Yale researchers have made a groundbreaking discovery by demonstrating that a thorough examination of the placenta can lead to the accurate pathologic determination of over 90% of previously unexplained pregnancy losses. This finding has the potential to reshape pregnancy care and offer solace to countless families affected by such losses. The study’s results were published on September 19 in the journal Reproductive Sciences.
In the United States, approximately 5 million pregnancies occur each year, with 1 million ending in miscarriage (defined as a loss occurring prior to 20 weeks of gestation), and over 20,000 culminating in stillbirth at or beyond 20 weeks of gestation. Alarmingly, up to 50% of these losses have historically been labeled as “unspecified.”
Senior author Dr. Harvey Kliman, a research scientist in the Department of Obstetrics, Gynecology, and Reproductive Sciences at Yale School of Medicine, emphasized the emotional toll such losses take on patients. He noted that individuals who experience these pregnancy outcomes are often left with the heartbreaking verdict that their loss is unexplained, a verdict that can exacerbate their grief and sense of responsibility.
Dr. Kliman expressed, “To have a pregnancy loss is a tragedy. To be told there is no explanation adds tremendous pain for these loss families. Our goal was to expand the current classification systems to decrease the number of cases that remained unspecified.”
To address this issue, Dr. Kliman collaborated with Beatrix Thompson, currently a medical student at Harvard University, and Parker Holzer, a former graduate student in Yale’s Department of Statistics and Data Science. Together, they developed an expanded classification system for pregnancy losses based on a comprehensive examination of placental tissue.
The study commenced with a dataset of 1,527 single-child pregnancies that ended in a loss. These cases were sent to Dr. Kliman’s consult service at Yale for evaluation. Following the exclusion of cases without adequate material for examination, the team examined 1,256 placentas from 922 patients. Among these, 70% were miscarriages, and 30% were stillbirths.
By introducing explicit categories such as “placenta with abnormal development” (dysmorphic placentas) and “small placenta” (placenta size below the 10th percentile for gestational age) to the existing categories like cord accidents, abruptions, thrombotic events, and infections, the authors achieved pathologic diagnoses for 91.6% of the pregnancies. This included 88.5% of miscarriages and an impressive 98.7% of stillbirths.
The study found that the most common pathologic feature observed in unexplained miscarriages was dysmorphic placentas (86.2%), which are indicative of genetic abnormalities. Meanwhile, unexplained stillbirths most frequently exhibited a small placenta (33.9%).
Dr. Kliman underscored the significance of this work, stating, “This work suggests that the over 7,000 small placentas per year associated with stillbirths could have been detected in utero — flagging those pregnancies as high risk prior to the loss. Likewise, the identification of dysmorphic placentas may be one way to potentially identify genetic abnormalities in the almost 1 million miscarriages that occur in our country every year.”
He added, “Having a concrete explanation for a pregnancy loss helps the family understand that their loss was not their fault, allows them to start the healing process, and, when possible, prevent similar losses — especially stillbirths — from occurring in the future.”
When questioned about effective measures to prevent stillbirths, Dr. Kliman offered a straightforward response, “Measure the placenta!”
