New targets? The decidua and micronutrients
The NEJM study reported a number of findings. Among them:
- Identifying six gene loci; EBF1, EEFSEC, and AGTR2, which were associated with both gestational length and preterm birth; and WNT4, ADCY5 and RAP2C, which were associated with gestational length, but not with preterm birth.
- The gene WNT4 strongly suggests that changes occurring in the decidua play a driving role in preterm birth, which indicates a new potential target for intervention.
- Another gene association, EEFSEC, points to the possible role of selenium in a woman’s diet, a micronutrient that had not been seen as important to a healthy pregnancy.
“These are exciting findings,” says Trevor Mundel, President of the Global Health Division at the Bill & Melinda Gates Foundation. “Not only did the study reveal several genes linked to preterm birth, it also identified a simple, low-cost solution—selenium supplements for expectant mothers—that, if confirmed, could save thousands of lives. It’s a great example of the power of public-private partnership.”
This study attracted wide-ranging attention in scientific circles and from the lay press. News coverage appeared on CBS This Morning, Newsweek, the Voice of America, Medscape, HealthDay, WebMD, and various outlets in Europe. More than 190 Twitter posts from scientists, clinicians, disease advocacy groups and others reached more than 860,000 followers.
“It’s a great example of the power of public-private partnership.”
Since publication, Muglia and colleagues have presented numerous lectures about the findings. The most notable ones have included the Presidential Plenary Lecture at the American Society for Reproductive Immunology in China, a special symposium on the genetics of preterm birth in Rome, and the Mac Keith Press Basic Science Lectureship at the American Academy for Cerebral Palsy and Developmental Medicine.
Muglia emphasizes that the study represents a beginning point. Potential diagnostic tests, new medications, improved dietary supplements or other changes that could help more women have full-term pregnancies will require several more years of study. However, the follow-up work has begun.
“We have received a Gates Foundation grant to extend the findings in the NEJM paper to non-European ancestry populations in Asia and Africa. It is currently in progress,” Muglia says. “We are also determining whether selenium deficiency, related to one of the genes we identified, is an independent risk factor. In addition, we have several spin-off studies seeking to determine the mechanisms by which the genetic loci we identified are functioning to determine birth timing.”
Zhang G, Feenstra B, Bacelis J, Liu X, Muglia LM, Juodakis J, Miller DE, Litterman N, Jiang PP, Russell L, Hinds DA, Hu Y, Weirauch MT, Chen X, Chavan AR, Wagner GP, Pavlicev M, Nnamani MC, Maziarz J, Karjalainen MK, Ramet M, Sengpiel V, Geller F, Boyd HA, Palotie A, Momany A, Bedell B, Ryckman KK, Huusko JM, Forney CR, Kottyan LC, Hallman M, Teramo K, Nohr EA, Davey Smith G, Melbye M, Jacobsson B, Muglia LJ. Genetic Associations with Gestational Duration and Spontaneous Preterm Birth. N Engl J Med. 2017 Sep 21;377(12):1156-1167.