A University of Pittsburgh scientist, along with researchers from around the world, has used March of Dimes-funded data to pose some out-of-this-world pregnancy hypotheses.
Relying partially on research from the March of Dimes Database for Preterm Birth Research, Dr. Afshin Beheshti and a broader research team found that mice who have been exposed to space-like conditions share something in common with women at risk of having small for gestational age (SGA) babies: 13 microRNAs. Abbreviated as miRNAs, these are tiny RNA molecules that affect the way genes are expressed, usually silencing them.
The findings, recently published in Communications Biology, a journal in the Nature family of journals, led the research team to theorize that space travel could put female astronauts at risk of having small babies after their return to earth.
While the theory has not been clinically proven, the scientists’ use of data across fields and species points to a new era of cross disciplinary scientific collaboration aided by March of Dimes’ collaborative programs and spirit of sharing data publicly.
Although this paper, which was partially funded by NASA, borrowed data from several public databases to inform their conclusions, data vital to the primary finding of the paper about space flight’s risk for SGA babies came from a 2020 study out of the March of Dimes Prematurity Research Center (PRC) at Imperial College London. That study’s data was made public by the March of Dimes Database for Preterm Birth Research at the University of California, San Francisco, and later accessed by the scientists.
The Imperial paper, published in the journal eBioMedicine, part of the Lancet family of journals, found two miRNAs that are highly predictive of having an SGA baby: hsa-miR-374a-5p and hsa-let-7d-5p. Tested as a pair, those miRNAs had a 77% accuracy in predicting risk.
The Imperial findings have since been validated, and the next step of the Imperial team, after publishing the validation data, is to begin the work of creating a screening test that can be used clinically to identify women at risk of having SGA babies based on their miRNA profile—an achievement that could become reality in just a few years.
While the theory presented in this paper about the potential increased SGA risk of space travel on female astronauts who get pregnant after they return to Earth needs additional validation, the March of Dimes researchers who contributed to the data that powered the theory are delighted the authors performed the analysis.
“I think it’s pretty exciting and cool,” said Dr. Vasso Terzidou, who leads miRNA and pregnancy research at the Imperial PRC and was the Imperial SGA paper’s senior author. “The study was exploratory, but the way it set a roadmap, in a sense, for combining information from different platforms was very interesting.”
Dr. Sung Hye Kim, a senior post-doctoral researcher focused on miRNA and pregnancy at the PRC who was the paper’s first author, said the computational work “opens up a lot of fields for further validation and highlights new areas of focus.”
And Dr. Marina Sirota, who heads the March of Dimes PRC at the University of California, San Francisco and founded the preterm birth research database that allowed the scientists to view and use the data, said the outcome is exactly in line with the purpose of sharing these data.
“The fact they are doing this means a lot to me, and it really demonstrates our reach,” said Dr. Sirota. “That they are taking these data and asking these questions, that’s exactly what our vision is for the database—speeding the pace of discovery by working together.”
A vault of every piece of molecular data that has come out of a March of Dimes PRC, the database comprises 76 studies with more than 45,000 experimental samples from nearly 31,000 participants and more than 30 types of measurements. It is the only public multi-omic data repository for preterm birth.
Because the study of the role of miRNA in pregnancy is only 15-20 years old, there’s still a lot to uncover about the function of these tiny yet influential molecules in pregnancy. Still, Drs. Terzidou and Kim stressed that the molecules are excellent early predictors of pregnancy complications.
“We know they are involved in cells that make up the early embryo, we know they affect the placenta, we know they are involved in fetal growth, in birth, and more,” said Dr. Terzidou. “And though we don’t exactly know what they do, we rely on their activity to give us a snapshot into the health and trajectory of the pregnancy.”
“They are reporters that tell us what biological processing are happening.”
Discovered in the early 90s by former March of Dimes Prize recipients and 2024 Nobel Prize winners Dr. Victor Ambros and Dr. Gary Ruvkun, miRNAs are the gatekeepers between messenger RNAs, or mRNAs, which translate your DNA into messages, and recipient proteins, which help carry out those messages in your body. miRNA under- or over- expression results in the inability of mRNA to translate its message into proteins, which results in either silencing or activation of genes. Usually, miRNA is overexpressed, and genes are silenced—this is the case with miRNA’s impact on the risk for SGA babies.
Affecting 5-10% of babies, an SGA diagnosis puts babies at risk of stillbirth, cerebral palsy, and cardiovascular conditions. Currently, ultrasound is the leading method used to detect babies with SGA, though it misses about 2/3 of cases. Plus, only women with a prior SGA baby will be screened using ultrasound, bypassing women pregnant with their first baby who may be at risk but don’t technically have any risk factors because it’s their first birth.
With 77% accuracy, the Imperial miRNA screening test has the potential to dramatically improve early detection and diagnosis, Dr. Kim said.
The blood test in development at the PRC could be offered to all pregnant women, regardless of risk factors, at 12-15 weeks’ gestation, Dr. Terzidou said, and those that are deemed high risk can get care that can prevent the worst outcomes.
“These women could then have appropriate follow up and interventions (like low dose aspirin) that could change the outcome, meaning reduce their risk of having an SGA pregnancy,” she said.
March of Dimes has a long legacy of collaborative, cross-disciplinary research, heading back to the development of the polio vaccine and the creation of the field of virology. This spirit leads to impactful findings and allows for more innovative types of experiments and new discoveries that could transform care for moms and babies.