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Stillbirth linked with placenta-related protein imbalance

Maya Brownstein

May 7, 2026

A closeup of a placenta and umbilical cord sample under a microscope. — Sinhyu / iStock

During pregnancy, an imbalance between two proteins produced by the placenta—soluble fms-like tyrosine kinase-1 (sFlt-1) and placental growth factor (PlGF)— may contribute to stillbirth, according to a new study led by Harvard T.H. Chan School of Public Health.

The study, published Apil 17 in JAMA Network Open, was led by Mi-Sun Lee, research scientist in the Christiani Lab. David Christiani, Elkan Blout Professor of Environmental Genetics, was a co-author.

Each year, an estimated 2.6 million fetal deaths occur around the world, mostly in low- and middle-income countries. What’s causing these stillbirths—and possible means of preventing them—“remains overlooked in policy and research,” the researchers wrote.

The researchers investigated the potential link between stillbirth and an imbalanced ratio of sFlt-1 and PlGF, which respectively inhibits and promotes the formation of new blood vessels critical to placental development and therefore fetal health. Too-high levels of sFlt-1 and too-low levels of PlGF are linked to placenta-related disorders such as preeclampsia and early-onset fetal growth restriction.

The study was based at two health clinics in Bangladesh, a country with one of the highest burdens of stillbirth in the world. The researchers analyzed blood samples from 125 pregnant women, 39 of whom had stillbirths, defined as fetal death at 28 weeks’ gestation or more. They found that participants with a ratio of sFlt-1 to PlGF greater than 38 had a 13-fold greater risk of stillbirth than those with a ratio equal to or lower than 38, which is considered a balanced or normal ratio during pregnancy.

According to the researchers, the findings suggest a new potential pathway to predict and prevent stillbirth, especially in low-resource settings. But they also noted the need for further investigation. “Larger, prospective studies are needed to confirm these results, evaluate potential clinical utility, and inform efforts to reduce the persistent burden of this silent epidemic,” they wrote.