Progesterone for prevention of preterm birth in women with short cervical length: 2-year infant outcomes.

OBJECTIVE: To evaluate the long-term outcomes of children born to women with a short cervix and otherwise low risk for preterm birth, after antenatal exposure to vaginal progesterone vs placebo. METHODS: This was a follow-up study of the Triple P trial, which randomized 80 low-risk women with a short cervix (≤ 30 mm) at 18-22 weeks' gestation to progesterone (n = 41) or placebo (n = 39). At 2 years of corrected age, children were invited for a neurodevelopmental assessment, using the Bayley Scales of Infant and Toddler Development, third edition (BSID-III), and a neurological and physical examination by an assessor blinded to the allocated treatment. Parents filled out the Ages and Stages Questionnaire, the Child Behavior Checklist (CBCL) and a general-health questionnaire. The main outcome of interest was mean BSID-III cognitive and motor scores. Additionally, a composite score of mortality and abnormal developmental outcome, including BSID-III ≤-1 SD, CBCL score in the clinical range and/or parental reported physical problems (at least two operations or at least two hospital admissions in the previous 2 years), was evaluated. Our sample size, dictated by the original sample of the Triple P trial, provided 80% power to detect a mean difference (MD) of 15 points (1 SD) between groups for the BSID-III tests. RESULTS: Of the 80 children born to the randomized women, one in the progesterone group and two in the placebo group died in the neonatal period. Follow-up data were obtained for 59/77 (77%) children and BSID-III outcomes in 57 children (n = 28 in the progesterone group and n = 29 in the placebo group) born at a median gestational age of 38 + 6 weeks (interquartile range (IQR), 37 + 3 to 40 + 1 weeks) with a median birth weight of 3240 g (IQR, 2785-3620 g). In the progesterone vs placebo groups, mean BSID-III cognitive development scores were 101.6 vs 105.0 (MD, -3.4 (95% CI, -9.3 to 2.6); P = 0.29) while mean motor scores were 102.4 vs 107.3 (MD, -4.9 (95% CI, -11.2 to 1.4); P = 0.13). No differences were seen between the two groups in physical (including genital and neurological examination), behavioral and health-related outcomes. CONCLUSION: In this sample of children born to low-risk women with a short cervix at screening, no relevant differences in neurodevelopmental, behavioral, health-related and physical outcomes were found between offspring exposed to vaginal progesterone and those exposed to placebo. © 2020 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Goal attainment scaling as an outcome measure in rare disease trials: a conceptual proposal for validation.

BACKGROUND: Goal Attainment Scaling (GAS) is an instrument that is intended to evaluate the effect of an intervention by assessing change in daily life activities on an individual basis. However, GAS has not been validated adequately in an RCT setting. In this paper we propose a conceptual validation plan of GAS in the setting of rare disease drug trials, and describe a hypothetical trial where GAS could be validated. METHODS: We have used the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) taxonomy to deduce which measurement properties of GAS can be evaluated, and how. As individual GAS scores cannot be interpreted outside the context of a RCT, the validation of GAS needs to be done on trial as well as on individual level. RESULTS: The procedure of GAS consists of three steps. For the step of goal selection (step 1) and definition of levels of attainment (step 2), face validity may be assessed by clinical experts. For the evaluation of the goal attainment (step 3), the inter and intra rater reliability can be evaluated on an individual level. Construct validity may be evaluated by comparison with change scores on other instruments measuring in the same domain as particular goals, if available, and by testing hypotheses about differences between groups. A difference in mean GAS scores between a group who received an efficacious intervention and a control group is an indication of well-chosen goals, and corroborates construct validity of GAS on trial level. Responsiveness of GAS cannot be evaluated due to the nature of the construct being assessed. CONCLUSION: GAS may be useful as an instrument to assess functional change as an outcome measure in heterogeneous chronic rare diseases, but it can only be interpreted and validated when used in RCTs with blinded outcome assessment. This proposed theoretical validation plan can be used as a starting point to validate GAS in specific conditions.

The patient's view on rare disease trial design - a qualitative study.

BACKGROUND: Clinical trials in rare diseases are more challenging than trials in frequent diseases. Small numbers of eligible trial participants, often complicated by heterogeneity among rare disease patients, hamper the design and conduct of a 'classical' Randomized Controlled Trial. Therefore, novel designs are developed by statisticians. However, it is important to be aware of possible design aspects that may jeopardize the feasibility of trial conduct. If the burden of participation is considered out of proportion by patients or parents, recruitment may fail or participants may drop out before trial completion. In order to maximize the chance of success of trials in small populations, it is important to know which aspects of trial design are considered important by patients. RESULTS: We have interviewed all ten members of the Patient Think Tank (PTT) of the ASTERIX project, a European research consortium on methodology for clinical trials in small populations. The PTT members are rare disease patient representatives who have completed extensive training in clinical trial methodology. We have analyzed the interviews qualitatively according to Grounded Theory using a thematic analysis, and we structured the topics in four chronologically ordered themes: 1. Involvement in trial design; 2. Opinions on trial design; 3. Trial participation; 4. Phase after the trial. Our main findings are that the PTT-members recommend that patients are involved in trial design from an early stage on, and have influence on the outcomes and measurement instruments that are chosen in the trial, the length of the study, the choice of participants, and the information that is sent to potential participants. Also, according to the PTT-members, patient groups should consider setting up disease registries, placebo groups should be minimized, and more education on clinical trials is advised. CONCLUSIONS: Rare disease patient representatives who have been educated about clinical trial methodology think it is important to involve patient representatives in research at an early stage. They can be of advice in trial design in such a way that the ratio of potential benefit and burden of trial participation as well as the chosen outcome measures and in- and exclusion criteria are optimized.

Statistical analysis of Goal Attainment Scaling endpoints in randomised trials.

Goal Attainment Scaling is an assessment instrument to evaluate interventions on the basis of individual, patient-specific goals. The attainment of these goals is mapped in a pre-specified way to attainment levels on an ordinal scale, which is common to all goals. This approach is patient-centred and allows one to integrate the outcomes of patients with very heterogeneous symptoms. The latter is of particular importance in clinical trials in rare diseases because it enables larger sample sizes by including a broader patient population. In this paper, we focus on the statistical analysis of Goal Attainment Scaling outcomes for the comparison of two treatments in randomised clinical trials. Building on a general statistical model, we investigate the properties of different hypothesis testing approaches. Additionally, we propose a latent variable approach to generate Goal Attainment Scaling data in a simulation study, to assess the impact of model parameters such as the number of goals per patient and their correlation, the choice of discretisation thresholds and the type of design (parallel group or cross-over). Based on our findings, we give recommendations for the design of clinical trials with a Goal Attainment Scaling endpoint. Furthermore, we discuss an application of Goal Attainment Scaling in a clinical trial in mastocytosis.

The POWER-tool: Recommendations for involving patient representatives in choosing relevant outcome measures during rare disease clinical trial design.

In clinical trials, it is relevant to ask patients and/or their caregivers which aspects concerning their disease they consider important to measure when a new intervention is being investigated. Those aspects, useful as outcome measures in a trial, are of pivotal importance for the result of the trial and the subsequent decision-making. In rare diseases the choice of outcome measures may be even more important, due to the small numbers and heterogeneity of the patients that are included. We have developed a tool to involve patients in the determination of outcome measures and the choice of measurement instruments. This tool was developed together with a patient think tank, consisting of a group of rare disease patient representatives, and by interviewing end users. We have road-tested our tool in an ongoing trial, and evaluated it during a focus group meeting. The tool consists of three steps: 1) Preparation, 2) Consultation of patients, 3) Follow-up during which the consultation results are implemented in the trial design. The tool provides guidelines for researchers to include the patient's opinion in the choice of outcome measures in the trial design stage. We describe the development of the POWER-tool (Patient participation in Outcome measure WEighing for Rare diseases), and first experiences of the tool in an ongoing trial.

A systematic review comparing neurodevelopmental outcome in term infants with hypoxic and vascular brain injury with and without seizures.

BACKGROUND: There is increasing evidence that neonatal seizures in term neonates with stroke, asphyxia or brain haemorrhage might be associated with adverse neurodevelopment and development of epilepsy. The extent of this association is not known. The objective of this study was to assess the possible impact of neonatal seizures on these outcomes and if possible calculate a relative risk. METHODS: A systematic review and meta-analysis was performed (study period January 2000-June 2015). PubMed, Medline and Embase were searched for cohort studies evaluating neurodevelopmental outcome at the age of at least 18 months or development of epilepsy in surviving term neonates with or without neonatal seizures. The methodological quality of included studies was assessed and data extractions were performed in a standardized manner by independent reviewers. Pooled Relative Risks (RR) with 95% confidence intervals for adverse outcome were calculated if possible. RESULTS: Out of 1443 eligible studies 48 were selected for full text reading leaving 9 cohort studies for the final analyses (4 studies on stroke, 4 on perinatal asphyxia and one on cerebral hemorrhage). For all cases with stroke or asphyxia combined the pooled risk ratio (RR) for adverse outcome when suffering neonatal seizures was 7.42 (3.84-14.34); for neonates with perinatal asphyxia: 8.41 (4.07-17.39) and for neonates with stroke: 4.95 (1.07-23.0). The pooled RR for development of late onset epilepsy could only be determined for infants suffering from stroke: 1.48 (0.82-2.68). Results were biased and evidence sparse. CONCLUSIONS: The presence of neonatal seizures in term newborns with vascular or hypoxic brain injury may have an impact on or be a predictor of neurodevelopmental outcome. The biased available data yield insufficient evidence about the true size of this association.

Pessary for prevention of preterm birth in twin pregnancy with short cervix: 3-year follow-up study.

OBJECTIVE: A recent randomized clinical trial (ProTWIN) showed that a cervical pessary prevented preterm birth and improved neonatal outcome in women with multiple pregnancy and cervical length (CL) < 38 mm. In this follow-up study, the long-term developmental outcome of these children was evaluated at 3 years' corrected age. METHODS: This was a follow-up study of ProTWIN, a multicenter trial conducted between 2009 and 2012 in which asymptomatic women with a multiple pregnancy were randomized to placement of a cervical pessary or no intervention. Current follow-up and analysis were limited to mothers with a mid-trimester CL < 38 mm (78 women (157 children) in the pessary group and 55 women (111 children) in the control group). At 3 years of corrected age, surviving children were invited for a Bayley Scales of Infant and Toddler Development-third edition (Bayley-III) assessment. Death after randomization or neurodevelopmental disability (Bayley-III score of ≤ 85, 1 SD below mean) rates were compared between the pessary and control groups, according to the intention-to-treat principle and using multiple imputation for missing data. Mean Bayley-III scores in surviving children were also assessed. A linear mixed-effects model was used to adjust for correlation between children of one mother. RESULTS: From the time of entry in the ProTWIN trial until follow-up at 3 years of age, a total of 27 children had died (six (5%) in the pessary vs 21 (26%) in the control group; odds ratio (OR), 0.13; 95% CI, 0.04-0.48). Bayley-III outcomes were collected for 173/241 (72%) surviving children (114 (75%) in the pessary vs 59 (66%) in the control group). The cumulative incidence of death or survival with a neurodevelopmental disability was 12 (10%) in the pessary vs 23 (29%) in the control group (OR, 0.26; 95% CI, 0.09-0.73). No statistical or clinically relevant differences were found with respect to cognitive, language and motor development among surviving children between the groups. Comparable results were found after multiple imputation. CONCLUSION: In women with twin pregnancy and a CL < 38 mm, the use of a cervical pessary strongly improved survival of the children without affecting neurodevelopment at 3 years' corrected age. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Population Pharmacokinetics of Amoxicillin in Term Neonates Undergoing Moderate Hypothermia.

The pharmacokinetics (PK) of amoxicillin in asphyxiated newborns undergoing moderate hypothermia were quantified using prospective data (N = 125). The population PK was described by a 2-compartment model with a priori birthweight (BW) based allometric scaling. Significant correlations were observed between clearance (Cl) and postnatal age (PNA), gestational age (GA), body temperature (TEMP), and urine output (UO). For a typical patient with GA 40 weeks, BW 3,000 g, 2 days PNA (i.e., TEMP 33.5°C), and normal UO, Cl was 0.26 L/h (interindividual variability (IIV) 41.9%) and volume of distribution of the central compartment was 0.34 L/kg (IIV of 114.6%). For this patient, Cl increased to 0.41 L/h at PNA 5 days and TEMP 37.0°C. The respective contributions of both covariates were 23% and 27%. Based on Monte Carlo simulations we recommend 50 and 75 mg/kg/24h amoxicillin in three doses for patients with GA 36-37 and 38-42 weeks, respectively.

Psychosocial problems of children whose parents visit the emergency department due to intimate partner violence, substance abuse or a suicide attempt.

BACKGROUND: High levels of maltreatment are found in children who are identified because their parents visit the emergency department due to partner violence, substance abuse or suicide attempt. However, it is unknown if these children experience psychosocial problems. This study aims to assess their levels of post-traumatic stress, anxiety, depression, behavioural problems and health-related quality of life. METHODS: A cross-sectional study was conducted in six hospitals. All consecutive families of which a parent visited the emergency department due to partner violence, substance abuse or suicide attempt between 1 July 2012 and 1 March 2014 with children aged 1.5-17 years were approached for participation. Parents and children aged 8 years and older filled out questionnaires measuring post-traumatic stress [13-item version of Children's Revised Impact of Event Scale (CRIES-13)], anxiety, depression (Revised Child Anxiety and Depression Scale), behavioural problems [Child Behavior Checklist (CBCL) and Youth Self-Report (YSR)] and health-related quality of life (PedsQL). Scores of participants were compared with reference data obtained in children in similar age ranges from representative Dutch community samples (CRIES-13, Revised Child Anxiety and Depression Scale, PedsQL and CBCL) and to a normed cutoff score (CRIES-13). RESULTS: Of 195 eligible families, 89 (46%) participated in the study. Participating children did not score different from community children, both on child-reported and parent-reported instruments. Standardized mean differences of total sum scores were 0 (CRIES-13 and CBCL 1.5-5), 0.1 (YSR), 0.2 (CBCL 6-18) and -0.3 (PedsQL) and not statistically different from community children. Thirty-five percent of the participating children scored above the cutoff score on the CRIES-13, indicating post-traumatic stress disorder, but this difference was not statistically significant from community children (mean difference 8%; 95% CI -4-22%). CONCLUSIONS: We found no differences in psychosocial problems between children whose parents visited the emergency department due to partner violence, substance abuse or suicide attempt and children from community samples. Because 35% of the children scored in the range of post-traumatic stress disorder, we advise healthcare providers to pay attention to post-traumatic stress symptoms.

Association between C-reactive protein levels and outcome in acute lung injury in children.

UNLABELLED: High plasma C-reactive protein (CRP) levels are associated with favorable outcome in adults with acute lung injury (ALI). The association between CRP levels and outcome has not been studied in ALI in children. We performed a historical cohort study in 93 mechanically ventilated children (0-18 years) with ALI. The CRP level within 48 h of disease onset was tested for association with 28-day mortality and ventilator-free days (VFD). Clinical parameters and ventilator settings were evaluated for possible confounding. Fourteen patients died within 28 days. The median (interquartile range) CRP level in nonsurvivors was 126 mg/L (64; 187) compared with 56 mg/L (20; 105) in survivors (p = 0.01). For every 10-mg/L rise in CRP level, the unadjusted odds (95% confidence interval (95% CI)) for mortality increased 8.7% (2.1-15.8%). Cardiovascular organ failure at onset of ALI was the strongest predictor for mortality (odds ratio, 30.5 (6.2-152.5)). After adjustment for cardiovascular organ failure, for every 10-mg/L rise in CRP level, the OR (95% CI) for mortality increased 4.7% (-2.7-12.6%; p = 0.22). Increased CRP levels were associated with a decrease in VFD (ρ = -0.26, p = 0.01). CONCLUSION: increased plasma CRP levels are not associated with favorable outcome in ALI in children. This is in contrast with findings in adults with ALI.

StaR Child Health: developing evidence-based guidance for the design, conduct, and reporting of pediatric trials.

Standards for Research in (StaR) Child Health was founded in 2009 to address the paucity and shortcomings of pediatric clinical trials. This initiative involves international experts who are dedicated to developing practical, evidence-based standards to enhance the reliability and relevance of pediatric clinical research. Through a systematic "knowledge to action" plan, StaR Child Health will make efforts to improve and expand the evidence base for child health across the world.

High prevalence of short-chain acyl-CoA dehydrogenase deficiency in the Netherlands, but no association with epilepsy of unknown origin in childhood.

Short-chain acyl-CoA dehydrogenase deficiency (SCADD) is an autosomal recessive inborn error of metabolism, most frequently associated with developmental delay and/or epilepsy. Most SCADD patients carry common SCAD-encoding gene ( ACADS) variants or these variants in combination with a rare ACADS mutation, in the Netherlands predominantly the c.1058C>T. Epilepsy in childhood often remains unexplained and patients with epilepsy related to SCADD may remain undiagnosed because studies for SCADD are often not performed. To test this hypothesis and to further estimate the extent of the Dutch SCADD population, we performed a study on blood spot samples in 131 paediatric patients with epilepsy and 909 anonymous newborns and investigated the presence of the 2 common ACADS variants and the rare c.1058C>T mutation. Overall, the 2 common ACADS variants and the rare c.1058C>T mutation were detected in either homozygous or compound heterozygous forms in 9.2% of the epilepsy and 7.5% of the reference group. A birth prevalence of SCADD with a mutation/variant genotype in the Netherlands as high as >1:1,000 was calculated. This is in contrast with the low number of patients diagnosed clinically and supports the hypothesis that SCADD is clinically irrelevant. Furthermore our study does not support an association between SCADD and epilepsy.

Central blood flow measurements in stable preterm infants after the transitional period.

BACKGROUND: Central blood flow measurements can provide detailed information on the hemodynamic condition of the preterm infant. However, reference values for right and left ventricular output (RVO and LVO) and superior vena cava flow (SVC flow) are only available for infants in the transitional period. The aim of this study was to determine RVO, LVO and SVC after the transitional period in stable preterm infants. METHODS: RVO, LVO and SVC flow were measured with functional echocardiography on days 7 and 14 of life in stable preterm infants less than 32 weeks gestation, with minimal respiratory support and no cardiovascular support. Infants with a clinical suspicion of an infection within 48 h after data collection or a ductal diameter >1.4 mm were excluded from analysis. RESULTS: We performed 111 measurements in 62 preterm infants with a median (range) gestational age of 28 (25-31) weeks and birth weight of 1105 (650-2370) g. 57 measurements were analysed on day 7 and 47 on day 14. The mean (SD) RVO, LVO and SVC flow were 429 (116), 296 (74) and 89 (33) ml/kg/min on day 7 and 433 (81), 300 (79) and 86 (26) ml/kg/min on day 14. There were no significant differences in flows between days 7 and 14 in the paired measurements. CONCLUSION: This study provides central blood flow values in stable preterm infants after the transitional period. The flow variables were shown to remain stable between days 7 and 14.

Intensive peri-operative use of factor VIII and the Arg593-->Cys mutation are risk factors for inhibitor development in mild/moderate hemophilia A.

BACKGROUND: A severe and challenging complication in the treatment of hemophilia A is the development of inhibiting antibodies (inhibitors) directed towards factor VIII (FVIII). Inhibitors aggravate bleeding complications, disabilities and costs. The etiology of inhibitor development is incompletely understood. OBJECTIVES: In a large cohort study in patients with mild/moderate hemophilia A we evaluated the role of genotype and intensive FVIII exposure in inhibitor development. PATIENTS/METHODS: Longitudinal clinical data from 138 mild/moderate hemophilia A patients were retrospectively collected from 1 January 1980 to 1 January 2008 and analyzed by multivariate analysis using Poisson regression. RESULTS: Genotyping demonstrated the Arg593Cys missense mutation in 52 (38%) patients; the remaining 86 patients had 26 other missense mutations. Sixty-three (46%) patients received intensive FVIII concentrate administration, 41 of them for surgery. Ten patients (7%) developed inhibitors, eight of them carrying the Arg593Cys mutation. Compared with the other patients, those with the Arg593Cys mutation had a 10-fold increased risk of developing inhibitors (RR 10; 95% CI, 0.9-119).The other two inhibitor patients had the newly detected mutations Pro1761Gln and Glu2228Asp. In both these patients and in five patients with genotype Arg593Cys, inhibitors developed after intensive peri-operative use of FVIII concentrate (RR 186; 95% CI, 25-1403). In five of the 10 inhibitor patients FVIII was administered by continuous infusion during surgery (RR 13; 95% CI, 1.9-86). CONCLUSION: The Arg593Cys genotype and intensive peri-operative use of FVIII, especially when administered by continuous infusion, are associated with an increased risk for inhibitor development in mild/moderate hemophilia A.

Survival in SMA type I: a prospective analysis of 34 consecutive cases.

Thirty-four children with genetically proven SMA type I (age at onset <6 months, unable to sit during study period) were included in a 3-year prospective cohort study and neurologically followed-up until death or the end of the study. At the end of the study period 31/34 children had died. The median age at death was 176 days (95% Confidence Interval 150-214 days), the median survival from the time of diagnosis was 158 days (95% CI 137-232 days). The median survival after diagnosis did not differ significantly between children diagnosed at birth (median survival 137 days, 95% CI 111-232 days) and those diagnosed later (median survival 159 days, 95% CI 141-256), implying that SMA I cases with different ages of onset show the same progression rate of the disease. The number of SMN2 copies was not clearly correlated with survival duration, possibly because of lack of statistical power due to the small number of cases with 1 or 3 SMN2 copies. The three cases alive at the end of the study had either three or an unknown number of SMN2 copies, which is in agreement with previously described cases showing longer survival with increasing number of SMN2 copies. All deceased children died of respiratory insufficiency and/or an intercurrent lung infection, indicating that the susceptibility of the child with SMA type I to respiratory infections plays an important role in determining the survival.

Efficient ways exist to obtain the optimal sample size in clinical trials in rare diseases.

OBJECTIVE: Recruitment of pediatric patients in randomized clinical trials is hampered by the rarity of many conditions and by ethical constraints. The objective of this paper is to give an overview of design options to obtain a statistically valid result while including a minimum number of subjects. STUDY DESIGN AND SETTING: Overview and discussion of several approaches to conduct valid randomized clinical trials in rare diseases and vulnerable populations. RESULTS: Sequential designs have been developed as efficient ways to evaluate accumulating information from a clinical trial, thereby reducing the average size of trials. Different sequential procedures exist, including group sequential designs, boundaries designs, and adaptive designs. The sample size attained at the end of the trial is unknown at the start. The sample size for a given set of alpha, beta, and effect size may turn out to be larger than with a classical fixed sample size approach. Simulations have shown that on average, sample sizes are smaller. CONCLUSION: There are several possibilities to optimize the number of subjects in a clinical trial. The rarity of many disorders in children and the ethical requirements in this patient population should not obstruct the performance of well-designed research to support clinical decision making.

A tuning algorithm for model predictive controllers based on genetic algorithms and fuzzy decision making.

Model Predictive Control is a valuable tool for the process control engineer in a wide variety of applications. Because of this the structure of an MPC can vary dramatically from application to application. There have been a number of works dedicated to MPC tuning for specific cases. Since MPCs can differ significantly, this means that these tuning methods become inapplicable and a trial and error tuning approach must be used. This can be quite time consuming and can result in non-optimum tuning. In an attempt to resolve this, a generalized automated tuning algorithm for MPCs was developed. This approach is numerically based and combines a genetic algorithm with multi-objective fuzzy decision-making. The key advantages to this approach are that genetic algorithms are not problem specific and only need to be adapted to account for the number and ranges of tuning parameters for a given MPC. As well, multi-objective fuzzy decision-making can handle qualitative statements of what optimum control is, in addition to being able to use multiple inputs to determine tuning parameters that best match the desired results. This is particularly useful for multi-input, multi-output (MIMO) cases where the definition of "optimum" control is subject to the opinion of the control engineer tuning the system. A case study will be presented in order to illustrate the use of the tuning algorithm. This will include how different definitions of "optimum" control can arise, and how they are accounted for in the multi-objective decision making algorithm. The resulting tuning parameters from each of the definition sets will be compared, and in doing so show that the tuning parameters vary in order to meet each definition of optimum control, thus showing the generalized automated tuning algorithm approach for tuning MPCs is feasible.

Development of a set of activities to evaluate the arm and hand function in children with obstetric brachial plexus lesion.

OBJECTIVE: To develop an observational instrument that can be used to evaluate the quality of arm and hand skills in daily functional activities in children with obstetric brachial plexus lesion (OBPL). A set of functional activities was constructed and standardized, and the intra-observer reliability of the assessment of this set of activities was studied. SETTING: Department of Occupational Therapy and Department of Rehabilitation Medicine, VU University Medical Centre. SUBJECTS: Twenty-six children with OBPL in the age range of 4 -6 years. INTERVENTIONS: The children were asked to perform 47 bimanual activities, which were recorded on videotape. MAIN MEASURES: The videotapes were scored twice by the same occupational therapist. RESULTS: The percentage of agreement in scoring 'hand-use', 'speed' and 'assistance' was over 80% for a substantial number of activities, indicating a strong agreement. However, in scoring 'deviations in movements and body posture' the percentage of agreement was insufficient in most activities. CONCLUSIONS: This set of activities has good potential for assessment of the performance of functional activities in children with OBPL. This study, however, showed a number of difficulties in observing and scoring the activities that have to be considered when developing a standardized video observation.