Feasibility and findings of electrocardiogram recording in older adults with intellectual disabilities: results of the Healthy Ageing and Intellectual Disabilities study.

BACKGROUND: Older adults with intellectual disabilities (ID) have a high risk of cardiovascular diseases (CVD). At the same time, challenging diagnostic work-up increases the likelihood of underdiagnosis of CVD in this population. To limit this underdiagnosis, it would be beneficial to use objective measures such as the electrocardiogram (ECG). However, little is known about the feasibility of ECG recording and the prevalence of ECG abnormalities in this population. Therefore, the aims of this study were to investigate the feasibility of resting ECG recording, to study the prevalence of ECG abnormalities, and to compare the frequency of ECG abnormalities with medical records in older adults with ID. METHOD: A cross-sectional study was performed within a cohort of older adults (≥60 years) with ID as part of the Healthy Ageing and Intellectual Disabilities (HA-ID) study. A resting 12-lead ECG was attempted, and the ECG recording was considered feasible if the recording could be made and if the ECG could be interpreted by a cardiologist and the Modular ECG Analysis System (MEANS). ECGs were assessed for the presence of ECG abnormalities and medical record review was performed. If the cardiologist or MEANS concluded that there was evidence of myocardial infarction, atrial fibrillation or QTc prolongation on the ECG in the absence of this ECG diagnosis in the participant's medical record, this was classified as a previously undiagnosed ECG diagnosis. RESULTS: ECG recording was feasible in 134 of the 200 participants (67.0%). Of these 134 participants (70.6 ± 5.8 years; 52.2% female), 103 (76.9%) had one or more ECG abnormality, with the most prevalent being prolonged P-wave duration (27.6%), QTc prolongation (18.7%), minor T-wave abnormalities (17.9%), first degree atrioventricular block (12.7%) and myocardial infarction (6.7%). Eight out of 9 (88.9%) myocardial infarctions and all cases of (significant) QTc prolongation (100%) were previously undiagnosed. CONCLUSIONS: This study showed that ECG recording is feasible in the majority of older adults with ID and revealed a substantial underdiagnosis of ECG abnormalities. These results stress the importance of ECG recording and warrant further research into the yield of opportunistic ECG screening in older adults with ID.

Long-term effects of environmental dynamic lighting on sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities.

BACKGROUND: Sleep-wake problems and depressive symptoms are common in people with intellectual disabilities (IDs) and are thought to be related to the unstable sleep-wake rhythm in this population. Previously, we showed that after increasing environmental light exposure, mid-sleep and sleep onset advanced, and mood improved over a period of 14 weeks after installing environmental dynamic light installations in the living room of people with IDs. We invited participants of that short-term study to take part in the current study on sleep-wake rhythm, mood and behaviour in older adults with IDs 1 year after installing environmental dynamic light installations in the common living rooms of six group homes. METHODS: A pre-post study was performed from October 2017 to February 2019. We included 45 participants (63.5 ± 8.5 years, 67% female) from six group home facilities who provided data at baseline (9, 4 and 1 weeks prior to installing light installations), short term (3, 7 and 14 weeks after installing light installations) and 1 year (54 weeks after installing light installations). Wrist activity was measured with actigraphy (GENEActiv) to derive the primary outcome of interdaily stability of sleep-wake rhythms as well as sleep estimates. Mood was measured with the Anxiety, Depression and Mood Scale. Behaviour was measured with the Aberrant Behaviour Checklist. RESULTS: One year after installing dynamic lighting, we did not find a change in interdaily stability. Total sleep time decreased (ß = -25.40 min; confidence interval: -10.99, -39.82), and sleep onset time was delayed (ß = 25.63 min; confidence interval: 11.18, 40.08). No effect on mood or behaviour was found. CONCLUSIONS: We did not find a change in sleep-wake rhythm, mood or behaviour in older persons with IDs living in care facilities 1 year after installing the light. We did find evidence for a long-term effect on sleep duration and sleep timing. The results have to be interpreted with care as the current study had a limited number of participants. The need for more research on the long-term effects of enhancing environmental light in ID settings is evident.

Shared decision making with frail people with intellectual disabilities in the palliative phase: A process evaluation of the use of the In-Dialogue conversation aid in practice.

BACKGROUND: This study reports the process evaluation of the In-Dialogue conversation aid to facilitate shared decision-making with people with intellectual disabilities in the palliative phase. METHODS: Training for In-Dialogue was evaluated by 53 support staff members through questionnaires. The use of In-Dialogue in four residential care facilities for frail people with mild to severe intellectual disabilities was evaluated with semi-structured interviews with five relatives, nine support staff and three people with intellectual disabilities. RESULTS: Most participants considered the training helpful to apply shared decision-making. Sixty-three people with intellectual disabilities participated in In-Dialogue conversations. Almost all interviewees stated that these conversations provided additional insight into people's concerns and preferences. Involvement of people with profound intellectual disabilities and their relatives appeared to be challenging. CONCLUSION: Conversations about illness and the end of life appeared to be feasible with the In-Dialogue conversation aid and provided insight into people's experiences and preferences.

Associations between physical fitness and cardiovascular disease in older adults with intellectual disabilities: Results of the Healthy Ageing and Intellectual Disability study.

BACKGROUND: Reduced physical fitness is a cardiovascular disease (CVD) risk factor in the general population. However, generalising these results to older adults with intellectual disabilities (ID) may be inappropriate given their pre-existing low physical fitness levels and high prevalence of co-morbidities. Therefore, the aim of this study is to investigate the difference in physical fitness between older adults with ID with and without CVD. METHOD: Baseline data of a cohort of older adults with borderline to profound ID (HA-ID study) were used (n = 684; 61.6 ± 8.2 years; 51.3% male). CVD status (coronary artery disease, heart failure, stroke) was obtained from medical files. Cardiorespiratory fitness (10-m incremental shuttle walking test), comfortable and fast gait speed (over 5 m distance) and grip strength (hand dynamometer) were measured. Multivariable linear regression models were used to investigate the association between these physical fitness components and the presence of CVD, adjusted for participant characteristics. RESULTS: Of the 684 participants 78 (11.4%) had CVD. Participants with CVD scored lower on cardiorespiratory fitness (-81.4 m, P = 0.002), comfortable gait speed (-0.3 km/h, P = 0.04) and fast gait speed (-1.1 km/h, P = 0.04). No significant differences were found for grip strength (-0.2 kg, P = 0.89). CONCLUSIONS: Older adults with CVD had significantly lower physical fitness levels than those without CVD, except for grip strength. Longitudinal research is needed to investigate causality.

Light up: an intervention study of the effect of environmental dynamic lighting on sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities.

BACKGROUND: Evidence-based interventions to improve the sleep-wake rhythm, mood and behaviour in older adults with intellectual disabilities (ID) are limited. Increasing light exposure has been shown to be effective in improving the sleep-wake rhythm, mood, and behaviour in other populations. The current study investigates the effect of installing environmental dynamic lighting in common living rooms of care facilities on sleep-wake rhythm, mood, and behaviour in older adults with ID. METHODS: A non-randomised, non-concurrent, multiple baseline study was performed from October 2017 to May 2018. Fifty-four participants [mean (SD) age of 63.42 (8.6) years, 65% female] in six care facilities were included. All participants had three baseline measurements (Weeks 1, 5 and 9). Dynamic lighting was installed in Week 10, after which three intervention measurements took place (Weeks 12, 17 and 24). Sleep characteristics and the sleep-wake rhythm were assessed using actigraphy (GENEActiv). Mood was measured with the Anxiety, Depression and Mood Scale (ADAMS) and behaviour with the Aberrant Behaviour Checklist (ABC). RESULTS: Mixed-effect regression analysis showed a worsening of the primary outcome interdaily stability (P = 0.001). This could be attributed to one care facility, whereas interdaily stability did not change in the other care facilities (P = 0.74). Dynamic lighting led to earlier mid-sleep (P = 0.003) and sleep onset (P < .0001) and improved mood as indicated by lower scores on the ADAMS depression (-0.64 SD, P < 0.001) and social avoidance (-0.47 SD, P = 0.004) subscales. The prevalence of screening above cut-off for depression decreased from 23 to 9.8% (OR = .16, P = 0.003). For behaviour, a decrease was seen in hyperactivity (-0.43 SD, P < 0.001), lethargy (-0.35 SD, P = 0.008) and irritability (-0.33 SD, P < .001) as measured with the ABC. No adverse effects were reported. CONCLUSION: Installing dynamic lighting in common living areas for older adults with ID improved the mood and behaviour of the residents up to 14 weeks after placement. Integrated dynamic lighting is a promising, undemanding and potentially effective addition to improve mood and behaviour in care organisations for people with ID, but does not seem to do so by improving sleep or sleep-wake rhythms.

Development and validation of a shortened and practical frailty index for people with intellectual disabilities.

BACKGROUND: There is no widely used instrument to detect frailty in people with intellectual disabilities (IDs). We aimed to develop and validate a shorter and more practical version of a published frailty index for people with IDs. METHOD: This study was part of the longitudinal 'Healthy Ageing and Intellectual Disability' study. We included 982 people with IDs aged 50 years and over. The previously developed and validated ID-Frailty Index consisting of 51 deficits was used as the basis for the shortened version, the ID-FI Short Form. Content of the ID-FI Short Form was based on statistics and clinical and practical feasibility. We evaluated the precision and validity of the ID-FI Short Form using the internal consistency, the correlation between the ID-FI Short Form and the original ID-Frailty Index, the agreement in dividing participants in the categories non-frail, pre-frail and frail, and the association with survival. RESULTS: Seventeen deficits from the original ID-Frailty Index were selected for inclusion in the ID-FI Short Form. All deficits of the ID-FI Short Form are clinically and practically feasible to assess for caregivers and therapists supporting people with ID. We showed acceptable internal consistency with Cronbach's alpha of 0.75. The Pearson correlation between the ID-Frailty Index and the ID-FI Short Form was excellent (r = 0.94, P < 0.001). We observed a good agreement between the full and short forms in dividing the participants in the frailty categories, with a kappa statistic of 0.63. The ID-FI Short Form was associated with survival; with every 1/100 increase on the ID-FI Short Form, the mortality probability increased by 7% (hazard ratio 1.07, P < 0.001). CONCLUSION: The first validation of the ID-FI Short Form shows it to be a promising, practical tool to assess the frailty status of people with ID.

Shedding light on light exposure in elderly with intellectual disabilities.

BACKGROUND: Light exposure affects mood and sleep regulation. Sleep problems and mood complaints are common in elderly with intellectual disabilities (ID) living in care facilities. Insufficient light exposure is hypothesised to contribute to the high prevalence of these problems. The current study is the first to describe the personal light exposure pattern during the waking day in elderly with ID. METHODS: The study sample consists of 82 elderly with ID (aged 62.3 ± 9.4 years) living in 16 residential homes of three care organisations in the Netherlands. Personal light exposure was measured continuously for 7-10 days using a HOBO data logger light sensor, measuring illuminance at chest height. Participants wore a wrist-worn accelerometer (Actiwatch or Geneactiv) to indicate the bedtimes to determine the waking day. RESULTS: The variation in illuminance is small during the waking day. Elderly with ID spend most of their waking day (mean duration = 14:32:43 h) in dim light (1-500 lux) environment and spend a median of 32 min in light > 1000 lux. Within participants, the threshold associated with better sleep (>50 min of light > 1000 lux) was reached for 34% of the days, and the threshold associated with less depressive symptoms (>30 min of light > 1000 lux) was reached in 46% of the days. Exposure > 1000 lux was lower during weekends than during weekdays. CONCLUSION: Elderly with ID spend most of their waking day in low light levels and did not meet the proposed values associated with better sleep and mood. Given the importance of adequate light exposure for regulation of sleep and mood, and the prevalence of sleep and mood problems in elderly with ID, the current study suggests that the lit environment for this already frail population should be given more attention.

Shared decision-making with people with intellectual disabilities in the last phase of life: A scoping review.

BACKGROUND: Shared decision-making (SDM) is the process in which healthcare professionals and patients jointly discuss and decide which care and treatment policy is to be followed. The importance of SDM is increasingly being recognised across health settings, including palliative care. Little is known about SDM with people with intellectual disabilities (IDs) in the last phase of life. This review aimed to explore to which extent and in which way people with ID in the last phase of life are involved in decision-making about their care and treatment. METHOD: In this scoping review, we systematically searched in the Embase, Medline and PsycINFO databases for empirical studies on decision-making with people with ID in the last phase of life. RESULTS: Of a total of 281 identified titles and abstracts, 10 studies fulfilled the inclusion criteria. All focused on medical end-of-life decisions, such as foregoing life-sustaining treatment, do-not-attempt-resuscitation orders or palliative sedation. All studies emphasise the relevance of involving people with ID themselves, or at least their relatives, in making decisions at the end of life. Still, only two papers described processes of decision-making in which persons with ID actively participated. Furthermore, in only one paper, best practices and guidelines for decision-making in palliative care for people with ID were defined. CONCLUSION: Although the importance of involving people with ID in the decision-making process is emphasised, best practices or guidelines about what this should look like are lacking. We recommend developing aids that specifically support SDM with people with ID in the last phase of life.

The association between medication use and gait in adults with intellectual disabilities.

BACKGROUND: Adults with intellectual disabilities (ID) often have polypharmacy and often use antipsychotics. Both polypharmacy and antipsychotics have a negative effect on gait in the general population, but this has not been studied in adults with ID. These negative effects may add to pre-existing gait disturbances in adults with ID and increase the risk for adverse health outcomes in this population. Therefore, the aim of this study is to investigate the difference in gait parameters between adults with ID with and without polypharmacy and between adults with ID using and not using antipsychotics. METHOD: The gait parameters of 31 participants were collected with the GAITRite walkway, a pressure sensitive walkway measuring spatial and temporal gait parameters, in addition to information about personal characteristics, prescribed medication and presence of polypharmacy. RESULTS: After adjustment for sex and body mass index, participants with polypharmacy had a significantly shorter step length [polypharmacy B (SE) = -0.079 (0.034), P = 0.03], shorter stride length [polypharmacy B (SE) = -0.157 (0.069), P = 0.03] and longer double support time [polypharmacy B (SE) = 0.0004 (0.0001), P = 0.047]. Participants using antipsychotics had a significantly longer double support time [antipsychotic use B (SE) = 0.0003 (0.0002), P = 0.019]. CONCLUSION: This study showed for the first time that both polypharmacy and using antipsychotics are associated with gait in adults with ID. The differences seem to resemble a more cautious gait. Further investigation with larger study samples, additional medication types and dosages are needed to acquire more insight in this important topic.

Non-pharmacological interventions for adults with intellectual disabilities and depression: a systematic review.

BACKGROUND: Although high rates of depression symptoms are reported in adults with intellectual disabilities (IDs), there is a lack of knowledge about non-pharmacological treatment options for depression in this population. The first research question of this paper is: Which non-pharmacological interventions have been studied in adults with ID and depression? The second research question is: What were the results of these non-pharmacological interventions? METHOD: Systematic review of the literature with an electronic search in six databases has been completed with hand searches. Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines have been followed. Selected studies met predefined inclusion criteria. RESULTS: Literature search resulted in 4267 papers of which 15 met the inclusion criteria. Five different types of non-pharmacological interventions have been studied: cognitive behavioural therapy, behavioural therapy, exercise intervention, social problem-solving skills programme and bright light therapy. CONCLUSION: There are only a few studies of good quality evaluating non-pharmacological interventions for adults with ID and depression. Some of these studies, especially studies on cognitive behavioural therapy, show good results in decreasing depressive symptoms. High-quality randomised controlled trials evaluating non-pharmacological interventions with follow-up are needed.

Feasibility and validity of a tool for identification of people with intellectual disabilities in need of palliative care (PALLI).

BACKGROUND: There is a need for a specific tool that supports healthcare professionals in timely identifying people with intellectual disabilities (ID) in need of palliative care. Therefore, we developed PALLI: a tool for screening deteriorating health, indicative of a limited life expectancy. AIMS: We evaluated feasibility, construct validity and predictive validity of PALLI. METHODS: 190 people with ID likely to be in need of palliative care were included. Physicians and daily care professionals (DCPs) completed PALLI and provided information on health outcomes at baseline, after 5-6 months and after 10-12 months. Linear Mixed Models and Generalized Linear Mixed Models were used to test validity. RESULTS: Feasibility was adequate: physicians and DCPs were able to answer most items with 'yes' or 'no' and within a short amount of time. Construct validity was promising: a higher PALLI score at baseline was related to a higher level of decline in health, a higher symptom burden, a lower quality of life and more ADL-dependency at baseline. Predictive validity: only a higher physician-reported PALLI score at baseline significantly increased risk of death within 12 months. CONCLUSIONS: PALLI shows promising feasibility and validity and has potential as a tool for timely identifying people with ID who may benefit from palliative care.

Physicians' recognition of death in the foreseeable future in patients with intellectual disabilities.

BACKGROUND: Physicians are increasingly confronted with people with intellectual disabilities (ID) who are facing life-threatening diseases. We aimed to explore when and based on which information sources and signals physicians recognised that a patient with ID would die in the foreseeable future. Insights may help in identifying patients in need of palliative care. METHOD: In this study, 81 physicians for people with ID and 16 general practitioners completed a retrospective survey about their last case of a patient with ID with a non-sudden death. RESULTS: More than 20% of all physicians foresaw death not until the last week of life. In 30% of all patients, the physician did not discuss the start of the palliative care phase until the last week. The most reported information sources based on which physicians foresaw death were the physicians themselves and professional caregivers. We found 40 different signals that lead to physicians' foreseeing death. These were not only medical signals but also behavioural and physical signals. CONCLUSIONS: Results indicate that the physicians' ability to foresee death is a result of a process of growing awareness in which multiple signals from different information sources converge. This demands continuous multi-disciplinary communication because people involved have their own unique interactions with the patient and can therefore contribute to a growing and timely awareness of patients' death in the future.

Bone mineral density in children and adolescents with Prader-Willi syndrome: a longitudinal study during puberty and 9 years of growth hormone treatment.

CONTEXT: Longitudinal data on bone mineral density (BMD) in children and adolescents with Prader-Willi Syndrome (PWS) during long-term GH treatment are not available. OBJECTIVE: This study aimed to determine effects of long-term GH treatment and puberty on BMD of total body (BMDTB), lumbar spine (BMDLS), and bone mineral apparent density of the lumbar spine (BMADLS) in children with PWS. DESIGN AND SETTING: This was a prospective longitudinal study of a Dutch PWS cohort. PARTICIPANTS: Seventy-seven children with PWS who remained prepubertal during GH treatment for 4 years and 64 children with PWS who received GH treatment for 9 years participated in the study. INTERVENTION: The children received GH treatment, 1 mg/m(2)/day (≅ 0.035 mg/kg/d). MAIN OUTCOME MEASURES: BMDTB, BMDLS, and BMADLS was measured by using the same dual-energy x-ray absorptiometry machine for all annual measurements. RESULTS: In the prepubertal group, BMDTB standard deviation score (SDS) and BMDLSSDS significantly increased during 4 years of GH treatment whereas BMADLSSDS remained stable. During adolescence, BMDTBSDS and BMADLSSDS decreased significantly, in girls from the age of 11 years and in boys from the ages of 14 and 16 years, respectively, but all BMD parameters remained within the normal range. Higher Tanner stages tended to be associated with lower BMDTBSDS (P = .083) and a significantly lower BMADLSSDS (P = .016). After 9 years of GH treatment, lean body mass SDS was the most powerful predictor of BMDTBSDS and BMDLSSDS in adolescents with PWS. CONCLUSIONS: This long-term GH study demonstrates that BMDTB, BMDLS, and BMADLS remain stable in prepubertal children with PWS but decreases during adolescence, parallel to incomplete pubertal development. Based on our findings, clinicians should start sex hormone therapy from the age of 11 years in girls and 14 years in boys unless there is a normal progression of puberty.

Eight years of growth hormone treatment in children with Prader-Willi syndrome: maintaining the positive effects.

BACKGROUND: The most important reason for treating children with Prader-Willi syndrome (PWS) with GH is to optimize their body composition. OBJECTIVES: The aim of this ongoing study was to determine whether long-term GH treatment can counteract the clinical course of increasing obesity in PWS by maintaining the improved body composition brought during early treatment. SETTING: This was a multicenter prospective cohort study. METHODS: We have been following 60 prepubertal children for 8 years of continuous GH treatment (1 mg/m(2)/d ≈ 0.035 mg/kg/d) and used the same dual-energy x-ray absorptiometry machine for annual measurements of lean body mass and percent fat. RESULTS: After a significant increase during the first year of GH treatment (P < .0001), lean body mass remained stable for 7 years at a level above baseline (P < .0001). After a significant decrease in the first year, percent fat SD score (SDS) and body mass index SDS remained stable at a level not significantly higher than at baseline (P = .06, P = .14, resp.). However, body mass index SDSPWS was significantly lower after 8 years of GH treatment than at baseline (P < .0001). After 8 years of treatment, height SDS and head circumference SDS had completely normalized. IGF-1 SDS increased to +2.36 SDS during the first year of treatment (P < .0001) and remained stable since then. GH treatment did not adversely affect glucose homeostasis, serum lipids, blood pressure, and bone maturation. CONCLUSION: This 8-year study demonstrates that GH treatment is a potent force for counteracting the clinical course of obesity in children with PWS.

Scoliosis in Prader-Willi syndrome: prevalence, effects of age, gender, body mass index, lean body mass and genotype.

BACKGROUND: The reported prevalence of scoliosis in children with Prader-Willi syndrome varies from 15% to 86%. OBJECTIVE: To study the prevalence of scoliosis and the effects of age, gender, body mass index (BMI), total lean body mass (LBM), LBM of the trunk (trunkLBM) and genotype. DESIGN: Radiographs were taken, length and weight were measured (BMI standard deviation scores (BMI SDS) and body surface area (BSA)), and dual energy x-ray absorptiometry was performed, measuring LBM and trunkLBM. PATIENTS: 96 children, median (interquartile range) age 4.8 years (2.1 to 7.5), were included in a multicentre study. None received growth hormone treatment. MAIN OUTCOME MEASURES: Two types of scoliosis were identified: (1) long C-curve type scoliosis (LCS) and (2) idiopathic scoliosis (IS). Children were divided into age categories (infants, 0-3 years; juveniles, 3-10 years; adolescents, 10-16 years). RESULTS: The prevalence of scoliosis was 37.5% and increased with age (infants and juveniles, approximately 30%; adolescents, 80%); 44% of children with scoliosis had a Cobb angle above 20 degrees . Children with scoliosis were significantly older than those without. Children with LCS were younger and more hypotonic than those with IS: median (interquartile range) age 4.4 years (1.7-5.9) vs 11.1 years (6.5-12.1) (p = 0.002) and trunkLBM/BSA ratio 7080 (6745-7571) vs 7830 (6932-8157) (p = 0.043). CONCLUSIONS: The prevalence of scoliosis in children with Prader-Willi syndrome is high (37.5%). Many children with scoliosis (13%) had undergone brace treatment or surgery. The type of scoliosis is affected by age and trunkLBM/BSA ratio.

Mental and motor development before and during growth hormone treatment in infants and toddlers with Prader-Willi syndrome.

BACKGROUND: Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, feeding difficulties and failure to thrive in infancy. GH treatment improves growth velocity and body composition. Research on the effects of GH on psychomotor development in infants with PWS is limited. OBJECTIVE: To evaluate psychomotor development in PWS infants and toddlers during GH treatment compared to randomized controls. DESIGN/PATIENTS: Forty-three PWS infants were evaluated at baseline. Twenty-nine of them were randomized into a GH group (n = 15) receiving 1 mg/m(2)/day GH or a non-GH-treated control group (n = 14). At baseline and after 12 months of follow-up, analysis with Bayley Scales of Infant Development II (BSID-II) was performed. Data were converted to percentage of expected development for age (%ed), and changes during follow-up were calculated. RESULTS: Infants in the GH group had a median age of 2.3 years [interquartile range (IQR) 1.7-3.0] and in the control group of 1.5 years (IQR 1.2-2.7) (P = 0.17). Both mental and motor development improved significantly during the first year of study in the GH group vs. the control group: median (IQR) change was +9.3% (-5.3 to 13.3) vs.-2.9% (-8.1 to 4.9) (P < 0.05) in mental development and +11.2% (-4.9 to 22.5) vs.-18.5% (-27.9 to 1.8) (P < 0.05) in motor development, respectively. CONCLUSION: One year of GH treatment significantly improved mental and motor development in PWS infants compared to randomized controls.

Thyroid hormone levels in children with Prader-Willi syndrome before and during growth hormone treatment.

BACKGROUND: Prader-Willi syndrome (PWS) is a neurogenetic disorder characterized by muscular hypotonia, psychomotor delay, obesity and short stature. Several endocrine abnormalities have been described, including GH deficiency and hypogonadotrophic hypogonadism. Published data on thyroid hormone levels in PWS children are very limited. OBJECTIVE: To evaluate thyroid function in children with PWS, before and during GH treatment. DESIGN/PATIENTS: At baseline, serum levels of T4, free T4 (fT4), T3, reverse T3 (rT3) and TSH were assessed in 75 PWS children. After 1 year, assessments were repeated in 57 of the them. These children participated in a randomized study with two groups: group A (n = 34) treated with 1 mg GH/m(2)/day and group B (n = 23) as controls. RESULTS: Median age (interquartile range, IQR) of the total group at baseline was 4.7 (2.7-7.6) years. Median (IQR) TSH level was -0.1 SDS (-0.5 to 0.5), T4 level -0.6 SDS (-1.7 to 0.0) and fT4 level -0.8 SDS (-1.3 to -0.3), the latter two being significantly lower than 0 SDS. T3 level, at 0.3 SDS (-0.3 to 0.9), was significantly higher than 0 SDS. After 1 year of GH treatment, fT4 decreased significantly from -0.8 SDS (-1.5 to -0.2) to -1.4 SDS (-1.6 to -0.7), compared to no change in untreated PWS children. However, T3 did not change, at 0.3 SDS (-0.1 to 0.8). CONCLUSIONS: We found normal fT4 levels in most PWS children. During GH treatment, fT4 decreased significantly to low-normal levels. TSH levels remained normal. T3 levels were relatively high or normal, both before and during GH treatment, indicating that PWS children have increased T4 to T3 conversion.

Adiponectin levels in prepubertal children with Prader-Willi syndrome before and during growth hormone therapy.

CONTEXT: Children with Prader-Willi syndrome (PWS) may have obesity and an abnormal body composition with a high body fat percentage, even if they have a normal body weight. Adiponectin has been inversely related to obesity and insulin resistance. OBJECTIVE: The objective of the study was to evaluate in prepubertal PWS children the following: 1) adiponectin levels, body composition, carbohydrate metabolism, and triglyceride levels; 2) associations between adiponectin and body composition, carbohydrate metabolism, and triglycerides; and 3) effects of GH treatment on these outcome measures. PATIENTS: Twenty prepubertal PWS children participated in the study. INTERVENTION: The subjects were randomized into a GH treatment group (n=10, 1 mg/m2.d) and a non-GH-treated control group (n=10). MAIN OUTCOME MEASURES: At baseline, after 1 and 2 yr of GH treatment, fasting levels of adiponectin, glucose, insulin, and triglycerides were assessed. Body composition and fat distribution were measured by dual energy x-ray absorptiometry. RESULTS: PWS children had significantly higher median (interquartile range) adiponectin levels [17.1 mg/liter (13.9-23.2)] than healthy sex- and age-matched controls [11.8 mg/liter (9.7-12.5), P<0.005]. Body fat percentage was significantly higher than 0 sd score [1.8 sd score (1.5-2.1), P<0.001]. Adiponectin levels were inversely related to triglyceride levels (r=-0.52, P=0.03). There was a tendency to an inverse relation with body fat percentage and body mass index, but no correlation with fasting insulin or glucose levels, the insulin to glucose ratio, or homeostasis model assessment index. During GH treatment, adiponectin levels increased significantly and did not change in randomized controls. CONCLUSION: Adiponectin levels were increased, and inversely associated with triglyceride levels, in prepubertal, not overweight PWS children, although they had a relatively high body fat percentage. During GH treatment, adiponectin levels further increased, whereas no change was found in the controls, which is reassuring with respect to the development of insulin resistance during GH treatment.

Sleep-related breathing disorders in prepubertal children with Prader-Willi syndrome and effects of growth hormone treatment.

CONTEXT: Recently, several cases of sudden death in GH-treated and non-GH-treated, mainly young Prader-Willi syndrome (PWS), patients were reported. GH treatment in PWS results in a remarkable growth response and an improvement of body composition and muscle strength. Data concerning effects on respiratory parameters, are however, limited. OBJECTIVE: The objective of the study was to evaluate effects of GH on respiratory parameters in prepubertal PWS children. DESIGN: Polysomnography was performed before GH in 53 children and repeated after 6 months of GH treatment in 35 of them. PATIENTS: Fifty-three prepubertal PWS children (30 boys), with median (interquartile range) age of 5.4 (2.1-7.2) yr and body mass index of +1.0 sd score (-0.1-1.7). INTERVENTION: Intervention included treatment with GH 1 mg/m2.d. RESULTS: Apnea hypopnea index (AHI) was 5.1 per hour (2.8-8.7) (normal 0-1 per hour). Of these, 2.8 per hour (1.5-5.4) were central apneas and the rest mainly hypopneas. Duration of apneas was 15.0 sec (13.0-28.0). AHI did not correlate with age and body mass index, but central apneas decreased with age (r = -0.34, P = 0.01). During 6 months of GH treatment, AHI did not significantly change from 4.8 (2.6-7.9) at baseline to 4.0 (2.7-6.2; P = 0.36). One patient died unexpectedly during a mild upper respiratory tract infection, although he had a nearly normal polysomnography. CONCLUSIONS: PWS children have a high AHI, mainly due to central apneas. Six months of GH treatment does not aggravate the sleep-related breathing disorders in young PWS children. Our study also shows that monitoring during upper respiratory tract infection in PWS children should be considered.