A first-of-its-kind multi-country analysis has determined that all known risk factors combined cannot account for two-thirds of the preterm births in high-income nations, including the United States, providing a more precise estimate than previously available.
The study was published today in PLOS ONE by researchers who represent the March of Dimes/FIGO (International Federation of Gynecology and Obstetrics) Working Group for Preterm Birth Prevention.
The researchers say that their unprecedented individual patient-level dataset, about five times larger than any used previously -- and the first that is cross-country -- and newly applied analytic approaches allowed them to make this and several other intriguing advances with the study.
“Preterm birth is the leading cause of death for children under age 5 around the world, but we can’t reliably prevent two-thirds with existing interventions,” said Joe Leigh Simpson, MD, March of Dimes Senior Vice President for Research and Global Programs and the corresponding author.
The researchers studied individual patient-level data from approximately 4.1 million singleton pregnancies, including 2.8 million from four Very High Human Development Index (VHHDI) countries-- New Zealand, Czech Republic, Slovenia, Sweden -- and 1.3 million from California as a comparator U.S. state. They confirmed that prior preterm birth and preeclampsia are the two strongest individual risk factors for preterm birth worldwide. Independent of all other associated risk factors, nulliparity (never having born a baby before) and male baby sex are top contributors overall to the population preterm rate. There is no plausible biological explanation for two-thirds (more than 65 percent) of preterm birth, the researchers say.
“This finding confirms the wisdom of the March of Dimes decision to invest in 2010 in a network of five Prematurity Research Centers bringing together the brightest minds from many diverse disciplines of science to find the unknown causes of preterm birth,” Dr. Simpson said. “This complements the March of Dimes National Prematurity Campaign to improve delivery of the known and effective treatments and interventions.”
Having a prior spontaneous preterm birth remains the number one risk factor for preterm birth. The authors of today’s paper say the biological explanations yet to be found for this will mostly likely include genetic, epigenetic, immunological, microbiological, anatomical, or environmental causes. The origins of preeclampsia (dangerously high blood pressure in pregnancy) also remain a medical mystery.
Dr. Simpson noted that an individual woman’s increased risk of preterm birth conferred by nulliparity and male baby sex is not as high as the risk from prior preterm birth or preeclampsia. However, because many more pregnancies involve first babies or male sex, the impact is greater in the overall population. He said there is no known biological explanation for why male sex or nulliparity confers increased risk.
About 15 million babies worldwide are born preterm each year, and about one million of them die as a result. Preterm birth is the #1 killer of babies in the United States. Babies who survive an early birth may have lifelong health problems such as cerebral palsy, vision and hearing loss, and intellectual disabilities.
Cross-Country Individual Participant Analysis of 4.1 Million Singleton Births in 5 Countries with Very High Human Development Index Confirms Known Associations but Provides No Biologic Explanation for 2/3 of All Preterm Births, by David M. Ferrero and colleagues appeared today in PLOS ONE, a journal of the Public Library of Science. March of Dimes co-authors were Jennifer L. Howse, Christopher P. Howson and Joe Leigh Simpson.