Nearly one in every eight U.S. babies is born too early – three weeks or more before the estimated due date. Such premature births are the leading cause of newborn deaths and put babies at risk for chronic lung disease and other serious health problems as well as lifelong learning and physical disabilities. While some causes of prematurity are known, more than half of women who deliver early have no known risks.
In an innovative approach, Justin Fay, Ph.D., assistant professor of genetics and Louis Muglia, M.D., professor of pediatrics, are searching human DNA for clues to help explain why some women deliver early. After all, they note, preterm births are rare, except in humans. By sifting through human DNA and comparing it to the DNA of other mammals, the researchers hope to identify genetic markers that help doctors predict which women are likely to give birth early. Ultimately, their research could lead to the novel ways to prevent preterm births and increase women’s chances of having healthy babies.
“We want to understand how the body determines the time of birth,” Fay said. “All humans have a built-in clock, but how does a woman’s body count to 40 weeks? If we could answer to that question, we could probably make a difference in lowering the rate of preterm births.”
Premature births have risen 30 percent in the past 20 years – accounting for more than 1,300 births per day. The rate has intensified due to the growing number of women who postpone pregnancy until they are well into their 30’s or beyond, or who become pregnant with more than one fetus through assisted reproduction. Other risk factors include being African American, overweight, a smoker, or having diabetes or high blood pressure. Drs. Fay and Muglia suspect that underlying genetic changes that have occurred over many centuries may also help explain why some women give birth early and others do not.
As humans evolved from primates, brain size increased dramatically and the pelvis was reshaped to facilitate walking upright. While these changes were critical for human evolution, they also made it more difficult for babies to squeeze through a narrow birth canal. In an evolutionary sense, preterm birth ensures that babies will be born before their heads are too large, but there’s a limit to how early babies can be born without inherent health risks.
“Human brain and head size are much larger than those of most other higher primates for a given body size,” Muglia said. “To accommodate this size difference, we suspect there was selective pressure put on genes to push the birth process to the earliest possible time that was compatible with good fetal survival.”
To zero in on genes potentially linked to premature birth, the researchers are scanning the genomes of humans, non-human primates such as chimpanzees and rhesus monkeys, dogs and mice to identify human genes that have accumulated significant changes. Such variations in the DNA code are of interest because they would indicate that a gene has acquired a new function as humans evolved from primates.
This process is likely to reveal about 1,000 to 2,000 genes with alterations. To determine whether any of these genes are linked to preterm birth, the investigators will identify precise variations within each gene that are unique to humans. Then, they will look to see whether women who have given birth prematurely or their preterm infants have any of the variations, which would indicate a link. The researchers will also determine whether any of the variations are common in women who have delivered babies on time or in their full-term infants, which would indicate a protective effect against premature birth.
By looking both at genes in both mothers and their babies, the researchers may uncover a combination of variations that is powerful enough to initiate preterm birth. Through their studies, the investigators hope to define critical molecular pathways involved in preterm birth, the genes involved in those pathways and their influence on risk factors such as nutrition, smoking and infection, which also contribute to preterm birth.