Preeclampsia is just as hard to accurately diagnose now as it was 100 years ago, said Baha Sibai, MD, a maternal-fetal medicine specialist with The University of Texas Health Science Center at Houston (UTHealth). Researchers at McGovern Medical School at UTHealth are looking for ways to change that.
Preeclampsia is a potentially life-threatening condition that develops during pregnancy or the postpartum period. It is characterized by high blood pressure in combination with high levels of protein in the urine, or one of the following: the new development of decreased blood platelets, impairment of kidney or liver function, fluid in the lungs, seizures, or visual disturbances.
The rate of preeclampsia in the U.S. has increased 25% in the last two decades and is a leading cause of maternal and infant illness and death, according to The American College of Obstetricians and Gynecologists (ACOG). Currently, there are no FDA-approved treatment options for severe preeclampsia.
Sibai, a professor with the Department of Obstetrics, Gynecology, and Reproductive Services at McGovern Medical School and international expert in preeclampsia, is overseeing several clinical research projects at UTHealth in collaboration with UT Physicians and Memorial Hermann hospitals to improve physicians’ ability to diagnose and appropriately treat it.
“I came up with the latest standards of expectant management for preeclampsia in 1984, and they are still used worldwide today,” Sibai said. “While I am proud of that accomplishment, I am also frustrated that we haven’t made even more strides in the field. Diagnosing preeclampsia remains extremely confusing, as the guidelines are always changing, and many of the symptoms exhibited by someone with the condition, like swelling, headaches, and visual changes, can also be seen in pregnant women in general.”
Under Sibai’s direction, Nana Ama Ankumah, MD, is the principal investigator on a study evaluating the diagnostic accuracy of a new test designed to detect misfolded protein in the urine of women who could have preeclampsia. The test, which is currently in development, is based on research that has shown a strong correlation between preeclampsia and the presence of these misfolded proteins.
“Regular urine samples are only tested for the presence of proteins, which are not specific to preeclampsia and could be indicative of other conditions, such as urinary tract infections or kidney disease,” said Ankumah, a maternal-fetal medicine specialist with McGovern Medical School, who also sees patients at UT Physicians. “Currently, a preeclampsia diagnosis requires evaluation of blood pressure, urine protein, various labs, and patient-reported symptoms. By measuring urine for the presence of specific preeclampsia-related proteins, the test could speed up and simplify the process of diagnosing the condition, allowing women to be treated sooner.”
The test could also help prevent false positives, Sibai said.
“If a woman is misdiagnosed with preeclampsia, she is filled with unnecessary stress. She has to come in for appointments much more than usual to undergo blood tests, ultrasounds, and nonstress tests. She could even be put on bed rest. This condition has serious implications and we need to make sure we are getting each and every diagnosis right,” Sibai said.
Sibai is the principal investigator for the study of an investigational drug that could allow the fetuses of pregnant women with severe preeclampsia to stay in utero longer. The drug may help suppress factors known to cause hypertension and kidney problems, which can lead to early delivery. The goal of the Phase II/III study is to reduce rates of severe complications and death within 36 weeks of gestation.
“They used to say delivery was the cure for preeclampsia, but that’s not the case anymore. Long-term complications, and even death, can happen when babies are delivered too early. Every day counts for these unborn babies – the longer they can stay in the womb, the better,” Sibai said.
Sibai is also overseeing a project assessing how much aspirin should be taken by women who are overweight, and thus at a higher risk of developing hypertension, to try to lessen their risk of preeclampsia. In 1993, he led the first study on aspirin’s capability to prevent preeclampsia in healthy, pregnant women who have never given birth before.
Aspirin has been proven effective in preeclampsia prevention and there have been numerous studies conducted to determine the ideal dose, Sibai said. ACOG published a committee opinion in July 2018 supporting the use of low-dose aspirin, 81 mg/day, for preeclampsia prevention for high-risk women. There have also been multiple trials that support the use of higher aspirin doses and the trial at UTHealth is evaluating the efficacy of doubling the dose to 162 mg/day.
“Since the first study I led, obesity has become more prevalent. In Harris County alone, nearly 75% of the population is overweight or obese, and if those people become pregnant, they are at a much higher risk for preeclampsia. We routinely see patients who have a BMI of 70 or higher and I recently treated someone with a BMI of 105. So the question becomes, ‘How much aspirin do they need to take to reap the same benefits?’” Sibai said. BMI stands for body mass index and is a measure of body fat calculated from height and weight.
“A ‘one dose fits all’ approach can’t be the answer,” said Farah Amro, MD, a maternal-fetal medicine fellow at McGovern Medical School at UTHealth and principal investigator of the higher dose aspirin trial. “High-risk overweight and obese women are more prone to aspirin resistance, and also have a high incidence of preeclampsia. It is critical they get the appropriate dose of the medicine to actually mitigate their risk.”