The Preeclampsia Puzzle – Making Sense of a Mysterious Pregnancy Disorder
Preeclampsia is a pregnancy-induced condition that affects about 5% of pregnant women. The American College of Obstetricians and Gynecologists has recently (November 2013) revised its definition of preeclampsia.
“According to the new ACOG guidelines, the diagnosis of preeclampsia no longer requires the detection of high levels of protein in the urine (proteinuria). Evidence shows organ problems with the kidneys and livers can occur without signs of protein, and that the amount of protein in the urine does not predict how severely the disease will progress. Prior to this time, most healthcare providers traditionally adhered to a rigid diagnosis of preeclampsia based on blood pressure and protein in the urine(proteinuria).
Preeclampsia is now to be diagnosed by persistent high blood pressure that develops during pregnancy or during the postpartum period that is associated with a lot of protein in the urine or the new development of decreased blood platelets, trouble with the kidney or liver, fluid in the lungs, or signs of brain trouble such as seizures and/or visual disturbances.”
Symptoms of preeclampsia may be vague or non-existent, or may include headaches, drowsiness, and a general malaise that feels like the flu, visual disturbances, upper abdominal pain, and swelling in the hands and face. Preeclampsia involves many organ systems, including the kidneys, the liver, and the brain. Complications include eclampsia or seizures and changes in the blood clotting factors. The risk of stillbirth to the baby is high if these complications occur. Currently, the only “cure” for these conditions is delivery of the baby. Preeclampsia remains one of the three main causes of maternal mortality in both the developed and the developing world, along with hemorrhage and infection.
In July 2006, in The New Yorker magazine, Jerome Groopman wrote a fascinating article about preeclampsia* and a young researcher who appears to have found the cause. Preeclampsia has been known, described, and feared for millenia, and countless theories about its cause as well as possible therapies have been described. The researcher, Ananth Karumanchi, working essentially alone in a nephrology (kidney disorder) lab at Boston’s Beth Israel Deaconess Medical Center, isolated a soluble protein named FLT in the blood of women suffering from preeclampsia. In women with severe disease, the amount of FLT was higher. Karumanchi couldn’t believe his success. “I was sifting though all of these data, and I said to myself, ‘It can’t be this obvious,'” he recalled. “‘It can’t be the predominant factor in preeclampsia, because people would have discovered it by now.’ This couldn’t be just waiting for me.”
But apparently it was. In addition, Karumanchi found another protein that seems to be associated with the development of HELLP syndrome, a severe complication of preeclampsia. Karumanchi had more difficulty persuading others of his find. There is a large literature on theories about the cause of preeclampsia, and there have been well-funded clinical trials by important researchers, all leading to dead-ends. No one believed that a novice researcher with no experience in pregnancy conditions could have achieved the results he was claiming. Eventually, however, Karumanchi and his colleagues managed to have their results published in the New England Journal of Medicine. Since then, Karumanchi and other researchers have expanded his theory and replicated his main findings many times. Several drug companies are trying to develop diagnostic tests and treatments from his research.
The story in The New Yorker (July 24, 2006) also includes a history of preeclampsia and efforts to solve its mystery through the ages. It is well-written and entertaining enough to read at the beach or keep on the bedside stand. However, for those of us who have experienced the effects of preeclampsia or eclampsia first-hand as patients or as care-providers, the article can only be a prelude to the actual research findings. For these, I would recommend that you start with a Medline search. Read more about Dr Karumanchi and his current work with preeclampsia in the articles cited below.
Lam C, Kee-Hak Lim, Karumanchi SA. Circulating angiogenic factors in the pathogenesis and prediction of preeclampsia. Hypertension/American Heart Association, Sept 2005.
Levine RJ. Maynard SE. Qian C. Lim KH. England LJ. Yu KF. Schisterman EF. Thadhani R. Sachs BP. Epstein FH. Sibai BM. Sukhatme VP. Karumanchi SA. Circulating angiogenic factors and the risk of preeclampsia.[see comment]. New England Journal of Medicine. 350(7):672-83, 2004 Feb 12.
More information for consumers and help for those who have experienced preeclampsia are available at the Preeclampsia Foundation website. Risk factors as well as signs and symptoms are discussed.
NOTE: Severe preeclampsia is a dangerous medical condition that requires care from an export obstetric provider such as a perinatologist. There is currently no “cure” for preeclampsia; it usually resolves spontaneously once the baby is delivered. If you have symptoms as described on the Preeclampsia Foundation website of your midwife suspects that you have this condition, she should promptly refer you to a perinatologist for evaluation and ongoing assessment.
NOTE: Women in first-world countries who receive good prenatal care rarely develop eclampsia, a progression of preeclampsia characterized by seizures (tonic and clonic convulsions), coma, and possible death. Eclampsia was more common in Europe and the U.S. before blood pressure measurement came into use in the early years of the 20th Century when stethoscopes and sphygnomanometers (blood pressure cuffs) became part of the physician’s standard equipment. When high blood pressure in pregnant women was recognized and found to be associated with eclamptic seizures, obstetricians began to “treat” women with signs and symptoms of pre-eclampsia with bedrest and dietary changes, while frequently measuring their blood pressure and the protein in their urine. If the woman’s condition worsened despite these treatments, induction of labor was attempted. As Williams said in the 5th Edition of his “Obstetrics” in 1923, “Induction of labor is the last resort, and should be regarded as a confession that our therapeutic resources have failed.” Unfortunately, little has changed in the 90 years since those words were written. However, close monitoring and a timely decision to deliver have almost eliminated the progress of this disease to the eclamptic stage.
In third-world countries where access to maternity care is limited or non-existent, eclampsia continues to occur with regularity and to be a major cause of maternal mortality. In my many years of practice as a midwife in the U.S., I never saw a case of eclampsia and only heard of one in our medical center (OHSU). However, in the past three years, working as a volunteer with nurses in a rural hospital in Nepal, I have seen three women brought to the center from outlying villages suffering from eclamptic seizures when they arrived. Fortunately, the hospital has drugs (magnesium sulfate, diazepam) to control the condition, and these women survived, although in two cases their babies did not. Until all pregnant women have access to prenatal and delivery care in pregnancy, or until research discovers an easy fix that can be used by remote village health workers, these deaths will continue to occur.