A population-based nested case control study on recurrent pneumonias in children with severe generalized cerebral palsy: ethical considerations of the design and representativeness of the study sample

BACKGROUND: In children with severe generalized cerebral palsy, pneumonias are a major health issue. Malnutrition, dysphagia, gastro-oesophageal reflux, impaired respiratory function and constipation are hypothesized risk factors. Still, no data are available on the relative contribution of these possible risk factors in the described population. This paper describes the initiation of a study in 194 children with severe generalized cerebral palsy, on the prevalence and on the impact of these hypothesized risk factors of recurrent pneumonias. METHODS/DESIGN: A nested case-control design with 18 months follow-up was chosen. Dysphagia, respiratory function and constipation will be assessed at baseline, malnutrition and gastro-oesophageal reflux at the end of the follow-up. The study population consists of a representative population sample of children with severe generalized cerebral palsy. Inclusion was done through care-centres in a predefined geographical area and not through hospitals. All measurements will be done on-site which sets high demands on all measurements. If these demands were not met in "gold standard" methods, other methods were chosen. Although the inclusion period was prolonged, the desired sample size of 300 children was not met. With a consent rate of 33%, nearly 10% of all eligible children in The Netherlands are included (n = 194). The study population is subtly different from the non-participants with regard to severity of dysphagia and prevalence rates of pneumonias and gastro-oesophageal reflux. DISCUSSION: Ethical issues complicated the study design. Assessment of malnutrition and gastro-oesophageal reflux at baseline was considered unethical, since these conditions can be easily treated. Therefore, we postponed these diagnostics until the end of the follow-up. In order to include a representative sample, all eligible children in a predefined geographical area had to be contacted. To increase the consent rate, on-site measurements are of first choice, but timely inclusion is jeopardized. The initiation of this first study among children with severe neurological impairment led to specific, unexpected problems. Despite small differences between participants and non-participating children, our sample is as representative as can be expected from any population-based study and will provide important, new information to bring us further towards effective interventions to prevent pneumonias in this population

Genetic and environmental factors in associations between infant growth and adult cardiometabolic risk profile in twins

Accelerated infant growth is associated with an altered, mostly adverse adult cardiometabolic risk profile. The importance of genetic and environmental factors to these associations is unclear.status: publishe

The association of socio-economic position across the life course and age at menopause: the British Women's Heart and Health Study.

OBJECTIVE: To assess the association of indicators of adverse socio-economic position from across the life course with age at menopause. DESIGN: Cross sectional study as part of the British Women's Heart and Health Study. SETTING: 23 British towns. POPULATION: Three thousand and five hundred and thirteen women aged 60-79 years from a total cohort of 4286. Women who underwent a hysterectomy or oophorectomy prior to their 'natural' menopause or who were taking hormone replacement therapy around the perimenopausal period and for whom a biological age at menopause could not be calculated were excluded from this study. MAIN OUTCOME MEASURES: Age at menopause. RESULTS: Most of the 10 indicators of adverse socio-economic position from childhood through to adulthood were linearly associated with a younger age at menopause. In age adjusted analyses, women from manual social classes in childhood began their menopause on average 0.68 years (95% confidence interval [CI] 0.11, 1.3) earlier than those from non-manual social classes. Those who lived in a house as a child without a bathroom began their menopause 0.47 years (95% CI 0.12, 0.82) earlier than those with a bathroom. Those who shared a bedroom began 0.36 years (95% CI 0.03, 0.70) earlier than those who had their own bedroom and finally those who lived in a household with no access to a car as a child began their menopause 0.47 years (95% CI 0.02, 0.95) earlier than those with access to a car. Adult indicators of adverse socio-economic position were similarly associated with earlier age at menopause. Age at completing full time education was not substantively associated with age at menopause. The inverse associations between each of the indicators of both childhood and adult socio-economic position and age at menopause were not importantly affected by adjustment for other reproductive factors but they attenuated by between 6% and 21% with adjustment for adult smoking and body mass index. The inverse associations between each of the childhood indicators of socio-economic position only and age at menopause attenuated markedly (between 12% and 70%) with adjustment for adult leg length. There was a cumulative effect of disadvantage across the life course demonstrated by a strong linear trend between a composite score of the 10 socio-economic indicators and young age at menopause. The age at onset of menopause for women who had 9 or 10 adverse socio-economic indicators was on average 1.70 years (95% CI 0.36, 3.0) younger than that of women with none or only one indicator. CONCLUSIONS: Adverse socio-economic circumstances in childhood, as well as in adulthood, are associated with an earlier age at menopause. The association between childhood deprivation and early menopause may at least in part be mediated via exposures, such as childhood diet, which affect both linear growth and age at menopause

Development of reaching during mid-childhood from a Developmental Systems perspective

Inspired by the Developmental Systems perspective, we studied the development of reaching during mid-childhood (5-10 years of age) not just at the performance level (i.e., endpoint movements), as commonly done in earlier studies, but also at the joint angle level. Because the endpoint position (i.e., the tip of the index finger) at the reaching target can be achieved with multiple joint angle combinations, we partitioned variability in joint angles over trials into variability that does not (goal-equivalent variability, GEV) and that does (non-goal-equivalent variability, NGEV) influence the endpoint position, using the Uncontrolled Manifold method. Quantifying this structure in joint angle variability allowed us to examine whether and how spatial variability of the endpoint at the reaching target is related to variability in joint angles and how this changes over development. 6-, 8- and 10-year-old children and young adults performed reaching movements to a target with the index finger. Polynomial trend analysis revealed a linear and a quadratic decreasing trend for the variable error. Linear decreasing and cubic trends were found for joint angle standard deviations at movement end. GEV and NGEV decreased gradually with age, but interestingly, the decrease of GEV was steeper than the decrease of NGEV, showing that the different parts of the joint angle variability changed differently over age. We interpreted these changes in the structure of variability as indicating changes over age in exploration for synergies (a family of task solutions), a concept that links the performance level with the joint angle level. Our results suggest changes in the search for synergies during mid-childhood development