A National Institutes of Health (NIH)-funded study led by University of Kansas Medical Center researchers could lead to a reduction in early preterm births -births before 34 weeks of gestation - which are a major burden on the health care system and a concern for mothers worldwide.
Susan Carlson, Ph.D., AJ Rice Professor of Nutrition in the Department of Dietetics and Nutrition, and Byron Gajewski, Ph.D., professor of biostatistics, are co-principal investigators along with Christina Valentine, M.D., a visiting professor at the University of Cincinnati College of Medicine, on a five-year study exploring the role docosahexaenoic acid (DHA) plays in the prevention of early preterm births. The $3 million study will examine approximately 1,200 women to determine whether giving them daily doses of a DHA supplement, an omega-3 fatty acid available over the counter, during the last half of their pregnancies can aid in preventing early premature births.
The study, titled "Assessment of DHA on Reducing Early-Preterm Birth (ADORE)," is funded through the NIH's Eunice Kennedy Shriver National Institute of Child Health and Human Development.
The multisite Phase III clinical trial will take place simultaneously at the KU Medical Center, the University of Cincinnati and The Ohio State University.
Science and serendipity
Carlson said an interesting blending of circumstances led to the study becoming a reality, starting with some surprising results that were found in a previous DHA study she and John Colombo, Ph.D., director of the Life Span Institute, had conducted. Carlson and her colleagues at KU Medical Center were investigating the role DHA plays in cognitive development in children, when they noticed an unexpected pattern in their findings. To their surprise, the researchers found that mothers who received a DHA supplement in the second half of their pregnancies were having a fivefold reduction in the number of early preterm births.
"It wasn't an idea we would have proposed before we did the last study," said Carlson. "We always teach our students that sometimes the things that don't work out the way we predicted are the most interesting problems to study."
One of the goals of the study is to determine whether there is an effective dosage to successfully decrease early preterm birth. In the clinical trial, slated to begin with subject recruitment in May, pregnant women will receive either 1,000 mg or 200 mg of DHA daily during the second half of their pregnancy. Two hundred milligrams is the daily DHA amount recommended for pregnant women by the World Health Organization (WHO) and the dose included in many prenatal vitamins. The average healthy woman in the United States takes in roughly 23 mg daily of DHA via her diet.
A second bit of luck
The next piece of unexpected luck leading up to the study came when Carlson went to the University of Cincinnati to give a lecture and Valentine, a neonatologist and nutritionist who has spent the last 27 years studying the effects dietary interventions have on pregnant women and births, was there with the prime intention of meeting her hero in DHA research – Susan Carlson. Valentine had been at Ohio State prior to Cincinnati, so she was instrumental in bringing the two Ohio universities into the fold.
"I have followed Dr. Carlson's work in maternal nutrition and focus on DHA. She is a rock star." Valentine said. "When I was invited to hear her speak, I set the stage to engage her and to discover if she would be interested in mentoring and collaborating, and so the momentum began."
Carlson said babies born before the last trimester often don't receive the proper nutrients, which are important for the development of their immune systems, from their mothers. The result is that the early preterm babies have a litany of health care problems and their extended hospital time they require exposes their immature immune systems to all sorts of infections. The cost of caring for preterm babies is estimated at $26 billion in the United States.
"There are many conditions that early preterm babies are prone to," Carlson said. "One of them is retinopathy of prematurity, which causes the retina to detach from the back of the eye leading to blindness. Another is necrotizing enterocolitis, a condition affecting the intestine of premature infants. And there's interventricular hemorrhage, which can cause bleeding into the brain's ventricular system."
How the study will work
Each of the research sites will work with between 350 and 400 women during the next five years. Researchers will be using a novel adaptive study design for more efficient trials. Basically, as the results come in and trends develop, more new subjects will be placed in the successful trial group.
While Carlson and her team are studying the effect of DHA on birth outcomes, other researchers at KU Medical Center led by Carl Wiener, M.D., MBA, FACOG, the K.E. Krantz Professor and Chair of the Department of Obstetrics and Gynecology, will also be examining the blood of test patients to explore whether there are any possible links between specific biomarkers and the mechanisms responsible for spontaneous premature births. If the DHA research is a success, it would mean finding a treatment before knowing what the root cause of the illness is.
"What's really exciting is that addressing a nutritional deficiency might be the way to have an impact on these spontaneous preterm births," Carlson said. "That would be huge."