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Contact the study team using the details below to take part. If there are no contact details below please ask your doctor in the first instance.
Makrina
Savvidou
m.savvidou@nhs.net
Rosalie
Wagener
r.wagener@nhs.net
Dr
Makrina
Savvidou
Makrina.Savvidou@chelwest.nhs.uk
Diabetes mellitusObesity and other hyperalimentationOther maternal disorders predominantly related to pregnancy
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Fetal growth is determined by genetic, maternal, fetal and placental factors. Offspring of wom-en with diabetes mellitus (DM) (gestational, GDM, and pre-existing) are exposed to an ad-verse fetal and early neonatal environment which is associated with alterations in fetal growth patterns which in turn predisposes to disease later on in life. Infants of women with GDM have been found to have a significant increase in fat mass and percentage body fat compared to normal glucose tolerant women (Durnwald et al, 2004). Frequencies of impaired glucose toler-ance in infants of pre-existing DM mothers rose from 9.4% at 1-4 years of age to 17.4% at 5-9 years of age, while in offspring of women with GDM an increase from 11.1% up to 20% was observed (Palgemann et al, 1997). A more recent study measured the glucose tolerance in adult offspring of mothers with uncomplicated pregnancies, those affected by type 1 DM and GDM. The adjusted odds ratios for type 2 diabetes/impaired glucose tolerance was almost 8 and 4 for the offspring of women with GDM and type 1 DM respectively compared to controls (Clausen et al, 2008). Research data also suggest that exposure to a diabetic intrauterine en-vironment is associated with an increase in dyslipidaemia, subclinical vascular inflammation and endothelial dysfunction all of which are linked with development of cardiovascular disease later on in life (Vrachnis et al, 2012).
Obesity in pregnancy is associated with increased risk of adverse pregnancy outcomes such as pre-eclampsia (PE), GDM, large babies and emergency Caesarean section (Metzger et al, 2008). Obese women begin pregnancy with greater insulin resistance as compared with their normal-weight counterpart. The 50-60% increase in insulin resistance of pregnancy in associa-tion with excess nutrients and cytokines further increase the metabolic stress in which the feto-placental unit develops (Catalano et al, 2011). There is evidence that maternal obesity has an effect on fetal/neonatal body composition. Infants of overweight women have been found to have a higher total body fat mass than infants of women with normal weight, as assessed by total body electrical conductivity evaluation of body composition (Sewell et al, 2006). Further-more, children of obese mothers are at increased risk of having metabolic syndrome, regard-less of birthweight (Ruager-Martin et al, 2010), cardiovascular events or death compared to offspring of women with normal body mass index (BMI) (Reynolds et al, 2013).
Consequently, offspring of both diabetic and obese women demonstrate increased susceptibil-ity to similar adverse long-term problems including obesity and metabolic syndrome and it is conceivable that for both of these conditions, the intra-uterine environment has a detrimental effect on long term health of those individuals. However, the underlying pathophysiological mechanisms of this increased propensity to disease later on in life are largely unknown and it is possible that both of these conditions, diabetes and obesity, operate through the same pathways. There are a number of studies comparing directly the fetal/neonatal profile, as as-sessed by measurements of fat distribution, insulin resistance, fat metabolites and cytokines in the cord blood, of uncomplicated pregnancies to those complicated by diabetes or obesity separately (Catalano et al, 2009) but there is no study comparing directly and comprehensive-ly the pregnancies, and offspring, complicated by diabetes and those complicated by obesity.
Worldwide rates of obesity are increasing dramatically and more individuals are opting for bar-iatric surgery as a solution, including an increasing number of women of childbearing
age. Given the known negative effects of obesity on both fertility and pregnancy outcomes, bariatric surgery in obese women hoping to get pregnant has generally been encouraged. However, recent studies have suggested that pregnancy following bariatric surgery is associ-ated with increased risk of preterm delivery and small babies but lower risk of pre-eclampsia, GDM and large babies compared to pregnancies with similar maternal pre-pregnancy and pre-surgery BMI (Roos et al, 2013). No differences were detected in the stillbirth or neonatal death rate. The exact mechanisms of the above alterations of pregnancy complications are unknown but it is likely that micronutrient deficiency plays a role although no studies have investigated this hypothesis. Conversely, understanding the mechanisms responsible for the beneficial ef-fects of bariatric surgery may help to explain the pathogenesis of some of the most common pregnancy complications.
Metabolomics is the study of all metabolites in a cell, tissue or organ which are the end prod-ucts of different processes and are believed to give information on the metabolic profile and how this changes as a result of different environmental factors, disease and extragenomic ef-fects such as gut microflora. Any molecule less than 1 kDa in mass can be sorted out by metabolomics technology as a single final product of active/inactive genes in a given condition (genome), its activation (mRNA transcriptome), the setup of enzymatic machineries (proteo-me) and their actual biological processes. Metabolomic studies in maternal blood, urine, vagi-nal secretions and faeces can provide different information. There is a limited number of stud-ies assessing maternal metabolomics (mainly in pre-eclampsia) but there has been no study including obese, diabetic pregnant women with or without previous bariatric surgery (Fanos et al, 2013). There is also increasing evidence that vaginal microbiome diversity is associated with preterm delivery (Hyman et al, 2014).
Some studies have shown that fat is altered in patients with increased body weight. Increased gene expression of LEP in subcutaneous fat has also been shown to be significantly increased in obese subjects (Viesti A Collares et al, 2014). We would like to investigate the expression of miRNA genes in the adipose tissue of women with previous bariatric surgery compared with controls. The samples of fat tissue (intra-abdominal and subcutaneous) would be obtained at the time of a clinically indicated Caesarean section.
The aim of the current project is to assess the effect of the maternal metabolic/obesogenic en-vironment, especially following bariatric surgery, on the biochemical and phenotypi-cal/metabolic profile of the offspring. Previous studies have assessed the neonatal fat body composition using anthropometric measurements and electric conductivity. However, regional differences in adipose tissue distribution are associated with differences in adipocyte metabo-lism and obesity-related morbidities. Whole body Magnetic Resonance Imaging (MRI) of healthy newborns, a safe and non-invasive method, has been used to determine the volumes of different compartment of the body adiposity, which may have an impact on metabolic health (Modi et al, 2009). Therefore, we would like to use whole body MRI to assess the fat distribu-tion of the newborns of women with previous bariatric surgery compared to controls.
Start dates may differ between countries and research sites. The research team are responsible for keeping the information up-to-date.
The recruitment start and end dates are as follows:
Observational type: Case-controlled study;
You can take part if:
You may not be able to take part if:
We will exclude women that: 1. do not belong to any of the above groups 2. are less than 18 years of age 3. have pre-existing medical conditions apart from diabetes 4. are pregnant with twins/triplets
Below are the locations for where you can take part in the trial. Please note that not all sites may be open.
Makrina
Savvidou
m.savvidou@nhs.net
Dr
Makrina
Savvidou
Makrina.Savvidou@chelwest.nhs.uk
Rosalie
Wagener
r.wagener@nhs.net
The study is sponsored by CHELSEA AND WESTMINSTER HOSPITAL NHS FOUNDATION TRUST and funded by THE BORNE FOUNDATION .
Your feedback is important to us. It will help us improve the quality of the study information on this site. Please answer both questions.
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for Trial ID: CPMS 37697
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