Children of obese mothers at greater risk of early heart death as adults

Main Category: Obesity / Weight Loss / Fitness
Also Included In: Cardiovascular / Cardiology
Article Date: 14 Aug 2013 - 0:00 PDT Current ratings for:
Children of obese mothers at greater risk of early heart death as adults

Children of obese and overweight women have a higher risk of early cardiovascular death as adults, finds a study published on bmj.com.

The findings highlight the urgent need for strategies to prevent obesity in women of childbearing age and the need to assess the offspring of obese mothers for their cardiovascular risk, say the authors.

Rates of maternal obesity have risen rapidly in the past two decades. In the United States, about 64% of women of reproductive age are overweight and 35% are obese, with a similar pattern in Europe.

Many studies have shown a link between maternal obesity and disease later in life, but it is still not clear whether maternal obesity is associated with increased death in offspring from cardiovascular causes.

Using birth and death records from 1950 to the present day, a team of researchers from the Universities of Edinburgh and Aberdeen in Scotland identified 28,540 women - whose body mass index (BMI) was recorded at their first antenatal visit - and their 37,709 offspring who were aged between 34 and 61 at the time of follow up.

BMI was defined as underweight (BMI 18.5 or less), normal weight (BMI 18.5-24.9), overweight (BMI 25-29.9), and obese (BMI 30 or more).

Relevant details about the pregnancy were collated, including the mother's age at delivery, number of previous pregnancies, mother and father's social class and infant sex, birth weight and gestation at delivery.

Among the mothers, 21% were overweight and 4% were obese. Among the 37,709 offspring there were 6551 premature deaths from any cause and, among the deceased, 294 had had obese mothers at birth.

The researchers found that the risk of premature death was 35% higher in the adult offspring of obese mothers compared to those whose mothers had had normal weight. This was after adjusting the results for factors including the mother's age at delivery, number of previous pregnancies, mother and father's social class and infant sex, birth weight and gestation at delivery.

They also found a 42% increased risk (adjusted for the same factors) of a hospital admission for a cardiovascular event in the adult offspring of obese mothers compared with offspring of mothers with normal BMI.

The offspring of overweight mothers also had a higher risk of adverse events later in life.

It is thought that being overweight in pregnancy may cause permanent changes in appetite control and energy metabolism in the offspring, leading to a greater risk of heart problems later in life.

With rising rates of excess weight among pregnant women, the authors say their findings are "a major public health concern" and indicate that the offspring of obese mothers are a high risk group who should be assessed for cardiovascular risk, and actively encouraged to maintain a healthy lifestyle.

"As one in five women in the UK is currently obese at antenatal booking, strategies to optimise weight before pregnancy are urgently required," they conclude.

Dr Sohinee Bhattacharya, of the University of Aberdeen, said: "This study highlights the importance of weight management in mothers and their offspring. We need to find out how to help young women and their children control their weight better so that chronic disease risk is not transmitted from generation to generation."

Jacqui Clinton, Health Campaigns Director at Tommy's, said: "This new study adds to a growing body of evidence that obesity during pregnancy can have a long term impact on children, affecting their adult weight, health and even their life expectancy. If we are to tackle obesity in the UK, we need to start at conception and help mums to limit the impact of their weight on their babies - research shows that eating a healthy diet and taking moderate exercise while pregnant can make a big difference. Looking after a baby's health while in the womb may not only increase the chances of a healthy birth, but of a longer, healthier life."

In an accompanying editorial, Dr Factor-Litvak from the Department of Epidemiology in New York, says that this study leaves open two questions. Firstly, what is the role of the early post natal environment and secondly, what is the role of parental obesity? She asks what the implications of the study are, concluding that along with recommended weight gain for overweight and obese women, "interventions should begin before pregnancy".

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Later-life death risks for children born to obese mothers

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Main Category: Obesity / Weight Loss / Fitness
Also Included In: Pediatrics / Children's Health;  Cardiovascular / Cardiology
Article Date: 14 Aug 2013 - 8:00 PDT Current ratings for:
Later-life death risks for children born to obese mothers

Approaching pregnancy with a healthy body is common sense, but a new study published in the British Medical Journal has quantified the risks of maternal obesity, finding that children born to obese mothers are more likely to die prematurely in their later adult years.

The authors of the BMJ study say that in the US, about 64% of women in the child-bearing age bracket are overweight and 35% are obese, creating "a major public health concern" for high-risk groups of people who should be assessed for their cardiovascular risk.

Researchers in Scotland who led the study used birth and death records beginning in 1950 and continuing to the present day. In total, they analyzed 28,540 women's files, which included a body mass index (BMI) reading from the first antenatal visit. The researchers also studied the resulting 37,709 offspring aged between 34 and 61 at the time of follow-up visits.

The researchers classified the women by four groups:

Underweight - BMI of 18.5 or underNormal weight - BMI between 18.5 and 24.9Overweight - BMI between 25 and 29.9Obese - BMI of 30 or more.

Of the women in the study, 21% were overweight and 4% were obese, which is a decidedly lower rate than today's numbers in the US cited by the researchers, of 65% and 35%, respectively.

Still, the results showed that the risk of premature death for the adult offspring of obese women, compared with offspring of normal weight mothers, was 35% higher.

Children of obese pregnant women had a higher risk of early death as adults

Additionally, there was a 42% higher risk for being admitted to the hospital due to a "cardiovascular event" in the adult offspring of obese mothers.

The findings show that the main cause of death from the entire offspring population was cardiovascular disease (24% of male deaths and 13% of female deaths) and cancer (26% of male deaths and 42% of female deaths).

The results adjusted for factors such as the mother's age at delivery, previous pregnancies, parental social class, as well as the infant's sex, weight and gestation at birth, say the researchers.

In an editorial response to the study, Pam Factor-Litvak from Columbia University notes that maternal obesity has already been associated with risks for the mother, including increased mortality, pre-eclampsia and diabetes.

Additionally, she says that risks for children of obese mothers have likewise been established: increased risk of becoming obese later in life themselves, hypertension, asthma or behavioral problems.

However, she also says this recent study is the first to link maternal obesity and risk of cardiovascular death in mid-life.

She notes that there may be some implications after the findings of the recent study:

"The US Institute of Medicine guidelines, adopted in 2009, recommend weight gains of 15 lbs. to 25 lbs., and 11-20 lbs. for overweight and obese pregnant women, respectively, with no more than 0.6-0.5 lb weight gain per week in the second and third trimesters."

Because these recommendations were made to balance risks involving fetal growth and other complications, Pam Factor-Litvak notes that appropriate diet and exercise should be discussed during pregnancy.

The authors of the study conclude by noting:

"Our findings highlight the urgent need for strategies to prevent obesity in women of childbearing age and the need to assess the offspring of obese mothers for their cardiovascular risk."

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The 4-point test to predict death risk from C. difficile

Main Category: Infectious Diseases / Bacteria / Viruses
Article Date: 05 Aug 2013 - 1:00 PDT Current ratings for:
The 4-point test to predict death risk from C. difficile

A Clostridium difficile (C. diff) infection is one that can affect the digestive system and most commonly affects people staying in hospital. It is not generally a problem for healthy people but may infect those on antibiotics with an imbalance of 'good bacteria' in the gut.

A research paper published on the 2nd August 2013, in BMC Infectious Diseases has for the first time identified a unique four-point test using easily measurable clinical variables which can be used to accurately predict the death risk to patients from C. diff. Accurate prediction means that those patients at risk can be managed accordingly by the clinical team.

There were 17,414 reported cases in England in 2011 and C. diff related deaths accounted for 1.1 per cent of all deaths in England and Wales between 2006 and 2010. Patients over the age of 65 have particular risk of dying from a C. diff infection. Of those, 20 per cent are likely to have a recurrence of infection once antibiotics are withdrawn, and there is growing concern regarding the increasing number of C. diff strains resistant to drug therapies.

The research team behind the study are from the University of Exeter and the Royal Devon & Exeter NHS Foundation Trust (RD&E) and are supported by the National Institute for Health Research Collaboration for Leadership in Applied Health Research and Care in the South West Peninsula (NIHR PenCLAHRC).

Joint lead author of the study was Dr. Steve Michell, Senior Lecturer in Molecular Microbiology at the University of Exeter. He said: "Our findings are exciting because they identify a simple, accurate and robust method to identify those patients who are at risk of dying from a C. diff infection. The clinical variables identified are easily measurable, using tests that are commonly carried out in hospital. The results of our study strengthen the evidence for establishing the use of this rule in clinical settings: the benefits to patient well-being, the efficient management of infection in hospital and potential savings to the NHS and other health services around the world, would be immense."

He added: "Our thanks go to colleagues at the RD&E and their patients for their involvement in this study."

The study analysed the clinical notes of 213 patients who had been transferred to the RD&E's specialised C. diff ward between 2007 and 2009. The RD&E's C. diff rate was below the national average during this timescale.

Analysis of the clinical notes, wider information gathered while the patients were in hospital and a follow-up a minimum of 30-days post-discharge, was used by the research team to identify the four points of the test.

These include:

serum albumin levels (protein in blood plasma)respiratory rateC-reactive protein (a protein found in blood, the levels of which rise in inflammation)and white cell count.

A simple four variable prediction rule was devised based on acceptable thresholds for the results of each test.

The rule's comparative simplicity, using fewer variables than those proscribed by other studies, means that it could be used by non-specialists when assessing patients within or around 48 hours of diagnosis. This in turn means that more clinicians could carry out assessments, with more patients assessed and management interventions put in place.

Dr. Ray Sheridan, Consultant Physician at the RD&E, said: "Patients with C. difficile are often much sicker than they might first look. They generally have a weak immune system and are being more prone to infections. Consequently, they don't generate the same immune response as healthier people would. This means that they don't always have the outward signs of infection; for example, they may have a severe infection but won't have a temperature.

"This makes it difficult for non-specialists to recognise how ill patients are and when to start the right treatment. It's important to get the treatment: too much treatment may see new antibiotic resistant strains emerge; too little and patients might die. There are also cost implications. Some of the more intensive treatments need to be really tailored to individual patients and some treatments aren't always very nice to have.

He added: "This really simple and quick tool, which any junior doctor could use in the middle of the night quickly and easily, flags up those who need a speedy and intensive treatment regime or more senior help. The quicker we get on with the right treatment for the right patient the better their chances of recovery are. This is a tool that should be used in every hospital in the UK as soon as possible: if we did so we would save more lives."

He said: "This study a great example of universities and hospitals working together for direct patient benefit."

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Easy and accurate identification of the Black Death

Main Category: Infectious Diseases / Bacteria / Viruses
Article Date: 27 Jul 2013 - 0:00 PDT Current ratings for:
Easy and accurate identification of the Black Death

Diagnosing the presence of Yersinia pestis, the cause of plague, may soon be easier than ever before. Scientists working with Peter Seeberger, Director at the Max Planck Institute of Colloids and Interfaces (MPIKG) in Potsdam and Professor at the Freie Universitat Berlin, have come up with a simple, inexpensive and reliable method of detecting the bacterium. The research team, specialising in glycochemistry glycobiology, first identified and synthesised an oligosaccharide structure on bacterial surface before combining it with a protein to heighten the immunological effect. The presence of antibodies against this surface glycan in the blood of infected patients can be a biomarker of diagnostic value in Yersinia pestis infections. The Potsdam-based scientists also used the antigen to create antibodies which can directly detect the plague pathogen in infected samples.

The Black Death is best known as a devastating medieval disease which affected Europe, Central Asia and China. The plague killed more than 200 million people through the ages. Yet it is by no means completely eradicated. In 2002 there was an outbreak of plague in the Indian state of Himachal Pradesh, and 2008 saw 18 cases reported in Madagascar. Ziketan, a city in north-west China, was quarantined after an outbreak in 2009, and in the same year there were 16 cases in Tobruk, Libya. Cases are also repeatedly reported in New Mexico, USA. As it is extremely infectious and indeed deadly, plague is one of the most dangerous bioweapons.

Although plague can be treated with antibiotics, survival rates decrease with every hour the disease remains undetected. Left untreated, plague can often lead to death within a very short time, depending on the disease type. "Early identification of an infection is of paramount importance for survival," says Chakkumkal Anish, Leader of the Glycobiology Research Group at the Max Planck Institute in Potsdam, "So our work may have direct and positive consequences on patient survival rates."

Antibodies are created with a glycoprotein as antigen

In order to specifically detect the plague pathogen, the scientists first had to identify an oligosaccharide in a lipopolysaccharide on the surface of Yersinia pestis. This oligosaccharide would serve as a specific antigen. They then synthesised the complex compound in a multi-step process. Subsequently, the chemists bound the sugar molecule to a protein which is used in many vaccines to heighten the immune reaction. The resulting glycoprotein produced by the sugar-protein compound was used to trigger an immune reaction in mice. The scientists used this circumstance to create antibodies to the plague pathogen using murine immune cells.

The antibodies can identify plague bacteria with high selectivity (accuracy) without the result being distorted by other bacteria biochemically related to plague. Thus the scientists have effectively produced a quick test for the Black Death. There are, in fact, many ways of using this particular research finding in medical practice. On the one hand, the glycan or its glycoconjugates can be applied to test strips where it acts as an antigen and catches antibodies from the blood of infected patients. The antigen-antibody complexes are very easy to detect with fluorescing proteins. On the other hand, the antibodies could provide a way of directly detecting the plague pathogen in infected tissue. Here, too, fluorescing proteins are used to identify whether the antibodies have docked onto the bacterial surface.

Advances in glycomics have a practical value in medicine

"These reliable tests are simple and economical to administer," says Peter Seeberger. This gives the new approach major advantages over the testing methods used to date. In the past, plague pathogens were detected by phenotyping or gene testing. The problem with these methods is that they are complex, expensive and slow - and, what's more, they have a high failure rate.

The new method is a direct result of research successes in glycomics. This field is dedicated to the study of carbohydrates, which includes all sugars, and their role in biology. Scientists are now able to identify and synthesise ever more complex carbohydrate molecules. "We have the ability to synthesise complex molecules from simple chemical building blocks, much like children using Lego bricks to build a space ship," explains Chakkumkal Anish. "This is just the start - we have only just begun exploiting the opportunities this brings." The chemical methods signify much more than just scientific advances. They also help scientists to come up with new methods of diagnosis and treatment, and to develop vaccinations for various diseases. "Basic research has an intrinsic value," says Peter Seeberger. "But in the field of glycomics, we are increasingly able to translate our research directly into applications with a practical value, very much like the value our latest development has for the medical world."

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How death spreads throughout an organism at the end of its life

Main Category: Seniors / Aging
Also Included In: Biology / Biochemistry
Article Date: 25 Jul 2013 - 0:00 PDT Current ratings for:
How death spreads throughout an organism at the end of its life

The final biological events in the life of a worm are described in a new article, published in the open access journal PLOS Biology. The paper reveals how death spreads like a wave from cell to cell until the whole organism is deceased.

The deaths of individual cells trigger a chemical chain reaction leading to the breakdown of cell components and a build-up of molecular debris. The molecular mechanisms of this process are reasonably well understood at a cellular level, but far less is known about how death spreads throughout an organism at the end of its life.

In worms, the spread of death can easily be seen under a microscope as a wave of blue fluorescence travelling through the gut of the worm. The new study, led by Professor David Gems from the Institute of Healthy Ageing at UCL, reveals that this fluorescence is caused by a cell death pathway called necrosis, and its spread throughout the organism is dependent on calcium signalling.

"We've identified the chemical pathways of self-destruction that propagate cell death in worms, which we see as this glowing blue fluorescence travelling through the body," explained Professor Gems. "It's like a blue Grim Reaper, tracking death as it spreads throughout the organism until all life is extinguished."

"We found that when we blocked this pathway, we could delay death induced by a stress such as infection, but we couldn't slow death from old age. This suggests that ageing causes death by a number of processes acting in parallel."

The mechanisms involved are similar to those active in mammals, confirming the worm can provide a useful model for understanding cell death, and how to prevent it, in other animals.

The study also links the mechanisms of cell death to the appearance of the blue fluorescence. The source of this fluorescence was previously thought to be a substance called lipofuscin, which emits light of a similar colour. Lipofuscin has previously been linked to ageing, since it accumulates with increasing molecular damage. However, the new findings implicate another molecule called anthranilic acid as the source of the blue hue and show that lipofuscin is not actually involved.

"Together, the findings cast doubt on the theory that ageing is simply a consequence of an accumulation of molecular damage. We need to focus on the biological events that occur during ageing and death to properly understand how we might be able to interrupt these processes," added Professor Gems.

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Funding: CC, CA, FC, and DG acknowledge funding from the BBSRC, the EU (FP7-259679 IDEAL, FP6-036894 and FP6-518230), and the Wellcome Trust (Strategic Award 098565/Z/12/Z). ZP was supported by a Jane Coffin Child postdoctoral fellowship, and ZP and FJS were supported by NIH R01 AG033921. KWN acknowledges support from the NSF (IOS 0919848: KN). EA was supported in part by a Ruth L. Kirschstein National Research Service Institutional Training Grant T32 GM068411. FM is supported by a Special Research Fund fellowship from the University of Ghent. FCS and PM were supported in part by the NIH (AG033839 and GM088290). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: Coburn C, Allman E, Mahanti P, Benedetto A, Cabreiro F, et al. (2013) Anthranilate Fluorescence Marks a Calcium-Propagated Necrotic Wave That Promotes Organismal Death in C. elegans. PLoS Biol 11(7): e1001613. doi:10.1371/journal.pbio.1001613

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