The aim of this study was (1) to prospectively evaluate the nationwide implementation of the ESPGHAN-guidelines for the diagnosis of celiac disease (CD), (2) to investigate the incidence and... Show moreThe aim of this study was (1) to prospectively evaluate the nationwide implementation of the ESPGHAN-guidelines for the diagnosis of celiac disease (CD), (2) to investigate the incidence and clinical presentation of diagnosed childhood CD (0-14 years) in the Netherlands, and (3) to compare the findings with national survey data from 1975 to 1990 and 1993 to 2000 using the same approach. From 2010 to 2013, all practicing paediatricians were invited to report new celiac diagnoses to the Dutch Pediatric Surveillance Unit. Data were collected via questionnaires. A total of 1107 children with newly diagnosed CD were reported (mean age, 5.8 years; range, 10 months-14.9 years; 60.5% female). After the introduction of the non-biopsy approach in 2012, 75% of the diagnoses were made according to the guideline with a significant decrease of 46.3% in biopsies. The use of EMA and HLA-typing significantly increased with 25.8% and 62.1%, respectively. The overall incidence rate of childhood CD was 8.8-fold higher than in 1975-1990 and 2.0-fold higher than in 1993-2000. During the study period, the prevalence of diagnosed CD was 0.14%, far below 0.7% of CD identified via screening in the general Dutch paediatric population. Clinical presentation has shifted towards less severe and extra-intestinal symptoms.Conclusion: ESPGHAN guidelines for CD diagnosis in children were effectively and rapidly implemented in the Netherlands. Incidence of diagnosed CD among children is still significantly rising with a continuous changing clinical presentation. Despite the increasing incidence of diagnoses, significant underdiagnosis still remains.What is Known:Since 2000 the incidence of diagnosed childhood CD in the Netherlands has shown a steady rise.The rise in incidence has been accompanied by a changing clinical presentation at diagnosis.What is New:The ESPGHAN guidelines 2012 for CD diagnosis were effectively and rapidly implemented in the Netherlands.The incidence of diagnosed childhood CD in the Netherlands has continued to rise significantly during the reported period. Show less
Background Mid-upper arm circumference (MUAC) is suggested as being a valid measure in detecting overweight/obesity in children and adolescents, due to the strong relation with weight. We examined... Show moreBackground Mid-upper arm circumference (MUAC) is suggested as being a valid measure in detecting overweight/obesity in children and adolescents, due to the strong relation with weight. We examined this relation and compared MUAC to body mass index (BMI) according to the International Obesity Task Force (IOTF) in children.Methods Anthropometric data including MUAC were collected in 2009 by trained healthcare professionals in the context of the fifth Dutch Nationwide Growth Study, in a sample of 6167 children (2891 boys and 3276 girls) aged 2-18 years of Dutch origin. We propose MUAC SDS cut-off values for overweight and obesity, and compared MUAC with BMI IOTF in sex-specific and age-specific categories (2-5, 6-11, 12-18 years).Results The area under the curve is used as a measure of diagnostic accuracy; the explained variance (R-2) is good to excellent (0.88-0.94). Sensitivity ranges from 51.8% to 95.3% and specificity from 71.4% to 93.8%. Across age and gender groups, 65.1% to 89.0% participants are classified by both MUAC and BMI as normal weight, overweight or obese. We constructed three equations to predict weight using MUAC, with small differences between observed and predicted weight with an explained variance ranging from 0.88 to 0.94.Conclusions Compared with BMI, MUAC is a valid measure for detecting overweight and obesity and thus a good alternative for BMI. When weight has to be estimated, it can be accurately predicted using MUAC. Based on our observations, we recommend developing diagrams with international (IOTF) cut-offs for MUAC SDS similar to BMI. Show less
Akkermans, M.D.; Vreugdenhil, M.; Hendriks, D.M.; Berg, A. van den; Schweizer, J.J.; Goudoever, J.B. van; Brus, F. 2017
OBJECTIVE Subfertility has been reported as a long-term complication of unrecognized and/or untreated coeliac disease (CD); however, the results from studies on this topic are ambiguous. We aimed... Show moreOBJECTIVE Subfertility has been reported as a long-term complication of unrecognized and/or untreated coeliac disease (CD); however, the results from studies on this topic are ambiguous. We aimed to determine the prevalence of unrecognized CD in subfertile male-female couples visiting a fertility clinic compared with the general population. METHODS Subjects included 1038 male-female couples (n = 2076) who visited the fertility clinic of the Leiden University Medical Center in the Netherlands between 2003 and 2009. All consecutive patients were routinely, serologically screened, and those with positive test results for antibodies against IgA anti-tissue transglutaminase type 2 and IgA endomysial antibodies were considered to have unrecognized CD. Clinical data on gender, age, height, weight, diagnosis of subfertility, and previously diagnosed CD were collected from the clinical files. Subsequently, after serological screening, all patients were anonymized. The prevalence of unrecognized CD was compared with the one in the general adult population in the Netherlands (0.35%). RESULTS The prevalence of unrecognized CD in subfertile male-female couples was 0.48% (10/2076; 6 females and 4 males) and was not significantly more frequent compared with the general population. Compared with the control group, similar CD prevalences were found within the different subfertility categories separately: unexplained subfertility, anovulation, tubal pathology, and male factor (p = NS). CONCLUSION In our large study cohort of subfertile male-female couples, the prevalence of unrecognized CD is comparable to the general population in the Netherlands. No association was observed between CD and subfertility in the different subfertility categories and genders. Show less
P>Background Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). Aim To evaluate the long-term efficacy of... Show moreP>Background Infliximab is effective for induction and maintenance of remission in children with moderately to severely active Crohn's disease (CD). Aim To evaluate the long-term efficacy of infliximab treatment in paediatric CD. Methods In this observational, multicentre study, all paediatric CD patients in The Netherlands treated with infliximab from October 1992 to November 2009 and with minimal follow-up of 3 months since start of infliximab, were studied. Results One hundred and fifty-two CD patients [81M; median age at start of infliximab 15.0 years (IQR 13.1-16.4)] received a median number of 10.5 infliximab infusions (IQR 6-21). Median follow-up after start of infliximab was 25 months (IQR 13-40). Kaplan-Meier analysis showed that the cumulative probability of losing response to infliximab in patients who initially required repeated infusions was 13%, 40% and 50% after 1, 3 and 5 years, respectively. Seventy-four patients (49%) needed dose adjustments, with a median time to any adjustment of 6 months. Conclusions Duration of effect of infliximab is limited as 50% of patients on infliximab maintenance treatment lose their therapeutic response after 5 years. Dose adjustments after start of infliximab are frequently needed to regain therapeutic benefit. These findings emphasise the need for effective, long-term treatment strategies for paediatric CD. Show less
We performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P-GWAS < 10(-4)... Show moreWe performed a second-generation genome-wide association study of 4,533 individuals with celiac disease (cases) and 10,750 control subjects. We genotyped 113 selected SNPs with P-GWAS < 10(-4) and 18 SNPs from 14 known loci in a further 4,918 cases and 5,684 controls. Variants from 13 new regions reached genome-wide significance (P-combined < 5 x 10(-8)); most contain genes with immune functions (BACH2, CCR4, CD80, CIITA-SOCS1-CLEC16A, ICOSLG and ZMIZ1), with ETS1, RUNX3, THEMIS and TNFRSF14 having key roles in thymic T-cell selection. There was evidence to suggest associations for a further 13 regions. In an expression quantitative trait meta-analysis of 1,469 whole blood samples, 20 of 38 (52.6%) tested loci had celiac risk variants correlated (P < 0.0028, FDR 5%) with cis gene expression. Show less
