“Omics” study takes a comprehensive look at premature birth

Seven layers of omics study
Seven layers of “omics” included in the PREM-MAP study

Every year, one in 10 new babies in the United States is born preterm, or before 37 weeks of gestation. With the last few weeks of pregnancy crucial to proper development of the lungs and brain, prematurely born infants can suffer lifelong problems.

Now scientists at Boston Children’s Hospital and Beth Israel Deaconess Medical Center have launched a comprehensive study to understand the reasons and risk factors for premature births. Earlier this year, Olaf Bodamer, MD, PhD was awarded a grant for this work from uBiome, a microbial genomics company.

Seven layers of pregnancy biology

The Precision Medicine & Prematurity project (PREM-MAP) is initially studying normal pregnancies, seeking markers that predict how well a pregnancy will do. Bodamer’s team is collecting blood and urine samples (blood, urine and so on) from the mothers once every trimester (during their routine checkups), around the time of delivery and six weeks post-delivery. The infants are sampled at birth and at six weeks of age.

The samples then undergo a comprehensive “omics” analysis.

“We look at seven layers,” says Bodamer, associate chief of genetics and genomics at Boston Children’s.

Namely:

  • The genome: The entire set of genetic material (DNA) within a cell.
  • The transcriptome: The complete assembly of RNA molecules made from DNA, containing the instructions to make proteins.
  • The proteome: The various proteins synthesized from RNA within a cell.
  • The methylome: The collection of modifications to DNA or RNA in a cell that alter transcription, through the addition of methyl groups.
  • The metabolome: The set of all small-molecule compounds or products of metabolism within a sample – such as blood and urine – at a given time.
  • The microbiome: The microorganisms that have colonized a particular environment. (In this study, these will initially be identified in stool samples, with the intention to expand to oral and skin microbiomes.)
  • The environmentalome: Environmental factors that could affect mother or infant, such as toxins in the air or water. (Bodamer’s group is using the mothers’ zip codes to determine the chemicals prevalent in their area.)

“At the end of the study, we should have information about how certain proteins and metabolites, for example, change over time during pregnancy,” said Bodamer.

The researchers can also examine how results from all these layers “play together.” They might learn how genetics decides which proteins are produced, and how this relates to the levels of different metabolites —all under the influence of the microbiome and environmental agents.

As of now, Bodamer’s group has recruited 100 Caucasian mother-infant pairs through ob/gyns at Beth Israel Deaconess Medical Center, with an ultimate goal of 250 to 500 pairs. They hope to publish the first results of their observations by the end of the year.

Although the study currently ends six weeks after delivery, Bodamer hopes to gain approval to follow the mothers and infants to observe long-term outcomes.

“Ideally, we’d like to follow them Framingham-style,” he says, referring to the famous Framingham Heart Study.

Risk-benefit analysis

Bodamer also hopes to procure funding for a second study to recruit mothers who deliver prematurely, but do not have any known risk factors such as smoking, obesity or others. By comparing the two cohorts, his group aspires to discover new metabolites and other markers associated with preterm birth.

“I could envisage a protein marker that gives us a clue about the risk of that pregnancy going to term or going to preterm,” Bodamer says.

In the long term, Bodamer thinks their findings could change the approach to maternal-fetal care. By identifying molecules associated with low or high risk, mothers could be grouped early on in their pregnancies and provided with appropriate care.

“Ultimately we need to translate our observations into something clinically meaningful,” he says.