An Interview with GAPPS Executive Director Craig E. Rubens
What need does GAPPS address?
GAPPS was formed to deal with a huge health service and public health problem: the fact that prematurity, the birth of preterm babies, is on the rise. In this country alone, prematurity has increased 30% since 1981, despite all our modern technology. And the ultimate worst outcomes are a stillborn infant and/or the death of a mother.
If you look at the major causes of maternal and child mortality around the world, a lot of them occur during pregnancy and the immediate postpartum period. And yet we don’t know why preterm babies are born preterm in the first place, and we don’t understand why a lot of babies are stillborn.
We need both a national and international research agenda. Right now in most low- and middle-income countries, preterm babies aren’t even dealt with.
Why has this been an under-researched area?
There has been research to prevent preterm birth, but the approach has been to try to use different derivations of other interventions—the same drugs but used in a different way. For example, infections are thought to play a big role in initiating preterm birth by starting inflammation around the placenta. And once that happens, it triggers the uterus to contract, membranes to rupture, and then the baby is delivered. We don’t know why those infections occur but there has been a lot of work over the past 20 years to try to interrupt that process.
What’s needed is to really understand the biology, the genetics, pathophysiology, environmental factors, and individual sociologic factors that appear to play a role in causing preterm birth. Probably one of the major problems with past approaches has been in trying to find a single cause for preterm birth. We now understand that it is multi-factorial—that there are multiple reasons why a woman may go into preterm birth.
How women’s particular genetic make-up may influence how they might interact with environmental exposures could play a role, as could the way women respond to the presence of certain types of micro-organisms in the reproductive tract. During the past five years, the understanding that there isn’t just a single factor that is responsible for preterm birth has, I think, revolutionized our approach to the problem.
So GAPPS came together because we saw that we needed new research to try to understand the basic biology as it correlates to the epidemiologic factors and then to use that research discovery to find ways to intervene and prevent preterm birth. There are probably going to be common as well as unique factors depending on what kind of country and environment people live in.
What are some of the unique factors?
Rates in low- and middle-income countries may reflect causes such as the availability of drugs and the availability of high technology. Perhaps the genetic make-up of the population is different and may respond differently to different types of environmental exposures. Stress may be a major factor. Nutrition could play a role; we don’t know exactly how, but it could be as simple as an aberrant immune system or the result of the stress of malnutrition.
In high-income countries, factors could be as simple as inconsistent prenatal care being delivered. For example, the quality of care at some hospitals may not be as even as it is in others or delivered as consistently. But some of those data are not easy to get a handle on.
What kind of research is most needed?
We’re really missing a lot of important information in understanding just the basic concepts of why a woman goes 40 weeks before she delivers a baby—understanding gestational biology. What’s the basis for the gestational clock? And part of that may be that a lot of the emphasis on obstetrics has been at the level of delivering care rather than really emphasizing the importance of understanding the reproductive process. Doing a better job of understanding it, we can then intervene when it doesn’t behave properly.
I think there is gradually more and more interest as the medical and health communities recognize this is a major public health problem. The [July 2007] Institute of Medicine report shows that it is one of the top public health problems in our own country. In our own backyard, we’re spending more than $26 billion a year to take care of mothers and their infants and the long-term care consequences of preterm birth—right here in a high-tech, high-income country.
So there’s a lot of new emphasis to understand why this is happening. The problem is encouraging researchers, who can actually do the work, to focus on this problem.
How did you assemble the GAPPS team?
We wanted to take advantage of basic science discovery, what we know about the epidemiology of the problems of preterm birth and stillbirth, and to meld those two together to come up with new interventional strategies both to prevent preterm births and to improve outcomes when they occur. And we didn’t want to do this with just our own national agenda but to improve what’s going on in low- and middle-income countries.
One of the biggest problems we’re learning about is that care at the time of delivery and immediate post-birth period is really lacking in low- and middle-income countries and that this situation has a strong impact on the survival of preterm infants as well as the mothers who deliver.
So, first, we looked for researchers with a lot of experience in trying to understand the magnitude of the problem. These folks have significant expertise in epidemiology, being able to develop systematic studies that analyze the breadth and depth of a particular problem. Once you understand the magnitude and scope—whether it’s within a specific country, district, or world region—you can tailor how you’re going to approach the problem.
Many of the folks working with us have a very strong understanding of the burden of disease around the world. Others are more basic science-oriented and work on understanding the genetic bases for factors that influence pregnancy and reproductive outcomes, the biological pathways involved in normal pregnancy, as well as those that lead to abnormal pregnancy outcomes.
In addition to the geneticists, biologists and epidemiologists, we are bringing in policy makers, including individuals who are working with grassroots organizations to advocate for more attention to the problem. We want to influence policy at the global level, but we need to ensure that policy makers put money in the most effective areas.
One major area now is research emphasis. We have a dearth of obstetricians doing research on poor pregnancy outcomes and reproductive health. The focus has been on health services and not prevention—this is another finding of the IOM report.
How will you and your partners work together?
The first thing we’re doing, and this is in partnership with the [Bill & Melinda] Gates Foundation, is to look at what we know and don’t know and synthesize that into a major report that we’re providing at our international conference next year. That will serve as the platform and foundation for work groups of individuals with specific expertise, including funding organizations, who will determine what needs to be done next, both in the short- and long-term.
We’ll identify clear milestones and clear deliverables, including how work is going to be funded and the best people to do the job. This is going to require a lot of individuals who represent different disciplines, including ethicists to help us work with low- and middle-income countries.
What types of barriers are you encountering?
Some are ethical and cultural. For example, consider the ethics of not providing care to an infant who is less than 28 weeks gestation. In some countries, delivery at 28 weeks or less is not considered a viable birth. We think that interventions should be aggressively pursued, but some of these infants are considered born dead, and they are left to die.
We’re finding that there are lots of issues around trying to date an infant in terms of how long a mother has been pregnant. A lot of this is done by verbal reporting, and many women can’t remember when their last menstrual period was—it’s just that they don’t focus on that in their culture. In many countries, infants aren’t weighed at birth and this certainly affects judgments about their viability.
Among other types of barriers, funding is a big issue. This isn’t necessarily a priority of some of the big funding organizations like [the National Institutes of Health]. You have to convince them that they need to be working on this at a higher level. A major obstacle is putting more emphasis on research that is going to lead to prevention efforts.
Hasn’t funding been shifting more to prevention?
Not that I’ve seen. We’ve done a great job of learning how to deal with a premature infant. Outcomes for premature infants in this country, especially at greater than 28 weeks, are wonderful compared to a lot of countries. But we’re not doing as well at 24-28 weeks, and we still don’t understand stillbirths.
That’s embarrassing given our technology—not to understand why some babies are born dead. We need to shift emphasis now to using our technological savvy to understanding the basic pathways that lead to normal births and well as abnormal ones. Then we can develop prevention strategies.
In the United States, we need to change our thinking; it’s not OK to have a 10% to 12% rate of our population delivering preterm infants. Although the greatest burden of disease in terms of actual numbers is higher in poorer countries, the rates of disease in the United States are comparable to what you see in low-income countries.
There may be some epidemiologic reasons for that. We do take care of infants that other countries don’t consider to be “alive,‿ and that influences our rates. But the rates are still very high for a country like ours that is technologically so advanced. Again, we need a better understanding of what’s happening.
Looking ahead five years, what do you hope GAPPS will have achieved?
I hope that in five years we have the resources to achieve a better understanding of the disease process, a deeper understanding of why preterm births and stillbirths occur, to the point that we’re developing interventions that can be deliverable to all types of settings.
Initially, these may be simple fixes to improve care at the time of delivery and immediately after. And then we can move from there to the more technologically advanced level, based on new data and research findings. These will take us to the next level of prevention.
—Alice Porter