Risk of Preterm Birth Assessed with a Simple Blood Test

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A study states that a simple blood test during routine prenatal visits can help identify women at risk of preterm birth.

Preterm birth is live birth that occurs before 37 weeks of pregnancy. On average, an annual 15 million babies worldwide are born preterm. Although low- and middle-income countries have one of the highest rates, the rates seem to be rising in other countries as well. In 2019, 1 in every 10 infants born in the United States was preterm. Infants born prematurely are at risk of feeding difficulties, cerebral palsy, respiratory problems, development delay, and various neurological disorders. According to the US Centers for Disease Control and Prevention (CDC), it accounted for 17% of infant deaths in 2018. Therefore, there is a need to identify mothers at risk of preterm birth to avoid complications and reduce the emotional and financial burden on families. 

Preterm births are common. If we know the mother is at risk for a preterm birth, her doctor can monitor her more closely.

Professor Hanne Hoffmann, study author

A team of researchers at Michigan State University (MSU) recruited 157 healthy mothers with no history of preterm births. 51 of these mothers went on to have a preterm birth; the remaining mothers formed the control group. Researchers collected maternal blood samples from the mothers in the second and third trimesters. They aimed to examine the link between circadian rhythm genes and the risk of preterm birth in the participants.

Just as humans have a circadian rhythm, so do our cells. Each cell has its own 24-hour clock that regulates the cell’s functions according to the sleep-wake cycle. Previous studies predict a link between disrupted cell circadian cycles and preterm birth. However, the underlying mechanism is unclear.

A Needle in the Haystack

The authors of the study looked at levels of various circadian rhythm transcripts and the occurrence of preterm births in the participants. Results revealed lower mRNA levels in the CRY2 and CLOCK genes. Both genes play a role in cell circadian rhythms.

During the 2nd trimester, maternal blood of women who had preterm births showed lower levels of both CRY2 and CLOCK transcripts. Thus, suggesting that their levels may be associated with a higher risk of preterm birth. The 20-week prenatal scan can serve as an ideal time for the measurement of these levels.

If we could measure women’s mRNA levels and tell them for their second or third pregnancies, that they aren’t at risk for a preterm birth because their levels are higher (in a normal/healthy range), that would be such a comfort to the mothers who previously had a preterm birth.

Professor Hanne Hoffmann, study author

However, it is unclear as to where the genes are coming from – mother or fetus. The researchers want to further examine the link by comparing mRNA levels of healthy women with those with a history of preterm births. Moreover, they also plan to investigate another circadian gene, called PER3 and its role in pregnancy-related disorders.


Guoli Zhou, Thu V Duong, Eric P Kasten, Hanne M Hoffmann, Low CLOCK and CRY2 in 2nd trimester human maternal blood and risk of preterm birth: a nested case-control study†, Biology of Reproduction, 2021;ioab119, https://doi.org/10.1093/biolre/ioab119


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