Why is one twin sometimes smaller than the other? The answer may lie in the placenta

placental oxygen transport may help determine fetal size

When a baby is born small, it’s often chalked up to genetics or to maternal risk factors like poor nutrition or smoking. A study of twin pregnancies, published today in Scientific Reports, finds another factor that can be measured prentally: slower transport of oxygen from mother to baby across the placenta.

The study, part of the NIH-funded Human Placenta Project, is the first to make a direct connection between placental oxygen transport and birth outcomes. It relies on a new, noninvasive technique called Blood-Oxygenation-Level-Dependent (BOLD) MRI. Developed by P. Ellen Grant, MD, director of the Fetal-Neonatal Neuroimaging and Developmental Science Center at Boston Children’s Hospital and Elfar Adalsteinsson, PhD at MIT, it maps oxygen delivery across the placenta in real time.

“Until now, we had no way to look at regional placental function in vivo,” says Grant. “Prenatal ultrasound or routine clinical MRI can assess placental structure, but cannot assess regional function, which is not uniform across the placenta. Doppler ultrasound can measure blood flow in the umbilical arteries and other fetal vessels, but it cannot tell how well oxygen or nutrients are being transported from mother to fetus.”

Real-time placental oxygen mapping

By studying identical twins, the researchers were uniquely able to control for both genetic factors and maternal risk factors. Although identical twins also share a placenta, it is divided into two separate compartments, and one may be healthier than the other.

placental oxygen transport and placental pathology
Compromised oxygen delivery: At right, fetal blood flows in blood vessels inside the villi. The villi are bathed in the mother’s blood, allowing oxygen to diffuse into the fetal circulation. In the abnormal placenta at left, the villi are sparser and some lack fetal blood vessels (arrows). The redder villi (asterisk) have more or larger fetal blood vessels, an attempt to compensate and provide sufficient oxygen. (Wikimedia/Jie Luo/Drucilla Roberts)

Grant, with research fellows Jie Luo, PhD, and Esra Abaci Turk, PhD, and co-senior investigator Julian Robinson, MD, chief of obstetrics at Brigham and Women’s Hospital, followed seven sets of identical twins all the way to birth. In all cases, one twin was smaller than the other.

At 29 to 34 weeks of pregnancy, the seven mothers underwent BOLD MRI for about 30 minutes. While they inhaled pure oxygen for 10-minute stretches, Grant’s team measured how long it took oxygen concentrations to peak in the placenta, known as the time to plateau (TTP). The team then tracked how long it took for the oxygen to pass through the umbilical cord into the fetus and penetrate the brain and liver.

To adjust for fetal motion, a team led by Polina Golland, PhD, at MIT used image-correction algorithms developed by MIT CSAIL.

The finding: A longer TTP in the placenta correlated with lower newborn birth weights as well as lower liver and brain volumes. TTP also correlated with placental pathology when placentas were examined after birth by pathologist Drucilla Roberts, MD, at Massachusetts General Hospital (MGH).

placental oxygen transport and fetal size
Placental health and fetal size: The MRI image at left shows the placenta partitioned into two sections, each supplying blood to one twin. At right, twin B, whose placenta delivered oxygen more slowly, is smaller and has a smaller liver and brain than twin A.

Pregnancy: Genes vs. environment

Grant hopes this work will lead to a better understanding of pregnancy risk factors, and ultimately to a prenatal test for mothers in whom placental dysfunction is suspected.

“Our next goal is to figure out what causes variation in oxygen transport in the placenta and identify a cutoff value that would be of concern in a pregnancy, including singleton pregnancies,” she says. “Then, we can think about potential treatments to improve placental oxygen transport, and use our methods to immediately assess the success of these treatments.”

Grant believes placental oxygen transport is a prime example of how environmental factors can modify our DNA. Future studies will investigate how placental oxygen transport affects fetal gene expression and specific measures of brain development and organ metabolism.

These studies will use a special MRI coil to improve image accuracy, developed for pregnant mothers by collaborator Larry Wald, PhD, at the Athinoula A. Martinos Center. William Barth, MD, chief of Maternal-Fetal Medicine at MGH and Chloe Zera, MD, MPH, an obstetrician at Brigham and Women’s, have also joined the team to guide the development of novel MR imaging strategies to improve prenatal care.

The research was funded by the NIH (U01 HD087211; R01 EB017337) and the Consejeria de Educacion, Juventud y Deporte de la Comunidad de Madrid through the Madrid-MIT M+Vision Consortium. Grant and several co-investigators are co-inventors on patent applications describing the BOLD MRI technique.