Yale Bulletin and Calendar

February 15, 2008|Volume 36, Number 18















Yale Ob-Gyn researchers discussed current work at Society for Maternal Fetal Medicine meeting

Members of Yale’s Department of Obstetrics, Gynecology & Reproductive Sciences (Yale Ob-Gyn) presented preliminary results from their research at the Society for Maternal Fetal Medicine Annual Meeting on Feb. 2 in Dallas, Texas. The following is a look at three of these studies. (See related story.)

Gene linked to preterm birth among Hispanic women

Researchers at Yale School of Medicine have found that the gene ENPP1 is linked to preterm birth and low birth weight among Hispanic women.

Dr. Errol Norwitz, associate professor in Yale Ob-Gyn, discussed this research at the Dallas gathering.

One out of eight babies in the United States is born prematurely — delivery prior to 37 weeks gestation. These babies don’t fare as well as their full-term counterparts, especially if they are born prior to 28 weeks gestation. In many cases, it is still unclear why preterm births occur, but Norwitz said that both the genetic make-up of the mother and the genetic make-up of the baby play a role.

Norwitz and his collaborators sought to understand the mechanisms responsible for the onset of labor at term and how these mechanisms are either overwhelmed or short-circuited, leading to preterm birth. Some women, especially African-American women, are genetically pre-disposed to preterm births, even after taking into account socioeconomic status, demographics, underlying medical conditions and multiple pregnancies. Norwitz said that multiple genes or a single particular genetic variant — single nucleotide polymorphism — may be involved.

In his study, Norwitz and colleagues tried to tease out some of the genetic factors that are important for preterm birth. They isolated DNA in blood samples from a largely Hispanic population of mothers with a history of preterm birth and compared them to the DNA of women who had only had full-term pregnancies. They then screened the DNA for 128 different genetic variations in 77 candidate genes. While these genetic variants have been known to cause clinical disorders, no one had ever investigated them in the context of preterm birth before.

Four polymorphisms were associated with premature birth, but — to the team’s surprise — a variant of the ENPP1 gene was the one most closely linked. ENPP1 has been associated with insulin resistance, glucose intolerance and a risk of developing type-2 diabetes. In certain people, it is associated with hardening of the arteries and high blood pressure. In the context of prematurity, say the researchers, it is possible that the variant form of ENPP1 is associated with deranged energy metabolism.

“In our original study, 85% of the population was Hispanic,” said Norwitz. “It appears that there are genetic variations unique to each ethnic population. We are now in the process of validating our findings in African-American, Caucasian and Native-American populations.”

Other authors on the study included Victoria Snegovskikh, Charles Lockwood, Edward Kuczynski, Louis Muglia, Daniel Robert Tilden, Beth Ann Kozel, Edmund Funai, Mert Ozan Bahtiyar, Guoyang Luo, Stephen Thung and Thomas Morgan.

New strategy helps reduce errors in obstetrical care

Yale School of Medicine researchers have implemented patient safety enhancements to dramatically reduce errors and improve the staff’s own perception of the safety climate in obstetrical care.

Dr. Edmund F. Funai, associate professor in Yale Ob-Gyn, presented the team’s preliminary results at the Dallas meeting.

An estimated 44,000 to 98,000 Americans die in hospitals each year as a result of errors. About half of medical errors are linked to communication errors and system failures. Obstetrics has lagged behind other specialties in attempts to improve safety because perinatal adverse events are both relatively uncommon and usually unexpected, occurring in previously healthy patients who are anticipating good outcomes.

“There is a crisis of confidence in American healthcare right now,” said Funai. “Reports in the media about patient injury in the hospital setting were causing concern, and we sought to apply some basic principles to obstetric care to make it a great deal safer than it is right now.”

Funai and his team designed and implemented clinical patient safety interventions at Yale-New Haven Hospital. These included communication training, standardizing interpretation of fetal monitoring and creating a novel staff role — the patient safety nurse. In tracking and analyzing 14 markers for adverse outcomes, the team found that the rate of adverse events decreased by about 60% over 2.5 years, while the staff’s own perception of the overall safety climate increased by 30%, according to a survey given by a third party.

Funai said that the main cause of adverse events and patient injury is a breakdown in communication, usually involving failure to recognize the severity of a given situation or condition, often involving a newborn’s status.

“Communication issues are only going to increase as a result of restrictions on resident work hours,” he said. “Patients are increasingly handed off from shift to shift and more attending physicians are practicing shift medicine. There is just more opportunity for errors in patient care. Everything we can do to standardize care and facilitate communication will make a big difference.”

Funai said, “After taking these surprisingly simple steps to address safety, both patients and staff report that the care is much more seamless and better organized. The staff is more comfortable and empowered to communicate their concerns about a patient. A comfortable staff often leads to more successful patient outcomes.”

Other authors on the abstract included Christian M. Pettker, Stephen Thung, Cheryl Raab, Errol Norwitz, Catalin Buhimschi, Joshua Copel and Charles Lockwood.

Risk of congenital heart defects higher among IVF twins

The prevalence of congenital heart disease (CHD) among in vitro fertilization (IVF) pregnancies is similar to that of the general population, but there is an increased risk of CHD among twins resulting from IVF, according to Yale School of Medicine researchers.

Dr. Mert Ozan Bahtiyar, assistant professor in Yale Ob-Gyn, presented the findings in Dallas.

“We found that twin pregnancies conceived through IVF have a higher prevalence of CHD than singletons,” he said, noting the group found a three-fold increase. “IVF twins are usually fraternal, but past studies of identical twins also showed up to a 13-fold increase in congenital heart defects.”

Working with the University’s Fetal Cardiovascular Center and Yale-New Haven Hospital, a central referral center for the State of Connecticut, Bahtiyar and his colleagues examined almost 2,000 patients using fetal echocardiography. Among those patients, 250 women were pregnant as a result of IVF. They did not have other medical problems that would require echocardiograms. Approximately 30% of these women had twin pregnancies.

Bahtiyar said that previous reports of increased CHD risk in pregnancies conceived via IVF might be due, in part, to a higher frequency of multiple pregnancies resulting from this form of conception. “The increased twinning seems to be the cause of the abnormality and not IVF per se,” he stated.

Bahtiyar and his team plan to do a larger study with more women.

“The next step is to explore why this is happening,” he said. “Knowing about the risk of these defects will help increase the likelihood of a child’s survival after birth.”

Other authors on the study included Antonette T. Dulay, Bevin P. Weeks, Alan H. Friedman and Joshua A. Copel.

Discussions about each of these topics can be found on Yale University iTunes U in the “Health and Medicine” section: http://deimos3.apple.com/WebObjects/Core.woa/Browse/yale.edu.1320598949.

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