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Noera Kieviet,1 Koert M Dolman,1 Adriaan Honig2 1Department of Paediatrics, 2Department of Psychiatry, Psychiatry Obstetrics Paediatrics Expert Center, Sint Lucas Andreas Hospital, Amsterdam, The Netherlands Abstract: Infants are at risk of developing symptoms of Poor Neonatal Adaptation (PNA) after exposure to psychotropic drugs in utero. Such symptoms are largely similar after exposure to antidepressants, antipsychotics and benzodiazepines and consist of mostly mild neurologic, autonomic, respirator and gastro-intestinal abnormalities. Most symptoms develop within 48 hours after birth and last for 2–6 days. After exposure to Selective Serotonin Reuptake Inhibitors (SSRIs), mirtazapine or venlafaxine in utero, breastfeeding is presumably protective for development of PNA. The dosage of antidepressants does not seem to be related to the risk of PNA. In order to objectify possible symptoms of PNA, observation of mother and child at the maternity ward is advisable. If PNA symptoms do not occur, an observation period of 48–72 hours is sufficient. This applies to all types of psychotropic drugs. When PNA symptoms are present it is advisable to observe the infant until the symptoms are fully resolved. Observation can be performed by trained nurses using the Finnegan scoring list. This observation list should be administered every 8 hours. Interpretation of the scores should be carried out by a paediatrician. In most cases symptoms are non-specific. Therefore other diagnoses, such as infection or neurologic problems, have to be excluded. When there is any doubt on possible intoxications during pregnancy, toxicological urine screening is indicated. Most cases of PNA are mild, of short duration and self-limiting without need for treatment. Supporting measures such as frequent small feedings, swaddling and increase of skin to skin contact with the mother is usually sufficient. In case of severe PNA it is advised to admit the infant to the Neonatal Care Unit (NCU). Phenobarbital is a safe therapeutic option. There seem to be no major long term effects; however, additional studies are necessary in order to draw definite conclusions. Keywords: withdrawal, neonatal abstinence, psychiatric disorders, SSRI, antidepressants

Background: Double inversion recovery (DIR) MRI has the potential to accentuate the synovium without using contrast agents, as it allows simultaneous signal suppression of fluid and fat. The purpose of this study was (1) to compare DIR MRI to conventional contrast-enhanced (CE) MRI for delineation of the synovium in the knee in children with juvenile idiopathic arthritis (JIA) and (2) to assess the agreement between DIR MRI and CE-MRI regarding maximal synovial thickness measurements., Results: In this prospective study, 26 children with JIA who consecutively underwent 3.0-T knee MRI between January 2018 and January 2021 were included (presence of knee arthritis: 13 [50%]; median age: 14 years [interquartile range [IQR]: 11-17]; 14 girls). Median confidence to depict the synovium (0-100 mm visual analogue scale; scored by 2 readers [consensus based]) was 88 (IQR: 79-97) for DIR MRI versus 100 (IQR: 100-100) for CE-MRI (p value = < .001). Maximal synovial thickness per child (millimeters; scored by 4 individual readers) on DIR MRI was greater (p value = < .001) in the children with knee arthritis (2.4 mm [IQR: 2.1-3.1]) than in those without knee arthritis (1.4 mm [IQR: 1.0-1.6]). Good inter-technique agreement for maximal synovial thickness per child was observed (r s  = 0.93 [p value = < .001]; inter-reader reliability: ICC DIR MRI = 0.87 [p value = < .001], ICC CE-MRI = 0.90 [p value = < .001])., Conclusion: DIR MRI adequately delineated the synovium in the knee of children with JIA and enabled synovial thickness measurement similar to that of CE-MRI. Our results demonstrate that DIR MRI should be considered as a child-friendly alternative to CE-MRI for evaluation of synovitis in children with (suspected) JIA., (© 2022. The Author(s).)

To directly compare and describe the differences between juvenile idiopathic arthritis (JIA) patients and pediatric controls regarding features of the synovial and tenosynovial membrane on contrast-enhanced magnetic resonance imaging (MRI) of the wrist. T1-weighted contrast-enhanced MRI scans of 25 JIA patients with clinically active wrist arthritis and 25 children without a history of joint complaints nor any clinical signs of joint inflammation were evaluated by two readers blinded to clinical data. The synovium was scored at five anatomical sites based on thickening of the synovium (0-3 scale) and synovial enhancement (0-2 scale). Thickening and/or enhancement of the tenosynovium was scored at four anatomical sites using a 0-3 scale. Significantly higher scores for synovial thickening (median 4 vs. 1, p < 0.001) and synovial enhancement (median 4 vs. 1, p < 0.001) are found in the wrist of JIA patients as compared to controls. JIA patients experienced the highest synovial scores at the mid-/inter-carpal, 2nd -5th carpometacarpal, and radiocarpal joints. No significant difference in tenosynovial scores is found between both groups (median 0 vs. 0, p = 0.220). This study highlights the higher synovial thickening/enhancement scores on contrast-enhanced MRI of the wrist in JIA patients compared to pediatric controls. Tenosynovial thickening and/or enhancement was rarely present in both groups. In JIA patients, synovial thickening and enhancement were particularly present at three anatomical sites. These results substantially support rheumatologists and radiologists when navigating through MRI of the wrist in search for JIA disease activity., (© 2021. The Author(s).)

Background: Knowledge on the role of synovial signal intensity (SI) grading on static contrast-enhanced (CE) MRI of the knee for assessment of disease activity in juvenile idiopathic arthritis (JIA) is lacking., Objectives: To assess the value of synovial SI on static CE-MRI of the knee for evaluation of disease activity in children with JIA., Materials and Methods: Children with clinically inactive and clinically active JIA who underwent static CE-MRI of the knee were included. Synovial SI was evaluated on post-contrast T1-weighted fat-saturated images using a 0.02 cm 2 region of interest drawn in the area of the synovium that contained visually the highest SI. To control for potential time-dependent post-contrast enhancement variability, a ratio between the SI of the synovium to the musculus gastrocnemius was calculated., Results: We included 427 JIA patients (clinically inactive JIA: 150 [35,1%]; clinically active JIA: 277 [64.9%]), 65.3% female, with a mean age of 13.3 ± 3.2 years. Mean SI synovium-to-muscle ratio was 2.1 ± 0.7 in patients with clinically inactive JIA versus 2.2 ± 0.8 in patients with clinically active JIA. Subgroup analysis showed no significant difference in SI synovium-to-muscle ratio between JIA patients with clinically inactive disease and JIA patients with clinically active disease (p-value 0.22)., Conclusions: Evaluation of the brightness of the synovium on static CE-MRI of the knee for assessment of JIA disease activity should be avoided, as this might lead to incorrect clinical conclusions., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Chronic stress is often accompanied by alterations in the diurnal rhythm of hypothalamus-pituitary-adrenal activity. However, there are limited data on the diurnal rhythmicity of breast milk glucocorticoids (GCs) among women with psychological distress. We compared mothers who sought consultation at an expertise center for pregnant women with an increased risk of psychological distress with control mothers for GC diurnal rhythmicity in milk and saliva obtained at the same time., Methods: We included 19 mothers who sought consultation at the psychiatry-obstetric-pediatric (POP) outpatient clinic and 44 control mothers. One month postpartum, mothers collected on average eight paired milk and saliva samples during a 24 h period. GC levels were measured using liquid chromatography-tandem mass spectrometry. GC rhythmicity parameters were determined with specialized software., Results: For both milk and saliva, no group differences regarding GC rhythms were found. Milk cortisol area under the curve with respect to the ground was lower in the POP group than in the control group ( p = 0.02). GC levels in human milk and saliva were highly correlated within each group ( p < 0.001)., Conclusion: Although there were no differences between groups in GC rhythmicity, the total amount of milk cortisol was lower in the POP group. Long-term follow-up is needed to address the impact of vertical transmission of breast milk GCs.

Objective: To assess the psychometric properties of 8 pediatric Patient-Reported Outcomes Measurement Information System (PROMIS) item banks in a clinical sample of children with juvenile idiopathic arthritis (JIA)., Methods: A total of 154 Dutch children (mean ± SD age 14.4 ± 3.0 years; range 8-18 years) with JIA completed 8 pediatric version 1.0 PROMIS item banks (anger, anxiety, depressive symptoms, fatigue, pain interference, peer relationships, physical function mobility, physical function upper extremity) twice and the Pediatric Quality of Life Inventory (PedsQL) and the Childhood Health Assessment Questionnaire (C-HAQ) once. Structural validity of the item banks was assessed by fitting a graded response model (GRM) and inspecting GRM fit (comparative fit index [CFI], Tucker-Lewis index [TLI], and root mean square error of approximation [RMSEA]) and item fit (S-X 2 statistic). Convergent validity (with PedsQL/C-HAQ subdomains) and discriminative validity (active/inactive disease) were assessed. Reliability of the item banks, short forms, and computerized adaptive testing (CAT) was expressed as the SE of theta (SE[θ]). Test-retest reliability was assessed using intraclass correlation coefficients (ICCs) and smallest detectable change., Results: All item banks had sufficient overall GRM fit (CFI >0.95, TLI >0.95, RMSEA <0.08) and no item misfit (all S-X 2 P > 0.001). High correlations (>0.70) were found between most PROMIS T scores and hypothesized PedsQL/C-HAQ (sub)domains. Mobility, pain interference, and upper extremity item banks were able to discriminate between patients with active and inactive disease. Regarding reliability, PROMIS item banks outperformed legacy instruments. Post hoc CAT simulations outperformed short forms. Test-retest reliability was strong (ICC >0.70) for all full-length item banks and short forms, except for the peer relationships item bank., Conclusion: The pediatric PROMIS item banks displayed sufficient psychometric properties for Dutch children with JIA. PROMIS item banks are ready for use in clinical research and practice for children with JIA., (© 2019 The Authors. Arthritis Care & Research published by Wiley Periodicals, Inc. on behalf of American College of Rheumatology.)

Objective: To study two neutrophil activation markers, myeloid-related protein (MRP) 8/14 and neutrophil elastase (NE), for their ability to predict treatment response and flare in patients with JIA., Methods: Using samples from two cohorts (I and II), we determined MRP8/14 and NE levels of 32 (I) and 81 (II) patients with new-onset, DMARD-naïve arthritis and compared patients who responded to treatment (defined as fulfilling ≥ adjusted ACRpedi50 response and/or inactive disease) with non-responders (defined as fulfilling < adjusted ACRpedi50 response and/or active disease) at 6 and 12 months. Secondly, we compared biomarker levels of 54 (I) and 34 (II) patients with clinically inactive disease who did or did not suffer from a flare of arthritis after 6 or 12 months. Receiver operating characteristic analyses were carried out to study the predictive value of MRP8/14 and NE for treatment response and flare., Results: For both cohorts, baseline MRP8/14 and NE levels for patients who did or did not respond to treatment were not different. Also, MRP8/14 and NE levels were not different in patients who did or did not flare. Receiver operating characteristic analysis of MRP8/14 and NE demonstrated areas under the curve <0.7 in both cohorts., Conclusion: In our cohorts, MRP8/14 and NE could not predict treatment response. Also, when patients had inactive disease, neither marker could predict flares., (© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Background: Knowledge of the synovial and tenosynovial appearance of the clinically non-arthritic symptomatic juvenile wrist using contrast-enhanced magnetic resonance imaging (MRI) is sparse., Objectives: To analyze contrast-enhanced MRI findings of the clinically non-inflamed symptomatic pediatric wrist, focusing on the enhancing synovial and tenosynovial membrane. To evaluate the coexistent presence of (teno)synovial enhancement, joint fluid, bony depressions and medullary changes suggestive of bone marrow edema., Materials and Methods: We included 20 children (15 girls; age range: 7.5-17.6 years) who underwent contrast-enhanced MRI of the wrist, based on initial clinical indication, and eventually turned out to be unaffected by arthritic or orthopedic disorders. Various imaging characteristics of the synovium, tenosynovium, joint fluid, bone tissue and bone marrow were evaluated using existing MRI scoring systems., Results: In 3/20 (15%) children, mild or moderate-severe synovial enhancement was observed and 2/20 (10%) children showed mild tenosynovial enhancement/thickening. Joint fluid (11/20 children; 55%), bony depressions (20/20 children; 100%) and medullary changes suggestive of bone marrow edema (6/20; 30%) were found in a substantial percentage of children. The most frequently observed combination of coexisting imaging characteristics was bony depressions with ≥2 mm joint fluid, which was found in 7/20 (35%) children. Simultaneous presence of synovial and tenosynovial enhancement/thickening, bony depressions and medullary changes suggestive of bone marrow edema was observed in one child., Conclusion: Several juvenile idiopathic arthritis-relevant MRI characteristics can be observed in the clinically non-inflamed symptomatic pediatric wrist.

Purpose: In previous studies, associations between breast-milk cortisol levels obtained on one occasion and infant neurodevelopment were demonstrated. However, more recent evidence indicates that breast-milk cortisol and cortisone concentrations follow the diurnal rhythm of maternal hypothalamus-pituitary-adrenal axis, peaking in the early morning and with a nadir at midnight. We studied associations between breast-milk glucocorticoid (GC) rhythmicity, and infant behavior and sleep., Methods: We included 59 mothers, and their infants, of whom 17 had consulted an expert center during pregnancy for an increased risk of psychological distress. At 1 month postpartum, breast milk was sampled (on average six times) over a 24 h period for assessment of cortisol and cortisone using LC-MS/MS, and experienced maternal distress was assessed using the Hospital Anxiety and Depression Scale questionnaire. Three months after birth, infant behavior was assessed with the Infant Behavior Questionnaire, and infant sleep pattern was quantified by questionnaire. Associations between breast-milk GC rhythm parameters (maximum, delta, and Area Under the Curve increase and ground) and infant behavior and sleep were tested with linear regression analyses., Results: No consistent associations between breast-milk GC rhythm parameters and infant behavior or sleep were found., Conclusions: Breast-milk GC rhythmicity at 1 month postpartum was not associated with infant behavior or sleep at the age of 3 months. Findings from previous studies linking breast-milk cortisol to infant neurodevelopment might be biased by the lack of GC measurements across the full diurnal cycle, and should therefore be interpreted with caution.

Background Diffusion-weighted imaging (DWI) can depict the inflamed synovial membrane in arthritis. Purpose To study the diagnostic accuracy of DWI for the detection of arthritis compared with the clinical reference standard and to compare DWI to contrast material-enhanced MRI for the detection of synovial inflammation. Materials and Methods In this institutional review board-approved prospective study, 45 participants with juvenile idiopathic arthritis (JIA) or suspected of having JIA (seven boys, 38 girls; median age, 14 years [interquartile range, 12-16 years]) were included between December 2015 and December 2018. Study participants underwent pre- and postcontrast 3.0-T MRI of the knee with an additional DWI sequence. For the clinical reference standard, a multidisciplinary team determined the presence or absence of arthritis on the basis of clinical, laboratory, and imaging findings (excluding DWI). Two data sets were scored by two radiologists blinded to all clinical data; data set 1 contained pre- and postcontrast sequences (contrast-enhanced MRI), and data set 2 contained precontrast and DWI sequences (DWI). Diagnostic accuracy was determined by comparing the scores of the DWI data set to those of the clinical reference standard. Second, DWI was compared with contrast-enhanced MRI regarding detection of synovial inflammation. Results Sensitivity for detection of arthritis for DWI was 93% (13 of the 14 participants with arthritis were correctly classified with DWI; 95% confidence interval [CI]: 64%, 100%) and specificity was 81% (25 of 31 participants without arthritis were correctly classified with DWI; 95% CI: 62%, 92%). Scores for synovial inflammation at DWI and contrast-enhanced MRI agreed in 37 of 45 participants (82%), resulting in a sensitivity of 92% (12 of 13 participants; 95% CI: 62%, 100%) and specificity of 78% (25 of 32 participants; 95% CI: 60%, 90%) with DWI when contrast-enhanced MRI was considered the reference standard. Conclusion Diffusion-weighted imaging (DWI) was accurate in detecting arthritis in pediatric participants with juvenile idiopathic arthritis (JIA) or suspected of having JIA and showed agreement with contrast-enhanced MRI. The results indicate that DWI could replace contrast-enhanced MRI for imaging of synovial inflammation in this patient group. © RSNA, 2020 Online supplemental material is available for this article.

Context: The hypothalamus-pituitary-adrenal (HPA) axis displays a diurnal rhythm. However, little is known about its development in early life., Objective: To describe HPA-axis activity and study possible influencing factors in 1-month-old infants., Design: Observational., Setting: Amsterdam University Medical Center, location VU University Medical Center (VUMC), and Onze Lieve Vrouwe Gasthuis (OLVG), Amsterdam., Participants: Fifty-five mother-infant pairs., Interventions: Collection of breast milk and infants' saliva 1 month postpartum for analysis of glucocorticoids (GCs; ie, cortisol and cortisone) using liquid chromatography- tandem mass spectrometry., Main Outcome Measure: GC rhythm in infants' saliva and associations with vulnerability for maternal psychological distress (increased Hospital Anxiety and Depression Scale [HADS] score) or consultation at the Psychiatric Obstetric Pediatric (POP clinic), season at sampling, sex, and breast milk GC rhythmicity analyzed with SigmaPlot 14.0 software (Systat Software, San Jose, CA, USA) and regression analyses., Results: A significant biphasic GC rhythm was detected in infants, with mean peaks [standard error of the mean, SEM] at 6:53 am [1:01] and 18:36 pm [1:49] for cortisol, and at 8:50 am [1:11] and 19:57 pm [1:13] for cortisone. HADS score, POP consultation, season at sampling, and sex were not associated with the infants' GC rhythm. Breast milk cortisol maximum was positively associated with infants' cortisol area-under-the-curve (AUC) increase and maximum. Higher breast milk cortisone AUC increase, AUC ground, and maximum were associated with an earlier maximum in infants. Breast milk and infant GC concentrations were associated between 6:00 am and 9:00 am., Conclusions: A biphasic GC rhythm, peaking in the morning and evening, was seen in 1-month-old infants at a group level. Breast milk GC parameters might be associated with the infants' GC rhythm, possibly caused by a signaling effect of breast milk GCs, or as an associative effect of increased mother-infant synchrony. These results contribute to an increased understanding of early life HPA-axis development., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Post-contrast synovial thickness measurement is necessary for scoring disease activity in juvenile idiopathic arthritis (JIA). However, the timing of post-contrast sequences varies widely among institutions. This variation in timing could influence thickness measurements., Objective: To measure thickness of the synovial membrane on early and late post-contrast knee magnetic resonance (MR) images of patients with JIA., Materials and Methods: Dynamic contrast-enhanced T1-weighted knee MR images of 53 children with JIA with current or past knee arthritis were used to study synovial thickness at time point 1 (about 1 min) and time point 2 (about 5 min after contrast administration). Two experienced readers, who were blinded for the time point, independently measured synovial thickness at a predefined, marked location in the patellofemoral compartment on randomized images. Synovial thickness at the two time points was compared using the Wilcoxon signed rank test. Repeatibility of the synovial thickness measurements was studied using intraclass correlation coefficients and Bland-Altman plots., Results: Median synovial thickness of the 53 patients (median age: 13.5 years, 59% female) increased with prolonged post-contrast interval with a synovial thickness of 1.4 mm at time point 1 and a synovial thickness of 1.5 mm at time point 2 (P<0.001). Repeated synovial thickness measurements showed an intraclass correlation coefficient (ICC) of 0.75, P<0.05 for time point 1 and an ICC of 0.91, P<0.05 for time point 2., Conclusion: Post-contrast synovial membrane thickness measurements are time-dependent. Therefore, standardization of post-contrast image acquisition timing is important to achieve consistent grading of synovial inflammation.

Objective: In a number of patients with clinically active juvenile idiopathic arthritis (JIA), contrast-enhanced MRI shows no signs of synovitis. The objective of this study was to assess the frequency and the patient characteristics in clinically active JIA patients in which MRI showed no signs of synovitis., Methods: From our cohort of 313 patients in which contrast-enhanced MRI of the knee had been performed, we selected 72 JIA patients with clinically active disease involving the target joint. The validated Juvenile Arthritis MRI Scoring (JAMRIS) system was used to evaluate synovial thickening. Patients were divided into two groups based on MRI outcome: Group 1: thickened synovium on MRI (JAMRIS score ≥1) or Group 2: normal synovium on MRI (JAMRIS score 0). Patient characteristics and disease activity parameters were then compared., Results: In 35% (25/72) of these patients, MRI results contrasted with the clinical assessment (Group 2). In comparison to Group 1, the patients with discrepant findings were significantly older at the date of examination and JIA had been diagnosed at later age (median age of 13.2 vs. 10.9 and median age 10.0 vs. 8.0 respectively). In Group 2 there were significantly more patients with RF-negative polyarticular disease., Conclusion: Patients with RF-negative polyarticular JIA who had been diagnosed at a later age and were older at the time of MRI were most likely to be considered clinically active while MRI showed no signs of synovitis. These particular JIA patients may benefit from monitoring of disease activity by MRI to prevent overtreatment., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Objective: Around one-third of patients with juvenile idiopathic arthritis (JIA) fail to respond to first-line methotrexate (MTX) or anti-tumor necrosis factor (TNF) therapy, with even fewer achieving ≥ American College of Rheumatology Pediatric 70% criteria for response (ACRpedi70), though individual responses cannot yet be accurately predicted. Because change in serum S100-protein myeloid-related protein complex 8/14 (MRP8/14) is associated with therapeutic response, we tested granulocyte-specific S100-protein S100A12 as a potential biomarker for treatment response., Methods: S100A12 serum concentration was determined by ELISA in patients treated with MTX (n = 75) and anti-TNF (n = 88) at baseline and followup. Treatment response (≥ ACRpedi50 score), achievement of inactive disease, and improvement in Juvenile Arthritis Disease Activity Score (JADAS)-10 score were recorded., Results: Baseline S100A12 concentration was measured in patients treated with anti-TNF [etanercept n = 81, adalimumab n = 7; median 200, interquartile range (IQR) 133-440 ng/ml] and MTX (median 220, IQR 100-440 ng/ml). Of the patients in the anti-TNF therapy group, 74 (84%) were also receiving MTX. Responders to MTX (n = 57/75) and anti-TNF (n = 66/88) therapy had higher baseline S100A12 concentration compared to nonresponders: median 240 (IQR 125-615) ng/ml versus 150 (IQR 87-233) ng/ml, p = 0.021 for MTX, and median 308 (IQR 150-624) ng/ml versus 151 (IQR 83-201) ng/ml, p = 0.002, for anti-TNF therapy. Followup S100A12 could be measured in 44/75 MTX-treated patients (34/44 responders) and 39/88 anti-TNF-treated patients (26/39 responders). Responders had significantly reduced S100A12 concentration (MTX: p = 0.031, anti-TNF: p < 0.001) at followup versus baseline. Baseline serum S100A12 in both univariate and multivariate regression models for anti-TNF therapy and univariate analysis alone for MTX therapy was significantly associated with change in JADAS-10., Conclusion: Responders to MTX or anti-TNF treatment can be identified by higher pretreatment S100A12 serum concentration levels.

Objectives: To define normative standards for the knee in healthy children using contrast-enhanced MRI, focusing on normal synovial membrane thickness. Secondly, presence of joint fluid and bone marrow oedema was evaluated., Methods: For this study, children without disorders potentially resulting in (accompanying) arthritis were included. Patients underwent clinical assessments, followed by contrast-enhanced MRI. MRI features were evaluated in consensus using the Juvenile Arthritis MRI Scoring (JAMRIS) system. Additionally, the presence of joint fluid was evaluated. No cartilage lesions or bone abnormalities were observed., Results: We included 57 healthy children. The overall mean thickness of the normal synovial membrane was 0.4 mm (min-max; 0.0-1.8mm). The synovium was thickest around the cruciate ligaments and retropatellar and suprapatellar regions. The mean overall diameter of the largest pocket of joint fluid was 2.8 mm (min-max; 0.9-8.0mm). Bone marrow changes were observed in three children (all in the apex patellae)., Conclusions: The normal synovial membrane was maximally 1.8 mm thick, indicating that the JAMRIS cut-off value of 2 mm can be considered a valid measure for evaluating synovial hypertrophy. Some joint fluid and bone marrow changes suggestive of bone marrow oedema in the apex patellae can be seen in healthy children., Key Points: • Knowledge on the normal synovial appearance using contrast-enhanced MR is lacking. • In healthy children, normal synovial membrane is maximally 1.8 mm thick. • Normal synovium is thickest around the cruciate ligaments, retropatellar and suprapatellar. • Bone marrow oedema in the apex patellae is seen in healthy children.

Background: Synovial thickening detected on magnetic resonance imaging (MRI) is present in a significant number of children with clinically inactive juvenile idiopathic arthritis (JIA)., Objective: To evaluate patient characteristics and disease activity parameters in a cohort of children with clinically inactive JIA, both with and without synovial thickening, in order to clarify the observed discrepancy between clinical and MRI assessments., Materials and Methods: We prospectively enrolled 52 clinically inactive JIA patients (median age 13.3 years, 63.5% girls) who underwent MRI of the knee as major target joint in JIA. Children were divided into two groups based on MRI outcome: group 1, with synovial thickening on MRI; and group 2, with no synovial thickening on MRI. We used the Juvenile Arthritis MRI Scoring system to evaluate synovial thickness. We compared patient characteristics and disease activity parameters between the groups., Results: Synovial thickening on MRI was present in 18 clinically inactive patients (group 1, 34.6%). The age was significantly lower for the patients in group 1 (median 10.7 versus 14.4, P=0.008). No significant differences were observed in any of the other patient characteristics nor the disease activity parameters tested., Conclusion: Synovial thickening on MRI was present in nearly 35% of the children with clinically inactive JIA. Children with synovial thickening on MRI were significantly younger than those without. This might indicate that younger patients are at risk of subclinical disease activity and under-treatment, although the exact clinical relevance of synovial thickening on MRI has not been determined.

Background: Hair glucocorticoids (GCs) offer a retrospective view on chronic GC exposure. We assessed whether maternal pre- and postnatal stress was associated with neonatal and maternal hair GCs postpartum (pp)., Methods: On the first day pp 172 mother-infant pairs donated hair, of whom 67 had consulted a centre of expertise for psychiatric disorders during pregnancy. Maternal stress was scored on the Hospital Anxiety and Depression Scale during the first/second (n = 46), third trimester (n = 57), and pp (n = 172). Hair cortisol and cortisone levels were determined by liquid chromatography-tandem mass spectrometry, and associations with maternal hospital anxiety subscale (HAS) and hospital depression subscale (HDS) scores, and antidepressant use were analyzed with linear regression., Results: Neonatal hair GCs were negatively associated with elevated HAS-scores during the first/second trimester, log 10 (β [95% CI]) cortisol -0.19 (-0.39 to 0.02) p = 0.07, cortisone -0.10 (-0.25 to 0.05) p = 0.17; third trimester, cortisol -0.17 (-0.33 to 0.00) p = 0.05, cortisone -0.17 (-0.28 to -0.05) p = 0.01; and pp, cortisol -0.14 (-0.25 to -0.02) p = 0.02, cortisone -0.07 (-0.16 to 0.02) p = 0.10. A similar pattern was observed for elevated HDS-scores. Maternal hair GCs were positively associated with elevated HAS-scores pp (cortisol 0.17 [0.01 to 0.32] p = 0.04, cortisone 0.18 [0.06 to 0.31] p = 0.01), but not prenatally or with elevated HDS-scores. Antidepressant use was associated with elevated maternal hair GCs (p ≤ 0.05), but not with neonatal hair GCs., Conclusion: Exposure to excessive pre- and perinatal maternal stress was associated with a decrease in neonatal hair GCs, while elevated stress-scores around birth were associated with increased maternal hair GCs and elevated stress-scores earlier in gestation were not associated with maternal hair GCs pp. Further studies are needed to test associations with infant neurodevelopment., (© 2018 S. Karger AG, Basel.)

Background: Glucocorticoids (GCs) measured in neonatal hair might reflect intrauterine as well as postpartum GC regulation. We aimed to identify factors associated with neonatal hair GC levels in early life, and their correlation with maternal hair GCs., Methods: In a single-center observational study, mother-infant pairs ( n  = 107) admitted for >72 h at the maternity ward of a general hospital were included. At birth and an outpatient visit (OPV, n  = 72, 44 ± 11 days postpartum), maternal and neonatal hair was analyzed for cortisol and cortisone levels by LC-MS/MS. Data were analyzed regarding: (1) neonatal GC levels postpartum and at the OPV, (2) associations of neonatal GC levels with maternal GC levels and (3) with other perinatal factors., Results: (1) Neonatal GC levels were >5 times higher than maternal levels, with a decrease in ±50% between birth and the OPV for cortisol. (2) Maternal and neonatal cortisol, but not cortisone, levels were correlated both at postpartum and at the OPV. (3) Gestational age was associated with neonatal GC postpartum (log-transformed β (95% CI): cortisol 0.07 (0.04-0.10); cortisone 0.04 (0.01-0.06)) and at the OPV (cortisol 0.08 (0.04-0.12); cortisone 0.00 (-0.04 to 0.04)), while weaker associations were found between neonatal GCs and other perinatal and maternal factors., Conclusions: Neonatal hair GCs mainly reflect the third trimester increase in cortisol, which might be caused by the positive feedback loop, a placenta-driven phenomenon, represented by the positive association with GA. Between birth and 1.5 months postpartum, neonatal hair cortisol concentrations decrease sharply, but still appear to reflect both intra- and extrauterine periods., (© 2017 The authors.)

Objectives: To compare dynamic-contrast-enhanced MRI (DCE) and diffusion-weighted imaging (DWI) in quantifying synovial inflammation in juvenile idiopathic arthritis (JIA)., Methods: Regions of interest (ROI) were drawn in the synovium of JIA patients on T1 DCE and T2 DWI, followed by extraction of the maximum enhancement (ME), maximum initial slope (MIS), time to peak (TTP), % of different time intensity curve shapes (TIC) and apparent diffusion coefficient (ADC) of the ROIs. Mann-Whitney-U test was used for comparing parameters between MRI-active and -inactive patients (defined by the juvenile arthritis MRI scoring system). Spearman's rank was used to analyse the correlation between DCE and DWI., Results: Thirty-five JIA patients (18 MRI active and 17 MRI inactive) were included. Median age was 13.1 years and 71% were female. ME, MIS, TTP, % TIC 5 and ADC were significantly different in MRI-active versus MRI-inactive JIA with median ADC 1.49 × 10 -3 mm 2 /s in MRI-active and 1.25 × 10 -3 mm 2 /s in MRI-inactive JIA, p = 0.001, 95% confidence interval of difference in medians =0.11-0.53 × 10 -3 mm 2 /s. ADC correlated to ME, MIS and TIC 5 shapes (r = 0.62, r = 0.45, r = -0.51, respectively, all p < 0.05)., Conclusions: Similar to DCE parameters, DWI-derived ADC is significantly different in MRI-active JIA as compared to MRI-inactive JIA. The non-invasiveness of DWI combined with its possibility to detect synovial inflammation shows the potential of DWI., Key Points: • MRI can quantify: dynamic contrast-enhanced and diffusion-weighted MRI can quantify synovitis • Both DWI and DCE can differentiate active from inactive JIA • The DWI-derived apparent diffusion coefficient (ADC) is higher in active JIA • DWI is non-invasive and thus safer and more patient-friendly • DWI is a potentially powerful and non-invasive imaging biomarker for JIA.

Objectives: To assess the capability of the pixel-by-pixel DCE-MRI time intensity curve (TIC)-shape analysis method in the evaluation of juvenile idiopathic arthritis (JIA) disease activity by correlating DCE-MRI parameters with semi-quantitative conventional-MRI scores of synovitis., Methods: Clinical, laboratory, and (DCE)-MRI datasets of 85 JIA patients were prospectively obtained. TIC-shapes of each voxel were classified into one of seven predefined color-coded TIC shape categories. Spatial information on the relative amount of TIC-shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV) was calculated of the synovial membrane. The grade of synovitis was scored on conventional MR images by two readers using the validated JAMRIS system. The Bonferroni method was used to correct for multiple testing, therefore, a P value of <0.0056 is considered significant (0.05/9=0.0056)., Results: The semi-quantitative JAMRIS synovitis score correlated substantially with the ME, EV, and iAUC (Rs=0.658, P<0.001; Rs=0.618, P<0.001; Rs=0.639, P<0.001), and moderately with MIS (Rs=0.453, P<0.001). A poor correlation was observed between the relative number of TIC-shapes 2-5 and the JAMRIS synovitis score (Rs=0.209, P=0.054; Rs=0.328, P=0.002; Rs=0.241, P=0.023; Rs=-0.241, P=0.026)., Conclusion: In this explorative study, both TIC shape and semi-quantitative DCE-MRI analysis methods showed moderate to substantial correlations with conventional MRI scores of disease activity, indicating that this methods are feasible. Further research is warranted whether DCE-MRI holds potential to become an objective and quantitative method for the evaluation of disease activity in JIA., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: The study was performed to determine whether conventional and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) parameters of a previously affected target joint in patients with clinically inactive juvenile idiopathic arthritis (JIA) have prognostic meaning for a flare of joint inflammation during follow-up., Material and Methods: Thirty-two JIA patients with clinically inactive disease at the time of MRI of the knee were prospectively included. DCE-MRI provided both descriptive measures and time-intensity-curve shapes, representing functional properties of the synovium. Conventional MRI outcome measures included validated scores for synovial hypertrophy, bone marrow edema, cartilage lesions and bone erosions. During a 2-year period the patients were monitored by their pediatric rheumatologist and clinical flares were registered., Results: MRI analysis revealed synovial hypertrophy in 13 (39.4%) of the clinically inactive patients. Twelve patients (37.5%) had at least one flare during 2-year clinical follow-up. Persistently inactive and flaring patients differed significantly in the maximum enhancement of the synovium on the DCE-MRI (p<0.05), whereas no difference was found between these two groups in any of the baseline scores of conventional MRI., Conclusions: Our prospective clinical follow-up study indicates that the assessment of 'maximum enhancement' upon DCE-MRI may be able to predict a clinical flare within 2 years in inactive JIA patients., (Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.)

Objective: Infants exposed to selective antidepressants (SADs) in utero are at risk to develop poor neonatal adaptation (PNA) postpartum. As symptoms are non-specific and the aetiology of PNA is unknown, the diagnostic process is hampered. We hypothesised that the serotonin metabolism plays a role in the aetiology of PNA., Methods: In this controlled study, infants admitted postpartum from February 2012 to August 2013 were included and followed for 3 days. Infants exposed to SADs during at least the last 2 weeks of fetal life were included in the patient group (n=63). Infants not exposed to psychotropic medication and admitted postpartum for another reason were included in the control group (n=126). The neonatal urinary 5-hydroxyindoleacetid acid (5-HIAA) levels of SAD-exposed infants who developed PNA, SAD-exposed infants who did not develop PNA and control infants were compared., Results: The course of the 5-HIAA levels over the first 3 days postpartum differed between infants with and without PNA (p≤0.001) with higher 5-HIAA levels in infants with PNA on day 1 (2.42 mmol/mol, p=0.001). Presence of maternal psychological distress modified this relationship., Conclusions: A transient disturbance of the neonatal serotonergic system may play a role in the aetiology of PNA. Other factors, including the presence of maternal psychological distress, also seem to play a role.

Background: Dynamic contrast-enhanced MRI provides information on the heterogeneity of the synovium, the primary target of disease in children with juvenile idiopathic arthritis (JIA)., Objective: To evaluate the feasibility of dynamic contrast-enhanced MRI in the wrist of children with JIA using conventional descriptive measures and time-intensity-curve shape analysis. To explore the association between enhancement characteristics and clinical disease status., Materials and Methods: Thirty-two children with JIA and wrist involvement underwent dynamic contrast-enhanced MRI with movement-registration and were classified using validated criteria as clinically active (n = 27) or inactive (n = 5). Outcome measures included descriptive parameters and the classification into time-intensity-curve shapes, which represent the patterns of signal intensity change over time. Differences in dynamic contrast-enhanced MRI outcome measures between clinically active and clinically inactive disease were analyzed and correlation with the Juvenile Arthritis Disease Activity Score was determined., Results: Comprehensive evaluation of disease status was technically feasible and the quality of the dynamic dataset was improved by movement registration. The conventional descriptive measure maximum enhancement differed significantly between clinically active and inactive disease (P = 0.019), whereas time-intensity-curve shape analysis showed no differences. Juvenile Arthritis Disease Activity Score correlated moderately with enhancing volume (P = 0.484)., Conclusion: Dynamic contrast-enhanced MRI is a promising biomarker for evaluating disease status in children with JIA and wrist involvement. Conventional descriptive dynamic contrast-enhanced MRI measures are better associated with clinically active disease than time-intensity-curve shape analysis., Competing Interests: Compliance with ethical standards Conflicts of interest None

Background: Psychiatric disorders and use of selective antidepressants during pregnancy can have negative effects on mother and infant postpartum. This study aimed to provide evidence-based recommendations on observation of antidepressant-exposed mother-infant dyads., Methods: In this observational study, mother-infant dyads were observed for possible consequences of either the maternal psychiatric disorder or fetal exposure to selective antidepressants during pregnancy. These possible complications can lead to medical interventions, including 1. adjustment of antidepressants 2. admission to the psychiatric department 3. additional investigations due to indistinctness about the origin of neonatal symptoms 4. treatment of poor neonatal adaptation and 5. consultation of an external organization for additional care. The type, number and time to medical interventions were analyzed., Results: In 61% of the 324 included mother-infant dyads one or more intrventions were performed. Adjustment of antidepressants and treatment of poor neonatal adaptation were most prevalent. In 75% of dyads the final intervention was performed within 48 h., Conclusions: The high prevalence and type of medical interventions requires professional observation of all mother-infant dyads exposed to selective antidepressants. In the absence of specialized home care, hospital admission is indicated whereby an observational period of 48 h seems sufficient for most dyads.

Background: As a marker for poor neonatal adaptation (PNA) is lacking, the diagnostic process is difficult and includes invasive additional testing., Aims: In order to develop a marker, it is essential to gain insight into the etiology of PNA. We hypothesized that the fetal cortisol level may play a role in this etiology., Study Design: Non-randomized, prospective controlled study., Outcome Measures: We examined hair cortisol levels of infants exposed and not exposed to selective antidepressants (SADs) during pregnancy. These cortisol levels represent the mean cortisol level during the last trimester of pregnancy. Infants exposed to SADs who developed PNA according to the pediatrician (PNA+, n=25), infants exposed to SADs who did not develop PNA (PNA-, n=40) and infants not exposed to SADs (controls, n=105) were compared., Results: In infants with PNA, hair cortisol levels were higher compared to infants without PNA. However this difference was only statistically significant in female infants (girls B0.33, p=0.04, boys B0.05, p=0.82). There was no correlation between nonspecific distress, measured by the Finnegan score and fetal hair cortisol levels (B-0.15, p=0.30). All analyses were adjusted for type of delivery and gestational age., Conclusions: Our results suggest that the hypothalamic pituitary adrenal (HPA) axis activity may play a sex-specific role in the development of PNA. As PNA is most likely of a multifactorial origin, it would be interesting to examine other factors possibly involved in the etiology of PNA in future studies, such as (epi) genetics., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Depression is common in pregnancy and associated with increased risk of adverse effects for the neonate. Treatment and prevention options include antidepressant therapy. The aim of this paper was to review the literature on safety of mirtazapine during pregnancy and lactation. In 31 papers a total of 390 cases of neonates exposed to mirtazapine during pregnancy or lactation have been described. There might be an association between mirtazapine and spontaneous abortion, however, this might be attributable to underlying psychiatric disease. An increased risk of major neonatal malformations associated with mirtazapine in pregnancy has not been reported. Although one study showed a nearly significant increase in occurrence of respiratory problems and hypoglycaemia, no indication of causality could be given. No other significant adverse effects on neonates were reported. Limited available data, four papers on 11 exposed neonates, suggest that use of mirtazapine during breastfeeding is safe due to a low relative infant dose. High plasma levels might be associated with increased body weight and sleep. However, the reported data are too scarce to come to a clear assessment of the risk of mirtazapine in lactation. No information is available on the use of mirtazapine in pregnancy and Poor Neonatal Adaptation Syndrome (PNAS) or neurobehavioral development at an age over one year. In conclusion, mirtazapine seems to be safe in pregnancy, especially regarding incidence of congenital malformations. There are not enough data available to come to a conclusion on the safety of mirtazapine during lactation., (Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.)

Objectives: To determine whether clinical, laboratory or Magnetic Resonance Imaging (MRI) measures differentiate Juvenile Idiopathic Arthritis (JIA) from other forms of active childhood arthritis., Materials and Methods: We prospectively collected data of 80 treatment-naïve patients clinically suspected of JIA with active non-infectious arthritis of (at least) one knee for <12 months duration. Upon presentation patients underwent clinical and laboratory assessments and contrast-enhanced MRI. MRI was not used as a diagnostic criterion., Results: Forty-four (55%) patients were clinically diagnosed with JIA, whereas in 36 (45%) patients the diagnosis of JIA was discarded on clinical or laboratory findings. MRI-based synovitis was present in 27 (61.4%) JIA patients and in 7 (19.4%) non-JIA patients (P < 0.001). Five factors (male gender, physician's global assessment of overall disease activity, joints with limited range of motion, HLA-B27, MRI-based synovitis) were associated with the onset of JIA. In multivariate analysis MRI-based synovitis proved to be independently associated with JIA (OR 6.58, 95% CI 2.36-18.33). In patients with MRI-based synovitis, the RR of having JIA was 3.16 (95% CI 1.6-6.4)., Conclusions: The presence of MRI-based synovitis is associated with the clinical onset of JIA. Physical examination could be supported by MRI, particularly to contribute in the early differentiation of different forms of non-infectious childhood arthritis., Key Points: • Juvenile Idiopathic Arthritis (JIA) is a diagnosis of exclusion. • Differentiating JIA and other forms of childhood arthritis can be difficult. • MRI-techniques have substantially improved evaluation of joint abnormalities in JIA patients. • MRI-based synovitis is significantly associated with the clinical onset of JIA. • MRI could support physical examination in the early differentiation of childhood arthritis.

Introduction: Approximately 30% of juvenile idiopathic arthritis (JIA) patients fail to respond to anti-TNF treatment. When clinical remission is induced, some patients relapse after treatment has been stopped. We tested the predictive value of MRP8/14 serum levels to identify responders to treatment and relapse after discontinuation of therapy., Methods: Samples from 88 non-systemic JIA patients who started and 26 patients who discontinued TNF-blockers were analyzed. MRP8/14 serum levels were measured by in-house MRP8/14 ELISA and by Bühlmann Calprotectin ELISA at start of anti-TNF treatment, within 6 months after start and at discontinuation of etanercept in clinical remission. Patients were categorized into responders (ACRpedi ≥ 50 and/or inactive disease) and non-responders (ACRpedi < 50) within six months after start, response was evaluated by change in JADAS-10. Disease activity was assessed within six months after discontinuation., Results: Baseline MRP8/14 levels were higher in responders (median MRP8/14 of 1466 ng/ml (IQR 1045-3170)) compared to non-responders (median MRP8/14 of 812 (IQR 570-1178), p < 0.001). Levels decreased after start of treatment only in responders (p < 0.001). Change in JADAS-10 was correlated with baseline MRP8/14 levels (Spearman's rho 0.361, p = 0.001). Patients who flared within 6 months after treatment discontinuation had higher MRP8/14 levels (p = 0.031, median 1025 ng/ml (IQR 588-1288)) compared to patients with stable remission (505 ng/ml (IQR 346-778)). Results were confirmed by Bühlmann ELISA with high reproducibility but different overall levels., Conclusion: High levels of baseline MRP8/14 are associated with good response to anti-TNF treatment, whereas elevated MRP8/14 levels at discontinuation of etanercept are associated with higher chance to flare.

Background: Treatment of juvenile idiopathic arthritis (JIA) has changed dramatically since the introduction of biological agents in 1999., Objective: To evaluate trends in prescription patterns of biological agents and the subsequent outcome of JIA., Methods: The Arthritis and Biologics in Children register (multicentre prospective observational study) aimed to include all consecutive patients with JIA in the Netherlands who had started biological agents since 1999. Patients were divided according to year of introduction of first biological agent. Patient characteristics at introduction of the first biological agent and its effectiveness were analysed over 12 years., Results: 335 patients with non-systemic JIA and 86 patients with systemic JIA started a biological agent between 1999 and 2010. Etanercept remained the most often prescribed biological agent for non-systemic JIA; anakinra became first choice for systemic JIA. The use of systemic glucocorticoids and synthetic disease-modifying antirheumatic drugs before biological agents decreased. During these 12 years of observation, biological agents were prescribed earlier in the disease course and to patients with lower baseline JADAS (Juvenile Arthritis Disease Activity Score) disease activity. All baseline disease activity parameters were lowered in patients with non-systemic JIA. In systemic JIA, prescription patterns changed towards very early introduction of biological agents (median 0.4 years of disease duration) in patients with a low number of joints with active arthritis and high erythrocyte sedimentation rates. These changes for both systemic and non-systemic JIA resulted in more patients with inactive disease after 3 and 15 months of treatment., Conclusions: Biological agents are increasingly prescribed, earlier in the disease and in patients with JIA with lower disease activity. These changes are accompanied by better short-term disease outcomes., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

The use of antidepressants in pregnancy is increasing. Concerns have risen about the use of antidepressants during pregnancy and the risk of postpartum hemorrhage (PPH). The aim of this systematic review is to summarize evidence on the association between use of antidepressants during pregnancy and the risk of PPH. An Embase and Pubmed search was conducted. English and Dutch language studies reporting original data regarding bleeding after delivery associated with exposure to antidepressants during pregnancy were selected. Quality appraisal was conducted using the Newcastle Ottawa Scale (NOS). Out of 81 citations, 4 studies were included. Based on the NOS, 3 were considered of good quality and 1 was considered of satisfactory quality. Two studies reported an increased incidence of PPH in women who used antidepressants during pregnancy. The other two studies identified no overall increased risk of PPH among pregnant women exposed to antidepressants. The existing evidence remains inconclusive whether use of antidepressants during pregnancy is associated with an increased risk of postpartum hemorrhage. If there is such an association the absolute increased risk will be low and the clinical relevance needs to be further examined., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Depression is a common disorder in pregnancy and associated with adverse effects for both mother and neonate. Pharmacological treatment and prevention options include mirtazapine. In a series of 56 cases, we investigated neonatal outcome after intrauterine exposure to mirtazapine and exposure through lactation in the first days postpartum.No increase in any neonatal complication was observed. None of the infants exposed to mirtazapine in the first trimester were born with a major malformation. Of the 54 infants exposed to mirtazapine in the third trimester, 14 were diagnosed with poor neonatal adaptation syndrome (PNAS). This incidence (25.9%) is similar to the incidence of PNAS after intrauterine exposure to other antidepressants. The incidence of PNAS after exposure to mirtazapine was significantly diminished in children who were partially or fully breastfed (18.6% versus 54.5%, P = 0.024).

Aim: Infants exposed to antidepressants in utero are at risk of developing poor neonatal adaptation (PNA). This study identified risk factors for PNA., Methods: In this cohort study, data on mothers and infants admitted to the maternity ward of a general hospital between 2007 and 2012 were analysed. All infants were exposed to an antidepressant during the last trimester of foetal life. The main outcome measure was PNA, defined as at least one Finnegan scores of four or more during admission. Risk factors analysed for their possible association with PNA included type of feeding, type and dosage of antidepressant, prematurity and maternal smoking, anxiety and depression., Results: We included 247 infants in the study and 157 (64%) developed PNA. Formula feeding was associated with an increased risk of PNA compared to breastfeeding or mixed feeding (OR 3.16 95% CI 1.40-7.13 p = 0.003). Selective serotonin reuptake inhibitors (SSRIs) were associated with an increased risk of PNA compared to serotonin and noradrenaline reuptake inhibitors (OR 2.52 95% CI 1.07-5.95 p = 0.04). Dosage did not influence the risk of PNA (OR 1.50 95% CI 0.89-2.52 p = 0.13)., Conclusion: Formula feeding and exposure to SSRIs were associated with development of PNA, but dosage was not., (©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.)

Objective: The Finnegan scoring list (FSL) is widely used to screen for poor neonatal adaptation in infants exposed to anti-depressants in utero. However, the large number of FSL-items and differential weighing of each item is time consuming. The aim of this study was to shorten and simplify the FSL yet preserving its clinimetric properties., Methods: This observational study examined infants exposed to an anti-depressant during pregnancy admitted for at least 72 h on a maternity ward. Trained nurses completed the FSL three times daily. Items for the adapted FSL were selected through forward analysis whereby the number of selected items was based on the area under the curve (AUC). Internal validity was assessed by cross-validation., Results: 183 infants met the inclusion criteria. By forward analysis eight equally-weighed items resulted in an AUC of 0.91. In cross-validation, the mean AUC was 0.89 for 8 items. This adapted FSL had a sensitivity of 97.7% and specificity of 37.0% and a sensitivity of 41.9% and specificity of 86.2% regarding a cut-off of, respectively, 1 and 2., Conclusions: An adapted FSL with eight equally-weighed items has acceptable clinimetric properties and can serve as an easy to apply screening tool in infants exposed to anti-depressants during pregnancy.

Objective: To determine the prevalence of hand- and wrist-related symptoms and impairments, with resulting activity limitations and participation restrictions in children being treated for juvenile idiopathic arthritis., Design and Patients: Cohort study of children, diagnosed in our hospitals between 2003 and 2008 with juvenile idiopathic arthritis, who received standard treatment with regular follow-ups in the same institutions. Patients were asked about hand and wrist symptoms, and underwent a standardized physical examination. For activity limitations, they were asked to complete the Dutch version of the Childhood Health Assessment Questionnaire (CHAQ). Concerning participation restrictions, children were asked about any hand- and/or wrist-related difficulties during daily activities., Results: Of all 152 eligible patients, 121 (80%) participated in the study; 34 boys and 87 girls, mean age 13.7 years (standard deviation (SD) 4.2), mean disease duration 2.6 years (SD 1.4), mean Juvenile Arthritis Disease Activity Score in 71 joints (JADAS-71) score 8 (SD 8), indicating low disease activity. Of these 121, 84 (69%) had at least 1 symptom and 40% had at least 1 impairment. The median CHAQ-total score was 0.5 (mean 0.75 (SD 0.77)), indicating mild-to-moderate activity limitations; and 54% reported having hand- and/or wrist-related problems at school., Conclusion: Despite low disease activity, many children appeared to have hand- and/or wrist-related symptoms and impairments, with resulting moderate to severe levels of activity limitations and participation restrictions at school.

Objectives: To compare DCE-MRI parameters and the relative number of time-intensity curve (TIC) shapes as derived from pixel-by-pixel DCE-MRI TIC shape analysis between knees of clinically active and inactive juvenile idiopathic arthritis (JIA) patients., Methods: DCE-MRI data sets were prospectively obtained. Patients were classified into two clinical groups: active disease (n = 43) and inactive disease (n = 34). Parametric maps, showing seven different TIC shape types, were created per slice. Statistical measures of different TIC shapes, maximal enhancement (ME), maximal initial slope (MIS), initial area under the curve (iAUC), time-to-peak (TTP), enhancing volume (EV), volume transfer constant (K(trans)), extravascular space fractional volume (V(e)) and reverse volume transfer constant (k(ep)) of each voxel were calculated in a three-dimensional volume-of-interest of the synovial membrane., Results: Imaging findings from 77 JIA patients were analysed. Significantly higher numbers of TIC shape 4 (P = 0.008), median ME (P = 0.015), MIS (P = 0.001) and iAUC (P = 0.002) were observed in clinically active compared with inactive patients. TIC shape 5 showed higher presence in the clinically inactive patients (P = 0.036)., Conclusions: The pixel-by-pixel DCE-MRI TIC shape analysis method proved capable of differentiating clinically active from inactive JIA patients by the difference in the number of TIC shapes, as well as the descriptive parameters ME, MIS and iAUC., Key Points: • The pixel-by-pixel TIC shape method differentiates clinically active and inactive JIA patients • Significantly higher numbers of TIC shape 4 were observed in clinically active patients • DCE-MRI parameters ME, MIS and iAUC differ between active and inactive patients • The pixel-by-pixel analysis method allows direct visualization of the heterogeneously distributed disease • The DCE-MRI TIC shape method may serve as a quantitative outcome measure.

Objective: The aim of this study in clinically active juvenile idiopathic arthritis (JIA) was to assess the frequency and distribution pattern of synovitis as hallmark of disease and additional soft-tissue and bony abnormalities on MRI in the knee and wrist as two target joints., Materials and Methods: MRI datasets of 153 clinically active JIA patients (110 with knee and 43 with wrist involvement) were evaluated independently by two readers for the presence of literature-based imaging features: "synovial hypertrophy," "bone marrow changes," "bone erosions," "tenosynovitis" (only in the wrist), and "cartilage lesions" (only in the knee) in accordance with validated definitions and scoring locations., Results: Synovial hypertrophy was most frequently observed--both in the knee and in the wrist (61.8-65.1% of cases). For the knee, the most frequently involved locations were the cruciate ligaments (46/183 locations [25.1%] affected with synovial hypertrophy) and medial patella (18/62 locations [29.0%] with bone marrow changes). Cartilage lesions and bone erosions were rare (5.5-7.3% of cases). For the wrist, most frequently involved were the radiocarpal joint (21/64 locations [32.8%] with synovial hypertrophy), lunate (7/46 locations [15.2%] with bone marrow changes), and capitate or triquetrum (6/28 locations [21.4%] with bone erosions). Tenosynovitis was a common wrist-specific feature (46.5% of cases). MRI showed no abnormalities in a subgroup of patients with clinically active knee (23.6%) and wrist (16.3%) involvement., Conclusion: The distribution pattern of MRI abnormalities in the knee and wrist of active JIA patients provides a practical tool to detect a signature of JIA disease activity in target joints.

Objectives: To assess the value of magnetic resonance imaging (MRI) in discriminating between active and inactive juvenile idiopathic arthritis (JIA) patients and to compare physical examination outcomes with MRI outcomes in the assessment of disease status in JIA patients., Methods: Consecutive JIA patients with knee involvement were prospectively studied using an open-bore MRI. Imaging findings from 146 JIA patients were analysed (59.6% female; mean age, 12.9 years). Patients were classified as clinically active or inactive. MRI features were evaluated using the JAMRIS system, comprising validated scores for synovial hypertrophy, bone marrow oedema, cartilage lesions and bone erosions., Results: Inter-reader reliability was good for all MRI features (intra-class correlation coefficient [ICC] = 0.87-0.94). No differences were found between the two groups regarding MRI scores of bone marrow oedema, cartilage lesions or bone erosions. Synovial hypertrophy scores differed significantly between groups (P = 0.016). Nonetheless, synovial hypertrophy was also present in 14 JIA patients (35.9%) with clinically inactive disease. Of JIA patients considered clinically active, 48.6% showed no signs of MRI-based synovitis., Conclusions: MRI can discriminate between clinically active and inactive JIA patients. However, physical examination is neither very sensitive nor specific in evaluating JIA disease activity compared with MRI. Subclinical synovitis was present in >35% of presumed clinically inactive patients., Key Points: • MRI is sensitive for evaluating juvenile idiopathic arthritis (JIA) disease activity. • Contrast-enhanced MRI can distinguish clinically active and inactive JIA patients. • Subclinical synovitis is present in 35.9 % of presumed clinically inactive patients. • Physical examination is neither sensitive nor specific in evaluating JIA disease activity.