Body

Philadelphia, January 24, 2020--In a follow-up to the landmark 2011 study that demonstrated prenatal surgery for spina bifida has measurable benefits over surgery after birth for one of the most disabling neural tube defects, researchers have published new findings. These findings show significant physical and emotional benefits a decade later in school-age children who received corrective surgery in the womb for myelomeningocele, the most severe form of spina bifida.

"These findings add to the growing body of literature demonstrating the benefits of prenatal surgery for spina bifida," said N. Scott Adzick, MD, Surgeon-in-Chief at Children's Hospital of Philadelphia (CHOP), Director of CHOP's Center for Fetal Diagnosis and Treatment, and co-author of the study, published January, 24, 2020 in Pediatrics. "Providers should take these findings into account when counseling expectant mothers to ensure that families considering prenatal surgery for their fetus understand the potential risks and benefits."

Spina bifida is a birth defect in which an area of the spinal column doesn't form properly, leaving a section of the spinal cord and spinal nerves exposed through an opening in the back. The condition affects approximately one in 1,500 births in the United States and often results in weakness or paralysis below the location of the defect, leading to an inability to walk unassisted and a loss of bladder and bowel control. It also changes the flow of spinal fluid, leading to a life-threatening buildup of spinal fluid in the brain that requires the insertion of a tube, or shunt, to drain the excess fluid.

The study, known as "MOMS2: Follow up of the Management Of Myelomeningocele Study," was a collaborative effort, involving researchers from CHOP, University of Pittsburgh, George Washington University Biostatistics Center, University of Houston, Vanderbilt University Medical Center, University of California, San Francisco, University of California, Davis, and Seattle Children's Hospital.

Results of the original MOMS trial

The original MOMS study, co-led by CHOP and published in 2011 in the New England Journal of Medicine, compared outcomes after prenatal and postnatal repair of myelomeningocele. Results demonstrated that prenatal repair can offer significantly better results than traditional postnatal repair. Babies with spina bifida who received prenatal surgery were better able to walk two and a half years after surgery than those operated on after birth and had better overall motor function. They were also less likely to need a shunt.

MOMS2 results, benefits of fetal surgery for spina bifida continue into childhood

Now, after following those two groups of patients for up to 10 years after birth, researchers in the follow-up MOMS2 trial have shown those benefits continue into childhood. More children in the prenatal surgery group were able to walk independently by the time they were school age, and they showed better gross and fine motor skills. They also demonstrated better control over their bladder and bowel movements; children who underwent prenatal surgery were almost six times as likely to go to the bathroom on their own than those operated on after birth.

Patients who received surgery in the womb continued to need fewer shunts, surgeries and catheterizations into childhood than patients who'd received surgery after birth. Children and families in the prenatal group also reported a better quality of life, with less stress on the family overall.

The study's primary outcome, which was adaptive behavior in the prenatal versus postnatal surgery group, did not show a measurable difference in the patients' ability to perform activities needed for communication, social interactions, and daily living in the everyday environment. The study also did not find cognitive benefits in the prenatal surgery group, though the authors noted that all children with myelomeningocele are at risk for significant learning and adaptation challenges, regardless of surgery type.

Study details

The study was conducted at the three centers that participated in the original MOMS trial (Children's Hospital of Philadelphia, Vanderbilt University, and the University of California, San Francisco), along with the independent data-coordinating center at the George Washington University Biostatistics Center. The Eunice Kennedy Shriver National Institute of Child Health and Human Development sponsored the research.

The original MOMS trial sought to enroll 200 patients, but the NIH ended the trial in December 2010, after 183 surgeries had occurred, based on clear evidence of efficacy for the prenatal procedure. Of the 183 babies in the original study, only 161 participated in the MOMS2 study, as eight children died before MOMS2 enrollment began, ten declined to participate, and four could not be reached.

MOMS 2 participation consisted of a single comprehensive study visit with the patient between June 2011 and April 2017, when the patients ranged in age from six to ten years old. Children underwent a neurodevelopmental and behavioral evaluation by a psychologist and a physical exam and functioning assessment by a physical therapist. A parent or caregiver also completed the Vineland Adaptive Behavior Scales II to evaluate adaptive behavior through an interview with a study psychologist.

Continued advances in fetal surgery for spina bifida

As a pioneer in the field, CHOP began performing fetal surgery for spina bifida in 1998, three years after CHOP launched the Center for Fetal Diagnosis and Treatment. Since then, the Center has continued to improve the technique and publish on the practice, leading to significant advances even since the MOMS trial.

At CHOP, the length of the fetal surgery itself has decreased, and the gestational age of the infants at the time of birth has increased - an important step, as many of the babies delivered in the MOMS study who'd undergone prenatal surgery were born prematurely. Doctors have also observed improved movement in the lower limbs and continue to follow up with those patients to monitor their progress and outcomes.

"It is extremely gratifying to see that the positive results from the initial MOMS trial endure into childhood," Adzick said. "Fetal surgery is a complex and serious procedure and should only be done by experienced teams. Research needs to continue to refine the technique in a way that will improve outcomes even further."

PHILADELPHIA --People with obesity are often treated with less respect than other people, discriminated against, and socially devalued because of their weight. This societal stigma can sometimes be internalized, leading individuals with obesity to blame and devalue themselves because of their weight. While it's known that weight "self-stigma" is associated with poor mental and physical health, little is known about how to help people combat it. Now, in a first-of-its-kind study, researchers at Penn Medicine showed that people who received a new stigma-reduction intervention, along with standard behavioral weight loss treatment, devalued themselves less due to their weight compared to participants who only received the weight loss treatment.

Their findings were published today in the Journal of Consulting and Clinical Psychology.

"Our findings suggest that incorporating an intervention that targets internalized weight stigma into weight management programs may be beneficial for individuals who struggle with poor self-image due to their weight," said the study's principal investigator and lead author Rebecca Pearl, PhD, an assistant professor of Psychology in Psychiatry in the Perelman School of Medicine at the University of Pennsylvania.

Research has found that, beyond the effects of body mass index (BMI) and depression, self-directed weight stigma is associated with heightened risk for cardiovascular and metabolic disease. Although there is increased awareness of the health effects of weight stigma, questions exist about effective strategies to mitigate it. For this study, the team conducted the first randomized controlled trial of an intervention designed to reduce internalized weight stigma as part of a weight management program.

Seventy-two adults with obesity who reported experiencing and internalizing weight stigma participated in the six-month weight loss study. In one group, participants received behavioral weight loss treatment and access to the Weight Bias Internalization and Stigma (BIAS) program, which provided skills to help them combat negative weight-related thoughts, cope with weight-stigmatizing experiences, and increase their self- and body-acceptance. The other group of participants only received behavioral weight loss treatment, which also included more information on cooking tips and recipes.

Using two validated measures, the team assessed self-reported weight stigma at baseline, week 12, and week 26. Researchers also examined other self-report measures of psychological and behavioral factors, along with weight, blood pressure, and waist circumference. The team found that participants who received the Weight BIAS program showed significantly greater decreases on one measure of internalized weight stigma--self-devaluation-- than participants who received weight loss treatment alone. However, researchers noted there were no differences between groups for the other measures of internalized weight stigma. Groups also did not differ in changes in other measures of psychological well-being, behavior change, or changes in weight and other health metrics, with participants in both groups showing improvements. For example, participants in the Weight BIAS program lost an average of 4.5 percent of their starting body weight at 6 months, compared with 5.9% for those in the standard weight loss group. Participants rated the Weight BIAS program highly in their assessment of how much they liked it and benefited from it. The weight loss intervention was also rated highly in both groups.

"Weight loss and stigma reduction can seem like contradictory goals to some people," said Pearl. "Our results, however, suggest that they can be complementary. We can promote both at the same time."

The human immune system uses two pre-programmed strategies to tackle infection. One is fever, a resistance mechanism that tries to eliminate a pathogen by raising the body's temperature. The other works in the opposite direction, cooling the body down in a controlled manner to permit temporary tolerance of the invader while protecting organs and systems. These two mechanisms act as alternatives according to the intensity of the attack and the overall state of the patient's health.

This innovative concept was recently presented by two researchers in the journal Trends in Endocrinology and Metabolism, published by Cell Press. The article proposes a combination of the two defense strategies to study and treat sepsis, a systemic inflammation usually triggered by a localized infection that spirals out of control. Sepsis is the main cause of death in Brazilian intensive care units (ICUs).

The study, which was supported by São Paulo Research Foundation - FAPESP, was conducted by Alexandre Steiner, a professor in the Immunology Department of the University of São Paulo's Biomedical Science Institute (ICB-USP) in Brazil, and Andrej Romanovsky, head of the Thermoregulation and Systemic Inflammation Laboratory (FeverLab) at St. Joseph's Hospital and Medical Center in Phoenix, Arizona (USA).

"We're proposing a model in which to observe not only the immune system in its host defense strategy but also aspects of human physiology. It's clear that the human organism has two defense strategies, and that the immune system and physiological system should be understood in a more integrated manner when analyzing infectious processes," Steiner told.

Evolving concepts

In the 1970s, researchers in the field of physiology developed what they called "fever theory", according to which a rise in body temperature was a key factor in the host defense strategy. "Fever was no longer considered part of the disease, but as part of the body's defense," Steiner said.

In the past two decades, studies with rats have also shown that when an infection becomes acute the host develops hypothermia instead of fever. "We observed the same phenomenon in septic patients admitted to ICUs, for example," Steiner said.

Hypothermia was initially seen as a process of dysregulation: the organism was dying and as its systems failed it became unable to maintain body temperature. Not until the 1990s did scientists succeed in analyzing the metabolic and thermoregulatory profile of patients with hypothermia, developing the theory that hypothermia was not a consequence of dysregulation but a deliberate and controlled defense mechanism.

In the early 2000s, Steiner performed experiments with rats to study thermal preference behavior, seeking to understand hypothermia: whether the organism actively pursues a cooler state and in what circumstances.

"This study showed that in less severe conditions the animals sought a warmer environment and developed fever, whereas when the inflammatory process became severe they preferred a cooler environment and were prone to hypothermia," he said.

If an animal seeks a cool environment, it is actively developing hypothermia, according to Steiner, who believes the process involves elements of the central nervous system that slow down the metabolism and produce a controlled fall in body temperature.

Fever, on the other hand, requires a significant expenditure of energy to maintain a high temperature and may also exacerbate oxidative stress, an imbalance between the production of oxidizing compounds and the action of anti-oxidant defense systems, impairing tissue homeostasis.

"The hypothesis was raised that hypothermia ensues when the metabolic costs of fever exceed the benefits, either because the immune challenge is too strong or because physical debilitation occurs. A regulated hypothermic response could act as a support for a state of immune tolerance in which the organism lives with the pathogen, 'switching off' non-essential systems and defending systems without which it can't survive," Steiner said.

In experiments performed between 2008 and 2012, Steiner detected a lower death rate among animals that resorted to hypothermia as a strategy to combat severe bacterial infection than among animals in which hypothermia was blocked. "This finding led us to the conclusion that hypothermia plays a beneficial role in animal physiology," he said.

Meanwhile, research in the field of immunology highlighted the phenomenon of immune system activation with the primary aim of killing a pathogen. A shift away from this scientific paradigm began about ten years ago, when scientists discovered that some animals develop a different strategy consisting of activation of a defense mechanism that enables them to tolerate the invader temporarily.

In the article published in Trends in Endocrinology and Metabolism, Steiner and Romanovsky advocate an approach to the human organism's defense system from the perspective of the dichotomies between fever and hypothermia - mechanisms studied by physiology - and between disease resistance and tolerance, which pertain to immunology. Thus they suggest a combination of these two knowledge areas that can see beyond the immune system in dealing with infection.

"It's a dynamic mechanism in which the organism switches between one strategy and the other. The immune system and the physiological system don't just take one line of defense and stick with it, especially in severe conditions like sepsis," Steiner said.

Besides the experiments with rats, Steiner and his team also studied a group of 50 septic patients treated at the University of São Paulo's teaching hospital (HU-USP). "We looked for a sub-group of patients who had hypothermia similar to the kind associated with the tolerance mechanism, which is characterized by being transitory and self-limiting. To our surprise, 97% of the 50 patients studied matched this profile," Steiner said. Their body temperature fell by at most 2.0 °C - 2.5 °C.

The patients' condition switched naturally between resistance to fever and hypothermia, possibly associated with tolerance. The shifts occurred as a response of the organism, without being induced by medication or cooling and warming techniques.

According to Steiner, the main evidence that the process does not consist merely of body dysregulation is that most of the 25 patients who eventually died had been feverish in the 12 hours prior to death. "If hypothermia were the result of organ dysfunction and failure, we would have observed more hypothermia in these 12 hours preceding death," he said.

The studies conducted by Steiner were supported by FAPESP via a Young Investigator Grant, a Regular Research Grant, and a Thematic Project Grant.

Next steps

The most immediate implication of the results obtained to date is a review of the treatment for sepsis. "Severe infections are currently approached one-dimensionally: the immune system is there either to kill the pathogen or to cause problems for the patient, in case it over-reacts or fails to succeed," Steiner said. "The new findings enable us to think about possible therapies and more personalized treatments based on an analysis showing whether the patient could benefit more from a fever/resistance strategy or a hypothermia/tolerance strategy."

Steiner and his group are now planning to test the theory put forward in the article by applying it in specific situations such as infection by fungi, viruses and bacteria. Another line of research will be to evaluate the influence of obesity in defense strategies against infection.

Researchers led by a team at Massachusetts Eye and Ear have identified a novel cellular entry factor for adeno-associated virus vector (AAV) types--the most commonly used viral vectors for in vivo gene therapy. AAVs are vectors-or vehicles--that are created from a virus that is made harmless by molecular engineering, and have shown promise transporting genetic therapy treatments to affected tissues.

The researchers identified that GPR108, a G protein-coupled receptor, served as a molecular 'lock' to the cell. GPR108 is required for most AAVs, including those used in approved gene therapies, to gain access to the cell. As gaining cellular access is a critical step in delivering gene therapy, this discovery may provide a crucial piece of information that could one day enable scientists to better explain, predict, and ultimately, direct AAV gene transfers to specific tissues.

The study was recently published in Molecular Therapy.

"For years we have known that AAV gene transfer is highly effective, but we have yet to learn how that is achieved and why some AAV types function differently than others," said senior study author Luk Vandenberghe, PhD, Director of the Grousbeck Gene Therapy Center at Mass. Eye and Ear and Associate Professor of Ophthalmology at Harvard Medical School. "We identified a molecular 'lock' to the cell that allows AAV vectors carrying the appropriate 'key' to gain access to the cell. This finding may enable scientists to better direct AAV gene transfers to targeted cell tissues, in order to treat specific genetic diseases."

Multiple AAV types are in clinical trials for diseases affecting the eye, muscles, and neurons. Luxturna™ and Zolgensma™, both recently approved by the U.S. Food and Drug Administration, are AAV gene therapy products for a form of blindness and neuromuscular disease. Yet, the exact mechanism by which this novel class of medicine accomplishes gene transfer has remained poorly understood.

AAV Therapy's Unknowns: Crossing a Ravine on a Jungle Gym

Gene therapy first emerged as a field about 50 years ago, but only in the past decade have scientists made progress delivering genetic material to target cells through AAVs.

Despite recent advances in AAV research, scientists have been limited in their ability to create and test additional treatments because the mechanism of action has been unclear.

Dr. Vandenberghe says delivering AAV genetic therapies to a cell is like crossing a ravine using monkey bars on a jungle gym. Each bar is a cellular factor that the AAV relies on to eventually make it into the nucleus of the cell. Notably, a few years ago, researchers from Stanford identified one important crossbar in a highly conserved AAV entry receptor called AAVR.

"Our new study identifies a second necessary cellular co-factor that might enable us to better design these vectors for specific purposes," said Dr. Vandenberghe.

Findings May Propel Genetic Therapy Field Forward

In the current study, researchers used a genome-wide CRISPR screening tool to look at 100,000 genes and determine which cells played a role in AAV targeting. They identified GPR108 as a highly conserved entry factor that was required for entry of all AAV variants tested except for one, the highly divergent AAV5. GPR108 was shown to be critical for most AAVs that are currently being studied clinically, including AAVs used in the two FDA-approved gene therapies.

These findings were found in both in vitro and in vivo mouse models, further providing a mechanistic understanding to help explain and predict how AAV gene therapies target tissues and cells, said lead study author Amanda M. Dudek, PhD, who completed this research at Mass. Eye and Ear and is now a postdoctoral researcher at Stanford University.

"Our study shines some light on the mechanistic role of GPR108 in AAV entry. With this knowledge, scientists can further increase their understanding of AAV gene therapy safety, gene targeting and other properties of this novel class of drugs," said Dudek.

Dr. Vandenberghe's team plans to further study this mechanism and the biology of AAVs with the hope of optimizing these vectors for therapies. Their team is working on developing vectors that target specific genetic eye diseases, such as retinitis pigmentosa and Usher syndrome.

"Gene-based therapies for eye diseases are a major focus of our research mission at Massachusetts Eye and Ear, where our goal is to end blindness. This latest work by Dr. Vandenberghe and colleagues is a major breakthrough in our understanding of viral vectors, and will guide further development of this promising class of AAV therapies," said Joan W. Miller, MD, Chief of Ophthalmology at Massachusetts Eye and Ear and Massachusetts General Hospital and Chair of Ophthalmology and David Glendenning Cogan Professor of Ophthalmology at Harvard Medical School.

(PHILADELPHIA)--About 50 % of women with uterine fibroids--non-cancerous muscle tumors that grow in the uterus--experience heavy menstrual bleeding and other symptoms. Surgery is commonly recommended when these symptoms are severe enough to prompt a woman to seek treatment. The most common surgery used to treat fibroids is removal of the uterus (hysterectomy), though in some cases, removal of the fibroids and repair of the uterus (myomectomy) are performed. Surgery is usually extensive in both cases. Long-acting hormone injections can reduce symptoms such as heavy bleeding in women with fibroids, but side effects can be significant and it can take months for the effects of the medications to wear off.

In a study published in the New England Journal of Medicine on January 23, 2020, researchers reported on the effectiveness of a new, rapidly reversible oral pill that was used to reduce heavy menstrual bleeding in women with uterine fibroids. The study, which included a large group of researchers from across the country, was led by Dr. William Schlaff, Chair of the Department of Obstetrics and Gynecology at the Sidney Kimmel Medical College at Thomas Jefferson University.

A total of 790 women, ages 18-51, with heavy bleeding due to fibroids, were enrolled into one of three study arms. One group received the oral pill, elagolix, which reduces the production of the hormones estrogen and progesterone normally produced by a woman's ovaries. When these hormones are suppressed, fibroids usually get smaller and bleeding is reduced. A second group received elagolix plus a low dose of estrogen and progestin ("add-back" therapy) with the hope that the additional hormones would produce the same benefit but reduce the side effects of elagolix used alone (like hot flushes and bone loss). A third group received identical placebo pills that did not contain elagolix or the "add back" hormones. All of the women enrolled in the two identical trials reported by these researchers were confirmed to have uterine fibroids by ultrasound and heavy menstrual bleeding (more than 80mLs of blood loss per cycle) for at least two cycles.

The results showed that 80.4% of the women treated with elagolix alone had a reduction of menstrual bleeding of 50% or more compared to 9.6% of the women in the placebo group. Of those women treated with elagolix plus "add back" therapy, 72% had a reduction of 50% or more. Women treated with elagolix alone had significantly more loss of bone mineral as compared with the women treated with placebo, a known and clinically significant side effect of this class of medications. However, there was no difference between the loss of bone mineral in the group treated with elagolix and "add-back" as compared to those in the placebo group.

For many women with fibroids, severe symptoms like bleeding have a major impact on the quality of life. Surgery and long-acting injectable medications are acceptable treatments for many, but certainly not all women in this situation.

"The potential value of an oral, easily reversible medication that can be combined with low-dose hormonal "add back" to reduce heavy menstrual bleeding while avoiding problematic symptoms and side effects could be a major step forward," says Dr. Schlaff.

According to an article published ahead-of-print in the April issue of the American Journal of Roentgenology (AJR), a Stanford University team has developed a quantitative framework able to sonographically differentiate between benign and malignant thyroid nodules at a level comparable to that of expert radiologists, which may prove useful for establishing a fully automated system of thyroid nodule triage.

Alfiia Galimzianova et al. retrospectively collected ultrasound images of 92 biopsy-confirmed nodules, which were annotated by two expert radiologists using the American College of Radiology's Thyroid Imaging Reporting and Data System (TI-RADS).

In the researchers' framework, nodule features of echogenicity, texture, edge sharpness, and margin curvature properties were analyzed in a regularized logistic regression model to predict nodule malignancy. Authenticating their method with leave-one-out cross-validation, the Stanford team used ROC AUC, sensitivity, and specificity to compare the framework's results with those obtained by six expert annotation-based classifiers.

The AUC of the proposed framework measured 0.828 (95% CI, 0.715-0.942)--"greater than or comparable," Galimzianova noted, "to that of the expert classifiers"--whose AUC values ranged from 0.299 to 0.829 (p = 0.99).

Additionally, in a curative strategy at sensitivity of 1, use of the framework could have avoided biopsy in 20 of 46 benign nodules--statistically significantly higher than three expert classifiers. In a conservative strategy at specificity of 1, the framework could have helped to identify 10 of 46 malignancies--statistically significantly higher than five expert classifiers.

"Our results confirm the ultimate feasibility of computer-aided diagnostic systems for thyroid cancer risk estimation," concluded Galimzianova. "Such systems could provide second-opinion malignancy risk estimation to clinicians and ultimately help decrease the number of unnecessary biopsies and surgical procedures."

Global climate change has raised concerns that mosquito-borne diseases could become increasingly prevalent in the United States as warmer temperatures lead to increased mosquito activity.

The 2015-2016 Zika outbreak, which impacted much of the Americas, prompted efforts to accelerate the development of a Zika vaccine. According to the Centers for Disease Control and Prevention (CDC), about 10 percent of babies born in the U.S. whose mother was confirmed with the Zika virus during pregnancy had associated birth defects. The birth defects, like congenital Zika syndrome, can be devastating, fatal, and costly. According to the World Health Organization (WHO), in high-income countries like the U.S., the associated costs of caring for a single child with Zika-related birth defects have been estimated to be as high as $10 million.

A new study led by researchers at the CUNY Graduate School of Public Health and Health Policy (CUNY SPH) and the National School of Tropical Medicine at Baylor College of Medicine found that routinely giving the Zika vaccine to women of childbearing age could save money if the risk of Zika is around that of other mosquito-borne diseases like dengue and chikungunya. These diseases have been endemics in many parts of Latin and South America. Both are febrile, cause severe joint pain and could be life threatening if left untreated. According to the CDC, the same mosquito that carries the Zika virus, the Aedes species mosquito, also carries dengue and chikungunya.

The team developed a computer model representing women of childbearing age in different countries in the Americas. The model represented what happens to a woman if she becomes infected with Zika, how it varies with pregnancy, and the potential benefits of a vaccine to prevent the Zika infection.

As the study demonstrates, it is critical for officials to monitor the incidence of Zika infections in their region to determine whether the risk becomes comparable to that of dengue and chikungunya. This information could help determine whether a routine vaccination would be necessary.

"The end of the 2015-2016 outbreak doesn't mean that Zika has gone away as a threat," says Bruce Y. Lee, executive director of PHICOR, headquartered at CUNY SPH. "Cases may still continue to occur in different locations. Plus, future outbreaks are still possible. Therefore, it is important to be proactive about preventing the further spread of Zika."

The findings, which were published in the American Journal of Preventive Medicine, show how computer simulation modeling can help guide vaccine development. Results from the model provide scientists, manufacturers, public health officials, funders, and policy makers targets to aim for when developing the Zika vaccine and deciding when and where to use it.

"The study shows that a Zika vaccine doesn't have to offer near perfect protection to be valuable," says Sarah M. Bartsch, project director at PHICOR and lead author of the study. "In fact, the study shows that in many cases a vaccine that only offers protection as low as 25 percent can still produce cost savings in certain situations."

CHICAGO -- Most youth living with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) have not been diagnosed, according to a new prevalence study from researchers at DePaul University and Ann & Robert H. Lurie Children's Hospital of Chicago, published by the journal Child & Youth Care Forum. Leonard A. Jason, a professor of psychology at DePaul University, led the seven-year study to screen more than 10,000 children and teenagers in the Chicago area.

The researchers found that less than 5% of youth in the study who tested positive for ME/CFS had been previously diagnosed with the illness. Of the children assessed, African American and Latinx youth were twice as likely to be living with undiagnosed ME/CFS. The study was funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, one of the National Institutes of Health. Jason has been studying ME/CFS for more than 30 years and says the illness can affect all aspects of a child's life, from physical functioning to attending school and participating in extracurricular activities.

"When you're talking about a condition that's as debilitating as this one, the health care response has not been good," said Jason. "There aren't that many physicians who are trained and skilled at diagnosing and treating this illness, and our health care system has not done a great job at trying to help people who are affected," said Jason, director of DePaul's Center for Community Research.

Working with Jason as co-principal investigator is Dr. Ben Z. Katz, a pediatric infectious disease specialist at the Ann & Robert H. Lurie Children's Hospital of Chicago. Katz is also a professor of pediatrics at Northwestern University Feinberg School of Medicine. He has collaborated with Jason and his group since the late 1990s.

"Our finding that most youth with ME/CFS have not been previously diagnosed is comparable to findings in adults," said Katz. "We definitely need better ways to identify people with this illness and to develop effective interventions for them. In particular, we need to reach African American and Hispanic youth, since in our study these groups had higher prevalence of ME/CFS. "

The prevalence of pediatric ME/CFS has been in dispute, so Jason and Katz set out to include a diverse sample of ethnic, socio-economic and demographic backgrounds. Other ME/CFS prevalence studies have drawn from tertiary care centers, which can exclude those without access to health care, explained Jason. The researchers tailored their approach by including a thorough medical and psychiatric examination, offering access to high-quality screening for those at-risk of having the illness.

Researchers screened a random sample of 10,119 youth ages 5-17 from 5,622 households. The first stage was a phone interview with parents and caretakers about the health and behavior of their children and teens. Missing school because of fatigue was one of the common symptoms among youth who showed a higher risk of having ME/CFS, and was a red flag for parents, said Jason.

Of those who screened positive over the phone, 165 youth went on to medical and psychiatric examinations. Following evaluations, a team of physicians made final diagnoses. Youth were given a diagnosis of ME/CFS if they met criteria for case definitions. Of the 42 youth diagnosed with ME/CFS, only 2 (4.8%) had been previously diagnosed with the illness.

Prevalence of pediatric ME/CFS was 0.75%, which is a bit less than 1%, with a higher prevalence among African American and Latinx youth compared to their Caucasian peers. "Clearly people of color do get this illness, and there are some myths that you have to be white middle class to have ME/CFS," said Jason.

A lack of access to health care, and therefore less opportunity for an earlier diagnosis, could explain this racial disparity, according to Jason. "There are barriers to researchers gaining access to underserved populations. They may not trust institutions as easily, and they may not also have time to bring their children into appointments," said Jason.

And, there is still stigma and misunderstanding about ME/CFS among health care providers. "They may not believe this is a condition, or might attribute it to fatigue," said Jason.

The findings point to the need for better ways to identify and diagnose youth with this illness, said Jason, who has secured more than $46 million in research grant support during his 45-year professional career at DePaul. Co-authors of the study are DePaul University graduate students Madison Sunnquist, Chelsea Torres, Joseph Cotler and Shaun Bhatia.

"We're trying to help people who have this illness have information that could be used to argue for more resources for diagnosis and treatment," said Jason.

Living near major roads or highways is linked to higher incidence of dementia, Parkinson's disease, Alzheimer's disease and multiple sclerosis (MS), suggests new research published this week in the journal Environmental Health.

Researchers from the University of British Columbia analyzed data for 678,000 adults in Metro Vancouver. They found that living less than 50 metres from a major road or less than 150 metres from a highway is associated with a higher risk of developing dementia, Parkinson's, Alzheimer's and MS--likely due to increased exposure to air pollution.

The researchers also found that living near green spaces, like parks, has protective effects against developing these neurological disorders.

"For the first time, we have confirmed a link between air pollution and traffic proximity with a higher risk of dementia, Parkinson's, Alzheimer's and MS at the population level," says Weiran Yuchi, the study's lead author and a PhD candidate in the UBC school of population and public health. "The good news is that green spaces appear to have some protective effects in reducing the risk of developing one or more of these disorders. More research is needed, but our findings do suggest that urban planning efforts to increase accessibility to green spaces and to reduce motor vehicle traffic would be beneficial for neurological health."

Neurological disorders--a term that describes a range of disorders, including Alzheimer's disease and other dementias, Parkinson's disease, multiple sclerosis and motor neuron diseases--are increasingly recognized as one of the leading causes of death and disability worldwide. Little is known about the risk factors associated with neurological disorders, the majority of which are incurable and typically worsen over time.

For the study, researchers analyzed data for 678,000 adults between the ages of 45 and 84 who lived in Metro Vancouver from 1994 to 1998 and during a follow-up period from 1999 to 2003. They estimated individual exposures to road proximity, air pollution, noise and greenness at each person's residence using postal code data. During the follow-up period, the researchers identified 13,170 cases of non-Alzheimer's dementia, 4,201 cases of Parkinson's disease, 1,277 cases of Alzheimer's disease and 658 cases of MS.

For non-Alzheimer's dementia and Parkinson's disease specifically, living near major roads or a highway was associated with 14 per cent and seven per cent increased risk of both conditions, respectively. Due to relatively low numbers of Alzheimer's and MS cases in Metro Vancouver compared to non-Alzheimer's dementia and Parkinson's disease, the researchers did not identify associations between air pollution and increased risk of these two disorders. However, they are now analyzing Canada-wide data and are hopeful the larger dataset will provide more information on the effects of air pollution on Alzheimer's disease and MS.

When the researchers accounted for green space, they found the effect of air pollution on the neurological disorders was mitigated. The researchers suggest that this protective effect could be due to several factors.

"For people who are exposed to a higher level of green space, they are more likely to be physically active and may also have more social interactions," said Michael Brauer, the study's senior author and professor in the UBC school of population and public health. "There may even be benefits from just the visual aspects of vegetation."

Brauer added that the findings underscore the importance for city planners to ensure they incorporate greenery and parks when planning and developing residential neighbourhoods.

Austin, Texas (Jan. 23, 2020) -- The Crohn's & Colitis Foundation and the American Gastroenterological Association (AGA) are committed to improving the lives of the estimated 3 million Americans living with inflammatory bowel diseases (IBD), including Crohn's disease and ulcerative colitis. That's why we've partnered on the Crohn's & Colitis Congress in Austin, Texas, Jan. 23-25, 2020, an annual meeting where IBD care providers gather to learn about the latest advancements in IBD patient care.

Below is a summary of five impactful studies to be presented at the Crohn's & Colitis Congress. To speak with the study authors or review all 191 abstracts being presented, email media@gastro.org.

Lymphoma not associated with anti-TNF therapy in pediatric IBD patients
Study title: Low risk of lymphoma in pediatric patients with inflammatory bowel disease treated using anti-tumor necrosis factor agents
Presented by Matthew D. Egberg, University of North Carolina, Chapel Hill

Significance: Anti-tumor necrosis factor (aTNF) drugs are among the most effective medications used to treat pediatric IBD. Despite their effectiveness, concerns regarding an association with lymphoma limit their use in everyday practice. Based on a large, geographically diverse administrative insurance claims database of 9,284 pediatric IBD patients, treatment with aTNF agents and/or immune modulators was not associated with an increased risk of malignancy. These results support prioritization of the clinical benefits of aTNF agents over the low risk for malignancy.

Noteworthy new drug in pipeline for Crohn's disease
Study title: AZD4205, a selective, GI tract-enriched selective JAK1 inhibitor for Crohn's disease: preclinical evidence and Phase I data
Presented by Mei Wang, Dizal Pharmaceuticals

Significance: There is no cure for Crohn's disease and currently available drugs do not work for all patients, so advances in treatments are closely watched by physicians and patients. An early Phase I study shows promise for AZD4205 for the treatment of Crohn's disease. AZD4205 is an oral, ATP-competitive, JAK1 selective inhibitor. Nonclinical data showed its higher drug concentration within the GI tract relative to plasma in the rodents, suggesting its potential as an effective and safe treatment option for patients with Crohn's disease. AZD4205 was also evaluated in a Phase I study in healthy volunteers where it was well-tolerated with no drug-related adverse events. A Phase II study in moderate-to-severe Crohn's disease is planned.

This microbiome-targeting diet improves symptoms for IBD patients
Study title: Diet as a microbiome-centered therapy for IBD
Presented by Ana Maldonado-Contreras, UMASS Medical School

Significance: IBD patients have an imbalance of gut bacteria, which contributes to inflammation. Researchers at UMASS Medical School developed the IBD-Anti-Inflammatory Diet to restore the balance between helpful and harmful bacteria while promoting good nutrition. In their trial, the majority (61.3%) of patients who complied with the diet for at least 8 weeks reported a dramatic decrease in disease severity. IBD-AID™ also prompted an increase in the abundance of bacteria that produce short-chain fatty acids (SCFAs) thus dampening inflammation and assisting in patient's remission. The diet focuses on increased intake of prebiotic and probiotic foods and other beneficial foods while substituting certain carbohydrates and other adverse foods.

This research was funded in part by the AGA Research Foundation.

Thanks to biologics, less ulcerative colitis patients need their colon removed
Study title: Natural history of colectomy among hospitalized patients with ulcerative colitis in the contemporary era of treatments
Presented by Fernando Velayos, Kaiser Permanente

Significance: The rate of colectomy (surgical removal of a patient's colon) within the first year after hospital admission for ulcerative colitis has declined in the modern era of biologics. A study conducted at a large health care delivery organization identified that 5.3% of patients underwent colectomy during their first hospitalization for ulcerative colitis and 11.9% underwent colectomy within the first year after hospitalization, compared to historical rates of 20% and 30%, respectively, in the same population pre-biologics. This research provides cause for optimism that the natural history of colectomy in acute severe ulcerative colitis may be different and modifiable in the modern biologic era compared to the past.

Siblings close in age may make the best fecal microbiota donor for ulcerative colitis patients
Study title: Donor selection of fecal microbiota transplantation is important to long-term maintenance of ulcerative colitis
Presented by Koki Okahara, Juntendo University Hospital

Significance: Fecal microbiota transplantation (FMT) is still an emerging treatment for ulcerative colitis. This study is the first to reveal importance of FMT donor selection for long-term maintenance for ulcerative colitis. Ulcerative colitis patients treated with fresh FMT from a spouse or relative following triple-antibiotic therapy (amoxicillin, fosfomycin and metronidazole) had a significantly higher response compared to patients who just received antibiotic therapy. Siblings relationship has a significantly higher maintenance rate at 12 months compared to parent-child relationship. Furthermore, response was significantly higher in cases where the age difference between donor and patient was less than 10 years.

All abstracts accepted to the Crohn's & Colitis Congress will be published in Inflammatory Bowel Diseases® (the official journal of the Crohn's & Colitis Foundation) and Gastroenterology (the official journal of the American Gastroenterological Association) on Jan. 23, 2020.

All print, broadcast and online journalists who receive the Obesity embargo alert agree to abide by the embargo and may not publish, post, broadcast or distribute embargoed news releases or details of the embargoed studies before the embargo date and time.

When writing about these studies, journalists are asked to attribute the source as the journal Obesity and to include the online link to the Obesity articles as provided below. Links become active when articles post at 3:00 a.m. (EST) on Jan. 23, 2020, unless indicated differently below.

About the journal - Obesity is the peer-reviewed, scientific journal of The Obesity Society.

Editors' Choice 1 - Appetite Responses to Overfeeding Linked to 5-Year Weight Gain, Tanya M. Halliday, tanya.halliday@utah.edu, Corey A. Rynders, Elizabeth Thomas, Audrey Bergouignan, Zhaoxing Pan, Elizabeth H. Kealey, Marc-Andre Cornier, and Daniel H. Bessesen
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22687)

Editors' Choice 2 - Extended Breastfeeding Yields Healthier Growth Trajectories, Miaobing Zheng, j.zheng@deakin.edu.au, Adrian J. Cameron, Catherine S. Birken, Charles Keown-Stoneman, Rachel Laws, Li Ming Wen, and Karen J. Campbell
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22688)

Editors' Choice 3 - The Underappreciated Synergy of Strength, Aerobic Training, Jason A. Bennie, jason.bennie@usq.edu.au, Katrien De Cocker, Toby Pavey, Emmanuel Stamatakis, Stuart J. H. Biddle, and Ding Ding
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22673) - already online

Also see accompanying commentary by Timothy S. Church (http://onlinelibrary.wiley.com/doi/10.1002/oby.22702), posting online on Jan. 23, 2020

Editors' Choice 4 - Novel Strategies Differentiate Dieters Who Maintain Weight Loss, Suzanne Phelan, sphelan@calpoly.edu, Tate Halfman, Angela Marinilli Pinto, and Gary D. Foster
(http://onlinelibrary.wiley.com/doi/10.1002/oby.22685)

Scroll down to find abstracts for each of the above papers. To request the full text of any of these studies and agree to the embargo policy, or to arrange an interview with a study's author or an obesity expert, please contact communications@obesity.org.

Editors' Choice Abstracts

Editors' Choice 1 - Appetite-Related Responses to Overfeeding and Longitudinal Weight Change in Obesity-Prone and Obesity-Resistant Adults

Objective: Appetite responses to 3 days of overfeeding (OF) were examined as correlates of longitudinal weight change in adults classified as obesity prone (OP) or obesity resistant (OR).

Methods: OP (n = 22) and OR (n = 30) adults consumed a controlled eucaloric and OF diet (140% of energy needs) for 3 days, followed by 3 days of ad libitum feeding. Hunger and satiety were evaluated by visual analog scales. Ghrelin and peptide YY (PYY) levels were measured during a 24-hour inpatient visit on day 3. Body weight and composition were measured annually for 4.0 ± 1.3 years.

Results: Dietary restraint and disinhibition were greater in OP than OR (mean difference: 3.5 ± 1.2 and 3.3 ± 0.9, respectively; P

Conclusions: Baseline disinhibition and PYY responses to OF differed between OP and OR adults. Dietary disinhibition was associated with 5-year longitudinal weight gain. Differences in appetite regulation may underlie differences in propensity for weight gain.

Editors' Choice 2 - Early Infant Feeding and BMI Trajectories in the First 5 Years of Life

Objective: This study examined the relative impact of breastfeeding duration and timing of solids introduction on BMI z score (BMIz) trajectory in early childhood.

Methods: This study conducted secondary analyses of data from the Melbourne Infant Feeding, Activity and Nutrition Trial (InFANT) Program (N = 542), a prospective cohort study with data collected at birth and 3, 9, 18, 42, and 60 months. Linear spline multilevel models were performed.

Results: Differential growth rates were observed from birth to 3 months and from 9 to 18 months by breastfeeding duration (≥ 6 vs.

Conclusions: Longer breastfeeding duration was associated with lower BMI's to 5 years of age, providing further support for infant feeding guidelines to prolong breastfeeding duration for healthy growth.

Editors' Choice 3 - Muscle Strengthening, Aerobic Exercise, and Obesity: A Pooled Analysis of 1.7 Million US Adults

Objective: Both aerobic physical activity and muscle-strengthening exercise are recommended for obesity prevention. However, at the population level, the independent and/or combined associations of these physical activity modalities with obesity are unknown. The aim of this study was to examine the associations between aerobic physical activity and muscle-strengthening exercise with obesity among a representative sample of adults.

Methods: Data were pooled from four US public health surveillance surveys from 2011 to 2017. Cross-sectional associations between adherence to the aerobic physical activity (≥ 150 min/wk) and muscle-strengthening exercise (≥ 2 times/wk) guidelines with different classes of BMI-defined obesity were examined using Poisson regression. Prevalence ratios are reported as both unadjusted and adjusted for sociodemographic and lifestyle characteristics.

Results: Data were available for 1,677,108 adults (≥ 18 years old). Compared with meeting neither guideline (reference category), meeting both guidelines was associated with the lowest adjusted prevalence ratios (APRs) for the following: Class I obesity and above (BMI ≥ 30.0 kg/m2), APR = 0.54 (95% CI: 0.53-0.54); Class II obesity and above (BMI ≥ 35.0 kg/m2), APR = 0.32 (95% CI: 0.31-0.33); and Class III obesity and above (BMI ≥ 40.0 kg/m2), APR = 0.21 (95% CI: 0.20-0.21).

Conclusions: Among nearly 1.7 million US adults, meeting both aerobic and muscle-strengthening exercise guidelines was associated with a lower obesity prevalence, and associations were more pronounced for higher obesity classes.

Editors' Choice 4 - Behavioral and Psychological Strategies of Long-Term Weight Loss Maintainers in a Widely Available Weight Management Program

Objective: The study's purpose was to use validated questionnaires to identify novel behavioral and psychological strategies among weight loss maintainers (WLMs) in a commercial weight management program.

Methods: Participants were 4,786 WLMs in WW (formerly Weight Watchers, New York, New York) who had maintained weight loss ≥ 9.1 kg (24.7 kg/23.8% weight loss on average) for 3.3 years and had a current mean BMI of 27.6 kg/m2. A control group of 528 weight-stable individuals with obesity had a mean BMI of 38.9 kg/m2 and weight change

Results: WLMs versus Controls practiced more frequent healthy dietary choices (3.3 vs. 1.9; ɳp2 = 0.37), self-monitoring (2.6 vs. 0.7; ɳp2 = 0.30), and psychological coping (2.5 vs. 1.1; ɳp2 = 0.25) strategies. WLMs also reported more willingness to ignore food cravings (4.4 vs. 3.5; ɳp2 = 0.16) and had greater habit strength for healthy eating (5.3 vs. 3.2; ɳp2 = 0.21). Standard canonical coefficients indicated that dietary (0.52), self-monitoring (0.40), and psychological (0.14) strategies as well as habit strength for healthy eating (0.15) contributed independently and most (49.5% of variance) to discriminating groups.

Conclusions: In a widely available weight management program, more frequent practice of healthy dietary, self-monitoring, and psychological coping strategies as well as development of greater habit strength for healthy eating differentiated long-term WLMs from weight-stable individuals with obesity.

WASHINGTON--Teens with obesity and polycystic ovary syndrome (PCOS) have more "unhealthy" gut bacteria, suggesting the microbiome may play a role in the disorder, according to new research published in the Endocrine Society's Journal of Clinical Endocrinology & Metabolism.

PCOS is complicated endocrine disorder affecting 6 percent to 18 percent of women of reproductive age and work in adult women indicates that changes in bacteria be involved. The hormone disorder is characterized by elevated testosterone levels in the blood that cause acne, excess hair growth and irregular periods. Teens with PCOS often also struggle with obesity and have a higher risk for type 2 diabetes, infertility, and depression.

"We found that in adolescents with PCOS and obesity, the bacterial profile (microbiome) from stool has more 'unhealthy' bacteria compared to teens without PCOS," said the study's corresponding author, Melanie Cree Green, M.D., Ph.D., of Children's Hospital Colorado in Aurora, Colo. "The unhealthy bacteria related to higher testosterone concentrations and markers of metabolic complications."

The researchers studied 58 teens with obesity and found that girls with PCOS have an altered gut microbiome compared to those without the condition. These girls had more "unhealthy" bacteria in their stool which was related to higher testosterone levels and other markers of metabolic syndrome, such as higher blood pressure, liver inflammation and plasma triglycerides

"The gut microbiome may play a role in PCOS and its related metabolic complications, and these changes can be found in teenagers who are early in the course of the condition," Green said.

A new study, published in the Journal of Allergy and Clinical Immunology, shows that exposure to diesel exhaust particles (DEPs) can increase an individual's susceptibility to pneumococcal disease.

The bacterium Streptococcus pneumoniae is the most common cause of pneumonia and meningitis and the leading cause of infectious disease deaths in under-5s and elderly groups worldwide. In the majority of healthy people, this bacterium lives harmlessly in the back of the nose and throat without causing any symptom. However, if the pneumococcus gains access to normally sterile sites in the body, such as the lungs and blood, it has the potential to cause life-threatening diseases.

To find out more about the conditions that allow this ordinarily harmless bacterium to progress into such severe invasive diseases researchers from the University of Liverpool, Queen Mary's University, London and Trinity College Dublin, conducted a study examining the role of DEPs in the development of pneumococcal disease.

Air pollution

The World Health Organisation (WHO) estimates that air pollution is responsible for 7 million deaths per year, with 7% of these attributable to pneumonia. An estimated 37% of the world's population live in areas where levels of airborne pollution exceed WHO guideline limits.

DEPs, a major component of air pollution worldwide, is the particulate component of diesel exhaust, which includes diesel soot and aerosols such as ash particulates, metallic abrasion particles, sulphates, and silicates.

The researchers, led by Professor Aras Kadioglu from the University of Liverpool's Institute of Infection & Global Health, used a combination of mouse models and lab-based assays in both mouse and human cells to provide insight into the link between DEP exposure and pneumococcal disease.

Results

The researchers found that following exposure to DEPs, airway macrophages, which are key immune cells for controlling bacterial infections and removing debris from the body, become congested with DEPs, reducing their ability to kill the pneumococcus. This allows the bacteria to survive more easily in the airways, invade the lungs, and cause significant inflammation, which eventually leads to bacterial translocation into blood, thereby causing severe disease.

Professor Aras Kadioglu, said: "We know that exposure to air pollution is harmful, responsible for millions of deaths every year, of which a significant proportion is due to pneumonia. What we did not know however, was how pollution, such as diesel exhaust particles, actually causes airway disease."

"In this study, we have now discovered the cellular mechanisms behind this. Our study highlights an urgent need to tackle airway pollution if we are to reduce life threatening respiratory diseases such as pneumonia."

Key factor in severe disease development

Dr Rebecca Shears, who is first author, added: "Our study shows that exposure to DEPs, which is a major airborne particulate pollutant both here in the UK and abroad, may be one of the key factors involved in the switch from harmless pneumococcal colonisation of the nasal tissues to severe disease, such as pneumonia."

"Our data provides further insight to support previous observations of increased pneumonia hospital admissions in countries such as China, where airborne pollution levels are highest."

"The reduced ability of DEP exposed airway macrophages to control the infection appears to be key in the increased number of cases of pneumococcal disease. This study adds further impetus to reduce global pollution levels."

Sepsis claims one life every four seconds. It is the primary cause of death in hospitals, and one of the ten leading causes of death worldwide. Sepsis is associated with the body's inflammatory response to a bacterial infection and progresses extremely rapidly: every hour that goes by before it is properly diagnosed and treated increases the mortality rate by nearly 8%. Time is critical with sepsis, but the tests currently used in hospitals can take up to 72 hours to provide a diagnosis.

Many scientists are working on this critical issue, including those at Abionic, an EPFL spin-off. Researchers at the Laboratory of Bionanophotonic Systems (BIOS) at EPFL's School of Engineering have just unveiled a new technology. They have developed an optical biosensor that slashes the sepsis diagnosis time from several days to just a few minutes. Their novel approach draws on recent developments in nanotechnology and on light effects at a nano scale to create a highly portable, easy-to-use device that can rapidly detect sepsis biomarkers in a patient's bloodstream. And their device takes just a few minutes to deliver a result, like a pregnancy test.

Because the biosensor uses a unique plasmonics technology, it can be built from small, inexpensive components, yet it can achieve an accuracy on par with gold-standard laboratory methods. The device can screen a large panel of biomarkers and be adapted for the rapid diagnosis of a number of diseases. It was installed at Vall d'Hebron University Hospital in Spain and used in blind tests to examine patient samples from the hospital's sepsis bank. The researchers' technology is patent-pending, and their findings were recently published in Small.

Trapping biomarkers in nanoholes

The device employs an optical metasurface - in this case a thin gold sheet containing arrays of billions of nanoholes. The metasurface concentrates light around the nanoholes so as to allow for exceptionally precise biomarker detection. With this type of metasurface, the researchers can detect sepsis biomarkers in a blood sample with nothing more than a simple LED and a standard CMOS camera.

The researchers begin by adding a solution of special nanoparticles to the sample that are designed to capture the biomarkers. They then distribute this mixture on the metasurface. "Any nanoparticles that contain captured biomarkers are trapped quickly by antibodies on the nanoholes," says Alexander Belushkin, the lead author of the study. When an LED is applied, those nanoparticles partially obstruct the light passing through the perforated metasurface. "These nano-scale interactions are imaged by the CMOS camera and digitally counted in real-time at high precision," says Filiz Yesilkoy, the study's co-author. The generated images are used to rapidly determine whether disease biomarkers are present in a sample and, if so, in what concentration. They used the new device to measure the blood serum levels of two important sepsis relevant biomarkers, procalcitonin and C-reactive protein. Doctors can use this information to accelerate the triage of sepsis patients, ultimately saving lives.

"We believe our low-cost, compact biosensor would be a valuable piece of equipment in ambulances and certain hospital wards," says Hatice Altug, the head of BIOS. Scientists already have possible applications in mind. "There is an urgent need for such promising biosensors so that doctors can diagnosis sepsis accurately and quickly, thereby keeping patient mortality to a minimum," say Anna Fàbrega and Juan José González, lead doctors at Vall d'Hebron University Hospital.

Daily low-dose aspirin, from as early as the sixth week of pregnancy through the 36th week, may lower the risk for preterm birth among first-time mothers, suggests a study funded by the National Institutes of Health. The clinical trial, which involved more than 11,000 women in several low- and middle-income countries, found that women taking daily low-dose aspirin were 11% less likely to deliver before the 37th week of pregnancy, compared to those given a placebo.

The study was conducted by Matthew K. Hoffman, M.D., of Christiana Care in Newark, Delaware, and colleagues in the Global Network for Women's and Children's Health Research, a clinical trials network funded by NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). It appears in The Lancet.

"Our results suggest that low-dose aspirin therapy in early pregnancy could provide an inexpensive way to lower the preterm birth rate in first-time mothers," said study author Marion Koso-Thomas, M.D., of NICHD's Pregnancy and Perinatology Branch.

Preterm birth is the most common cause of infant death and the leading cause of long-term neurological disability in children. According to the study authors, advances in newborn care have improved survival for preterm infants, but this care is limited or unavailable in many parts of the world. Earlier studies have suggested that low-dose aspirin may reduce the risk of preterm birth and preeclampsia, a potentially life-threatening blood pressure disorder of pregnancy. However, these studies were not large enough to statistically determine the therapy's effectiveness in reducing preterm birth.

The researchers enrolled 11,976 women with a first-time pregnancy from seven sites in India, Pakistan, Zambia, Democratic Republic of the Congo, Guatemala and Kenya. Roughly half were assigned at random to receive 81 milligrams of aspirin daily; the other group received a daily placebo. Women were included in the study only if they maintained a pregnancy for more than 20 weeks.

Preterm birth (before 37 weeks) occurred in 11.6% of the women who took aspirin and in 13.1% of the women who took the placebo. Similarly, birth before 34 weeks (early preterm delivery) occurred in 3.3% of the aspirin group and 4% of the placebo group (a 25% reduction). Women in the aspirin group also had a lower rate of perinatal mortality (stillbirth or newborn death in the first seven days of life), compared to the placebo group (45.7 per 1,000 births vs 53.6 per 1,000 births). The risk of high blood pressure disorders of pregnancy at term did not differ significantly between the groups.

The authors note that the low cost and safety of low-dose aspirin therapy suggest that it could be easily adapted for widescale use.