The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies.

BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). METHODS: Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. RESULTS: At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. CONCLUSIONS: Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin

Indicators of dietary patterns in Danish infants at 9 months of age

Background: It is important to increase the awareness of indicators associated with adverse infant dietary patterns to be able to prevent or to improve dietary patterns early on. Objective: The aim of this study was to investigate the association between a wide range of possible family and child indicators and adherence to dietary patterns for infants aged 9 months. Design: The two dietary patterns ‘Family Food’ and ‘Health-Conscious Food’ were displayed by principal component analysis, and associations with possible indicators were analysed by multiple linear regressions in a pooled sample (n=374) of two comparable observational cohorts, SKOT I and SKOT II. These cohorts comprised infants with mainly non-obese mothers versus infants with obese mothers, respectively. Results: A lower Family Food score indicates a higher intake of liquid baby food, as this pattern shows transition from baby food towards the family's food. Infants, who were younger at diet registration and had higher body mass index (BMI) z-scores at 9 months, had lower Family Food pattern scores. A lower Family Food pattern score was also observed for infants with immigrant/descendant parents, parents who shared cooking responsibilities and fathers in the labour market compared to being a student, A lower Health-Conscious Food pattern score indicates a less healthy diet. A lower infant Health-Conscious Food pattern score was associated with a higher maternal BMI, a greater number of children in the household, a higher BMI z-score at 9 months, and a higher infant age at diet registration. Conclusions: Associations between infant dietary patterns and maternal, paternal, household, and child characteristics were identified. This may improve the possibility of identifying infants with an increased risk of developing unfavourable dietary patterns and potentially enable an early targeted preventive support

The association between newborn regional body composition and cord blood concentrations of C-peptide and insulin-like growth factor I

Third trimester fetal growth is partially regulated by C-peptide and insulin-like growth factor I (IGF-I). Prenatal exposures including maternal obesity and high gestational weight gain as well as high birth weight have been linked to subsequent metabolic disease. We evaluated the associations between newborn regional body composition and cord blood levels of C-peptide and IGF-I.We prospectively included obese and normal-weight mothers and their newborns; cord blood was collected and frozen. Analyses of C-peptide and IGF-I were performed simultaneously, after recruitment was completed. Newborn regional body composition was assessed with dual-energy X-ray absorptiometry scanning (DXA) within 48 hours of birth.Three hundred thirty-six term infants were eligible to participate in the study; of whom 174 (52%) infants had cord blood taken. Total, abdominal and arm and leg fat mass were positively associated with C-peptide (p < 0.001). Arm and leg fat mass was associated with IGF-I concentration: 28 g [95% confidence interval: 4, 53] per doubling of IGF-I. There was no association between total or abdominal fat mass and IGF-I. Fat-free mass was positively associated with both C-peptide (p < 0.001) and IGF-I (p = 0.004).Peripheral fat tissue accumulation was associated with cord blood C-peptide and IGF-I. Total and abdominal fat masses were related to C-peptide but not to IGF-I. Thus, newborn adiposity is partially mediated through C-peptide and early linear growth is associated with IGF-I

Intake of Sweets, Snacks and Soft Drinks Predicts Weight Gain in Obese Pregnant Women: Detailed Analysis of the Results of a Randomised Controlled Trial

Background: Lifestyle interventions targeting obese pregnant women often result in modest reduction in gestational weight gain, pregnancy complications and related risk factors. Examining adherence to the intervention can, however, provide valuable information on the importance of the different factors targeted. Objective: To evaluate improvements and relevance of different dietary factors targeted with respect to gestational weight gain in a 3-arm Randomised Controlled Trial (n=342) among obese pregnant women with BMI≥30 kg/m2. Methods: Randomisation 1:1:1 to either hypocaloric Mediterranean type of diet and physical activity intervention (D+PA); physical activity intervention alone (PA); or control (C). Diet was assessed at baseline (weeks 11–14) and endpoint (weeks 36–37) using a validated food frequency questionnaire. Results: During the intervention women in the D+PA group significantly lowered their intakes of added sugars and saturated fat and increased their protein intake by ~1% of total energy compared to controls. Of these dietary variables only intakes of added sugar appeared to be related to GWG, while no association was observed for saturated fat or protein. Further analyses revealed that foods that contributed to intake of added sugars, including sweets, snacks, cakes, and soft drinks were strongly associated with weight gain, with women consuming sweets ≥2/day having 5.4 kg (95% CI 2.1-8.7) greater weight gain than those with a low (<1wk) intake. The results for soft drinks were more conflicting, as women with high weight gain tended to favour artificially sweetened soft drinks. Conclusion: In our sample of obese pregnant women, craving for sweets, snacks, and soft drinks strongly predicts GWG. Emphasis on reducing intakes of these foods may be more relevant for limiting gestational weight gain than encouraging strict compliance to more specific diets. Trial Registration ClinicalTrials.gov NCT0134514

Acceptability of financial incentives and penalties for encouraging uptake of healthy behaviours: focus groups

BACKGROUND: There is evidence that financial incentive interventions, which include both financial rewards and also penalties, are effective in encouraging healthy behaviours. However, concerns about the acceptability of such interventions remain. We report on focus groups with a cross-section of adults from North East England exploring their acceptance of financial incentive interventions for encouraging healthy behaviours amongst adults. Such information should help guide the design and development of acceptable, and effective, financial incentive interventions. METHODS: Eight focus groups with a total of 74 adults were conducted between November 2013 and January 2014 in Newcastle upon Tyne, UK. Focus groups lasted approximately 60 minutes and explored factors that made financial incentives acceptable and unacceptable to participants, together with discussions on preferred formats for financial incentives. Verbatim transcripts were thematically coded and analysed in Nvivo 10. RESULTS: Participants largely distrusted health promoting financial incentives, with a concern that individuals may abuse such schemes. There was, however, evidence that health promoting financial incentives may be more acceptable if they are fair to all recipients and members of the public; if they are closely monitored and evaluated; if they are shown to be effective and cost-effective; and if clear health education is provided alongside health promoting financial incentives. There was also a preference for positive rewards rather than negative penalties, and for shopping vouchers rather than cash incentives. CONCLUSIONS: This qualitative empirical research has highlighted clear suggestions on how to design health promoting financial incentives to maximise acceptability to the general public. It will also be important to determine the acceptability of health promoting financial incentives in a range of stakeholders, and in particular, those who fund such schemes, and policy-makers who are likely to be involved with the design, implementation and evaluation of health promoting financial incentive schemes. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12889-015-1409-y) contains supplementary material, which is available to authorized users

Skin care interventions in infants for preventing eczema and food allergy

BackgroundEczema and food allergy are common health conditions that usually begin in early childhood and often occur together in the same people. They can be associated with an impaired skin barrier in early infancy. It is unclear whether trying to prevent or reverse an impaired skin barrier soon after birth is effective in preventing eczema or food allergy.ObjectivesPrimary objectiveTo assess effects of skin care interventions, such as emollients, for primary prevention of eczema and food allergy in infantsSecondary objectiveTo identify features of study populations such as age, hereditary risk, and adherence to interventions that are associated withthe greatest treatment benefit or harm for both eczema and food allergy.Search methodsWe searched the following databases up to July 2020: Cochrane Skin Specialised Register, CENTRAL, MEDLINE, and Embase. We searched two trials registers and checked reference lists of included studies and relevant systematic reviews for further references to relevant randomised controlled trials (RCTs). We contacted field experts to identify planned trials and to seek information about unpublished or incomplete trials.Selection criteriaRCTs of skin care interventions that could potentially enhance skin barrier function, reduce dryness, or reduce subclinical inflammation in healthy term (> 37 weeks) infants (0 to 12 months) without pre‐existing diagnosis of eczema, food allergy, or other skin condition were included. Comparison was standard care in the locality or no treatment. Types of skin care interventions included moisturisers/emollients; bathing products; advice regarding reducing soap exposure and bathing frequency; and use of water softeners. No minimum follow‐up was required.Data collection and analysisThis is a prospective individual participant data (IPD) meta‐analysis. We used standard Cochrane methodological procedures, and primary analyses used the IPD dataset. Primary outcomes were cumulative incidence of eczema and cumulative incidence of immunoglobulin (Ig)E‐mediated food allergy by one to three years, both measured by the closest available time point to two years. Secondary outcomes included adverse events during the intervention period; eczema severity (clinician‐assessed); parent report of eczema severity; time to onset of eczema; parent report of immediate food allergy; and allergic sensitisation to food or inhalant allergen.Main resultsThis review identified 33 RCTs, comprising 25,827 participants. A total of 17 studies, randomising 5823 participants, reported information on one or more outcomes specified in this review. Eleven studies randomising 5217 participants, with 10 of these studies providing IPD, were included in one or more meta‐analysis (range 2 to 9 studies per individual meta‐analysis).Most studies were conducted at children's hospitals. All interventions were compared against no skin care intervention or local standard care. Of the 17 studies that reported our outcomes, 13 assessed emollients. Twenty‐five studies, including all those contributing data to meta‐analyses, randomised newborns up to age three weeks to receive a skin care intervention or standard infant skin care. Eight of the 11 studies contributing to meta‐analyses recruited infants at high risk of developing eczema or food allergy, although definition of high risk varied between studies. Durations of intervention and follow‐up ranged from 24 hours to two years.We assessed most of this review's evidence as low certainty or had some concerns of risk of bias. A rating of some concerns was most often due to lack of blinding of outcome assessors or significant missing data, which could have impacted outcome measurement but was judged unlikely to have done so. Evidence for the primary food allergy outcome was rated as high risk of bias due to inclusion of only one trial where findings varied when different assumptions were made about missing data.Skin care interventions during infancy probably do not change risk of eczema by one to two years of age (risk ratio (RR) 1.03, 95% confidence interval (CI) 0.81 to 1.31; moderate‐certainty evidence; 3075 participants, 7 trials) nor time to onset of eczema (hazard ratio 0.86, 95% CI 0.65 to 1.14; moderate‐certainty evidence; 3349 participants, 9 trials). It is unclear whether skin care interventions during infancy change risk of IgE‐mediated food allergy by one to two years of age (RR 2.53, 95% CI 0.99 to 6.47; 996 participants, 1 trial) or allergic sensitisation to a food allergen at age one to two years (RR 0.86, 95% CI 0.28 to 2.69; 1055 participants, 2 trials) due to very low‐certainty evidence for these outcomes. Skin care interventions during infancy may slightly increase risk of parent report of immediate reaction to a common food allergen at two years (RR 1.27, 95% CI 1.00 to 1.61; low‐certainty evidence; 1171 participants, 1 trial). However, this was only seen for cow’s milk, and may be unreliable due to significant over‐reporting of cow’s milk allergy in infants. Skin care interventions during infancy probably increase risk of skin infection over the intervention period (RR 1.34, 95% CI 1.02 to 1.77; moderate‐certainty evidence; 2728 participants, 6 trials) and may increase risk of infant slippage over the intervention period (RR 1.42, 95% CI 0.67 to 2.99; low‐certainty evidence; 2538 participants, 4 trials) or stinging/allergic reactions to moisturisers (RR 2.24, 95% 0.67 to 7.43; low‐certainty evidence; 343 participants, 4 trials), although confidence intervals for slippages and stinging/allergic reactions are wide and include the possibility of no effect or reduced risk.Preplanned subgroup analyses show that effects of interventions were not influenced by age, duration of intervention, hereditary risk, FLG mutation, or classification of intervention type for risk of developing eczema. We could not evaluate these effects on risk of food allergy. Evidence was insufficient to show whether adherence to interventions influenced the relationship between skin care interventions and risk of developing eczema or food allergy.Authors' conclusionsSkin care interventions such as emollients during the first year of life in healthy infants are probably not effective for preventing eczema, and probably increase risk of skin infection. Effects of skin care interventions on risk of food allergy are uncertain.Further work is needed to understand whether different approaches to infant skin care might promote or prevent eczema and to evaluate effects on food allergy based on robust outcome assessments

Erratum to: Methods for evaluating medical tests and biomarkers

[This corrects the article DOI: 10.1186/s41512-016-0001-y.]

Integrated genomic characterization of pancreatic ductal adenocarcinoma

We performed integrated genomic, transcriptomic, and proteomic profiling of 150 pancreatic ductal adenocarcinoma (PDAC) specimens, including samples with characteristic low neoplastic cellularity. Deep whole-exome sequencing revealed recurrent somatic mutations in KRAS, TP53, CDKN2A, SMAD4, RNF43, ARID1A, TGFβR2, GNAS, RREB1, and PBRM1. KRAS wild-type tumors harbored alterations in other oncogenic drivers, including GNAS, BRAF, CTNNB1, and additional RAS pathway genes. A subset of tumors harbored multiple KRAS mutations, with some showing evidence of biallelic mutations. Protein profiling identified a favorable prognosis subset with low epithelial-mesenchymal transition and high MTOR pathway scores. Associations of non-coding RNAs with tumor-specific mRNA subtypes were also identified. Our integrated multi-platform analysis reveals a complex molecular landscape of PDAC and provides a roadmap for precision medicine

Evidence synthesis to inform model-based cost-effectiveness evaluations of diagnostic tests: a methodological systematic review of health technology assessments

Background: Evaluations of diagnostic tests are challenging because of the indirect nature of their impact on patient outcomes. Model-based health economic evaluations of tests allow different types of evidence from various sources to be incorporated and enable cost-effectiveness estimates to be made beyond the duration of available study data. To parameterize a health-economic model fully, all the ways a test impacts on patient health must be quantified, including but not limited to diagnostic test accuracy. Methods: We assessed all UK NIHR HTA reports published May 2009-July 2015. Reports were included if they evaluated a diagnostic test, included a model-based health economic evaluation and included a systematic review and meta-analysis of test accuracy. From each eligible report we extracted information on the following topics: 1) what evidence aside from test accuracy was searched for and synthesised, 2) which methods were used to synthesise test accuracy evidence and how did the results inform the economic model, 3) how/whether threshold effects were explored, 4) how the potential dependency between multiple tests in a pathway was accounted for, and 5) for evaluations of tests targeted at the primary care setting, how evidence from differing healthcare settings was incorporated. Results: The bivariate or HSROC model was implemented in 20/22 reports that met all inclusion criteria. Test accuracy data for health economic modelling was obtained from meta-analyses completely in four reports, partially in fourteen reports and not at all in four reports. Only 2/7 reports that used a quantitative test gave clear threshold recommendations. All 22 reports explored the effect of uncertainty in accuracy parameters but most of those that used multiple tests did not allow for dependence between test results. 7/22 tests were potentially suitable for primary care but the majority found limited evidence on test accuracy in primary care settings. Conclusions: The uptake of appropriate meta-analysis methods for synthesising evidence on diagnostic test accuracy in UK NIHR HTAs has improved in recent years. Future research should focus on other evidence requirements for cost-effectiveness assessment, threshold effects for quantitative tests and the impact of multiple diagnostic tests