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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 infants 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 womens 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 bodys 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 wasnt known whether the increased risk for Caesarean delivery and other problems seen with mild elevations in blood sugar during 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 mothers 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.

The researchers concluded by recommending that future studies on the effectiveness of treatments should consider measuring employment status and earnings over the long term to document the effects of mental disorders on a persons functioning and ability to remain productive.

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Major mental disorders cost the nation at least $193 billion annually in lost earnings alone, according to a new study funded by the National Institutes of Healths National Institute of Mental Health (NIMH). The study was published in the May 2008 issue of the American Journal of Psychiatry.

"Lost earning potential, costs associated with treating coexisting conditions, Social Security payments, homelessness and incarceration are just some of the indirect costs associated with mental illnesses that have been difficult to quantify," said NIMH Director Thomas R. Insel, M.D. "This study shows us that just one source of these indirect costs is staggeringly high."

Direct costs associated with mental disorders like medication, clinic visits, and hospitalization, are relatively easy to quantify, but they reveal only a small portion of the economic burden these illnesses place on society. Indirect costs like lost earnings likely account for enormous expenses, but they are very difficult to define and estimate.

In the new study, Ronald C. Kessler, Ph.D., of Harvard University, and colleagues analyzed data from the 2002 National Comorbidity Survey Replication (NCS-R), a nationally representative study of Americans age 18 to 64.

Using data from 4,982 respondents, the researchers calculated the amount of earnings lost in the year prior to the survey among people with serious mental illness (SMI). SMI is a broad category of illnesses that includes mood and Anxiety disorders that have seriously impaired a persons ability to function for at least 30 days in the year prior to the survey. It also includes cases of any mental disorder associated with life-threatening suicidal behaviors or repeated acts of violence.

Eighty-six percent of respondents reported earning income in the previous year. But those with SMI reported earning significantly less — around $22,545 — than respondents without SMI, who averaged $38,852. Although men with SMI took a greater hit in earnings than women with SMI, men still earned more overall than women with and without SMI.

By extrapolating these results to the general population, the researchers calculated that SMI costs society $193.2 billion annually in lost earnings. The researchers attributed about 75 percent of this total to the reduced income that people with SMI likely earn, while 25 percent is attributed to the increased likelihood that people with SMI would have no earnings.

"The results of this study confirm the belief that mental disorders contribute to enormous losses of human productivity," said Kessler. "Yet this estimate is probably conservative because the NCS-R did not assess people in hospitals or prisons, and included very few participants with Autism, schizophrenia or other chronic illnesses that are known to greatly affect a persons ability to work. The actual costs are probably higher that what we have estimated."

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A survey conducted by the World Health Organization (WHO) research consortium found that the United States had among the highest lifetime rates of tobacco and alcohol use and led in the proportion of participants reporting cannabis (marijuana) or cocaine use at least once during their lifetime. The study, led by Dr. Louisa Degenhardt of the University of New South Wales, Sydney, Australia and colleagues, looked at patterns in the use of alcohol, tobacco, cannabis and cocaine in 17 countries representing all six WHO regions (the Americas, Europe, Asia, the Middle East, Africa and Oceania). The study, funded in part by the National Institute on Drug Abuse (NIDA), part of the National Institutes of Health (NIH) is published in the July 1, 2008 issue of the open access journal PLoS Medicine.

"These findings add to our understanding of substance abuse world-wide, and suggest that drug use is still a major problem in this country, pointing to the need for more effective prevention interventions," said Dr. Elias A. Zerhouni, NIH director.

"A survey of lifetime use does not provide the entire picture; however, because it does not reflect current use or trends over time," said Dr. Volkow, sounding a note of caution. "For example, although lifetime use of tobacco was reported by this study to be 74 percent in the U.S., current use has been documented at approximately 30 percent. Moreover, NIDAs Monitoring the Future survey has been consistently reporting a decrease in the past year use of illicit drugs over the past decade, so this survey may reflect a longer history of drug use in certain countries relative to others, but not necessarily current trends."

Among the significant findings of this study were:

• Across countries and across the drug types in this survey, drug use is becoming more common over time.
• Males were more likely than females to have used all drug types in all countries and all age groups.
• Younger adults were more likely than older adults to have used these substances.
• Those with higher incomes were more likely to have used legal and illegal drugs.
• Alcohol had been used by the vast majority of survey participants in the Americas, Europe, Japan, and New Zealand, compared to smaller proportions in the Middle East, Africa and China.
• Alcohol use by age 15 was far more common in European countries than in the Middle East or Africa.
• Lifetime tobacco use was most common in the United States (74 percent), Lebanon (67 percent) Mexico and the Ukraine (60 and 61 percent), followed by the Netherlands (58 percent.)

"In addition to the factors measured in this study, the role of culture, drug availability and knowledge about drug use are likely to be important in the types and patterns of drug use throughout the world," said Dr. Nora D. Volkow, NIDA director. "Even within the United States, rates and patterns of substance use differ based on geographical location and ethnicity, among other factors."

The authors point out that the survey is limited to those countries that had the resources and willingness to participate, and that efforts were made to account for possible cultural differences in participants willingness to answer truthfully, which could impact measures of actual drug use. For more information about the survey Toward a Global View of Alcohol, Tobacco, Cannabis and Cocaine Use: Findings from the WHO Mental Health Surveys, go to www.plosmedicine.org .

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Study Implicates Disruption of Genes Regulated by Early Experience

Many of the seemingly disparate mutations recently discovered in Autism may share common underlying mechanisms, say researchers supported in part by the National Institute of Mental Health (NIMH), a part of the National Institutes of Health (NIH). The mutations may disrupt specific genes that are vital to the developing brain, and which are turned on and off by experience-triggered neuronal activity.

A research team led by Christopher Walsh, M.D., Ph.D., and Eric Morrow, M.D., Ph.D., of Harvard University, found two large sections missing on Chromosomes in people with autism and traced them to likely inherited mutations in such genes regulated by neuronal activity. They report their findings in the July 11, 2008 issue of Science. The study was also supported in part by the NIHs National Center for Research Resources, National Human Genome Research Institute, Eunice Kennedy Shriver National Institute of Child and Human Development, and the National Institute on Neurological Disorders and Stroke.

The study breaks new ground for complex disorders like autism, taking advantage of a shortcut to Genetic discovery by sampling families in which parents are cousins. The researchers found genes and mutations associated with autism in 88 families from the Middle East, Turkey and Pakistan in which cousins married and had children with the disorder.

The emerging picture of the genetics of autism is quite surprising. There appear to be many separate mutations involved, with each family having a different genetic cause, explained NIMH Director Thomas R. Insel, M.D. The one unifying observation from this new report is that all of the relevant mutations could disrupt the formation of vital neural connections during a critical period when experience is shaping the developing brain.

Earlier studies had suggested that the individually rare mutations are present in at least 10 percent of sporadic cases of autism, which is the most common form.

The researchers used a technique that pinpoints from a relatively small group of families genes responsible for disorders that can be amplified by parenthood among relatives, which can increase transmission of recessive diseases. Evidence had hinted at such transmission in autism, and the large amount of genetic information obtainable from such families reduced the need for a much larger sample including many families with multiple affected members.

The ratio of females to males with autism  normally one female to four males  was less lopsided in such families in which parents share a common recent ancestor. This ratio equalized even more in a subset of these families with more than one affected member, suggesting a doubling of the rate of autism, due to recessive causes on non-sex-linked chromosomes. Also, autism-linked spontaneous deletions and duplications of genetic material were relatively uncommon in these families, suggesting recessive inherited causes.

The researchers found multiple different genetic causes of autism in different individuals with little overlap between the families in which parents shared ancestry. Yet a few large inherited autism-linked deletions, likely mutations, in a minority of families stood out. The largest turned out to be in or near genes regulated, directly or indirectly, by neuronal activity.

Autism symptoms emerge at an age when the developing brain is refining the connections between neurons in response to a childs experience, explained Walsh. Whether or not certain important genes turn on is thus dependent on experience-triggered neural activity. Disruption of this refinement process may be a common mechanism of autism-associated mutations.