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Women who carry excess fat around their waists were at greater risk of dying early from cancer or heart disease than were women with smaller waistlines, even if they were of normal weight, reported researchers from Harvard and the National Institutes of Health.

Previous studies have shown that the tendency to deposit fat around the waist increases the risk for health problems. The current study is the largest, most comprehensive of its kind undertaken to show that accumulation of abdominal fat can increase the risk of death.

To conduct the study, the researchers analyzed data from more than 44,000 women in the Nurses’ Health study, which followed the health history of thousands of registered nurses in 11 states.

“As we know from the work of the NIH Obesity Research Task Force, reversing the epidemic of obesity is challenging,” said Elias A. Zerhouni, M.D., Director of the National Institutes of Health. “The current findings highlight the role that research can play in understanding the risks of obesity.”

The research team that conducted the study was led by Cuilin Zhang, M.D., Ph.D., of NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD). Dr. Zhang conducted much of her work on the study while at the Harvard School of Public Health. She concluded her analysis after joining the staff of the NICHD. The study was conducted in the research group of Dr. Frank Hu, M.D., Ph.D., of the Harvard School of Public Health, and by researchers from Brigham and Women’s Hospital and Harvard School of Medicine. Funding for the study was provided by the NIH’s National Institute of Diabetes and Digestive and Kidney Diseases and the National Cancer Institute. The Nurse’s Health Study was supported by NIH’s National Heart, Lung and Blood Institute.

The study was published online in Circulation.

There is increasing evidence that excess abdominal fat is a risk factor for long-term conditions like diabetes and heart disease. However, the relationship between abdominal obesity and risk of death has not been widely studied. The current study is one of the largest extended investigations of abdominal obesity and women’s risk of premature death.

Researchers followed more than 44,000 women over the course of 16 years to track their medical history and lifestyle. Because the majority of the women who took part in the study were white, the researchers do not know if their findings pertain to other groups of women or to men.

All the women included in the study were registered nurses. At the beginning of the study the women were asked to measure their waists and hips. Every two years, the women completed questionnaires about their health, providing information about their age, activity level, smoking status, diet, blood pressure and cholesterol levels.

The researchers examined the cause of death for all women who died over the course of the study. In total, 3,507 deaths occurred—of these, 1,748 were due to cancer and 751 were due to heart disease.

The researchers discovered that women with greater waist circumferences were more likely to die prematurely, particularly from heart disease, when compared to women with smaller waists. For example, women with waist size equal to or greater than 35 inches were approximately twice as likely to die of heart disease as were women with a waist size less than 28 inches, regardless of their body mass index. Similarly, women with a waist size equal to or greater than 35 inches also were twice as likely to die of cancer as were women with a waist size less than 28 inches.

Women who had a greater waist circumference and were also obese were at the greatest risk of premature death. Researchers determined if a woman was overweight by calculating her body mass index (BMI), a measure of a person’s weight in relation to height. BMI is used to estimate the proportion of a person’s weight that derives from body fat. A BMI between 18.5 and 24.9 is considered healthy. A BMI of 30.0 - 39.9 is regarded as obese.

Greater waist circumference is a sign of collecting excess fat around one’s midsection, called abdominal obesity. According to the Clinical Guidelines on the Identification, Evaluation and Treatment of Overweight and Obesity in Adults published by NHLBI in cooperation with NIDDK in 1998, a healthy waist limit for women is 35 inches and, for men, 40 inches. Waist circumference is determined by measuring around the waist at the navel line. The NHLBI lists information on waist circumference and BMI at http://www.nhlbi.nih.gov/health/public/heart/obesity/lose_wt/risk.htm

In 2004, over one-half of U.S. adults had abdominal obesity by these standards, said Dr. Zhang.

The researchers also studied waist-to-hip ratio–a measure of the narrowest part of the waist compared to the circumference at the broadest part of the hip–as a potential determinant of mortality risk. Waist-to-hip ratio was found to be as strongly associated with risk of early death as the measurement of waist size alone. However, waist-to-hip ratio requires two measurements and therefore may be less convenient to calculate than measuring waist circumference alone, said Dr. Zhang.

The study authors wrote that results from previous studies have been inconsistent because of the relatively small number of people who took part and the short duration of the studies. The current study provides the strongest evidence so far regarding the adverse effects of abdominal obesity on the risk of death in women. The authors called for future studies to investigate abdominal obesity and the risk of death in men and other ethnic groups.

“Although maintaining a healthy weight should continue to be a corner stone in the prevention of chronic diseases and premature death, maintaining a healthy waist size should also be an important goal,” the study authors wrote.

Source: National Institute of Child Health and Human Development, NIH, DHHS

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Pregnant women with blood sugar levels in the higher range of normal—but not high enough to be considered diabetes—are more likely than women with lower blood sugar levels to give birth to babies at risk for many of the same problems seen in babies born to women with diabetes during pregnancy, according to a study funded in large part by the National Institutes of Health.

These problems included a greater likelihood for Caesarean delivery and an abnormally large body size at birth.  Infants born to women with higher blood sugar levels were also at risk for shoulder dystocia, a condition occurring during birth, in which an infant’s shoulder becomes lodged inside the mother’s body, effectively halting the birth process.

The study authors declined to make recommendations for acceptable blood sugar levels for pregnant women.  The researchers were unable to identify a precise level where an elevation in blood sugar increased the risk for any of the outcomes observed in the study.  Rather, the chances for the outcomes were observed to increase gradually, corresponding with increases in the women’s blood sugar levels.

It is well known that high blood sugar levels characteristic of the diabetes that occurs during pregnancy present risks for expectant mothers and the infants born to them.  The current study is the first to document that higher blood sugar levels, not high enough to be considered diabetes, also convey these increased risks.  Furthermore, when the researchers mathematically adjusted for other potential causes of these risks—such as older maternal age, obesity, and high blood pressure—the increased risks due to higher blood sugar levels were still present.

“These important new findings highlight the risks of elevated blood sugar levels during pregnancy,” said Duane Alexander, M.D., director of the NIH’s Eunice Kennedy Shriver National Institute of Child Health and Human Development, which provided much of the funding for the study.  “NIH-supported studies now in progress will provide guidance on how to manage them.  Until the results of those studies are available, all pregnant women should consult a health care professional about being screened for diabetes during pregnancy.”

Additional NIH funding was provided by the National Institute of Diabetes and Digestive and Kidney Diseases, and the National Center for Research Resources.

Diabetes results from difficulty transferring sugar (glucose) from the blood to the body’s tissues.  It occurs in roughly 5 percent of all pregnancies in the United States.  Mothers with diabetes during pregnancy are also at increased risk for preeclampsia, a potentially fatal disorder involving dangerously high blood pressure.  Babies born to mothers with diabetes—when they reach adulthood—are at higher risk for obesity as well as diabetes, high blood pressure, and heart disease.

The seven-year study involved more than 23,000 pregnant women at 15 centers in 9 countries.

The results of the Hyperglycemia and Adverse Pregnancy Outcomes (HAPO) study appear in the May 8 New England Journal of Medicine.  The researchers were led by Boyd E. Metzger, M.D. Professor of Medicine at the Northwestern University Feinberg School of Medicine in Chicago.

Dr. Metzger explained that before the current study, physicians were not sure at which point elevated maternal blood sugar posed a risk for the baby.  Frequently, high maternal blood sugar levels accompany such conditions as obesity, high blood pressure and older maternal age—all known to increase the likelihood for Caesarean delivery.  For this reason, it wasn’t known whether the increased risk for Caesarean delivery and other problems seen with mild elevations in blood sugarduring pregnancy were caused by the elevated blood sugar levels, or by these accompanying conditions.  In their study, however, the researchers made adjustments for these accompanying conditions and found that the higher blood sugar levels still conveyed increased risks.

To conduct the study, the researchers performed an oral glucose tolerance test on each woman, from the 24th through the 32nd week of pregnancy.  For the test, the women fasted, after which their blood glucose level was measured.  Next, the women drank a glucose solution, and then their blood glucose was measured at predetermined intervals.  Women with blood sugar levels high enough to raise safety concerns were referred for treatment and were not included in the study.  The remaining women were observed throughout the study until they gave birth.

The researchers found that the higher the mother’s blood sugar levels, the greater the chances that they would deliver by Caesarean section.  In addition, the higher the mother’s blood sugar levels, the more likely the infants were to have high insulin levels and low blood sugar levels at birth.  Both conditions indicate exposure to high glucose levels in the womb.  Moreover, the higher the mother’s blood sugar levels, the more likely the women were to develop preeclampsia, and the more likely their infants were to be born prematurely, and to experience shoulder dystocia.  So, for example, women with the lowest fasting blood sugar levels gave birth to abnormally large babies roughly 5 percent of the time, while women with the highest blood sugar level gave birth to large babies 26 percent of the time.

“These relationships are continuous and generally increase incrementally over the range of blood glucose levels we saw in the study,” he said.

Source: National Institute of Child Health and Human Development, NIH, DHHS

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The journey of hope to improve the lives of infants born with oxygen deprivation has taken 65 years. Loss of oxygen to the brain may result in death or a lifetime of blindness, mental retardation, or cerebral palsy. In October 2005, Seetha Shankaran and her colleagues in the NICHD Neonatal Research Network reported that lowering a newborn’s body temperature a few degrees could reduce the likelihood of death or disability associated with depleted oxygen.

Complications of Birth
Oxygen deprivation, or hypoxia, typically occurs as a complication of birth. For example, if the umbilical cord becomes trapped between a baby’s head and the wall of the uterus, pressure on the cord may cut off the baby’s oxygen supply. Hypoxia may also result from blood loss, perhaps when the placenta tears free of the uterine wall, or the uterus ruptures. Blood loss or hypoxia at birth may lead to hypoxic ischemic encephalopathy (HIE), a condition experienced by up to 1 in every 1,000 newborns.

In 1949, James A. Miller first reported in Science that lowering body temperature could increase survival in newborn animals deprived of oxygen. He cooled newborn guinea pigs by wetting them with rubbing alcohol and placing them in front of an electric fan. When deprived of oxygen, the guinea pigs whose body temperatures had been lowered by as few as 4 degrees survived significantly longer than did littermates that had not been cooled. Miller undertook the study because he questioned the then routine practice of warming babies who were deprived of oxygen at birth. Chemical reactions, including those needed to sustain life, occur progressively faster as temperature increases. Miller hypothesized that reducing the speed of those reactions by reducing body temperature could increase survival. Between 1959 and 1972, several reports appeared about using a cooling treatment—by then known as hypothermia—for infants who had not responded within five minutes to standard resuscitation techniques.

Typically, an infant was placed in a cold-water bath, with only its nose, eyes, and mouth above water. Although infants treated with hypothermia appeared to be more likely to survive and less likely to have permanent disabilities, most of these early studies were too small to allow statistically valid conclusions. By the early 1970s, however, several research teams had shown that preterm infants were more likely to survive if they were cared for in warmer environments, and clinical interest in hypothermia waned.

Rebirth of a Field
It took 17 years before researchers began to reconsider hypothermia as a potential treatment for HIE. In 1987, Raul Busto and his coworkers found that lowering body temperatures in adult rats that had undergone a surgical technique designed to mimic stroke could lessen brain damage. Encouraged by this finding, researchers resumed testing hypothermia in oxygen-deprived newborn animals. Most of these studies conducted in the mid-1990s showed that cooling immediately after hypoxia reduced the severity of brain damage. Earlier research showed that while the loss of oxygen damaged brain tissue, the initial damage started a chain of reactions that worsened the original injury with each passing hour. It seemed that early cooling might blunt the secondary damage and preserve brain tissue.

Finding the Window of Opportunity
Immediate cooling, however, was often impractical in the delivery room. Efforts to stabilize the heart rate and other vital functions of newborns could take several hours, delaying when cooling could begin. Thus, researchers sought to discover whether benefits could still be gained if cooling the infant was delayed. Working with lambs, researcher Alistair Gunn and his coworkers found that the cooling treatment could be delayed for 5 ½ hours and still effectively reduce the extent of brain injury. In their research, the scientists used a special cooling cap, which circulates water around the head, lowering brain temperature while maintaining normal temperatures in the rest of the body. After showing that the cold cap was safe for newborn infants with HIE, the researchers later found that it could reduce the effects of moderate brain injury in newborns.

Uniform Brain Cooling
At the same time, Abbot Laptook was also searching for a more effective means to provide cooling therapy. An earlier study of adult stroke patients demonstrated that a cooling blanket could lower brain temperature. Like the cold cap, the blanket’s temperature was controlled by circulating water and was used to effectively lower body temperature. However, when comparing head cooling to the cooling blanket in newborn swine, Laptook and his coworkers found that head cooling most effectively lowered temperatures in brain areas nearest the skull, while inner brain areas remained warm. By comparison, the blanket cooled the entire brain uniformly. Shortly thereafter, the researchers demonstrated the blanket’s safety in newborns with oxygen loss.

In July of 2000, Laptook, Shankaran, and other colleagues in the NICHD Neonatal Research Network began enrolling oxygen-deprived term newborns in a large-scale study of the cooling blanket. In October 2005, the researchers published their findings, showing that using the blanket to lower body temperature to about 92°F within the first six hours of life reduced the chance for disability and death among full-term infants with HIE. Unlike earlier cold cap findings, however, this study showed that the blanket’s more uniform cooling could reduce the extent of death and disability resulting from both severe and moderate brain injury.

Continuing the Journey to Success
Currently, the NICHD is consulting with the American Academy of Pediatrics as the organization develops practice recommendations to treat hypoxia at birth. Three ongoing hypothermia treatment studies will provide additional information on the most effective ways to provide the treatment. These continuing refinements should accelerate access to the therapy for all infants who could benefit from its use.

Source: National Institute of Child Health and Human Development, NIH, DHHS

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