestational weight gain, and paternal anthropometrics were related to foetal and post-natal growth measures and the risk of overweight until the age of 4 years. Analyses were based on 5674 mothers, fathers and their children. RESULTS: Both pre-pregnancy maternal and paternal height, weight and body mass index were associated with corresponding foetal and post-natal anthropometric measures. Maternal body mass index had a significantly stronger effect on childhood body mass index than paternal body mass index. As compared to children from parents with normal body mass index, children from two obese parents had an increased risk of overweight at the age of 4 years (odds ratio 6.52 (95% confidence interval 3.44, 12.38). Maternal gestational weight gain was only among mothers with normal body mass index associated with body mass index and the risk of overweight in the children. CONCLUSION: Maternal and paternal anthropometrics affect early growth in pre-school children differently. Gestational weight gain in mothers without overweight and obesity is related to the risk of overweight in early childhood.
    Pediatric Obesity 12/2012; · 2.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Congenital central hypothyroidism occurs either in isolation or in conjunction with other pituitary hormone deficits. Using exome and candidate gene sequencing, we identified 8 distinct mutations and 2 deletions in IGSF1 in males from 11 unrelated families with central hypothyroidism, testicular enlargement and variably low prolactin concentrations. IGSF1 is a membrane glycoprotein that is highly expressed in the anterior pituitary gland, and the identified mutations impair its trafficking to the cell surface in heterologous cells. Igsf1-deficient male mice show diminished pituitary and serum thyroid-stimulating hormone (TSH) concentrations, reduced pituitary thyrotropin-releasing hormone (TRH) receptor expression, decreased triiodothyronine concentrations and increased body mass. Collectively, our observations delineate a new X-linked disorder in which loss-of-function mutations in IGSF1 cause central hypothyroidism, likely secondary to an associated impairment in pituitary TRH signaling.
    Nature Genetics 11/2012; · 35.21 Impact Factor
  • Annemieke J Lem, Danielle C M van der Kaay, Anita C S Hokken-Koelega
    [Show abstract] [Hide abstract]
    ABSTRACT: Context:Postponement of puberty by GnRH analog (GnRHa) in addition to GH treatment might increase adult height (AH) in short adolescents born small for gestational age (SGA). GnRHa treatment is thought to have negative effects on bone mineral density (BMD) and body composition.Objective:The objective of the study was to assess the BMD of total body (BMD(TB)), lumbar spine (BMD(LS)), bone mineral apparent density lumbar spine (BMAD(LS)), lean body mass, fat mass, and fat distribution during GH treatment, with or without an additional 2 yr of GnRHa.Patients and Design:This was a prospective GH trial involving short SGA adolescents (≥8 yr). Eighty-eight children (50 girls) were treated until AH (GH randomized 1 or 2 mg/m(2) · d during puberty); 52 of these children received additional GnRHa. BMD and body composition were longitudinally assessed by dual-energy X-ray absorptiometry.Results:Baseline BMD(TB) sd score (SDS) and BMD(LS) SDS were significantly reduced (both P < 0.001), but BMAD(LS) SDS was comparable with zero (P = 0.129). BMD(TB) SDS and BMD(LS) SDS improved (both P < 0.001) from the start until AH, whereas BMAD(LS) SDS remained similar (P = 0.168). At AH, 93% of patients had a normal BMD(TB), 99% a normal BMD(LS), and 98% a normal BMAD(LS) (> -2 and < +2 SDS). From the start until AH, lean body mass SDS(height) and fat mass SDS increased significantly toward zero (both P <0.001). Multiple regression analyses showed that additional GnRHa treatment had no adverse effect on the changes in BMD and body composition during GH treatment, also after correction for influencing variables.Conclusion:Untreated short SGA adolescents had reduced BMD(TB) and BMD(LS) but normal bone size-corrected BMAD(LS). During GH treatment, BMD(TB) and BMD(LS) increased significantly, leading to a normal adult BMD in almost all patients. Two years of GnRHa in addition to GH treatment had no adverse effect on BMD or body composition.
    The Journal of Clinical Endocrinology and Metabolism 11/2012; · 6.31 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Context:Anti-Müllerian hormone (AMH) is an accurate marker of ovarian reserve. However, sufficiently large sets of normative data from infancy to the end of reproductive life are scarce.Objective:This study was an assessment of serum AMH levels in healthy females.Subjects:In 804 healthy females ranging from infancy until the end of the reproductive period, serum AMH levels were measured with an enzyme-linked immunometric assay. All adults had regular menstrual cycles. The majority was proven fertile and none of them had used oral contraceptive pills prior to study inclusion.Results:In the total cohort, AMH was inversely correlated with age (r = -0.24; P < 0.001). The age at which the maximum AMH value was attained was at 15.8 yr. In girls younger than 15.8 yr, serum AMH and age were positively correlated (r = +0.18; P = 0.007). Thereafter AMH levels remained stable (r = -0.33; P = 0.66), whereas from the age of 25.0 yr onward, an inverse correlation between AMH and age (r = -0.47; P < 0.001) was observed. At any given age, considerable interindividual differences in serum AMH levels were observed.Conclusion:During infancy AMH levels increase, whereas during adolescence, a plateau until the age of 25 yr was observed. From the age of 25 yr onward, serum AMH levels correlate inversely with age, implying that AMH is applicable as a marker of ovarian reserve only in women of 25 yr old and older. Our nomogram may facilitate counseling women on their reproductive potential.
    The Journal of Clinical Endocrinology and Metabolism 09/2012; · 6.31 Impact Factor

Publication Stats

4k Citations
943.02 Total Impact Points

Institutions

  • 2002–2014
    • Erasmus MC
      • • Department of Rheumatology
      • • Department of Endocrinology
      • • Department of Pediatrics
      Rotterdam, South Holland, Netherlands
  • 1990–2012
    • Erasmus Universiteit Rotterdam
      • • Department of Internal Medicine
      • • Department of Endocrinology
      Rotterdam, South Holland, Netherlands
  • 2009
    • Canisius-Wilhelmina Ziekenhuis
      Nymegen, Gelderland, Netherlands
  • 1994–2008
    • Het Oogziekenhuis Rotterdam
      Rotterdam, South Holland, Netherlands
  • 2007
    • Centre Hospitalier Universitaire de Toulouse
      Tolosa de Llenguadoc, Midi-Pyrénées, France
  • 2005
    • University of Leuven
      Louvain, Flanders, Belgium