Low levels of a protein produced by the placenta in early pregnancy may serve as an early warning sign for two dangerous pregnancy complications, according to a new study published in Nature Medicine. The research identifies the protein, isthmin-2 (ISM2), as a potential predictor of preeclampsia and fetal growth restriction, conditions that pose serious risks to both mothers and babies.
Preeclampsia, characterized by high blood pressure and often protein in the urine, can lead to seizures, organ damage, and preterm birth. Fetal growth restriction occurs when a baby does not reach its expected size in the womb, often due to placental insufficiency. Both conditions are leading causes of maternal and infant illness and death worldwide, yet they are frequently detected only after symptoms appear, when intervention options are limited.
The study, led by researchers analyzing serum proteomics from pregnancy cohorts, found that ISM2 is involved in extravillous trophoblast invasion — the process by which placental cells anchor into the uterine wall and remodel blood vessels to supply the fetus. When levels of ISM2 are lower in the first trimester, the risk of developing preeclampsia or fetal growth restriction later in pregnancy increases significantly.
This early signal could change how clinicians monitor pregnancies. Currently, screening for these complications relies on a combination of maternal risk factors, blood pressure measurements, and ultrasound findings, which often do not identify at-risk women until the second half of pregnancy. A blood test measuring ISM2 in the first trimester could allow earlier identification of high-risk pregnancies, enabling closer monitoring and earlier interventions.
The findings also point to a possible avenue for prevention. Because ISM2 appears to play a direct role in placental development, it may offer a therapeutic target. If researchers can find ways to support or enhance ISM2 function, they might be able to prevent or mitigate the placental dysfunction that underlies both conditions.
The research team examined serum samples from multiple pregnancy cohorts, comparing protein levels in women who later developed complications with those who had uncomplicated pregnancies. The consistent association between low ISM2 and adverse outcomes across different groups strengthens the case for its use as a biomarker.
While the results are promising, the authors note that further validation in larger, more diverse populations will be needed before the test can be adopted in clinical practice. Questions also remain about the precise mechanisms by which ISM2 influences trophoblast invasion and whether interventions targeting this pathway would be safe and effective.
Despite these caveats, the study represents a meaningful step toward earlier detection of pregnancy complications that have long been difficult to predict. For clinicians, a reliable first-trimester marker could transform prenatal care, shifting the focus from managing complications after they arise to identifying and supporting at-risk pregnancies from the start.
The findings add to a growing body of research aimed at understanding the placenta's role in pregnancy outcomes. As scientists continue to map the molecular signals that govern placental development, the hope is that more complications can be anticipated and prevented, improving outcomes for mothers and infants alike.
