Medical research bears fruit

When the stork brings a mother a new baby, it sometimes brings high blood pressure, excessive bleeding or pre-term labor with it. That is why doctors in the Department of Obstetrics, Gynecology and Reproductive Sciences at the School of Medicine are researching the causes of these complications.

The Maternal-Fetal Medicine Section has recently grown into one of the best-funded obstetrics and gynecology divisions in the country, and the team of 10 prenatologists is producing cutting-edge research on high-risk pregnancy.

“Our mission is twofold,” said Dr. Errol Norwitz, co-chief of the division. “One, to provide excellent care to people with high-risk pregnancies … The other mission is to develop the research component of the division.”

Norwitz said the doctors’ research focuses on the causes of pregnancy problems, how to predict those problems, and how to prevent them.

“If there was a theme to our division, it would be complications of all pregnancy but mostly pre-term birth,” he said. “I think people are appreciating that pre-term labor is one of the biggest concerns.”

Norwitz said about 20 percent of pre-term births are due to obstetric intervention; however, these births are rarely problematic because delivery is late enough that the newborn is developed and not in much danger. Spontaneous pre-term births often occur earlier in pregnancy, he said. If a birth happens before the 29th week, the baby is dangerously premature.

Of spontaneous premature births, Norwitz said, one-third are due to ruptured membranes, one-third to infection and one-third remain unexplained. He said a possible explanation is an inflammatory cascade — when there is a problem with the prenatal environment, the fetus initiates labor.

“It turns out that the fetus triggers labor in almost all circumstances, and it does that by the inflammatory response system,” he said. “The baby realizes the environment is hostile, and it responds to that.”

Norwitz said that maternal stress and depression can also lead to pre-term birth.

As of yet, doctors do not know how to avoid pre-term labor.

“The problem is, you really can’t prevent it, and that’s where we’re heading,” Norwitz said.

The division also studies preeclampsia, a high blood pressure condition that affects 5 to 7 percent of pregnant women. There is no known cure for preeclampsia, but the mother’s blood pressure returns to normal after she gives birth.

Dr. Edmund Funai, the other co-chief of the MFM division, recently completed a study linking preeclampsia and cardiovascular risk later in life.

“The conventional wisdom has always been that women go through it, it resolves and they’re fine,” Funai said. “But there wasn’t any follow-up after preeclampsia to see what would happen.”

Funai analyzed a data set taken from women in Jerusalem between 1964 and 1976. Scientists there took detailed histories of women when they presented preeclampsia, allowing Funai to study which women are still alive and what the causes of death were for the deceased women.

Funai said preeclamptic women were more than two times more likely to die from cardiovascular pathologies.

“Essentially, we found that the common belief that after preeclampsia women don’t have any long-term complications is completely untrue,” he said. “What we don’t know is whether preeclampsia is a direct cause of cardiovascular problems or whether cardiovascular problems and preeclampsia are both related to the same underlying factor.”

Dr. Catalin Buhimschi of the MFM division has conducted a study to determine whether preeclampsia can be predicted from proteins found in urine. For the study, he collected urine from 68 women.

“We tried to identify if different proteins that we call angiogenic factors can be found in the urine and if the ratio of them can predict who has and who doesn’t have preeclampsia,” he said.

Buhimschi built off of other studies that showed an increase of a protein called sFlt-1 in women with preeclampsia. His research suggested the ratio of this protein and a placental growth hormone can be used to identify preeclamptic women, he said.

Buhimschi conducted a follow-up study to determine the source of the increased proteins. He hypothesized that the kidneys of severely preeclamptic women are damaged and the angiogenic factors leak into the urine but found his hypothesis untrue.

“The breaking news is that the fractional excretion of this [growth hormone] cannot be simply explained via kidney damage,” he said.

Buhimschi said there is most likely independent, additional production of these proteins in preeclamptic women.

Dr. Michael Paidas, a member of Yale’s MFM section, also studies pre-term delivery and preeclampsia, as well as fetal growth restriction and bleeding. He recently finished a study that concluded women with low levels of a certain anti-clotting protein, protein Z, are up to four times more likely to encounter these problems.

Paidas said he was interested in looking at the formation of thrombin, an enzyme crucial to blood clotting. He said protein Z regulates the final step of thrombin creation.

To conduct his study, Paidas collected blood samples from pregnant women. At the conclusion of the pregnancies, he identified which women had normal pregnancies, complications or thrombophilic conditions. Then he analyzed the samples from each of the different groups.

Paidas said there are a number of conditions that can put people at risk for blood clotting, and only about 10 percent of the time do people with these conditions show complications. Protein Z had previously been associated with this group of complications, he said, but scientists did not know what the link was.

“Women with thrombophilic conditions and pregnancy complications had lowest levels of protein Z,” he said. “There’s a nice story that’s beginning to come together.”

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