No evidence for involvement of SDHD in neuroblastoma pathogenesis

BACKGROUND: Deletions in the long arm of chromosome 11 are observed in a subgroup of advanced stage neuroblastomas with poor outcome. The deleted region harbours the tumour suppressor gene SDHD that is frequently mutated in paraganglioma and pheochromocytoma, which are, like neuroblastoma, tumours originating from the neural crest. In this study, we sought for evidence for involvement of SDHD in neuroblastoma. METHODS: SDHD was investigated on the genome, transcriptome and proteome level using mutation screening, methylation specific PCR, real-time quantitative PCR based homozygous deletion screening and mRNA expression profiling, immunoblotting, functional protein analysis and ultrastructural imaging of the mitochondria. RESULTS: Analysis at the genomic level of 67 tumour samples and 37 cell lines revealed at least 2 bona-fide mutations in cell lines without allelic loss at 11q23: a 4bp-deletion causing skip of exon 3 resulting in a premature stop codon in cell line N206, and a Y93C mutation in cell line NMB located in a region affected by germline SDHD mutations causing hereditary paraganglioma. No evidence for hypermethylation of the SDHD promotor region was observed, nor could we detect homozygous deletions. Interestingly, SDHD mRNA expression was significantly reduced in SDHD mutated cell lines and cell lines with 11q allelic loss as compared to both cell lines without 11q allelic loss and normal foetal neuroblast cells. However, protein analyses and assessment of mitochondrial morphology presently do not provide clues as to the possible effect of reduced SDHD expression on the neuroblastoma tumour phenotype. CONCLUSIONS: Our study provides no indications for 2-hit involvement of SDHD in the pathogenesis of neuroblastoma. Also, although a haplo-insufficient mechanism for SDHD involvement in advanced stage neuroblastoma could be considered, the present data do not provide consistent evidence for this hypothesis

Reappraisal of Gestational Weight Gain Recommendations in Obese Pregnant Women: A Population-Based Study of 337,590 Births

BACKGROUND AND OBJECTIVE: Maternal obesity is an epidemic health problem that is aggravated by excessive gestational weight gain (GWG) and postpartum weight retention. Current US Institute of Medicine (now US National Academy of Medicine) guidelines (2009) for GWG need to be evaluated against the current rise in obesity in the general and pregnant population. We wanted to study the relation between GWG and pregnancy and birth outcomes and to relate this to the current recommendations for GWG. METHODS: Population-based study. We performed an epidemiological analysis in a cohort of Belgian pregnant women with singleton live births at term (≥37 weeks) between 2009 and 2014 (n = 337,590). Logistic regression was used to determine the optimal GWG in relation to relevant pregnancy and birth outcomes. RESULTS: The prevalence of maternal obesity significantly increased from 10.3% in 2009 to 11.4% in 2014. The mean (SD) body mass index at the start of the pregnancy significantly increased from 23.9 (4.5) in 2009 to 24.2 (4.6) in 2014. Excessive GWG was frequent, especially in overweight (56.8%) and obese (52.9%) pregnant women. In the logistic regression model, the amount of GWG associated with the lowest incidence of both large-for-gestational-age and small-for-gestational-age infants was 21 kg in underweight women, 14 kg in normal weight, 8 kg in overweight, 0 kg in obese class I, -4 kg in obese class II and -5 kg in obese class III. CONCLUSION: The prevalence of maternal obesity has risen in Belgium between 2009 and 2014. Current GWG guidelines, based on historic observational data, are probably too liberal for class II and III obese women in which better outcomes are being predicted for lower weight gain than recommended.status: publishe

Perinatal Resilience for the First 1,000 Days of Life. Concept Analysis and Delphi Survey

Background: The ability to cope with challenges and stress in life is generally understood as resilience. Pregnancy and parenthood are challenging times. The concept of resilience is receiving increasing interest from researchers, clinicians, and policy staff because of its potential impact on health, well-being, and quality of life. Nevertheless, the concept is less studied during the perinatal period. Objectives: The aim of this study is to understand the concept of perinatal resilience, including the underlying processes and more specifically for the first 1,000 days of life. Methods: A concept analysis according to the Walker and Avant (2011) framework was used, to investigate the basic elements of the concept. Concurrently, a two-round Delphi survey involving researchers, clinicians, epidemiologists, mothers, and fathers (N = 21), was conducted to prioritize the terms associated with perinatal resilience. Data collection took place between January and April 2019. Results: Through concept analysis and Delphi survey, five defining attributes for perinatal resilience were identified: social support, self-efficacy, self-esteem, sense of mastery and personality. The additional terms, rated important by the Delphi survey, were linked to the consequences of being resilient during the perinatal period for the individual and his/her family. Specifically, highlighted were the experiences of families in personal growth and achieving family balance, adaptation, or acceptance. Conclusion: Based on the results of the concept analysis and Delphi survey, we describe perinatal resilience for the first 1,000 days as a circular process towards a greater well-being in the form of personal growth, family balance, adaptation or acceptance, when faced with stressors, challenges or adversity during the perinatal period. The presence of resiliency attributes such as social support, sense of mastery, self-efficacy, and self-esteem enhance the capacity to be resilient and probably prevent mental health problems.status: publishe