Babies in peril
New insights may lead to less danger from the disease of preeclampsia
When Alisa Schultz awoke at 6 a.m. with cramps 36 weeks into her first pregnancy, she did the right thing and went to the doctor's office. Diagnosed with early labor, she was sent home. Within an hour, she started feeling terrible, with abdominal pain and nausea. Her husband rushed her to the hospital near their home in McLean, Va. They didn't know they were already too late. Their daughter Lindsey was stillborn.
The doctors discovered that Schultz had preeclampsia, a complication of pregnancy that can threaten the life of both mother and child. It is the leading cause of maternal death worldwide. Severe preeclampsia is characterized by dangerously high blood pressure--Schultz's had soared from normal to 180/120 within two hours--as well as deteriorating kidney and liver function, and damage to blood vessels throughout the mother's body. It can progress to the seizures and coma of eclampsia, and death.
Preeclampsia isn't rare--it affects about 5 percent of pregnant women, most expecting their first child. But its cause remains a mystery. "Since the beginning of time, people have been trying to understand preeclampsia," says Richard Levine, a researcher at the National Institute of Child Health and Human Development. "We know that the placenta does not develop normally. It's thought to make a toxic substance that is released and carried throughout the mother's blood." The disease, also known as toxemia, has defied all efforts to prevent or cure it. Doctors are reduced to stopping it by delivering the child, which also removes the placenta, the engine for the fetus. Because the disease can develop as early as 20 weeks into a pregnancy, those forced deliveries are a major cause of fetal death, as well as of the many complications of premature birth, including blindness, mental retardation, and cerebral palsy. Pregnant women are routinely tested for elevated blood pressure and protein in the urine, two signs that preeclampsia is developing. When those signs are found, doctors and patients find themselves in a perilous balancing act, trying to contain symptoms with bed rest and, at times, antihypertension drugs long enough for the child to have a chance at survival, while not putting the mother's life at undue risk. But because preeclampsia often develops suddenly, some mothers, like Schultz, never get that chance.
Forewarned. In the past few years scientists have gained a much better understanding of preeclampsia's toxic workings. Last week, researchers announced that they had found abnormally low levels of a placental growth factor in the urine of women who later went on to develop preeclampsia. The deficiency was apparent by the 28th week of pregnancy. The hope is that these findings, once confirmed and expanded, will lead to a good early test for preeclampsia. "People could get better treatment. Doctors would be warned; patients would be warned," says Ananth Karumanchi, a nephrologist at Beth Israel Deaconess Medical Center in Boston, who collaborated with Levine and others on the study, which was published in last week's Journal of the American Medical Association. Earlier, Karumanchi's lab had found abnormally high levels of a protein, called sFlt-1, in women with preeclampsia. They then induced preeclampsia in rats by injecting them with the human gene for sFlt-1, proving that the errant protein is a cause, not a symptom. The theory is that sFlt-1 blocks the action of both placental growth factor and vascular endothelial growth factor, which are essential for fostering blood vessel growth and maintaining the health of cells lining vessels in the placenta and throughout the mother's body.
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