Research Review: A Prenatal Blood Test that Accurately Determines Gestational Age and Prematurity Risk?

prematurity test.jpgPremature babies face additional challenges right from the start, and the impact of being born too early can set up special needs that impact the entire lifespan of the individual.  According to the March of Dimes, who evaluated information released earlier this spring from the Centers for Disease Control in the United States, the rate of prematurity (babies born before 37 weeks) rose to 9.93 in 2017, up from 2016 numbers. In fact, this is the third year in a row that the prematurity rate has risen, when the previous seven years had shown a decline. Families of color, particularly Hispanic and Black people have carried the brunt of this increase as the prematurity rate for white people has remained stable. 

The gestational age of a fetus is currently determined by calculations from the last menstrual period of the pregnant person, along with ultrasound estimates if available.  The earlier the ultrasound is done to calculate fetal age, the more accurate the estimate.  This leads to many pregnant people receiving ultrasounds in the first trimester, and then again for a second-trimester anatomy scan, often followed by a late third-trimester scan to estimate fetal weight and assess the baby.  Ultrasounds are expensive, have a large margin of error the later in pregnancy they happen and are not able to predict who might be at risk for preterm labor.  Many populations in underresourced places in the Majority World do not have access to ultrasound machines.  Having an accurate estimate of gestational age and identifying who is at risk for birthing preterm are important details of maternal-infant care,

A small but very positive study just released, "Noninvasive blood tests for fetal development predict gestational age and preterm delivery" has demonstrated the ability to determine gestational age with a blood test as accurately as early ultrasound (most reliable of any ultrasound).  This could be a very economical and useful tool, especially in low resourced areas. The current standards of trying to determine who is at risk of premature birth include transvaginal ultrasounds to detect cervical change and the fetal fibronectin test which has a high rate of false positives.

When there is inaccurate or uncertain information being relied on to determine gestational age, unnecessary interventions, such as inductions and cesareans, may take place that increases mortality and morbidity for both the birthing person and the baby.  When the risk of premature birth is uncertain, actions cannot be taken to lower the likelihood of a premature baby.

About this new research

Blood samples were taken weekly from 31 Danish people throughout their pregnancy. The samples were analyzed by highly multiplexed real-time polymerase chain reaction (PCR) using a panel of genes with expression specific to the placenta or to the immune system, or highly enriched in the fetal liver. Samples were collected and analyzed to determine the levels of different genes that had free-floating RNA in the parent's blood. This RNA had varying origins (fetal liver, placental, maternal immune system and more) and levels could be tracked over time. Nine different RNA genes allowed fetal age to be predicted. The testing model predicted the correct gestational age to within 14 days 45% of the time.  Ultrasound imaging carried out in the first trimester of pregnancy (considered the most accurate, with the least margin of error) was correct 48% of the time for the 31 people in the study.  These findings suggested that cfRNA corresponding to placental genes might provide an accurate estimate of fetal development and gestational age throughout pregnancy.

In samples from parents suspected of being at risk of delivering prematurely, seven RNA genes helped to predict the likelihood of premature birth. Blood sampling accurately identified four out of five people who had gone on to spontaneously give birth early but mistakenly flagged 17% of those who actually delivered at full term.  A larger sample size is needed to develop confidence in the predictive ability of this test.

Researchers acknowledge the limitations of their study with these small samples sizes.  Conducting a larger study will help to determine the reliability of this low-invasive and economical tool to accurately assess fetal age and identify those at risk of delivering prematurely. Being able to accurately determine gestational age from a blood test will reduce expensive time-consuming interventions that require a lot of financial, staffing and personal resources and do not improve outcomes.  For the Majority World, ultrasounds are not reliably available and are very expensive to own and operate.  Developing this blood test that is readily available to all regardless of location can help to determine gestational age and risk of delivering a premature baby so that appropriate care can be provided.  I look forward to further research in this area to fine tune the reliability of such a prenatal blood test.

Resources

Hamilton BE, Martin JA, Osterman MJK, Driscoll AK, Rossen LM. Births: Provisional data for 2017. Vital Statistics Rapid Release; no 4. Hyattsville, MD: National Center for Health Statistics. May 2018. Available from: https :// www .cdc. gov/nchs/data/vsrr/report004.pdf.

Ngo, T. T., Moufarrej, M. N., Rasmussen, M. L. H., Camunas-Soler, J., Pan, W., Okamoto, J., ... & Tibshirani, R. (2018). Noninvasive blood tests for fetal development predict gestational age and preterm delivery. Science360(6393), 1133-1136.

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