A discussion of statistical methods to characterize early growth and its impact on bone mineral content later in childhood

Background Many statistical methods are available to model longitudinal growth data and relate derived summary measures to later outcomes. Aim To apply and compare commonly used methods to a realistic scenario including pre- and postnatal data, missing data and confounders. Subjects and methods Data were collected from 753 offspring in the Southampton Women’s Survey with measurements of bone mineral content (BMC) at age 6 years. Ultrasound measures included crown-rump length (11 weeks’ gestation) and femur length (19 and 34 weeks’ gestation); postnatally, infant length (birth, 6 and 12 months) and height (2 and 3 years) were measured. A residual growth model, two-stage multilevel linear spline model, joint multilevel linear spline model, SITAR and a growth mixture model were used to relate growth to 6-year BMC. Results Results from the residual growth, two-stage and joint multilevel linear spline models were most comparable: an increase in length at all ages was positively associated with BMC, the strongest association being with later growth. Both SITAR and the growth mixture model demonstrated that length was positively associated with BMC. Conclusions Similarities and differences in results from a variety of analytic strategies need to be understood in the context of each statistical methodology

Experiences of caring for a partner with Huntington’s Disease through pre and post clinical diagnosis : an interpretative phenomenological analysis

Huntington’s disease (HD) is a neurodegenerative genetic condition for which a predictive genetic test by mutation analysis has been available since 1993. However, whilst revealing the future presence of the disease, testing may have an adverse psychological impact given that the disease is progressive, incurable and ultimately fatal. The current literature review aimed to explore the published evidence base examining the psychological impact of predictive genetic testing for HD. Based on the synthesis of eight research studies, the process of predictive genetic testing was not found to be psychological neutral with fluctuating levels of distress irrelevant of test result. Methodological weaknesses were identified highlighting the needs of individuals not accessing testing or follow-up services, warranting further assessment. The research study sought to understand the lived experiences of partner carers of individuals diagnosed with HD throughout the disease trajectory. Qualitative interviews were conducted with six carers whose partners were currently accessing HD services. Analysis using Interpretative Phenomenological Analysis (IPA) revealed five super-ordinate themes with 18 sub-themes allowing for idiosyncrasies of respondents’ experiences to be accounted for. Themes were considered in relation to previous literature within HD and parallel fields with clinical implications highlighted. A need for further exploratory and subsequent quantitative research of phenomena was warranted and recommended. The critical appraisal provides the Researcher’s reflective account of the research process

Fetal growth does not modify the relationship of infant weight gain with childhood adiposity and blood pressure in the Southampton women’s survey

Background: Rapid infant weight gain is a risk factor for childhood obesity. This relationship may depend on whether infant weight gain is preceded by in-utero growth restriction. Aim: Examine whether fetal growth modifies the relationship between infant weight gain and childhood adiposity and blood pressure. Subjects and methods: 786 children in the Southampton Women’s Survey. We related infant weight gain (weight at 2 years-birth weight) to body mass index (BMI), %body fat, trunk fat (kg), systolic (SBP) and diastolic blood pressure (DBP) at age 6-7 years. Mean estimated fetal weight (EFW) between 19-34 weeks and change in EFW (19-34 weeks) were added to models as effect modifiers. Results: Infant weight gain was positively associated with all childhood outcomes. We found no evidence that these effects were modified by fetal growth (p>0.1 for all interaction terms). For example, a 1 standard deviation (SD) increase in infant weight gain was associated with an increase in BMI z-score of 0.51 (95% CI 0.37;0.64) when EFW-change was set at -2 SD-scores compared with an increase of 0.41 (95% CI 0.27;0.54,p(interaction)=0.48) when set at 2 SD-scores. Conclusion: The documented adverse consequences of rapid infant weight gain may occur regardless of whether growth was constrained in-utero.</p

Infection with EBV but not CMV downregulates antibody responses to measles.

<p>Infection with EBV is associated with reduced antibody responses to measles unless infants are coinfected with CMV. Plots of serum haemagglutinin-inhibiting activity at eleven months of age, plotted against the serostatus at <b>A</b> the time of vaccination at nine months of age and <b>B</b> the time of sampling at eleven months of age. Titres are expressed as log₂. Grey bars indicate medians. Significances refer to the statistical interaction between the effects of EBV and CMV infection.</p

Primers used for quantification of EBV by real-time PCR.

<p>Primers used for quantification of EBV by real-time PCR.</p

Antibody responses to meningococcus A and C, grouped by EBV/CMV serostatus at eleven months.

<p>*Calculated by linear regression model. Significant values in bold.</p><p>Infection with EBV at eleven months predicts reduced antibody responses to both meningococcus A and C, but infection with CMV has no effect. Groups refer to EBV and CMV serostatus at the time of sampling at 11 months.</p

Study Design.

<p><b>A</b> Study design showing times at which samples were collected, EBV and CMV serology was carried out, vaccines were administered and vaccine-specific responses were measured. <b>B</b> numbers of infants in the cohort and involved in analysis, and numbers infected with EBV and CMV at nine and eleven months.</p

Antibody responses to meningococcus A and C, grouped by EBV/CMV serostatus at nine months.

<p>*Calculated by linear regression model. Significant values in bold.</p><p>Infection with EBV at time of vaccine administration at nine months predicts reduced antibody responses to both meningococcus A and C, but infection with CMV has no effect. Groups refer to the CMV and EBV serostatus at the time the vaccine was administered at nine months.</p

Mean z scores for femur length, abdominal circumference and biparietal diameter for fetuses exposed to maternal smoking relative to non-exposed fetuses.

<p>The vertical lines correspond to 95% confidence intervals.</p

Summary of results from the papers identified in the systematic review.

<p>Summary of results from the papers identified in the systematic review.</p