Summary Obesity is rising in the obstetric population, yet there is an absence of services and guidance for the management of maternal obesity. This systematic review aimed to investigate relationships between obesity and impact on obstetric care. Literature was systematically searched for cohort studies of pregnant women with anthropometric measurements recorded within 16‐weeks gestation, followed up for the term of the pregnancy, with at least one obese and one comparison group. Two researchers independently data‐extracted and quality‐assessed each included study. Outcome measures were those that directly or indirectly impacted on maternity resources. Primary outcomes included instrumental delivery, caesarean delivery, duration of hospital stay, neonatal intensive care, neonatal trauma, haemorrhage, infection and 3rd/4th degree tears. Meta‐analysis shows a significant relationship between obesity and increased odds of caesarean and instrumental deliveries, haemorrhage, infection, longer duration of hospital stay and increased neonatal intensive care requirement. Maternal obesity significantly contributes to a poorer prognosis for mother and baby during delivery and in the immediate post‐partum period. National clinical guidelines for management of obese pregnant women, and public health interventions to help safeguard the health of mothers and their babies are urgently required.

Objective The aim of this study was to identify trends in maternal obesity incidence over time and to identify those women most at risk and potential-associated health inequalities.Design Longitudinal database study.Setting James Cook University Hospital maternity unit, Middlesbrough, UK. Methods Trends in maternal obesity incidence over time were analysed using chi-square test for trend. Demographic predictor variables were analysed using multivariate logistic regression, adjusting for confounding factors after testing for multicollinearity. National census data were used to place the regional data into the context of the general population.Main outcome measure Trends in maternal obesity incidence. Demographic predictor variables included ethnic group, age, parity, marital status, employment and socio-economic disadvantage.Results The proportion of obese women at the start of pregnancy has increased significantly over time from 9.9 to 16.0% (P < 0.01). This is best described by a quadratic model (P < 0.01) showing that the rate is accelerating; by 2010, the rate will have increased to 22% of this population if the trend continues. There is also a significant relationship with maternal obesity and mothers' residing in areas of most deprivation (odds ratio [OR] = 2.44, 95% CI = 1.98, 3.02, P < 0.01), with increasing age (OR = 1.04, 95% CI = 1.04, 1.05, P < 0.01), and parity (OR = 1.17, 95% CI = 1.12, 1.21, P < 0.01).Conclusions The incidence of maternal obesity at the start of pregnancy is increasing and accelerating. Predictors of maternal obesity are associated with health inequalities, particularly socio-economic disadvantage.

BackgroundGermline pathogenic variants in SDHB/SDHC/SDHD are the most frequent causes of inherited phaeochromocytomas/paragangliomas. Insufficient information regarding penetrance and phenotypic variability hinders optimum management of mutation carriers. We estimate penetrance for symptomatic tumours and elucidate genotype–phenotype correlations in a large cohort of SDHB/SDHC/SDHD mutation carriers.MethodsA retrospective survey of 1832 individuals referred for genetic testing due to a personal or family history of phaeochromocytoma/paraganglioma. 876 patients (401 previously reported) had a germline mutation in SDHB/SDHC/SDHD (n=673/43/160). Tumour risks were correlated with in silico structural prediction analyses.ResultsTumour risks analysis provided novel penetrance estimates and genotype–phenotype correlations. In addition to tumour type susceptibility differences for individual genes, we confirmed that the SDHD:p.Pro81Leu mutation has a distinct phenotype and identified increased age-related tumour risks with highly destabilising SDHB missense mutations. By Kaplan-Meier analysis, the penetrance (cumulative risk of clinically apparent tumours) in SDHB and (paternally inherited) SDHD mutation-positive non-probands (n=371/67 with detailed clinical information) by age 60 years was 21.8% (95% CI 15.2% to 27.9%) and 43.2% (95% CI 25.4% to 56.7%), respectively. Risk of malignant disease at age 60 years in non-proband SDHB mutation carriers was 4.2%(95% CI 1.1% to 7.2%). With retrospective cohort analysis to adjust for ascertainment, cumulative tumour risks for SDHB mutation carriers at ages 60 years and 80 years were 23.9% (95% CI 20.9% to 27.4%) and 30.6% (95% CI 26.8% to 34.7%).ConclusionsOverall risks of clinically apparent tumours for SDHB mutation carriers are substantially lower than initially estimated and will improve counselling of affected families. Specific genotype–tumour risk associations provides a basis for novel investigative strategies into succinate dehydrogenase-related mechanisms of tumourigenesis and the development of personalised management for SDHB/SDHC/SDHD mutation carriers.

SummaryPPARγ is essential for adipogenesis and metabolic homeostasis. We describe mutations in the DNA and ligand binding domains of human PPARγ in lipodystrophic, severe insulin resistance. These receptor mutants lack DNA binding and transcriptional activity but can translocate to the nucleus, interact with PPARγ coactivators and inhibit coexpressed wild-type receptor. Expression of PPARγ target genes is markedly attenuated in mutation-containing versus receptor haploinsufficent primary cells, indicating that such dominant-negative inhibition operates in vivo. Our observations suggest that these mutants restrict wild-type PPARγ action via a non-DNA binding, transcriptional interference mechanism, which may involve sequestration of functionally limiting coactivators.

Purpose Mutations in the mitochondrial enzyme succinate dehydrogenase (SDH) subunit genes are associated with a wide spectrum of tumours including phaeochromocytoma and paraganglioma (PPGL) 1, 2, gastrointestinal stromal tumours (GIST) 3, renal cell carcinoma (RCC) 4 and pituitary adenomas5. SDH-related tumorigenesis is believed to be secondary to accumulation of the oncometabolite succinate. Our aim was to investigate the potential clinical applications of MRI spectroscopy (1H-MRS) in a range of suspected SDH-related tumours. Patients and methods Fifteen patients were recruited to this study. Respiratory-gated single-voxel 1H-MRS was performed at 3T to quantify the content of succinate at 2.4 ppm and choline at 3.22 ppm. Results A succinate peak was seen in six patients, all of whom had a germline SDHx mutation or loss of SDHB by immunohistochemistry. A succinate peak was also detected in two patients with a metastatic wild-type GIST (wtGIST) and no detectable germline SDHx mutation but a somatic epimutation in SDHC. Three patients without a tumour succinate peak retained SDHB expression, consistent with SDH functionality. In six cases with a borderline or absent peak, technical difficulties such as motion artefact rendered 1H-MRS difficult to interpret. Sequential imaging in a patient with a metastatic abdominal paraganglioma demonstrated loss of the succinate peak after four cycles of [177Lu]-DOTATATE, with a corresponding biochemical response in normetanephrine. Conclusions This study has demonstrated the translation into clinical practice of in vivo metabolomic analysis using 1H-MRS in patients with SDH-deficient tumours. Potential applications include non-invasive diagnosis and disease stratification, as well as monitoring of tumour response to targeted treatments.