New RNA-Based Tool Could Assess Preeclampsia Risk


Transcripts circulating in the blood provide real-time information about maternal, fetal, and placental health.

by Amanda Heidt

Preeclampsia, a potentially fatal complication that affects roughly 5 percent of pregnancies worldwide, can only be diagnosed after the onset of symptoms such as high blood pressure, so treatment is always reactive. “The next really big need is better methods to diagnose or predict risk of pregnancy complications such as preeclampsia,” says Fiona Kaper, a senior director of scientific research at the biotech company Illumina.

To identify possible biomarkers of the condition, Kaper and her colleagues drew blood from 40 pregnant women with early-onset severe preeclampsia and 73 unaffected expecting mothers. Circulating in the blood of each mom-to-be is her own RNA, as well as transcripts from the placenta and the fetus. Studying these circulating RNAs (cRNAs), the team identified 30 maternal, fetal, or placental genes with altered expression patterns in women with preeclampsia compared with controls. A machine algorithm also identified 49 genes with altered expression, including 12 that overlapped with the earlier list, suspected of being linked to preeclampsia.

To test the ability of the 49 suspect genes to predict preeclampsia, the researchers classified an independent cohort of two dozen women, half with early-onset preeclampsia and half without signs of the condition. The model predicted which women had preeclampsia with 85 percent to 89 percent accuracy.

While large-scale, prospective studies are still needed, cRNA screening represents a step toward earlier preemptive diagnosis, says Kathryn Gray, an obstetrician at Brigham and Women’s Hospital who was not involved in the study. She notes that researchers have been doing something similar in detecting circulating tumor DNA for cancer screening. “It’s really exciting that we’re applying some of these . . . strategies that have been used in cancer to pregnancy. We’re always a bit behind in women’s health and pregnancy in applying the most cutting-edge technologies.”

S. Munchel et al., “Circulating transcripts in maternal blood reflect a molecular signature of early-onset preeclampsia,” Sci Transl Med, 12:eaaz0131, 2020.

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This Pregnant Medieval Woman With Head Wound ‘Gave Birth’ In Her Grave


Female burial from near Bologna Italy (c. 7th c AD)

by Kristina Killgrove

An early Medieval grave near Bologna, Italy, was revealed to contain an injured pregnant woman with a fetus between her legs. Based on the positioning of the tiny bones, researchers concluded this was a coffin birth, when a baby is forcibly expelled from its mother’s body after her death. The pregnancy and the woman’s head trauma may also be related.

The burial, dating to the 7th-8th century AD, was found in the town of Imola in northern Italy in 2010. Because the adult skeleton was found face-up and intact, archaeologists determined it to be a purposeful burial in a stone-lined grave. The fetal remains between her legs and the injury to her head, however, triggered an in-depth investigation, which was recently published in the journal World Neurosurgery by researchers at the Universities of Ferrara and Bologna.

Based on the length of the upper thigh bone, the fetus was estimated to be about 38 weeks’ gestation. The baby’s head and upper body were below the pelvic cavity, while the leg bones were almost certainly still inside it. This means it was positioned like a near-term fetus: head down in preparation for birth. But it also means that the fetus was likely partially delivered.

Although rare in the contemporary forensic-medical literature and even more so in the bioarchaeological record, this appears to be a case of post-mortem fetal extrusion or coffin birth. Bioarchaeologist Siân Halcrow of the University of Otago explains that, in the case of the death of a pregnant woman, sometimes the gas that is created during normal decomposition builds up to such an extent that the fetus is forcibly expelled.

The actual mechanism of coffin birth is somewhat less understood, however. “The cervix shouldn’t relax with death after rigor mortis disappears,” Dr. Jen Gunter, a San Francisco Bay area OB/GYN, says. “I suspect that what happens is the pressure from the gas builds up, and the dead fetus is delivered through a rupture – it basically blows a hole through the uterus into the vagina, as the vagina is much thinner than the cervix.”

This example of coffin birth is interesting from an archaeological standpoint, but the state of the mother’s health makes it completely unique: she had a small cut mark on her forehead and a 5 mm circular hole next to it. Taken together, these are suggestive of trepanation, an ancient form of skull surgery. Not only was the pregnant woman trepanned, but she also lived for at least a week following the primitive surgery.

In the World Neurosurgery article, the Italian researchers proposed a correlation between the mother’s surgery and her pregnancy: eclampsia. “Because trepanation was once often used in the treatment of hypertension to reduce blood pressure in the skull,” they write, “we theorized that this lesion could be associated with the treatment of a hypertensive pregnancy disorder.”

Eclampsia is the onset of seizures in a pregnant woman with preeclampsia (high blood pressure related to pregnancy) and, particularly in the time periods prior to modern medicine, was likely a common cause of maternal death. A pregnant woman suffering in early Medieval times from high fevers, convulsions, and headaches may very well have been recommended trepanation as a cure.

“Given the features of the wound and the late-stage pregnancy,” the authors note, “our hypothesis is that the pregnant woman incurred preeclampsia or eclampsia, and she was treated with a frontal trepanation to relieve the intracranial pressure.”

If the researchers’ conclusions are correct, the mother’s condition was not cured by the cranial surgery and she was buried, still pregnant, in a stone-lined grave. As her body decomposed, her deceased fetus was partially extruded in a coffin birth. Halcrow, however, cautions that this may not be the best explanation. “In this instance,” she says, “the woman could just as likely have died as the result of normal complications from childbirth.”

Whether or not the trepanation and pregnancy are linked, Halcrow does note that “it is pleasing to see a study that is focused on maternal and infant mortality and health in the past, because this subject is often overlooked.” The unique case of the demise of a pregnant woman soon after invasive skull surgery is unparalleled in the archaeological record and therefore important for our understanding of ancient health and disease.

https://www.forbes.com/sites/kristinakillgrove/2018/03/23/pregnant-medieval-woman-gave-birth-in-grave/#17697bc81663