Irregular collagen in uterine scars linked to placenta accreta development

Placenta accreta spectrum (PAS) used to be a rare pregnancy condition, but it now affects roughly 14,000 pregnancies annually, posing a major cause of maternal death. Yet why it happens is still not well understood. Placenta accreta occurs when the placenta grows too deeply into the uterine wall, and doesn’t detach after birth, often resulting in life-threatening bleeding and a need for a hysterectomy.

The strongest and most common risk factor is a previous cesarean delivery, as scarring from prior cesarean births can change how the placenta attaches in future pregnancies. New research led by UCLA Health suggests that how this scar tissue heals could be the key to better understand how PAS develops, who is at risk and why the placenta attaches abnormally.

“Our findings show that the main problem in placenta accreta isn’t the placenta growing abnormally – it’s how uterine scarring changes the structure and organization of collagen in the uterus to increase delivery risks,” said Yalda Afshar, MD, associate professor of obstetrics and gynecology in the division of maternal fetal medicine at the David Geffen School of Medicine at UCLA, co-director of the UCLA Health Accreta Care Program and corresponding author of the study. 

The study, published in the American Journal of Obstetrics and Gynecology, used surgical specimens, a mouse model, and a lab-grown “accreta-in-a-dish” system to explore how collagen structure, when it becomes tangled or irregular, instead of neatly aligned, contributes to abnormal placental attachment. Through advanced 3D imaging, researchers found that tangled or irregular collagen at old uterine scars breaks down the normal boundary between the uterus and placenta, creating a permissive environment for abnormal placental attachment, and creating a high-risk delivery. 

Researchers collected samples from 13 patients with PAS and 10 with accreta risk factors but without PAS, taking tissue from where the placenta stuck and where it did not. Their findings showed that persistent inflammation and immune cells called macrographes interfere with normal scar remodeling, leading to abnormal collagen architecture that promotes abnormal placenta attachment. 

Not all scars heal the same way. This work helps explain why some patients with prior cesarean develop placenta accreta while other do not and points to new ways we might identify risk earlier, before pregnancy or early in gestation.” 

Yalda Afshar, MD, associate professor of obstetrics and gynecology, division of maternal fetal medicine, David Geffen School of Medicine, UCLA