Neurology

Study Suggests Origins of Pregnancy-Linked High Blood Pressure

TUESDAY, Oct. 11 -- Preeclampsia, a potentially dangerous spike in blood pressure during pregnancy, may be due to a microscopic battle going on within the placenta between cells directed by the father's genes and those directed by the mother, a new study suggests.

Though not the first research to link preeclampsia with the activity of cells in the placenta, the new report adds more details about the underlying mechanism that may be causing the problem.

During prenatal growth, certain genes are expressed or repressed, depending on their parental origin. In the placenta, the father's gene expression dominates.

In a normal pregnancy, trophoblasts, a father-directed cell, invade and attack the blood vessels that bring blood from the mother into the placenta. The trophoblasts attach to the walls of blood vessels, increasing the flow of blood and enabling the baby to grow and receive the nutrients it needs to thrive, explained study author Dr. Harvey Kliman, a research scientist in the department of obstetrics, gynecology and reproductive sciences at Yale University School of Medicine.

But at the same time, the mother's immune system cells (lymphocytes) rush to kill the invasive trophoblasts. If the lymphocytes succeed in killing the trophoblasts, then there isn't enough blood flow to the placenta -- causing blood pressure to rise.

"The placenta is responsible for keeping the fetus alive. It will do whatever is necessary to do that," Kliman said. "The placenta has a sensor, a molecular mechanism that senses how much blood is flowing into the placenta. If there's not enough blood, you will become hypertensive."

Though his research didn't investigate that mechanism specifically, it's well known that an obstruction to blood flow to another organ, the kidney, leads quickly to primary renal hypertension, a type of high blood pressure. The placenta, he says, has a similar internal thermostat. If it's not getting enough blood, blood pressure goes up in an attempt to get more blood into the organ and prevent the fetus from dying.

So, to outwit the mother's lymphocytes, the father's trophoblasts create a diversion. Trophoblasts make a protein (PP13), which exits the blood vessels and travels into the lining of the uterus.

The lymphocytes rush to deal with that inflammation, ignoring the trophoblasts.

"All of the mother's soldiers are being diverted and focusing on the PP13 instead of going after the trophoblasts," Kliman said. "It's very sneaky."

The findings are published in the Oct. 11 online issue of Reproductive Sciences.

In the study, researchers used placental tissue from women in the United States and Israel.

Prior research had found that when levels of the PP13 protein are low early in pregnancy, women were more likely to develop preeclampsia several months later, but why PP13 contributed to that wasn't understood.

Kliman said the molecular battle is driven by the father-directed trophoblasts, which are trying to create conditions for a big, healthy baby, while mother needs to tamp down on growth so that the fetus is small enough to get through the birth canal.

"The mother does not want to die. The father wants a big baby. So they compromise," he said. "If the invasive trophoblasts are killed, the blood vessels wouldn't open up, and the baby would die. If the father wins the battle and the trophoblasts are able to go into the uterus, the baby would grow too big and the woman would die."

Dr. Jill Rabin, chief of ambulatory care in the obstetrics and gynecology department and head of urogynecology at Long Island Jewish Medical Center in New Hyde Park, N.Y., said the research adds "teeth" to the theory of the role of trophoblasts in preeclampsia.

"It makes a lot of sense that the mother's immune system had to be tricked somehow, otherwise how would this happen that a placenta or a fetus could set up housekeeping inside the mother?" Rabin said. "The placenta is very smart."

Eventually, the hope is that understanding the underlying biological mechanism that causes preeclampsia will lead to treatments, Rabin said, adding that more studies are needed to confirm the findings.

Preeclampsia usually shows up in the latter half of pregnancy. Many cases are mild, but it can progress to eclampsia, or severely elevated blood pressure and protein in the urine that can lead to seizures and puts a woman at risk of stroke or organ damage. The only cure for it is to deliver the baby, experts said.

SOURCES: Harvey Kliman, M.D., Ph.D., research scientist, department of obstetrics, gynecology and reproductive sciences, Yale University School of Medicine, New Haven, Conn.; Jill Rabin, M.D., chief, ambulatory care, department of obstetrics and gynecology, and head, urogynecology, Long Island Jewish Medical Center, New Hyde Park, N.Y., Oct. 11, 2011, Reproductive Sciences, online

TUESDAY, Oct. 11 -- Preeclampsia, a potentially dangerous spike in blood pressure during pregnancy, may be due to a microscopic battle going on within the placenta between cells directed by the father's genes and those directed by the mother, a new study suggests.

Though not the first research to link preeclampsia with the activity of cells in the placenta, the new report adds more details about the underlying mechanism that may be causing the problem.

During prenatal growth, certain genes are expressed or repressed, depending on their parental origin. In the placenta, the father's gene expression dominates.

In a normal pregnancy, trophoblasts, a father-directed cell, invade and attack the blood vessels that bring blood from the mother into the placenta. The trophoblasts attach to the walls of blood vessels, increasing the flow of blood and enabling the baby to grow and receive the nutrients it needs to thrive, explained study author Dr. Harvey Kliman, a research scientist in the department of obstetrics, gynecology and reproductive sciences at Yale University School of Medicine.

But at the same time, the mother's immune system cells (lymphocytes) rush to kill the invasive trophoblasts. If the lymphocytes succeed in killing the trophoblasts, then there isn't enough blood flow to the placenta -- causing blood pressure to rise.

"The placenta is responsible for keeping the fetus alive. It will do whatever is necessary to do that," Kliman said. "The placenta has a sensor, a molecular mechanism that senses how much blood is flowing into the placenta. If there's not enough blood, you will become hypertensive."

Though his research didn't investigate that mechanism specifically, it's well known that an obstruction to blood flow to another organ, the kidney, leads quickly to primary renal hypertension, a type of high blood pressure. The placenta, he says, has a similar internal thermostat. If it's not getting enough blood, blood pressure goes up in an attempt to get more blood into the organ and prevent the fetus from dying.

So, to outwit the mother's lymphocytes, the father's trophoblasts create a diversion. Trophoblasts make a protein (PP13), which exits the blood vessels and travels into the lining of the uterus.

The lymphocytes rush to deal with that inflammation, ignoring the trophoblasts.

"All of the mother's soldiers are being diverted and focusing on the PP13 instead of going after the trophoblasts," Kliman said. "It's very sneaky."

The findings are published in the Oct. 11 online issue of Reproductive Sciences.

In the study, researchers used placental tissue from women in the United States and Israel.

Prior research had found that when levels of the PP13 protein are low early in pregnancy, women were more likely to develop preeclampsia several months later, but why PP13 contributed to that wasn't understood.

Kliman said the molecular battle is driven by the father-directed trophoblasts, which are trying to create conditions for a big, healthy baby, while mother needs to tamp down on growth so that the fetus is small enough to get through the birth canal.

"The mother does not want to die. The father wants a big baby. So they compromise," he said. "If the invasive trophoblasts are killed, the blood vessels wouldn't open up, and the baby would die. If the father wins the battle and the trophoblasts are able to go into the uterus, the baby would grow too big and the woman would die."

Dr. Jill Rabin, chief of ambulatory care in the obstetrics and gynecology department and head of urogynecology at Long Island Jewish Medical Center in New Hyde Park, N.Y., said the research adds "teeth" to the theory of the role of trophoblasts in preeclampsia.

"It makes a lot of sense that the mother's immune system had to be tricked somehow, otherwise how would this happen that a placenta or a fetus could set up housekeeping inside the mother?" Rabin said. "The placenta is very smart."

Eventually, the hope is that understanding the underlying biological mechanism that causes preeclampsia will lead to treatments, Rabin said, adding that more studies are needed to confirm the findings.

Preeclampsia usually shows up in the latter half of pregnancy. Many cases are mild, but it can progress to eclampsia, or severely elevated blood pressure and protein in the urine that can lead to seizures and puts a woman at risk of stroke or organ damage. The only cure for it is to deliver the baby, experts said.

SOURCES: Harvey Kliman, M.D., Ph.D., research scientist, department of obstetrics, gynecology and reproductive sciences, Yale University School of Medicine, New Haven, Conn.; Jill Rabin, M.D., chief, ambulatory care, department of obstetrics and gynecology, and head, urogynecology, Long Island Jewish Medical Center, New Hyde Park, N.Y., Oct. 11, 2011, Reproductive Sciences, online

FRIDAY, Oct. 7 -- Traffic-related air pollution may put pregnant women at risk for a premature birth, according to a new study.

Researchers looked at 100,000 births among women in California who lived within five miles of an air quality monitoring station. The births spanned a 22-month period from June 2004.

Exposure to traffic-related air pollutants such as polycyclic aromatic hydrocarbons ( PAH) was associated with up to a 30% greater risk of premature birth; exposure to ammonium nitrate fine particles was associated with a 21% increased risk, and exposure to benzene and fine particulate matter from diesel fumes was associated with a 10% higher risk, the University of California researchers found.

The study is published online Oct. 6 in the journal Environmental Health.

"Air pollution is known to be associated with low birth weight and premature birth. Our results show that traffic-related PAH are of special concern as pollutants, and that PAH sources besides traffic contributed to premature birth," Dr. Beate Ritz said in a journal news release.

"The increase in premature birth risk due to ammonium nitrate particles suggests secondary pollutants are also negatively impacting the health of unborn babies. To reduce the effects of these pollutants on public health, it is important that accurate modeling of local and regional spatial and temporal air pollution be incorporated into pollution policies," Ritz added.

-- Robert Preidt

SOURCE: Environmental Health, news release, Oct. 6, 2011

-- Morning sickness is an unpleasant, yet common side effect of pregnancy. When episodes of nausea and vomiting become severe, it's time to call the doctor.

The Nemours Foundation mentions these warning signs that morning sickness should be evaluated by a physician:

  • Having nausea that is so persistent that you cannot eat or drink anything.
  • Vomiting to the point where food doesn't stay in the stomach.
  • Vomiting blood.
  • Fainting, feeling dizzy or losing weight.
  • Urinating less frequently and having frequent headaches.
  • Having a rapid heartbeat.
  • Feeling extremely confused or fatigued.
  • Noticing a bad, fruity odor to the breath or body.
  • MONDAY, Oct. 3 -- Pregnant women who eat a healthy diet appear to reduce the risk of having a baby with a major birth defect, such as spina bifida or a cleft lip or palette, a new study suggests.

    Neural tube birth defects -- including spina bifida and other brain abnormalities -- are known to decrease when pregnant women take supplements of folic acid, a type of vitamin B that also has been added to a variety of foods. However, folic acid alone does not prevent all birth defects, the researchers said.

    "There may be certain qualities of foods that have benefits that aren't captured by examining just one nutrient at a time," said lead researcher Suzan L. Carmichael, an associate professor of pediatrics at Stanford University.

    Diet could also be related to reducing birth defects because a combination of nutrients from a variety of foods may act together in a beneficial way, Carmichael said. "It is also possible that a healthy diet is a marker for other characteristics of a woman's lifestyle.

    "Our study supports recommendations that have been made for many years for pregnant women," she said. "Eat a variety of foods, include a lot of fruits and vegetables and whole grains in your diet and take a vitamin supplement that contains folic acid."

    Although folic acid can prevent up to 40% of neural tube defects, it's not the whole story, Carmichael said. "Babies are still born with neural tube defects, so we need to keep looking for answers," she said.

    The report was published in the Oct. 3 online edition of the Archives of Pediatrics & Adolescent Medicine.

    Using data from the U.S. National Birth Defects Prevention Study for October 1997 through December 2005, Carmichael's team looked at the role diet plays in birth defects. During telephone interviews, mothers described their diet.

    The researchers looked at cases of 936 infants born with neural tube defects, 2,475 with oral clefts, and compared these with 6,147 infants without birth defects.

    They found that women with diets similar to the Mediterranean Diet -- which is rich in fruits, vegetables, whole grains and fish and light in fats and sugar -- or the Food Guide Pyramid of the U.S. Department of Agriculture were at lower risk of having a baby with a neural tube defect or oral cleft, compared to women who reported eating less-healthy diets.

    This finding remained even after adjusting for other factors such as taking a vitamin or mineral supplement, the researchers noted. "We found that diet was important whether a women took a vitamin supplement or not," Carmichael said.

    Most women who gave birth to an infant who did not have a birth defect were white and had more than a high school education, the researchers found. Among mothers in the survey, 19% smoked, 38% drank, 78% took folic acid supplements and 16% were obese.

    David R. Jacobs, Jr., the Mayo Professor of Public Health at the University of Minnesota in Minneapolis, and co-author of an accompanying journal editorial, said, "We have confused the constituents of food with food itself. Food is a complex mixture."

    There may be a number of right ways to eat, and some diets that are not so good, he said. Generally, foods are better than supplements except when there is a deficiency, he added.

    Jacobs noted that foods are more complex than drugs that contain only a single element and have been tested. "Food are not well understood," he said.

    "There are some better ways to eat and supplements are probably not the right answer -- we should eat food," Jacobs said. One should not eat too much and eat mostly plants, he added.

    Commenting on the study, Gail Harrison, a professor of public health at the University of California, Los Angeles, and spokeswoman for the March of Dimes, said, "I am not surprised that there is an independent effect of total diet quality."

    The finding underscores the importance of the mother's nutrition both before and during pregnancy and the effect it can have on the developing infant, she said. "A lot that goes on that determines pregnancy outcome goes on very early in the pregnancy -- before women even realize they're pregnant," she said.

    Harrison noted that healthy eating needs to start even before pregnancy. "Women who are capable of becoming pregnant really need to pay attention to overall diet quality," she said.

    SOURCES: Suzan L. Carmichael, Ph.D., associate professor of pediatrics, Stanford University, Stanford, Calif.; David R. Jacobs, Jr., Ph.D., Mayo Professor of Public Health, University of Minnesota, Minneapolis; Gail Harrison, Ph.D., professor of public health, University of California, Los Angeles, spokeswoman, March of Dimes; Oct. 3, 2011, Archives of Pediatrics & Adolescent Medicine, online

Date 17 - 10 - 2011
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