Tag: obesity

Categories : COVID VaccinesTags :

COVID Vaccination Protection Wanes Faster in People with Obesity

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According to new research from the Universities of Cambridge and Edinburgh, COVID vaccination protection in people with severe obesity wanes faster than in people of normal weight. The study suggests that people with obesity are likely to need more frequent booster doses to maintain their immunity.

Previous studies on COVID vaccines have suggested that antibody levels may be lower in vaccinated people who have obesity and that they may remain at higher risk of severe disease than vaccinated people with normal weight. The reasons for this have, however, remained unclear.

This study, published in the journal Nature Medicine, shows that the ability of antibodies to neutralise the virus (their ‘neutralisation capacity’) declines faster in vaccinated people who have obesity. The findings have important implications for vaccine prioritisation policies around the world.

During the pandemic, people with obesity were more likely to be hospitalised, require ventilators and to die from COVID. In this study, supported by the NIHR Bioresource and funded by UKRI, the researchers set out to investigate how far two of the most extensively used vaccines protect people with obesity compared to those with a normal weight, over time.

A team from the University of Edinburgh looked at real-time data tracking the health of 3.5 million people in the Scottish population as part of the EAVE II study. They looked at hospitalisation and mortality from COVID in adults who received two doses of COVID vaccine (either Pfizer-BioNTech or AstraZeneca).

They found that people with severe obesity (a BMI > 40kg/m2) had a 76% higher risk of severe COVID outcomes, compared to those with a normal BMI. A modest increase in risk was also seen in people with obesity (30-39.9kg/m2), which affects a quarter of the UK population, and those who were underweight. ‘Break-through infections’ after the second vaccine dose also led to hospitalisation and death sooner (from 10 weeks) among people with severe obesity, and among people with obesity (after 15 weeks), than among individuals with normal weight (after 20 weeks).

University of Edinburg leader Prof Sir Aziz Sheikh said: “Our findings demonstrate that protection gained through COVID vaccination drops off faster for people with severe obesity than those with a normal body mass index. Using large-scale data assets such as the EAVE II Platform in Scotland have enabled us to generate important and timely insights that enable improvements to the delivery of COVID vaccine schedules in a post-pandemic UK.”

The University of Cambridge team studied people with severe obesity attending the Obesity clinic at Addenbrooke’s Hospital in Cambridge, and compared the number and function of immune cells in their blood to those of people of normal weight.

They studied people six months after their second vaccine dose and then looked at the response to a third ‘booster’ vaccine dose over time. The Cambridge researchers found that six months after a second vaccine dose, people with severe obesity had similar levels of antibodies to the COVID virus as those with a normal weight – but those antibodies were less effecctive.

The antibodies’ neutralisation capacity was reduced in 55% of individuals with severe obesity were found to have unquantifiable or undetectable ‘neutralising capacity’ compared to 12% of people with normal BMI.

“This study further emphasises that obesity alters the vaccine response and also impacts on the risk of infection,” said first author Dr Agatha van der Klaauw. “We urgently need to understand how to restore immune function and minimise these health risks.”

The researchers found that antibodies produced by people with severe obesity were less effective at neutralising the SARS-CoV-2 virus, potentially because the antibodies were not able to bind to the virus with the same strength.

When given a third (booster) dose of a COVID vaccine, neutralisation capacity was restored in both the normal weight and severely obese groups. But the researchers found that immunity again declined more rapidly in people with severe obesity, putting them at greater risk of infection with time.

Categories : Metabolic Disorders Skeletal SystemTags :

Gastric Surgery for Weight Loss Harms Adolescents’ Bone Development

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In sleeve gastrectomy (SG), about 80% of the stomach is removed to reduce obesity and its complications. It has been observed to be associated with bone loss in adolescents, prompting a prospective study published in the Journal of Bone and Mineral Research, that revealed through imaging tests that SG decreases strength and bone mineral density of the lumbar spine in adolescents and young adults.

The researchers followed 29 adolescents and young adults with obesity underwent SG and 30 were without surgery over 12 months. At baseline and 12 months, participants underwent computed tomography of the lumbar spine for bone assessments and magnetic resonance imaging of the abdomen and thigh for body composition assessments.

Participants in the SG group lost an average of 34.3 kg 12 months after surgery, whereas weight was unchanged in controls. There were significant reductions in abdominal fat tissue and thigh muscle in the SG group compared with controls. Also, bone strength and bone mineral density decreased in the SG group compared with controls. Reductions in bone strength and bone mineral density were associated with reductions in body mass index, abdominal fat tissue, and muscle.

“Weight loss surgery is very effective in treating obesity and obesity-associated comorbidities in adolescents and young adults with obesity; however, it can cause loss of bone density and strength. We hope that our study raises awareness of the importance of bone health after weight loss surgery, so physicians can make sure that children eat a healthy diet with enough calcium and vitamin D and engage in weight-bearing activity to build up muscle mass, which is good for bones,” said corresponding author Miriam A. Bredella, MD, of Massachusetts General Hospital. 

Source: Wiley

Categories : Metabolic Disorders PaediatricsTags :

Autism in Children Linked to Diabetes, Dyslipidaemia

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Studies have shown that children with autism spectrum disorder (ASD) have an increased risk of obesity. In turn, obesity has been linked to increased risks for diabetes, dyslipidaemia and other cardiometabolic disorders. However, the question of whether or not there is an association between autism, cardiometabolic disorders and obesity remains largely unanswered.

To help provide an insight into the possible link between ASD and cardiometabolic diseases, Texas Tech University researchers conducted a systematic review and meta-analysis. Their findings were published in JAMA Pediatrics.

In this latest meta-analysis, the researchers evaluated 34 studies that included 276 173 participants who were diagnosed with ASD and 7 733 306 who were not. The results indicated that ASD was associated with greater risks of developing diabetes overall, including both type 1 and type 2 diabetes.

The meta-analysis also determined that autism is associated with increased risks of dyslipidaemia and heart disease, though there was no significant increased risk of hypertension and stroke associated with autism. However, meta-regression analyses revealed that children with autism were at a greater associated risk of developing diabetes and hypertension when compared with adults.

Study leader Chanaka N. Kahathuduwa, MD, PhD, said the overall results demonstrate the associated increased risk of cardiometabolic diseases in ASD patients, which should prompt clinicians to more closely monitor these patients for potential contributors, including signs of cardiometabolic disease and their complications.

“We have established the associations between autism and obesity, as well as autism and cardiometabolic disease, including diabetes and dyslipidaemia,” Kahathuduwa said. “We don’t have data to support a conclusion that autism is causing these metabolic derangements, but since we know that a child with autism is more likely to develop these metabolic complications and derangements down the road, I believe physicians should evaluate children with autism more vigilantly and maybe start screening them earlier than the usual.”

Kahathuduwa also believes the study shows that physicians should think twice before prescribing medications such as olanzapine that are well known to have metabolic adverse effects to children with autism.

“Our findings should also be an eye opener for patients with autism and parents of kids with autism to simply be mindful about the higher risk of developing obesity and metabolic complications,” Kahathuduwa added. “Then they can talk with their physicians about strategies to prevent obesity and metabolic disease.”

Kahathuduwa said the next logical step for the collaborative team would be to generate evidence that either supports or rejects causality with regard to the observed associations.

Source: Texas Tech University Health Sciences Center

Categories : Metabolic DisordersTags :

Childhood Obesity is a Risk Factor for Blood Clots in Adulthood

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Being overweight in childhood and in early adulthood are discrete risk factors for blood clots (thrombi) later in life, according to a study using school health care and military service records, according to a study published in the Journal of Internal Medicine.

The association between obesity and blood clots is already established. However, to date it has been unclear how much influence a raised BMI in childhood and puberty exerts. Thrombi usually arise in the legs, often starting in a blood vessel in the calf. Swelling, pain and redness are common symptoms. Though easily treated if caught early, they can result pulmonary embolism may be life-threatening.

The present study comprises 37 672 men in Sweden, born between 1945 and 1961. It is based on information about height, weight, and BMI from the men’s records, first from school health care services (at the age of 8 years) and, second, from medical examinations on enrolment in the Armed Services (at age 20), along with register data on any blood clots up to age 62 on average.

Distinctly elevated thrombus risk

The results showed that BMI at both ages 8 and 20, independently of each other, can be linked to venous blood clots. These may occur in, for example, the leg (deep vein thrombosis, DVT) or the lung (pulmonary embolism).

In adulthood, two groups were found to be at a significantly increased risk of venous thrombi. The first was individuals who had been overweight both as children and as young adults, while the second was composed of those whose weight in childhood was normal and who became overweight only in early adulthood.

Moreover, being overweight in both childhood and young adulthood was found to raise the risk of arterial thrombi – clots resulting from constricted blood vessels with fatty deposits and inflammation. Since there were few cases of arterial blood clots in the study, however, further studies are needed to confirm these findings. All comparisons in the study were made with the control group, whose weight was normal at both 8 and 20 years of age.

Overweight in puberty an important factor

The first and corresponding author of the study is Lina Lilja, a doctoral student at Sahlgrenska Academy, University of Gothenburg, and paediatrician. At the time of the study, she worked at the Kungshöjd paediatric clinic in Gothenburg. Today, she is a senior physician in child health care in Region Västra Götaland.

“Our study shows that both overweight in childhood and overweight in young adulthood increase the risk of venous blood clots later in life. The latter, overweight when the men were young adults, proved to be a more influential factor than overweight when they were children,” Lilja notes.

The study includes data from the BMI Epidemiology Study (BEST) in Gothenburg, a population study, and from Swedish national registers.

Source: University of Gothenburg

Categories : Metabolic Disorders PaediatricsTags :

Childhood Obesity Linked to Adult Diabetes Risk

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Child obesity is linked to increased risk of developing diabetes in adulthood, both autoimmune forms of diabetes and different forms of type 2 diabetes, according to a new study in the journal Diabetologia. The risk of developing the most insulin-resistant form of diabetes is, for example, three times as high in children with obesity.

Diabetes affects ~7% of the adult population and is one of the world’s fasted growing diseases. It has traditionally been divided into two subgroups – type 1 and type 2 diabetes – but research suggests that this is a simplification.

In 2018, a Swedish study identified five subgroups of adult-onset diabetes, characterised by auto-immunity, severe insulin deficiency, serious insulin resistance, overweight and advanced age.

One way the researchers say that the relevance of these subgroups can be highlighted is to examine if the influence of known risk factors for diabetes differs between the proposed diabetes types.

“Our study is one of the first attempts to find this out,” says the study’s first author Yuxia Wei, doctoral student at Karolinska Institutet. “Childhood obesity has been linked to several chronic diseases, but has never been studied in relation to the recently proposed diabetes subgroups.”

Wanted to investigate the effect of child obesity

The purpose of the present study was therefore to see if the effect of childhood obesity differs. The researchers used a method called Mendelian randomisation, which uses genetic information to study the correlation between an environmental risk factor and disease risk while taking into account the impact of other risk factors.

Basing their analysis on genetic data from over 400 000 UK Biobank participants, the researchers compared children who considered themselves larger than other children with children who rated their weight as normal.

The results showed that overweight/obesity in childhood was linked to a 62% higher risk of autoimmune diabetes, a doubling of the risk of diabetes characterised by insulin deficiency, almost a tripling of the risk of the most insulin-resistant form of diabetes and a seven-times higher risk of the form of diabetes primarily characterised by overweight. 

“Our analyses show that children who are larger than others are more likely to develop four of the five proposed new subgroups of adult-onset diabetes,” says Wei. “In other words, obesity in childhood seems to be a risk factor in effectively all types of adult diabetes, with the exception of age-related diabetes. This underscores how important it is to prevent obesity in children since it can have lasting effects on their future health.”

The study was a collaboration among researchers at Karolinska Institutet, Bristol University (UK) and Sun Yat-Sen University (China).

Source: Karolinska Institutet

Categories : Metabolic DisordersTags :

Excess Weight is a Greater Mortality Risk than BMI Alone Suggests

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Excess weight or obesity raises mortality risk by between 22% to 91%, a significantly higher rate than previously believed, while the mortality risk of being slightly underweight has likely been overestimated, according to new research published in the journal Population Studies.

The analysis of nearly 18 000 participants counters prevailing wisdom that excess weight boosts mortality risk only in extreme cases, and it also challenges the use of body mass index (BMI) to investigate health outcomes due to its inherent biases. After accounting for those biases, it estimates that about 1 in 6 deaths in the US are related to excess weight or obesity.

“Existing studies have likely underestimated the mortality consequences of living in a country where cheap, unhealthy food has grown increasingly accessible, and sedentary lifestyles have become the norm,” said author Ryan Masters, associate professor of sociology at CU Boulder. “This study and others are beginning to expose the true toll of this public health crisis.”

Challenging the obesity paradox

While numerous studies show that heart disease, high blood pressure and diabetes (which are often associated with being overweight) elevate mortality risk, very few have shown that groups with higher BMIs have higher mortality rates.

Instead, in what some call the “obesity paradox,” most studies show a U-shaped curve: Those in the “overweight” category (BMI 25–30) surprisingly have the lowest mortality risk. Those in the “obese” category (30–35) have little or no increased risk over the so-called “healthy” category (18.5–25). And both the “underweight” (< 18.5) and extremely obese (> 35) are at increased risk of death.

“The conventional wisdom is that elevated BMI generally does not raise mortality risk until you get to very high levels, and that there are actually some survival benefits to being overweight,” said Masters, a social demographer who has spent his career studying mortality trends. “I have been suspicious of these claims.”

He noted that BMI, which doctors and scientists often use as a health measure, is based on weight and height only and doesn’t account for differences in body composition or how long a person has been overweight.

“It’s a reflection of stature at a point in time. That’s it,” said Masters, noting that Tom Cruise (at 170cm and an extremely muscular 91kg at one point), had a BMI of 31.5, famously putting him in the category of “obese.” “It isn’t fully capturing all of the nuances and different sizes and shapes the body comes in.”

Taking these nuances, Masters accessed data from the National Health and Nutrition Examination Survey (NHANES) the from 1988 to 2015, analysing 17 784 people, including 4468 deaths.

He discovered that a full 20% of the sample characterised as “healthy” weight had been in the overweight or obese category in the decade prior. When set apart, this group had a substantially worse health profile than those in the category whose weight had been stable.

Masters pointed out that a lifetime carrying excess weight can lead to illnesses that, paradoxically, lead to rapid weight loss. If BMI data is captured during this time, it can skew study results.

“I would argue that we have been artificially inflating the mortality risk in the low-BMI category by including those who had been high BMI and had just lost weight recently,” he said.

Meanwhile, 37% of those characterised as overweight and 60% of those with obese BMI had been at lower BMIs in the decade prior. Notably, those who had only recently gained weight had better health profiles.

“The health and mortality consequences of high BMI are not like a light switch,” said Masters. “There’s an expanding body of work suggesting that the consequences are duration-dependent.”

By including people who had spent most of their life at low-BMI weight in the high-BMI categories, previous studies have inadvertently made high BMI look less risky than it is, he said.

When he looked at differences in fat distribution within BMI categories, he also found that variations made a huge difference in reported health outcomes.

Exposing a public health problem

Collectively, the findings confirm that studies have been “significantly affected” by BMI-related bias.

When re-crunching the numbers without these biases, he found not a U-shape but a straight upward line, with those with low BMI (18.5–22.5) having the lowest mortality risk.

Contrary to previous research, the study found no significant mortality risk increases for the “underweight” category.

Previous studies attributed 2 to 3% of UA adult deaths to high BMI, but his study estimates an eight times higher rate.

Masters said he hopes the research will alert scientists to be “extremely cautious” when making conclusions based on BMI. But he also hopes the work will draw attention to what he sees not as a problem for individuals alone to solve but rather a public health crisis fuelled by an unhealthy or “obesogenic” environment in the US.

“For groups born in the 1970s or 1980s who have lived their whole lives in this obesogenic environment, the prospects of healthy aging into older adulthood does not look good right now,” he said. “I hope this work can influence higher-level discussions about what we as a society can do about it.”

Source: University of Colorado at Boulder

Categories : Cancer Metabolic DisordersTags :

A Metabolic Switch for Childhood Obesity and Cancer

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Researchers have unlocked a means to modify the function of an enzyme crucial to fat production, a finding could lead to more effective treatments for childhood obesity and cancer.

While the research, published in the Proceedings of the National Academy of Sciences, was in fruit fly larvae, the ability to alter the rates of lipid metabolism could have significant implications for human health, said Hua Bai, an associate professor of genetics, development and cell biology at Iowa State University.

“We’ve identified what’s basically a metabolic switch. It’s like the accelerator on a car,” he said.

The initial aim was investigating how ageing was affected by fatty acid synthase, an enzyme that plays a role in de novo lipogenesis, which is the process of turning excess dietary carbohydrates into fat. Typically, levels of fatty acid synthase rise and fall based on an animal’s cellular needs and diet.

Surprisingly, the researchers noticed that early in a fruit fly’s development, de novo lipogenesis increases without an accompanying boost in the expression of fatty acid synthase. That suggested there must be some other factor at play, Bai said.

After proteins such as fatty acid synthase are created based on genetic code, their function can be altered by one of several different types of post-translational modification. Bai’s team found one of those processes, acetylation, affected one of the 2540 amino acids that combine to make fatty acid synthase, changing how effective it was at producing fat.

In addition to its role in obesity, elevated levels of de novo lipogenesis are linked to cancer, so controlling it through a single amino acid could lead to highly targeted treatments, Bai said.

“Fine tuning the acetylation levels of fatty acid synthase would be a much more precise treatment than blocking the entire protein,” he said.

Though the findings may be applicable to humans, any medical application in humans is years away, he said.

“The potential is high, but further testing is needed in other animals,” he said.

Source: Iowa State University

Categories : Gender Metabolic DisordersTags :

Why Obesity’s Health Impacts are Worse for Males

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A newly published study in iScience sheds light on the biological underpinnings in sex differences in obesity-related disease, with researchers observing “striking” differences in the cells that build blood vessels in the fatty tissue of male versus female mice.

Men are more likely than women to develop conditions associated with obesity such as cardiovascular disease, insulin resistance and diabetes, says study leader Professor Tara Haas at York University.

“People have used rodent models to study obesity, and the diseases that are associated with obesity – like diabetes – but they’ve typically always studied male rodents, because females are resistant to developing the same kinds of diseases,” says Haas. “We were really interested in exploring that difference because, to us, it spoke of something really fascinating happening in females that protects them.”

In earlier work, Haas and her team saw that when mice become obese, females grow a lot of new blood vessels to supply the expanding fat tissue with oxygen and nutrients, whereas males grow a lot less. For this study, Haas and her co-authors focused on differences in the endothelial cells that make up the building blocks of these blood vessels in fat tissue.

The team used software to help sift through thousands of genes to zero in on the ones that would be associated with blood vessel growth. They discovered that processes associated with the proliferation of new blood vessels were high in the female mice, whereas the males had a high level of processes associated with inflammation.

“It was very striking the extent of inflammation-associated processes that were prevalent in the males,” Haas recalls. “Other studies have shown that when endothelial cells have that kind of inflammatory response, they’re very dysfunctional, and they don’t respond to stimuli properly.”

York PhD student Alexandra Pislaru, who works in Haas’ lab and is a co-first author of the study, participated in this project as part of her dissertation.

“It is exciting to observe the continuing resilience that female endothelial cells display even when stressed by a long-term high-fat diet,” Pislaru says. “The findings from our study can help researchers to get a better understanding of why obesity manifests differently in men and women.”

The researchers also examined the behaviour of the endothelial cells when they were taken out of the body and studied in petri dishes.

“Even when we take them out of the body where they don’t have the circulating sex hormones or other kinds of factors, male and female endothelial cells still behave very differently from each other,” Haas explains.

Female endothelial cells replicated faster, while male endothelial cells displayed greater sensitivity to an inflammatory stimulus. By comparing with previously published data sets, the researchers found endothelial cells from aged male mice also displayed a more inflammatory profile compared to female cells.

“You can’t make the assumption that both sexes are going to respond to the same series of events the same way,” says Haas. “This isn’t just an obesity related issue – I think it’s a much broader conceptual problem that also encompasses healthy aging. One implication of our findings is that there will be situations where the treatment that is ideal for men is not going to be ideal for women and vice-versa.”

While humans and mice have different genes that may be turned up or down, Haas believes the general findings would likely apply and is interested studying the same cells in humans in future research.

Source: York University

Categories : Metabolic Disorders PaediatricsTags :

New Guidelines Recommend Aggressive Intervention in Childhood Obesity

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New clinical guidelines from the American Academy of Pediatrics (AAP) advise “immediate, intensive obesity treatment to each patient” upon diagnosis of childhood obesity. Published in the journal Pediatrics, these recommendations stands in marked contrast from other, previous guidelines.

The guidelines are summarised in key action statements, some of which recommend children ages 6 and up (and sometimes 2 to 5) with overweight or obesity to intensive health behaviour and lifestyle therapy.

In children 12 and older, the guidelines advise consideration of weight-loss pharmacotherapy. In case of severe obesity (BMI ≥35 or 120% of the 95th percentile for age and sex, whichever is lower) for adolescents 13 and older, clinicians should offer referrals for evaluation for metabolic and bariatric surgery.

Author Sarah Armstrong, MD, co-director of the Duke Center for Childhood Obesity Research told Medpage Today that “This is one of the most important messages that differentiates our current clinical practice guidelines from the prior recommendations, and that is to say 15 years of data have taught us that ‘watchful waiting’ only leads to greater increase in child BMI, accumulation of comorbidities, and more challenges in trying to reverse some of this.”

The guidelines also recommend regularly screening children ages 2 years and up for obesity, and comprehensively evaluating children and adolescents with overweight and obesity for related comorbidities.

Clinicians are also advised to treat children and adolescents for overweight/obesity and comorbidities concurrently, in line with principles of the chronic care model, using a non-stigmatising approach centred around the family.

The guidelines are based on a comprehensive evidence review of controlled and comparative effectiveness trials and high-quality longitudinal and epidemiologic studies. In a pair of accompanying technical reports, the authors give detailed descriptions of the evidence review behind the development of the guidelines.

Categories : Cardiovascular Disease Obstetrics & GynaecologyTags :

Diet and Exercise for Obese Mothers Lowers Cardiovascular Risk in Infants

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A new study, published in the International Journal of Obesity, found that 3-year-old children were more likely to exhibit risk factors for future heart disease if their mother was clinically obese during pregnancy. A behavioural lifestyle intervention reduced this risk.

There is increasing evidence to suggest that obesity in pregnancy is associated with cardiometabolic dysfunction in children, and that serious cardiovascular disease may begin in the womb.

The UPBEAT trial, conducted at Guy’s and St Thomas’ NHS Foundation Trust, randomised women with obesity (a BMI of over 30 kg/m2) in early pregnancy to a diet and exercise intervention or to standard pregnancy care. The intervention included one-to-one counselling, restricting dietary intake of saturated fat, eating foods with a low glycaemic index such as vegetables and legumes, moderate and monitored physical activity and tools to record exercise. The intervention arm saw improvements in weight gain in pregnancy, physical activity, a healthier diet, and a healthier metabolic profile across pregnancy.

Follow-up of the children at age three showed that children of women with clinical obesity had evidence of cardiac remodelling, a risk factor for future cardiovascular disease. Changes included increased heart muscle thickness, elevated resting heart rate, evidence of early impairment to the heart’s relaxation function and increased sympathetic nerve activity compared to women of normal weight. The children of women who were allocated to the intervention arm were protected from these early changes in heart structure and function.

Study lead Dr Paul Taylor, from King’s College London, said: “Maternal obesity appears to adversely impact the developing foetal nervous system and foetal heart development which is apparent up to 3 years-of-age. A complex lifestyle intervention in pregnancy was associated with protection against cardiac remodelling in infants. We can hypothesise that these changes to the heart and its function will get worse over time, putting the child at increased risk of cardiovascular disease in the future.”

The study suggests that maternal obesity may have a lasting impact on the child’s cardiovascular health. Promoting dietary changes and physical activity during pregnancy may reduce this risk.

Source: King’s College London