New study finds distinct molecular signatures in newborns with SCT
Findings may help inform future screening and monitoring of health risks
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Newborns with sickle cell trait (SCT), meaning they carry a mutation in one copy of the HBB gene but do not have sickle cell disease (SCD), show abnormalities in certain biological markers that can be detected within the first week after birth, a new study reports.
Differences were found in markers related to liver, kidney, and blood-related biology — systems that are also affected in people with overt SCD. Researchers say studying these markers may help scientists better understand potential long-term health risks associated with SCT.
“These results open new opportunities for molecular studies of SCT to inform novel approaches to diagnose, prognose, prevent, and treat its clinical manifestations,” the researchers wrote.
The study, “Newborns with Sickle Cell Trait have distinct peripheral blood molecular signatures across the first week of life,” was published in Blood RCI by an international team of researchers.
How sickle cell trait differs from sickle cell disease
Everyone inherits two copies of the HBB gene, one from each biological parent. This gene provides instructions for making hemoglobin, the protein in red blood cells that carries oxygen throughout the body.
SCD occurs when both copies of the HBB gene carry a disease-causing mutation. This leads to the production of an abnormal form of hemoglobin that causes red blood cells to become rigid and sickle-shaped, which is how the disease gets its name.
People with SCT have one mutated copy of the gene and one healthy copy. “Although SCT is typically considered a low-risk carrier state, it is linked to multi-organ complications,” the researchers wrote.
These complications can include kidney disease, certain cancers, and liver cirrhosis (irreversible scarring of the liver). Acute chest syndrome — a serious complication of SCD marked by shortness of breath, chest pain, and wheezing that can progress to lung failure — has also been reported in people with SCT. Symptoms may be triggered by stressors such as dehydration, low oxygen levels, or extreme physical exertion.
However, little is known about how SCT may affect a baby’s biology in the days immediately after birth. “Further research to explore molecular alterations associated with SCT in early life can provide crucial biological insights into the mechanisms that precede or modulate SCT-associated health and immune outcomes,” the researchers wrote.
Researchers analyze newborn data from vaccine study
To learn more, the international team analyzed data from a clinical trial (NCT03246230) that was conducted between 2017 and 2022.
The trial was part of a neonatal systems vaccinology study examining immune responses to vaccines given at birth, including hepatitis B. Part of the research was conducted at a center in The Gambia, a West African country where sickle cell is more common than in many other parts of the world.
Using genetic data from 680 infants in the trial, the researchers identified 118 babies (about 17%) with SCT, as well as four newborns with two mutated HBB copies, meaning they would develop SCD. A separate group of 45 newborns from The Gambia, including seven with SCT, was also analyzed to validate the findings.
The researchers then analyzed molecular and gene activity data collected at birth and during the first week of life to assess biological pathways that might be linked to SCT. These pathways fell into several categories of interest, including those related to blood, red blood cells, kidney function, liver function, oxygen transport, and sickle cell disease.
The researchers found that more than 2,000 biological pathways were significantly enriched in newborns with SCT compared with newborns without the trait during the first week of life. Of these, 149 pathways were associated with the categories of interest.
Liver, kidney, and blood pathways most affected
“The highest number of pathways, 25 out of 149, belonged to the liver category, and 8 out of the 25 were enriched at [7 days of life],” the researchers wrote. Other enriched pathways were linked to kidney and blood-related processes.
“Our findings suggest that despite the lack of overt clinical manifestations, molecular profiles of [newborns with SCT] demonstrate similarities to SCD and associations with features and pathways involved in [blood], [kidney], and [liver] disorders,” the scientists wrote.
It remains unclear whether these molecular differences are linked to health outcomes later in life. However, the fact that they are detectable at birth and during the first week of life provides a starting point for identifying markers that could help predict long-term health outcomes, the researchers said.
“Further validation of these findings in larger [studies] may enable screening and monitoring in early life to predict and prevent future adverse clinical outcomes,” the team concluded.
