Unravelling the clinical heterogeneity of undefined recurrent fever over time in the European registries on Autoinflammation.

BACKGROUND: Systemic autoinflammatory disorders (SAIDs) represent a growing spectrum of diseases characterized by dysregulation of the innate immune system. The most common pediatric autoinflammatory fever syndrome, Periodic Fever, Aphthous Stomatitis, Pharyngitis, Adenitis (PFAPA), has well defined clinical diagnostic criteria, but there is a subset of patients who do not meet these criteria and are classified as undefined autoinflammatory diseases (uAID). This project, endorsed by PRES, supported by the EMERGE fellowship program, aimed to analyze the evolution of symptoms in recurrent fevers without molecular diagnosis in the context of undifferentiated AIDs, focusing on PFAPA and syndrome of undifferentiated recurrent fever (SURF), using data from European AID registries. METHODS: Data of patients with PFAPA, SURF and uSAID were collected from 3 registries including detailed epidemiological, demographic and clinical data, results of the genetic testing and additional laboratory investigations with retrospective application of the modified Marshall and PRINTO/Eurofever classification criteria on the cohort of PFAPA patients and preliminary SURF criteria on uSAID/SURF patients. RESULTS: Clinical presentation of PFAPA is variable and some patients did not fit the conventional PFAPA criteria and exhibit different symptoms. Some patients did not meet the criteria for either PFAPA or SURF, highlighting the heterogeneity within these groups. The study also explored potential overlaps between PFAPA and SURF/uAID, revealing that some patients exhibited symptoms characteristic of both conditions, emphasizing the need for more precise classification criteria. CONCLUSIONS: Patients with recurrent fevers without molecular diagnoses represent a clinically heterogeneous group. Improved classification criteria are needed for both PFAPA and SURF/uAID to accurately identify and manage these patients, ultimately improving clinical outcomes.

Humoral and cellular immune response to tick-borne-encephalitis (TBE) vaccination depends on booster doses in patients with Juvenile Idiopathic Arthritis (JIA).

Juvenile Idiopathic Arthritis (JIA) patients living in areas with high prevalence of tick-borne-encephalitis-virus-(TBEV)-infection are recommended for administration of inactivated TBE-vaccination. However, there are serious concerns regarding protective vaccine-induced immune responses against TBEV in immunocompromised patients. The present study aimed to analyze the humoral and cellular immune response to TBE-vaccination in previously TBE-vaccinated JIA patients compared to healthy controls (HC) including investigation of IgG-anti-TBEV avidity, neutralization capacity, cellular reactivity by IFNgamma-ELISPOT and cytokine secretion assays. Similar IgG-anti-TBEV antibody concentrations, neutralization titers and cellular reactivity were found between JIA and HC. The number and the early timing of booster vaccinations after primary vaccination had the most prominent effect on neutralizing antibodies in JIA and on IgG-anti-TBEV concentrations in both JIA and HC. Administration of booster vaccinations made it more likely for JIA patients to have IgG-anti-TBEV concentrations ≥165 VIEU/ml and avidities >60%. TNF-alpha inhibitors had a positive and MTX administration a negative effect on humoral immune responses. In conclusion, irrespective of having JIA or not, vaccinated children showed similar humoral and cellular immunity against TBEV several years after primary TBE-vaccination. However, in JIA, booster vaccinations mounted a significantly higher humoral immune response than in JIA without boosters. Our results highlight the need for timely administration of boosters particularly in JIA. Although immunosuppressive treatment at vaccinations in diagnosed JIA had a negative effect mainly on TBEV-specific cellular immunity, most JIA patients mounted a favorable humoral immune response which was maintained over time. Thus, successful TBE-vaccination seems highly feasible in JIA patients with immunosuppressive regimens.

[Therapeutic options in juvenile idiopathic arthritis : Surgical and conservative orthopedic rheumatological treatment]. / Therapeutische Optionen bei juveniler idiopathischer Arthritis : Operative und konservative orthopädisch-rheumatologische Behandlung.

The treatment of juvenile idiopathic arthritis (JIA) has made substantial progress within the last 25 years. Modern medicinal treatment enables inflammatory activity of the disease to be controlled in most of the cases. Mutilating courses of disease, which were formerly the rule have now become the exception. Today remission of disease is the aim of pediatric rheumatological treatment. Apart from effective control of inflammation this includes complete restoration of functional abilities of affected joints and the surrounding structures also affected. To achieve this goal a holistic and foresighted view of each patient's course is required. Therefore, even in an apparently uncomplicated course of disease in some cases of JIA it is advisable to plan an early interdisciplinary consultation including the pediatric rheumatologist and the orthopedic surgeon, in order to discuss an early surgical intervention, which can then be carried out in a timely manner, if necessary. This article provides an overview of the orthopedic rheumatological indications and options.

[Rheumatic pain and chronic pain in children, adolescents and young adults]. / Rheumaschmerz und chronischer Schmerz bei Kindern, Jugendlichen und jungen Erwachsenen.

BACKGROUND: Rheumatic diseases, such as juvenile idiopathic arthritis (JIA), are typically associated with acute pain mainly caused by inflammation. Chronic pain is described as pain lasting at least 3 months. In JIA patients chronic pain may occur despite successful treatment. Chronic pain and pain disorders frequently occur during the course of the disease despite successful control of inflammation. OBJECTIVE: Possible interrelations between JIA and pain disorders are presented. METHOD: Besides a review of the available literature, a retrospective cohort study was conducted, including 906 patients with a chronic pain disorder with somatic and psychological factors (CPD) and/or a complex regional pain syndrome type I (CRPS I). The frequency of pre-existing rheumatic illnesses was analyzed. RESULTS: The JIA is a risk factor for the development of a CPD. Especially polyarticular, extended oligoarticular, enthesitis-associated JIA and psoriatic arthropathy were found to be significantly associated with an increased risk for developing CPD. In contrast, an increased risk for development of CRPS I was not observed. CONCLUSION: Our study demonstrates JIA to be a risk factor for the development of chronic pain not only as a result from malpositioning or arthrosis but also as a chronic pain disorder (CPD). Further studies are necessary to clarify the relevance of disease activity and duration and also of psychological factors for the pathogenesis.

[Injuries in children and adolescents with inflammatory rheumatic diseases : Special risks and techniques for fracture treatment of the growing skeleton]. / Verletzungen bei Kindern und Jugendlichen mit entzündlich rheumatischen Erkrankungen : Besondere Risiken und Techniken der Frakturversorgung am wachsenden Skelett.

BACKGROUND: Inflammatory rheumatic diseases in childhood and adolescence are a special challenge in the treatment of acute trauma. The pharmaceutical treatment strategies for children and adolescents have been modified. OBJECTIVE: Which special aspects must be considered in young patients suffering from rheumatism when a trauma necessitates an operative procedure? MATERIAL AND METHOD: A literature search was carried out to elaborate recommendations for the practice. RESULTS: The joint-related alterations in young patients suffering from rheumatism differ with respect to the differently altered inflammatory rheumatic destruction. The extent of these inflammatory destructive alterations dictates the operative approach. Consequences arise in paying attention to the concurrent medication with respect to avoidance of events triggering an exacerbation and tissue infections. The bone strength necessitates an individualized selection of implants and sometimes influences the duration of follow-up treatment. In the early stages of the inflammatory process the approach in cases of trauma is no different to that for healthy patients but in later stages (Larsen stage III) it does differ. CONCLUSION: An interdisciplinary concept can help to avoid disadvantages in the treatment of the underlying disease. Due to the special dysplastic anatomy and tissue alterations, trauma in these patients is a particular challenge.

Adalimumab versus adalimumab and methotrexate for the treatment of juvenile idiopathic arthritis: long-term data from the German BIKER registry.

OBJECTIVE: Adalimumab (ADA) has become a valuable treatment option for juvenile idiopathic arthritis (JIA). The importance of combination with methotrexate (MTX) is unclear. METHOD: Data from the German Biologics in Paediatric Rheumatology (BIKER) registry are reported. Response to treatment was analysed using JIA American College of Rheumatology (ACR) scores, 10-joint Juvenile Arthritis Disease Activity Score (JADAS10), and improvement of functional status and ACR inactive disease criteria. Compa-risons between rates of adverse events (AEs) and serious adverse events (SAEs) provided data for the safety assessment. RESULTS: Overall, 584 patients with non-systemic JIA started ADA therapy, 61% of whom received concomitant MTX treatment at baseline. The latter patients were younger (p < 0.001), with shorter disease duration (p = 0.001), more frequently had antinuclear antibodies (p = 0.04), and had higher baseline JADAS10 scores (p = 0.03). In patients with ADA monotherapy, enthesitis-related arthritis (p = 0.004) and presence of human leucocyte antigen-B27 (p = 0.008) were documented more often. Mean treatment duration in both cohorts was 15 months. Comparable last follow-up rates for JIA ACR 30/50/70/90% response, JADAS minimal disease activity, JADAS remission, and ACR inactive disease were, respectively, 75/72/64/49%, 66%, 46%, and 58% for ADA monotherapy, and 77/72/61/45%, 64%, 48%, and 55%, for ADA + MTX. During 1082 patient-years (PY) of ADA exposure, 725 AEs (67/100 PY), including 57 SAEs (5.3/100 PY), were reported. Serious infections were reported in 10 patients (0.9/100 PY) and 11 (1.0/100 PY) had varicella infections/zoster reactivation. Rates of AEs, SAEs, infectious events, and serious infections did not differ between the cohorts. Elevated transaminases (p = 0.005) and gastrointestinal events (p < 0.0001) were reported more often in the combination cohort. Two pregnancies and no deaths were reported. CONCLUSION: ADA demonstrated an acceptable risk profile and high percentages of patients in both cohorts showed sufficient treatment response. No differences in treatment response or adherence to treatment were found.

[Treatment options in juvenile idiopathic arthritis : Part 2: Orthopedics und surgery]. / Therapeutische Optionen bei juveniler idiopathischer Arthritis : Teil 2: Orthopädische und chirurgische Behandlung.

In most cases of juvenile idiopathic arthritis (JIA), disease remission can be achieved by a multidisciplinary approach using modern medication. However, JIA is currently incurable An interdisciplinary concept is therefore needed for long-term development of affected joints and tendons. Only early interdisciplinary treatment strategies can improve long-term outcomes in patients with a complicated disease course or persistent disease activity, thereby delaying or even avoiding joint replacement. An early interdisciplinary assessment and treatment planning according to surgical orthopedic rheumatology aspects is now state of the art and will continue to be in the future, especially in treatment-refractory disease courses.

[Therapeutic options in juvenile idiopathic arthritis : Part 1: Nonsurgical treatment]. / Therapeutische Optionen bei juveniler idiopathischer Arthritis : Teil 1: Konservative Behandlung.

The treatment of children and adolescents with juvenile idiopathic arthritis (JIA) has progressed substantially during recent years. Multiple different factors have played a role in this advancement: improved medical treatment due to the introduction of new drugs, structural improvements with provision of units specializing in childhood rheumatology, multidisciplinary treatment concepts, structured educational programs for patients and parents, improved functional treatment including sports therapy, and selective surgical and orthopedic interventions improving functional capacities. Current treatment strategies in JIA are aimed at achieving disease remission, i.e., control of disease activity and re-establishment of age-appropriate functional capacities. This review summarizes important developments in the conservative treatment of JIA. Part 2 deals with orthopedic and surgical treatment strategies.

[Back to school physical education despite rheumatism : Development and testing of a sport scientific-based physical education certification]. / Zurück in den Schulsport trotz Rheuma : Entwicklung und Überprüfung einer sportwissenschaftlich basierten Schulsportbescheinigung.

BACKGROUND: Taking part in physical education is an important element of social participation for children with chronic diseases. Nevertheless, children suffering from rheumatism mostly receive recommendations to stop sport activities either completely or partially, without underlying scientific guidelines. OBJECTIVE: The aim was the development of an IT-tool based on scientific data in order to create individualized recommendations for sport activities plus verification of its practical feasibility. MATERIAL AND METHODS: An interdisciplinary group of experts developed and approved a prototype of the rheumatism and sports compass (Rheuma und Sport Kompass, RSK) based on the literature and own experience. They considered individual health factors and biomechanics of sports functions. The prototype was tested, revised and reconsidered in an interim evaluation. The resulting RSKv1 was evaluated in a clinical observation phase with 61 patients. The results were subsequently incorporated into the final version of RSK during an interdisciplinary decision-making process. This was verified in a feasibility study with a follow-up survey of rheumatic patients with a RSK partial participation certification for physical education including: clinical assessment during 8 lessons of physical education and after 8 lessons of physical education. Teachers rated the RSK online after 8 lessons. The evaluation was descriptive and differences in mean values were tested. RESULTS AND DISCUSSION: In this study 50 patients and 31 teachers were evaluated. The affliction of pain decreased in terms of frequency, amount and duration after physical education with RSK. No worsening in health was reported after participation in sports. The teachers rated the RSK as understandable, practicable and they felt confident to allow the patients to participate in classes. The RSK was rated significantly better than a standard certification text. With the RSK, patients can be advised to safely take part in physical education.

IL-6 blockade in systemic juvenile idiopathic arthritis - achievement of inactive disease and remission (data from the German AID-registry).

BACKGROUND: Systemic juvenile idiopathic arthritis (sJIA) is a complex disease with an autoinflammatory component of unknown etiology related to the innate immune system. A major role in the pathogenesis has been ascribed to proinflammatory cytokines like interleukin-6 (IL-6), and effective drugs inhibiting their signaling are being developed. This study evaluates sJIA patients treated with the IL-6 inhibitor tocilizumab (TCZ) concerning clinical response rate, disease course and adverse effects in a real-life clinical setting. METHODS: In 2009 a clinical and research consortium was established, including an online registry for autoinflammatory diseases (AID) ( https://aid-register.de ). Data for this retrospective TCZ study were documented by 13 centers. RESULTS: From 7/2009 to 4/2014, 200 patients with sJIA were recorded in the AID-registry. Out of these, 46 (19 m, 27 f, age 1-18 years) received therapy with TCZ. Long term treatment (median 23 months) has been documented in 24/46 patients who were evaluated according to Wallace criteria (active disease 6/24, inactive disease 5/24, remission 13/24 cases). Under observation co-medication were used in 40/46 cases. Adverse events were reported in 11/46 patients. The clinical response rate (no clinical manifestation, no increased inflammation parameters) within the first 12 weeks of treatment was calculated to be 35%. CONCLUSION: Out of 200 sJIA children reported in the German AID-registry, 46 were treated with TCZ, showing a clinical response rate of 35% during the first 12 weeks, and inactive disease and/or remission under medication in 75% after one year. Adverse events were seen in 24% and severe adverse events in 4%. TRIAL REGISTRATION: The AID-Registry is funded by the BMBF (01GM08104, 01GM1112D, 01GM1512D).

Fine-mapping the MHC locus in juvenile idiopathic arthritis (JIA) reveals genetic heterogeneity corresponding to distinct adult inflammatory arthritic diseases.

OBJECTIVES: Juvenile idiopathic arthritis (JIA) is a heterogeneous group of diseases, comprising seven categories. Genetic data could potentially be used to help redefine JIA categories and improve the current classification system. The human leucocyte antigen (HLA) region is strongly associated with JIA. Fine-mapping of the region was performed to look for similarities and differences in HLA associations between the JIA categories and define correspondences with adult inflammatory arthritides. METHODS: Dense genotype data from the HLA region, from the Immunochip array for 5043 JIA cases and 14 390 controls, were used to impute single-nucleotide polymorphisms, HLA classical alleles and amino acids. Bivariate analysis was performed to investigate genetic correlation between the JIA categories. Conditional analysis was used to identify additional effects within the region. Comparison of the findings with those in adult inflammatory arthritic diseases was performed. RESULTS: We identified category-specific associations and have demonstrated for the first time that rheumatoid factor (RF)-negative polyarticular JIA and oligoarticular JIA are genetically similar in their HLA associations. We also observe that each JIA category potentially has an adult counterpart. The RF-positive polyarthritis association at HLA-DRB1 amino acid at position 13 mirrors the association in adult seropositive rheumatoid arthritis (RA). Interestingly, the combined oligoarthritis and RF-negative polyarthritis dataset shares the same association with adult seronegative RA. CONCLUSIONS: The findings suggest the value of using genetic data in helping to classify the categories of this heterogeneous disease. Mapping JIA categories to adult counterparts could enable shared knowledge of disease pathogenesis and aetiology and facilitate transition from paediatric to adult services.

[Pain syndrome of the musculoskeletal system in children and adolescents]. / Schmerzsyndrome des Bewegungsapparates bei Kindern und Jugendlichen.

Chronic pain syndromes in children and adolescents are defined as continuous or recurrent pain without an underlying causative diagnosis and lasting for more than 3 months. It is estimated that every fourth child in Germany suffers from chronic pain with every twentieth suffering from extreme recurrent pain. The incidence of chronic pain in children and adolescents is increasing with headache, abdominal pain and musculoskeletal pain being the most frequent. The quality of life declines not only due to the pain but to relieving postural and psychological factors, such as fear and sadness. School attendance, social activities and hobbies are mostly affected. This review summarizes the background of chronic pain syndromes and introduces a multimodal therapeutic approach.

Leflunomide is associated with a higher flare rate compared to methotrexate in the treatment of chronic uveitis in juvenile idiopathic arthritis.

OBJECTIVES: Chronic anterior uveitis is a serious complication of juvenile idiopathic arthritis (JIA); disease flares are highly associated with loss of vision. Leflunomide (LEF) is used successfully for JIA joint disease but its effectiveness in uveitis has not been determined. The aim of this study was to determine whether LEF improves flare rates of uveitis in JIA patients compared to preceding methotrexate (MTX) therapy. METHOD: A single-centre retrospective study of consecutive children with JIA and chronic anterior uveitis was performed. All children initially received MTX and were then switched to LEF. Demographic, clinical, and laboratory data, dose and duration of MTX and LEF therapy, concomitant medications and rate of anterior uveitis flares, as determined by an expert ophthalmologist, were obtained. Flare rates were compared using a generalized linear mixed model with a negative binomial distribution. RESULTS: A total of 15 children were included (80% females, all antinuclear antibody positive). The median duration of MTX therapy was 51 (range 26-167) months; LEF was given for a median of 12 (range 4-47) months. Anti-tumour necrosis factor (anti-TNF-α) co-medication was given to four children while on MTX. By contrast, LEF was combined with anti-TNF-α treatment in six children. On MTX, JIA patients showed a uveitis flare rate of 0.0247 flares/month, while LEF treatment was associated with a significantly higher flare rate of 0.0607 flares/month (p = 0.008). CONCLUSIONS: Children with JIA had significantly more uveitis flares on LEF compared to MTX despite receiving anti-TNF-α co-medication more frequently. Therefore, LEF may need to be considered less effective in controlling chronic anterior uveitis.

[Incidence and duration of therapy of pathological hip findings in U2 and U3 examinations (SNiP study)]. / Inzidenz und Therapiedauer pathologischer Hüftbefunde im Rahmen der U2- und U3-Untersuchung (SNiP Studie).

INTRODUCTION AND OBJECTIVES: Determination of the efficacy of an early ultrasound examination followed by immediate treatment of hip joint dysplasia as well as measuring the therapeutic success in a population-based cohort study of neonates. MATERIAL AND METHODS: The Survey of Neonates in Pomerania (SNiP) study included 4,093 neonates which represents 95.1 % of the total neonatal population. Of these children 2,534 (61.9 %) underwent ultrasound examination of the hip joint during the U2 stage (3-10 days after birth). The mean gestational age was 38.9 weeks. The sonographic classification was performed according to Graf. RESULTS: Initially (U2 stage) 42 (1.66 %) children were reported to be in need of therapy (stage IIc or higher according to Graf). The analysis showed a significantly higher incidence in girls (32 girls vs. 10 boys, p < 0.023, χ(2) test) and in children who had a breech birth (116, 4.6 %). A genetic predisposition was ascertained in 180 (7.1 %) children. The children could be subdivided into two groups: 1) children who underwent hip joint ultrasound during both U2 and U3 and 2) children who were first screened at the U3 stage. Of the 49 out of 54 neonates where the ultrasound findings were positive at the U2 examination the hip joint was matured in 32 children at U3 (4-8 weeks), 11 children had to be treated for 8-12 weeks 5 children were treated for over 3 months and1 child needed surgical correction. CONCLUSION: The early diagnosis of hip maturation disorders and joint dysplasia facilitates early implementation of effective treatment. At our clinic over 60 % of the infants underwent the U2 check up and, given a pathological finding, could undergo early treatment. It was possible to successfully treat 78 % of these children with a Tübingen hip flexion splint in just 4-8 weeks. In contrast, infants who were first examined at the U3 stage needed treatment for 4-12 months. In our opinion, early diagnosis at the age of 3-10 days should be carried out for all newborns.

Genotype-phenotype and genotype-origin correlations in children with mediterranean fever in Germany - an AID-net study.

Familial Mediterranean fever (FMF) is the most inherited common autoinflammatory disease (AID) with mutations in the MEFV (MEditerraneanFeVer) gene.The Mor- and Pras-Score modified for children and C-reactive protein (CRP) were used to assess FMF disease severity in Germany. We evaluate the applicability of the 2 severity scores and the correlations between ethnic origin, phenotype, and genotype.Among 242 children (median 5 age at diagnosis), we detected 431 pyrin mutations and 22 different sequence variants, including one new mutation (p.Gly488Asp). The 5 most -frequent alterations were p.Met694Val (55.2%), p.Met680lle (11.8%), p.Val726Ala (10%), p.Glu148Gln (7.9%) and p.Met694IIe (2.3%). The prevailing ancestries of 223 cases were Turkish (82.5%) and Lebanese (8.1%). Homozygous p.Met694Val substitution (30.2%) was associated with a more severe disease activity by Mor-Score, as well as with a higher mean CRP (74 mg/l) compared to patients with other mutations. Indeed, Mor- and Pras-Score were inconsistent with each other. A typical distribution of mutations in different ethnic populations was obvious, but not statistically verifiable due to the low number of cases.The homozygous p.Met694Val substitution was associated with a more severe disease activity in our German cohort. The common severity scores were inconsistent in -children.

[Screening investigations during intensified immunosuppression in children and adolescents. Part 1]. / Vorsorgeuntersuchungen während intensivierter Immunsuppression bei Kindern und Jugendlichen. Teil 1.

The increasing use of combination therapies, including disease-modifying antirheumatic drugs (DMARD) and biologicals has improved the outcome for children and adolescents in several rheumatic diseases. However, this strategy has increased the risk of drug-specific side-effects, such as an increased risk of infections. Furthermore, the underlying rheumatic disease itself often includes an increased risk of infections and some patients additionally present with immunological or organic comorbidities (e.g. complement deficiency and interstitial pulmonary disease) further increasing the susceptibility to infections. The presented review is based on an analysis of the currently available literature proposing a checklist of diagnostic procedures and immunological laboratory tests specific for the detection of patients prone to infections. The combined stratification of the underlying disease, comorbidities and the immunological mechanisms of the medication enables (1) an individual risk stratification of planned immunosuppressive therapy and (2) a prediction of the risks of infection for the patient.

[Medicinal prophylaxis during intensified immunosuppression in children and adolescents : part 2]. / Medikamentöse Prophylaxe während intensivierter Immunsuppression bei Kindern und Jugendlichen : Teil 2.

The goal of modern antirheumatic therapy is to achieve an optimized disease control. This is individually achieved by an intensified immunosuppression (IS) frequently combining different immunosuppressive agents. Intensified IS should be accompanied by a standardized protocol to monitor immunological changes in the patient. This should include checklists (see Part 1 Screening during intensified IS in children and adolescents). An individual risk stratification according to the planned IS allows a prediction of infectious disease risks for the patient and, thus, individual infection prophylaxis. In addition, standardized management of patients with fever while receiving intensified IS may prevent further complications.

Ultrasound screening strategies for the diagnosis of congenital anomalies of the kidney and urinary tract.

PURPOSE: Congenital anomalies of the kidneys and urinary tract (CAKUT) are among the most common anomalies in newborn infants, and may cause chronic renal disease in newborns. We investigated the sensitivity and specificity of different ultrasound-based screening strategies for CAKUT. MATERIALS AND METHODS: Newborns (n = 4331) were analyzed for CAKUT in at least one ultrasound examination as a part of the Survey of Neonates in Pomerania (SNiP), a 7-year population-based study on neonates in Western Pomerania (Germany). Intrauterine ultrasound examinations were compared with early postnatal ultrasound findings (from days 3 - 7 of life) and pathological findings within the first 6 months of postnatal life. RESULTS: Cases of CAKUT were detected in 309 (3.7 %) kidneys in one ultrasound examination at the following points of time at least: (i) prenatally in 56 newborns (18.2 %), (ii) 3 - 7 days postnatally in 201 newborns (65.2 %) and (iii) in 52 newborns (17 %) during the 6-month follow-up. The prevalence was significantly higher in male infants, and hydronephrosis was found to be the most frequent obstructive nephropathy (83.3 %). Significant co-morbidity was observed with CNS malformations. The diagnostic sensitivity was significantly higher in postnatal ultrasound screening (79.6 vs. 18.2 % prenatally), while the specificity was above 99 % at all time points. CONCLUSION: This study demonstrates a high prevalence of CAKUT and demonstrates the importance of combined prenatal and postnatal ultrasound examinations for early CAKUT diagnosis.