New accessible placental measurement method could help prevent stillbirths

When Ann O'Neill suffered a stillbirth in 2018, she was bewildered. She was already a mother to three healthy children and therefore had received no information on stillbirth prevention from her doctors. But when she brought the placental pathology results from the son she lost to Harvey Kliman, a physician-scientist specializing in pregnancy complications at the Yale School of Medicine, he found one critical abnormality that had been overlooked: a very small placenta.

Each year, about 21,000 stillbirths occur in the United States. Previous research has found that abnormalities in the placenta, the organ that a fetus depends on for oxygen, fluids, and nutrients, are associated with adverse pregnancy outcomes, including stillbirth. Measuring placental volume is an important step toward identifying pregnancies with one such abnormality — a placenta that is disproportionately small relative to the size of its fetus.

But placental monitoring is rare, in part because the organ's irregular geometry — often compared to a beanie cap — makes the placenta difficult to measure. Virtual Organ Computer-aided Analysis (VOCAL), the current method for measuring volume by ultrasound, requires advanced equipment, trained operators, and time to perform a three-dimensional (3D) ultrasound.

Now, however, a new study, published in The Journal of Perinatal Medicine, points to a promising, accessible alternative to VOCAL: Estimated Placental Volume (EPV), an inexpensive, rapid method that can be performed with two-dimensional (2D) ultrasound equipment. This method, the study shows, provides placental volume estimates that are almost identical to those produced by VOCAL.

This study has demonstrated that the simple, Yale-developed 2D EPV method is equivalent to the gold standard — but expensive and complex — VOCAL method. This may facilitate earlier assessment of placental size during pregnancy."

Harvey Kliman, research scientist, Department of Obstetrics, Gynecology, and Reproductive Sciences at the Yale School of Medicine (YSM)

Kliman hopes that the findings will encourage further clinical evaluation of placental monitoring — a goal he and his late father, the mathematician Merwin Kliman, had in mind when they developed EPV together over a decade ago.

The method requires only an inexpensive, hand-held ultrasound device. With minimal training, healthcare providers can use the device to measure the width, height, and thickness of the placenta — measurements that they can plug into a volume-estimating equation, written by Merwin Kliman, to obtain an estimated placental volume. The test takes only thirty seconds.

In this study, Kliman and senior author Roberto Romero, chief of the Pregnancy Research Branch in the Division of Intramural Research of the Eunice Kennedy Shriver National Institute of Child Health and Human Development, performed 2D and 3D ultrasounds on 58 patients with healthy pregnancies during the same clinical visit. They used the 2D ultrasounds to calculate placental volume with the EPV method; for the 3D ultrasounds, they used the VOCAL method.

When they compared the placental volume estimates obtained using each method, Kliman and Romero found a near-perfect correlation between the two.

"Obstetricians have monitored fetal growth for decades, yet we have lacked a practical method to monitor the growth of the organ that supports fetal life. This study shows that the estimated placental volume obtained with 2D ultrasound provides placental size estimates comparable to those obtained with a more complex 3D method," Romero said. "We hope it will enable the studies needed to determine whether abnormalities in placental growth can identify pregnancies at risk before clinical complications develop."

In fact, Kliman is already planning another study that aims to determine which patients who receive ultrasounds during their prenatal care might have benefitted from performing an EPV to identify pregnancies with small placentas.

For her part, O'Neill, who founded the organization Measure the Placenta to advocate for prenatal care to routinely include placental measurement, hopes that the study will offer support for further research. "We can do better for pregnant patients than ignoring this critical organ," O'Neill said.

Other co-authors of the study included Arun Meyyazhagan, Adi L. Tarca, Tinnakorn Chaiworapongsa, and Awoniyi Awonuga, all of Wayne State University School of Medicine; and Cecilia Avila of the State University of New York, Stony Brook Medicine.

This work was supported by funding from the National Institutes of Health.