Good news! This could be a breakthrough!
"In a study published today [8/31/2026] ... scientists who analyzed blood samples from thousands of pregnant women found that low levels of a protein called ISM2 during the first trimester were associated with higher risk of both preeclampsia and fetal growth restriction later on.
Follow-up lab studies of placental cells showed ISM2 likely plays a causal role in the disorders, meaning the findings could help in the development of treatments, too. ...
The researchers measured blood levels of nearly 3000 proteins and found one in particular associated with both preeclampsia and fetal growth restriction: ISM2, a little-studied protein produced by the placenta. Specifically, lower blood levels of the protein at the 12-week blood test were linked to higher risks of preeclampsia, fetal growth restriction, or both. ...
What’s more, ISM2 levels were a better predictor of each condition than currently used proteins. ...
In lab experiments, the team found that blocking the production of ISM2 in stem cells that usually develop into normal, uterus-invading EVTs stopped that process from happening.
By contrast, artificially adding ISM2 into a cell line that usually lacks it induced recipient cells to migrate around lab dishes more like EVTs would. ..."
"... Both of these conditions are known to be linked to problems with the placenta not developing properly early in pregnancy, in particular a failure of specialised placental cells known as the extravillous trophoblast (EVT) to invade the mother’s womb and establish a healthy blood supply. ...
Of all mammals, humans have the deepest placental invasion, which reflects the massive demands of oxygen and nutrients required to manufacture the most complex machine ever known, the human brain. ..."
From the abstract:
"Preeclampsia and fetal growth restriction (FGR) are major causes of global morbidity and mortality.
Both conditions are associated with impaired invasion of the uterus by extravillous trophoblast (EVT).
We performed proteomics in maternal serum obtained at ~12 weeks of gestational age in a prospective pregnancy cohort (Pregnancy Outcome Prediction Study). Here we show that low maternal serum isthmin-2 (ISM2) was the strongest protein signal (out of 2,904) in the first trimester of pregnancy for preeclampsia or FGR.
We validated the association in two independent cohorts (Pregnancy Outcome Prediction Study 2 and Improving Maternal Pregnancy And Child ouTcomes study).
ISM2 protein and mRNA are almost exclusively produced in the placenta, and, within the placenta, ISM2 mRNA is highly enriched in EVT.
Knocking down ISM2 in cultured human trophoblast stem cells profoundly inhibited EVT invasion.
Conversely, expressing ISM2 in a cell line lacking endogenous ISM2 (HEK293 cells) promoted migration.
We conclude that ISM2 may be causally involved in the early pathophysiology of failed trophoblast invasion and that the protein and its associated pathways are potential targets for the prediction and prevention of preeclampsia and FGR."
Pre-eclampsia discovery could lead to new test and treatments for at-risk pregnancies (original news release) "Cambridge scientists have identified a key protein that could act as a predictor for pre-eclampsia and fetal growth restriction, two of the major causes of stillbirth and of sickness among mothers and newborns."
Fig. 2: The association between ISM2 and PE and FGR.
Fig. 3: ISM2 regulates EVT differentiation.
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