Artificial Insemination

The largest study of its kind, this research shows that the risk of childhood obesity rises in tandem with a pregnant woman's blood sugar level and that untreated gestational diabetes nearly doubles a child's risk of becoming obese by age 5 to 7. The study also shows for the first time that by treating women with gestational diabetes, the child's risk of becoming obese is significantly reduced. In fact, children whose moms were treated for gestational diabetes had the same risk for becoming obese as children whose mothers had normal blood sugar levels.

Researchers at Kaiser Permanente's Center for Health Research (CHR) in Portland and Hawaii used the organization's integrated databases to analyze medical records of 9,439 mother-child pairs. The subjects were members of the health plan in Oregon, Washington and Hawaii and gave birth between 1995 and 2000. The authors found that treating gestational diabetes lowers the child's risk of becoming obese during childhood to the same levels of those pregnant mothers with normal blood sugar levels.

Gestational diabetes, the condition in which pregnancy triggers insulin resistance and raises the woman's blood glucose level (hyperglycemia), affects up to 8 percent of pregnant women each year in the United States. The rate of childhood obesity in this country more than doubled in the last two decades, so much so that it is now one the nation's fastest growing health conditions. Nearly 7 million overweight and obese children in the United States today will grow up to become overweight or obese adults.

"Hyperglycemia during pregnancy is clearly playing a role in America's epidemic of childhood obesity," said Teresa Hillier, MD, MS, an endocrinologist and senior investigator at CHR Northwest and Hawaii, and the lead author of the study. "The key finding here is that the risk of overweight and obese children rises in step with higher levels of blood sugar during pregnancy. The good news for pregnant women is that by treating gestational diabetes, your children's risk of becoming overweight or obese drops considerably."

The target of these drugs is an enzyme called COX-2, which is produced in response to infection or injury and releases pain- and fever-inducing byproducts. Thus blocking COX-2 reduces pain.

But blocking Cox-2 in mice, according to the new study, also stimulated the production of a protein called tissue factor, or TF, which initiates blood clotting. As heart attacks and strokes are often triggered by blood clots, it is possible that the production of TF is in part responsible for the drug's adverse side-effects in humans.

In the drug-treated mice, the high levels of TF in the blood were countered by administering TF-reducing drugs. Thus it is theoretically possible to treat people safely with Vioxx and other Cox-2 inhibitors if existing TF-blocking drugs are given simultaneously.

The new study will be published online in the The Journal of Experimental Medicine on August 27.

Co-authors on the paper were biostatisticians M. Elizabeth (Betz) Halloran, M.D., D.Sc., and Yang Yang, Ph.D.; and epidemiologist Jonathan Sugimoto, M.H.S., a pre-doctoral research associate. All are within the Hutchinson Center's Public Health Sciences Division and Vaccine and Infectious Disease Institute.

The researchers based their findings on a cluster of eight flu cases within an extended family in northern Sumatra. Using a computerized disease-transmission model that took into account the number of infected cases, the number of people potentially exposed, the viral-incubation period and other parameters, the researchers produced the first statistical confirmation of humans contracting the disease from each other rather than from infected birds.

The cluster contained a chain of infection that involved a 10-year-old boy who probably caught the virus from his 37-year-old aunt, who had been exposed to dead poultry and chicken feces, the presumed source of infection. The boy then probably passed the virus to his father. The possibility that the boy infected his father was supported by genetic sequencing data. Other person-to-person transmissions in the cluster are backed up with statistical data. All but one of the flu victims died, and all had had sustained close contact with other ill family members prior to getting sick - a factor considered crucial for transmission of this particular flu strain.

In an attempt to contain the spread of the virus, the local health authorities eventually placed more than 50 surviving relatives and close contacts under voluntary quarantine and all, except for pregnant women and infants, received antiviral medication as a precaution.

"The containment strategy was implemented late in the game, so it could have been just luck that the virus burned out," Longini said. "It went two generations and then just stopped, but it could have gotten out of control. The world really may have dodged a bullet with that one, and the next time we might not be so lucky," he said.

Should a strain of avian flu acquire the ability to cause sustained human-to-human transmission, the results could be catastrophic, Longini said. "If not contained, the outbreak could spread worldwide through the global transportation network faster than the appropriate vaccine supply could be made available. That's why it's so important to ascertain whether human-to-human transmission is happening as well as the virulence of the strain." The researchers estimated the secondary-attack rate of the virus in Indonesia - the risk of one infected person passing it to another - to be 29 percent, a level of infectiousness similar to statistical estimates for seasonal influenza A in the United States.