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New Study Unveils the Cellular Mechanism of Umbilical Cord Vessel Closure Following Delivery

Researchers have discovered that umbilical cord arteries contain components that naturally promote narrowing at birth, and ensure a sequence in which the arteries close before the vein, supporting delayed cord clamping following delivery in most uncomplicated deliveries.

10/01/2020

New findings from a study published in eLife related to umbilical cord biology, and led by a team of researchers in the Department of Biomedical Engineering, suggesting that delayed cord clamping following delivery may better align with how nature designed the umbilical arteries and vein. The study was initiated through the efforts of Elliot Philipson, MD, former Chair of Maternal-Fetal Medicine at Cleveland Clinic.

The human umbilical cord contains two arteries and one vein. The arteries transport unoxygenated fetal blood to the placenta, and the vein carries oxygenated blood to the fetus. In modern obstetric practice, the human umbilical cord is typically clamped after delivery to prevent fetal blood loss and aseptically separate mother and child.

This new study asked whether there were intrinsic design features of the umbilical arteries that enabled their rapid closure after birth--which seems to occur in humans and other mammals--whereas the vein remains open longer. The researchers found that umbilical arterial properties, including the expression and arrangement of certain proteins and contracting smooth muscle cells, enabled the umbilical arteries to naturally close.

These findings contrasted with what was observed in the vein, suggesting a natural basis for the different responses of the arteries and vein. The research were supported by biomechanics and computational analysis in collaboration with a group at Yale University led by Jay Humphrey, PhD. 

“Cord closure is a natural process,” noted Sumeda Nandadasa, PhD, a research associate in the lab of Suneel S. Apte, MBBS, PhD, and first author of the study. “Cord clamping, on the other hand, might not be strictly necessary. It might just be an option in case resuscitation is needed or if there is severe maternal hemorrhage.”

Scientific justification for not clamping the cord

Using three-dimensional imaging, staining techniques and gene expression analysis, the researchers, including undergraduates Caroline M. Kraft and Anna O’Donnell, together with Martina Viegl, David Sedwick and Vai Pathak at Case Western Reserve University, studied the vasculature of human umbilical cords obtained following healthy vaginal or Caesarean section births.

They determined that the umbilical cord arteries have an inner layer loaded with the proteoglycans aggrecan and versican, the former usually found in cartilage. In fact, one of the key discoveries of the study is that there is more aggrecan in the arteries than expected. Additionally, the researchers found that the outer layers of the arteries are rich in smooth muscle cells, whose contraction provokes buckling (and narrowing) within the inner layers of the arteries. Both of these features promote artery contraction, causing them to close in the moments after birth.

To understand how this came about, Dr. Humphrey’s team at Yale created a computational bilayered arterial model of the umbilical cord to recreate the biomechanics of inner layer buckling. They note that the computational model could be helpful in the future for designing engineered blood vessels with specific properties.

Application to obstetric practice

Currently, the American College of Obstetricians and Gynecologists (ACOG) has recommended a delay of 30 to 60 seconds before clamping the cord to allow complete placental transfusion from the open umbilical vein.

“Although our study does not put forth any recommendations,” said Dr. Nandadasa, “our findings do call into question the necessity of clamping, and certainly support delayed rather than immediate clamping at birth."

“We do not expect that clamping will become obsolete anytime soon,” said Dr. Philipson. “More immediately, our work at least supports the recent ACOG recommendation to delay clamping following delivery. Delayed clamping allows the fetus to get a final infusion of blood from the placenta via the open placental vein to help it on its way.”

The project was supported by funding from the National Institutes of Health and the Allen Distinguished Investigator Program, jointly with the American Heart Association, Sabrina’s Foundation, The Swedish Heart-Lung Foundation, and the Mark Lauer Pediatric Research Grant.

Image: Transverse sections through a human umbilical artery (left) and vein (right) immunostained for phosphorylated myosin light chain (green) and smooth muscle myosin heavy chain (red). The umbilical artery which contains a proteoglycan-rich inner smooth muscle cell layer undergoes rapid arterial occlusion at birth via contraction of smooth muscle cells (SMCs) in the outer layer (yellow cells). The umbilical vein lacks the proteoglycan-rich inner layer and does not undergo rapid occlusion despite the presence of the contractile SMCs. Dotted lines mark the lumen of each vessel.



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