Cytokine storm detected before AFE symptoms in AJOG case report

Extraordinary elevations of inflammatory cytokines were found in maternal blood before symptom onset in a patient who later died of amniotic fluid embolism (AFE), according to a case report published in the American Journal of Obstetrics & Gynecology. Related findings in AFE survivors add support to the idea that measurable immune activation may come before cardiovascular collapse in this condition.^1,2

AFE is the second leading cause of maternal death within the first 24 hours after delivery, behind postpartum hemorrhage. The condition has long been attributed to amniotic fluid embolizing into the maternal pulmonary circulation. That mechanical model has been questioned, in part because the amount of amniotic material found in the lungs appears insufficient to explain abrupt collapse. Earlier work from the same research group found markedly elevated tumor necrosis factor-α at admission, before symptoms began, in 2 women who died with a clinical diagnosis of AFE.

What did cytokine testing show before AFE symptoms began?

Investigators analyzed 2 plasma samples from a patient at 41 5/7 weeks' gestation who was in spontaneous labor with meconium-stained amniotic fluid. She developed a fever after epidural analgesia and was delivered by vacuum extraction. She then experienced postpartum disseminated intravascular coagulation (DIC) and cardiopulmonary collapse, and died 19 hours after delivery. Specimens came from the Perinatology Research Branch biobank at Wayne State University and Detroit Medical Center. Cytokines were measured with a multiplex assay on the Meso Scale Discovery platform.

The admission sample was collected while the patient was asymptomatic. Compared with healthy women in term labor, it showed:

• IL-6: 51,735 pg/mL (approximately 103,000-fold increase)
• IL-8: 5042 pg/mL (approximately 2800-fold increase)

• IL-10: 269 pg/mL (approximately 700-fold increase)

These levels were higher than those previously reported in clinical chorioamnionitis, fetal death, or severe postpartum hemorrhage. The sample drawn at AFE diagnosis showed that the inflammation persisted:

• IL-6: 16,340 pg/mL (approximately 32,500-fold increase)
• IL-8: 1599 pg/mL (approximately 884-fold increase)
• IL-10: 298 pg/mL (approximately 784-fold increase)

Did AFE survivors show the same early immune signal?

The AFE Registry and Biorepository held blood samples from 2 patients who survived classic AFE. The samples were collected 17 and 21 hours before cardiovascular collapse. Both patients already had elevated circulating cytokines before symptoms appeared, and IL-8 was the most prominent signal. Levels then rose substantially around the time of collapse and DIC. The findings are consistent with the concept that dysregulated maternal inflammation may precede, and possibly contribute to, the cardiovascular collapse and coagulopathy seen in AFE.²

“This is a small report involving two AFE patients, but it provides an important window into the biology of AFE before the emergency becomes clinically apparent and demonstrates the extraordinary value of collecting and preserving biospecimens through the AFE Registry and Biorepository,” wrote the Amniotic Fluid Embolism (AFE) Foundation in a LinkedIn post on September 28, 2026.

“Every sample has the potential to move us closer to understanding why AFE happens, how it develops, and what may one day help us identify it earlier,” the Foundation added.

Could early cytokine testing help predict AFE?

The AJOG authors noted that a subset of patients who develop AFE may have a cytokine storm detectable in maternal blood before symptoms appear. The levels far exceeded those seen in normal labor or clinical chorioamnionitis, which indicates a nonphysiologic response. The trigger remains unknown and may involve microbial or sterile inflammation. Postpartum decompensation may relate partly to the loss of the placenta's immunoregulatory functions after delivery.¹

The authors suggested that admission blood samples could identify at-risk patients before deterioration. They added that therapies used in other cytokine storm syndromes, including severe COVID-19, may warrant cautious exploration. Reduced C1 esterase inhibitor (C1-INH) activity has been reported in some patients with AFE. It may permit unchecked activation of the complement, contact, and kallikrein-kinin systems, and restoring C1-INH activity may have therapeutic value in a subset of patients.

IL-6 assays are now available on widely used automated chemiluminescent immunoassay platforms, with turnaround times of 1 to 3 hours, which makes prospective preclinical detection feasible.

“Comprehensive prospective studies are urgently needed to define the frequency, mechanisms, and predictive value of preclinical cytokine activation in AFE and to determine whether early recognition and targeted intervention can reduce maternal deaths from a catastrophic condition first described almost a century ago and still poorly understood,” the authors wrote.

“This is now feasible because assays for cytokines such as IL-6 can now take 1-3 hours using widely available automated chemiluminescent immunoassays.”

References:

1. Romero R, Meyyazhagan A, Gudicha DW, et al. A subclinical cytokine storm is present before the clinical diagnosis of amniotic fluid embolism: implications for the prediction and prevention of maternal death. Am J Obstet Gynecol. Published 2026. https://pmc.ncbi.nlm.nih.gov/articles/PMC13379053/
2. AFE Foundation. Statement on new AJOG research on preclinical cytokine activation in amniotic fluid embolism. Published September 29, 2026. Accessed September 29, 2026. https://www.linkedin.com/feed/update/urn:li:activity:7510413087938682880/