By Rebecca Bowers

EXECUTIVE SUMMARY

In pilot studies of pregnant women, data indicate that ribonucleic acid-based tests of maternal blood can predict delivery date and risk of early childbirth.

If proven successful in advanced trials, such tests could aid in decreasing the preterm birth rate in the United States, which has recorded its third consecutive annual increase after steady declines during the previous seven years.

  • Babies who are born too early have higher rates of death and disability. Research indicates that 17% of infant deaths in 2015 were attributed to preterm birth and low birth weight.
  • Infants who are born too early may experience problems with breathing, feeding, vision, and hearing, as well as cerebral palsy and developmental delay.

In pilot studies of pregnant women, data indicate that ribonucleic acid-based tests of maternal blood can predict delivery date and risk of early childbirth.1 If proven successful in advanced trials, such tests could aid in decreasing the preterm birth rate in the United States, which has recorded its third consecutive annual increase after steady declines during the previous seven years.2

Babies who are born too early have higher rates of death and disability. Data from the Centers for Disease Control and Prevention show that 17% of infant deaths in 2015 were attributed to preterm birth and low birth weight.3 Infants who are born too early may experience problems with breathing, feeding, vision, and hearing, as well as cerebral palsy and developmental delay.

Currently, there has not been a reliable way to determine which women will experience premature delivery. It is challenging for clinicians, particularly those in low-resource settings, to pinpoint delivery dates accurately.

According to preliminary research, the new blood test, led by a team of researchers at Stanford University, detects within 75-80% accuracy whether pregnancies will end in premature birth. The same technique also can be used to estimate a fetus’s gestational age as reliably as and less expensively than ultrasound, researchers conclude.1

Stephen Quake, PhD, professor of bioengineering at Stanford and co-senior author of the current paper, praises the collaboration of researchers around the globe in developing the test. The research was funded by the Bill and Melinda Gates Foundation, the March of Dimes Prematurity Research Center at Stanford University, the March of Dimes Prematurity Initiative Grant at the University of Pennsylvania, and the Chan Zuckerberg Biohub.

“We have worked closely with the team at the Stanford March of Dimes Prematurity Research Center, and the research involved collaborations with scientists in Denmark, Pennsylvania, and Alabama,” said Quake in a press statement. “It’s really team science at its finest.”

Review the Results

Researchers developed the gestational-age test by studying a group of 31 Danish women, who gave blood weekly throughout their term pregnancies. The investigators used the blood samples from 21 of the women to build a statistical model, which identified nine cell-free ribonucleic acids (RNAs) that predict gestational age. Researchers then validated the model by using samples from the other 10 women. The gestational age estimates using the model were accurate about 45% of the time, compared to the accuracy of 48% for estimates that used first-trimester ultrasound, the researchers noted.1

By measuring cell-free RNA in mothers’ blood, clinicians also may be able to gather valuable information about fetal growth, says Thuy Ngo, PhD, now research assistant professor of medicine at Oregon Health and Science University.

“This gives a super-high resolution view of pregnancy and human development that no one’s ever seen before,” said Ngo. “It tells us a lot about human development in normal pregnancy.”

To use testing to predict preterm birth, researchers studied blood samples from 38 American women with a risk for premature delivery because of early contractions or a previous preterm birth. Each woman submitted one blood sample during the second or third trimester of her pregnancy. Thirteen women delivered prematurely, while 25 delivered at term. Data from the test indicated that levels of cell-free RNA from seven genes from the mother and the placenta could indicate which women would have premature deliveries.1

More Research Needed

The research team plans to evaluate the new tests further with larger groups of women. Although scientists still don’t know the mechanism that causes preterm birth, they plan to study genes further to gain more understanding. The researchers also hope to determine whether drugs may be able to help prevent premature births.

“By measuring cell-free RNA in the circulation of the mother, we can observe changing patterns of gene activity that happen normally during pregnancy, and identify disruptions in the patterns that may signal to doctors that unhealthy circumstances like preterm labor and birth are likely to occur,” said David Stevenson, MD, the principal investigator of the March of Dimes Prematurity Research Center at Stanford University. “With further study, we might be able to identify specific genes and gene pathways that could reveal some of the underlying causes of preterm birth, and suggest potential targets for interventions to prevent it.”

Clinicians can help pregnant women to have healthy pregnancies and reduce their risk of preterm birth. The Centers for Disease Control and Prevention suggests these recommendations for pregnant women:

  • Stopping smoking;
  • Obtaining prompt prenatal care as soon as a woman thinks she is pregnant, followed by routine care throughout pregnancy;
  • Seeking medical attention for any warning signs or symptoms of preterm labor; and
  • Talking with a healthcare provider about the use of progesterone treatment if a woman has had a previous preterm birth.

REFERENCES

  1. Ngo TTM, Moufarrej MN, Rasmussen MH, et al. Noninvasive blood tests for fetal development predict gestational age and preterm delivery. Science 2018;360:1133-1136.
  2. Hamilton BE, Martin JA, Osterman MJK, et al. Births: Provisional Data for 2017. Hyattsville, MD: National Center for Health Statistics. National Vital Statistics System, Vital Statistics Rapid Release Program. Available at: https://bit.ly/2IpZRkA. Accessed June 22, 2018.
  3. Xu J, Murphy SL, Kochanek KD, Arias E. Mortality in the United States, 2015. NCHS data brief, no 267. December 2016. Hyattsville, MD: National Center for Health Statistics. Available at: https://bit.ly/2icuU9p. Accessed June 22, 2018.