Years-old dried blood spots collected from newborns hold vital clues in the discovery of early environmental exposure links to disease, new studies show.
Lauren Petrick, PhD, Assistant Professor of Environmental Medicine and Public Health at the Icahn School of Medicine at Mount Sinai has shed light on the etiology of childhood leukemia by using a novel ‘time travel’ method that analyzes metabolites found in dried blood spots. An analytical chemist and exposure biologist, Dr. Petrick is a pioneer in the new field of untargeted metabolomics, which uses sophisticated technology to analyze molecules in blood and tissues and then map those metabolites to exposures from the external environment and interactions with the internal exposome, including factors such as stress.
Dried blood spots are unique and important biospecimens to understanding causes of pediatric disease. You can go back in time to the neonatal period to do direct measurements. We’ve shown that dried blood spot metabolomics is a tool for discovering biology linking early life exposures to cancer prior to the onset of symptoms.Dr. Lauren Petrick
“Dried blood spots are unique and important biospecimens to understanding causes of pediatric disease,” says Dr. Petrick, whose groundbreaking study was published last year in Cancer Letters. “You can go back in time to the neonatal period to do direct measurements. We’ve shown that dried blood spot metabolomics is a tool for discovering biology linking early life exposures to cancer prior to the onset of symptoms.”
Dr. Petrick analyzed dried blood spots sampled from heel pricks taken as part of routine screenings for congenital disorders from more than 650 babies born in California between 1985 and 2005. One group of dried blood specimens belonged to children who were later diagnosed with leukemia. According to the study’s ‘nested case control’ design, the control group included dried blood spots from healthy children who were matched individually with the first group according to sex, ethnicity and date of birth.
Untargeted high-resolution mass spectrometry results revealed a positive correlation between the presence of metabolites linked to linoleic acid, an essential nutrient found in higher levels in baby formula compared with early breast milk, and children who became diagnosed after age 6 with Acute Lymphocytic Leukemia (ALL). ALL is the most common form of the disease.
“They’ve shown in epidemiological studies that breastfeeding may be protective for childhood leukemia,” said Dr. Petrick, Head of Untargeted Metabolomics for the Institute for Exposomic Research’s laboratories. “We saw evidence that supports this. Our next goal is to understand why — what is it about breast milk that is protective? The answers can help us potentially formulate infant formulas to be better.”
The incidence of childhood leukemia is rising, with an average of 0.7 percent more cases each year over the last ten years.Associated migration and generational shifts suggest that environmental factors are the cause, says Dr. Petrick.
Dr. Petrick also found a positive correlation between maternal pre-pregnancy body mass index and the presence of metabolites linked to linoleic acid in their babies’ dried blood spots, which reinforces the likelihood that early nutrition plays a role in ALL risk.
California, other U.S. states and countries including Sweden have saved dried blood spots sampled within 48 hours of birth from millions of newborns since the 1970s or 80s, offering a vast source of biospecimens and the potential for providing snapshots of early life environmental exposures for every known disease and disorder, according to Dr. Petrick.
“If you think about it, there’s a dried blood spot for every disease or disorder that has been diagnosed in the past 30 years,” she says. “The idea is that we can go back in time using a ‘nested case control’ study to investigate cancer, autism, and other diseases and disorders. The dried blood spots allow us to go back in time to collect actual biological samples before the onset of clinical symptoms and diagnosis.”
Dried blood spots hold special promise in helping find causes of rare pediatric disorders because researchers cannot collect blood samples from large numbers of children, as is possible with adults.
Compared with fresh plasma and serum samples, dried blood specimens contain 80 percent of the same internal-body metabolites such as hormones and steroids, phospholipids and fatty acids.
“I developed this metabolomics assay to specifically investigate childhood leukemia,” says Dr. Petrick, whose research partners include scientists from the University of California at Berkeley and University of Southern California. “Now I can use this assay for other diseases and disorders.”
As part of a validation study with her collaborators, Dr. Petrick plans to layer in untargeted metabolomics of maternal blood collected during pregnancies of children that developed leukemia. She expects to combine results of the replication study with methylation data, which spotlight mechanisms that ‘turn’ genes on or off by addition of methyl groups to DNA chains, as well as ‘adductomics’ data, which analyze reactive small blood proteins known as protein adducts that are too transient to be detected using untargeted methods.
“We’re trying a ‘multi -omics’ analysis of childhood leukemia to get the broadest view possible of the exposome,” says Dr. Petrick. “I’m going to measure as many things as I can.”