Derived from the Greek word for "lightning," preeclampsia seems to come on suddenly and unexpectedly late in pregnancy.
First described by Hippocrates some 2,400 years ago, preeclampsia is characterized by dangerously high maternal blood pressure that can damage the mother's organs and lead to premature birth. It is estimated to occur in 5% of all pregnancies and cause 15% of maternal deaths and 25% of neonatal deaths. Yet doctors still don't know exactly what causes it, how to predict it, or how to prevent it.
"There's a lot of evidence that local and systemic immune dysfunction may be one of the triggers," says Tal Korem, assistant professor in systems biology and reproductive sciences (in obstetrics and gynecology) at Columbia University Vagelos College of Physicians and Surgeons. "We think that the vaginal microbiome could play an important role due to its influence on inflammation in the reproductive tract."
Tal Korem's research suggests that vaginal microbes present early in pregnancy are strongly linked to the development of preeclampsia. Photo by John Abbott.
There's also evidence that the triggers of preeclampsia operate early in pregnancy, even though preeclampsia does not typically occur until around the third trimester. But only a couple of studies have looked at the vaginal microbiome in the context of preeclampsia, and in those studies, samples were collected late in pregnancy.
Korem's first study suggests that microbes present early in pregnancy have a strong link to the development of preeclampsia. The results, still in peer review, found that among 124 pregnant women, half of whom had severe preeclampsia, a first-trimester signature of vaginal microbes and immune factors was strongly associated with subsequent preeclampsia.
"The connection is strong and could predict preeclampsia five to seven months before it emerged," he says, "but we need to confirm our findings in a larger number of cases."
Korem's new study, recently funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development, is the largest and most comprehensive of its kind. It aims to confirm his initial finding and further investigate the role of the vaginal ecosystem-its microbes, its metabolites, and the host's immune system-in preeclampsia. In collaboration with Uma Reddy and Anne-Katrine Uhlemann at Columbia, the study is analyzing samples taken at three stages of pregnancy from 778 participants in the NIH's nuMoM2b (Nulliparous Pregnancy Outcomes Study: Monitoring Mothers-to-Be) study.
The analysis will go beyond cataloging and counting the bacterial members of the vaginal microbiome in the pregnant participants. With the use of metagenomic sequencing, Korem's team will detect each microbe's functional capabilities along with the microbe's identity. Working with Pieter Dorrestein at UCSD, they will also comprehensively measure the levels of various small molecules, whether they originate from microbes, human cells, or the environment."Often, the only effective therapy is to deliver the baby, many times prematurely. We desperately need new ways to prevent and treat this condition."
In addition to identifying predictors of preeclampsia, "we hope these techniques will highlight mechanisms that underlie the condition, ultimately paving the way for new diagnostics and therapeutics," Korem says.
At present, doctors have few treatment options. "Mostly, it's a delicate balance between keeping the fetus in the womb for as long as possible without compromising the mother's health," says Korem. "Often, the only effective therapy is to deliver the baby, many times prematurely. We desperately need new ways to prevent and treat this condition."
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Additional information
Tal Korem's new research is supported by NIH grant 1R01HD114715.
