A blood test that measures a familiar component of connective tissue may offer doctors an earlier warning when newborns with Down syndrome develop a potentially dangerous blood disorder, according to a study published in the Journal of Perinatology. Researchers report that serum hyaluronic acid could help identify infants at risk of severe disease from transient abnormal myelopoiesis, a condition unique to the biology of Down syndrome and capable of progressing rapidly in the first days of life.
Transient abnormal myelopoiesis, or TAM, occurs in a significant proportion of newborns with Down syndrome. The disorder is marked by the temporary expansion of abnormal myeloid cells—immature blood-forming cells related to the cells that normally produce granulocytes, monocytes and other components of the innate immune system. In many infants, TAM resolves spontaneously as the abnormal clone disappears. In others, however, the disease can cause life-threatening complications involving the liver, lungs, heart and circulation. The challenge for clinicians is determining early which infants will follow a mild course and which will deteriorate.
The biological basis of TAM is closely linked to changes in the blood-forming system of fetuses with trisomy 21. Many affected infants carry acquired mutations in the GATA1 gene, which regulates the development of megakaryocytes and other myeloid-lineage cells. The combination of an extra copy of chromosome 21 and a GATA1 mutation can produce a temporary but highly abnormal population of circulating blasts. Although the disorder is called “transient,” its short-term effects may be severe, and some survivors later develop myeloid leukemia associated with Down syndrome. This makes reliable early risk assessment essential, particularly when conventional blood counts do not fully reveal the danger developing in internal organs.
The new study by Eto, Inoue, Goto and colleagues focuses on hyaluronic acid, a large sugar molecule found throughout the extracellular matrix—the intricate network that surrounds and supports cells. Hyaluronic acid helps tissues retain water, maintain structure and regulate interactions between cells. It is especially abundant in connective tissues, blood vessels and organs undergoing repair or inflammation. In healthy physiology, hyaluronic acid is continuously produced and broken down. Much of it is removed from the bloodstream by specialized endothelial cells lining the liver’s sinusoidal vessels, making serum levels sensitive to changes in tissue turnover and hepatic clearance.
In the context of severe TAM, an increase in circulating hyaluronic acid may reflect several overlapping processes. Abnormal myeloid cells can trigger inflammatory signaling and damage the vascular and connective-tissue environment. The liver may become stressed by infiltration, inflammation or impaired circulation, reducing its ability to remove hyaluronic acid from the blood. At the same time, injury to tissues and blood vessels can stimulate the production and release of additional hyaluronic acid. The molecule is therefore not simply a marker of abnormal blood cells; it may act as a biochemical readout of systemic tissue injury and organ dysfunction.
That distinction could be clinically important. A complete blood count can identify leukocytosis, circulating blasts and abnormalities in platelet numbers, but the degree of blood-cell expansion does not always predict the extent of organ damage. Some infants with striking laboratory abnormalities may remain stable, while others with less dramatic initial findings can develop rapidly progressive complications. A serum marker that reflects the condition of the liver and vascular system could provide a different layer of information, potentially revealing biological deterioration before it becomes obvious through respiratory distress, abdominal enlargement, fluid accumulation or circulatory instability.
The researchers examined serum hyaluronic acid in newborns with Down syndrome and TAM, comparing its behavior with clinical severity. Their findings indicate that higher levels were associated with more serious disease and that the marker may provide an early signal of infants likely to develop severe complications. The significance of the result lies not in replacing established assessments, but in adding a measurable indicator of tissue stress to the information already obtained from blood counts, liver-function tests, imaging and physical examination. In a neonatal intensive-care setting, even a modest period of advance warning can influence monitoring, consultations and treatment decisions.
TAM management is complicated because many cases resolve without intensive therapy, while high-risk disease may require urgent intervention. Supportive care can include close observation of blood counts, management of fluid balance, treatment of respiratory or cardiac complications and surveillance for liver dysfunction. In selected infants with severe symptoms or organ involvement, low-dose cytarabine may be considered to reduce the abnormal myeloid-cell population. The decision to treat must balance the risks of chemotherapy in a newborn against the possibility of rapid deterioration. A reliable early biomarker could help clinicians identify which infants need the most intensive surveillance and which may be safely managed with careful observation.
The study also highlights why disease biomarkers should be interpreted as part of a biological network rather than as isolated numbers. Hyaluronic acid can rise in several conditions, including liver disease, inflammation, fibrosis and vascular injury. It is not specific to TAM, and an elevated result alone cannot establish that a newborn will develop severe complications. Future research will need to determine how levels change over time, how they compare with other markers of organ injury, and whether combining hyaluronic acid with blast counts, platelet measurements, liver enzymes and genetic information improves prediction. Large, multicenter studies will also be needed to establish age-specific reference ranges and clinically useful thresholds for newborns.
For families and clinicians, the central message is that a simple blood measurement may help clarify one of the most difficult early decisions in Down syndrome–associated TAM: whether a seemingly temporary blood disorder is likely to remain mild or become a multisystem emergency. The findings do not turn hyaluronic acid into a standalone diagnostic test, but they strengthen the case for using the extracellular matrix and vascular biology as windows into neonatal disease. If validated in broader populations, serum hyaluronic acid could become part of an early-warning strategy designed to detect organ stress before irreversible injury develops, giving vulnerable infants a better chance of receiving precisely timed care.
Subject of Research: Serum hyaluronic acid as an early indicator of disease severity in transient abnormal myelopoiesis associated with Down syndrome
Article Title: Serum hyaluronic acid as an early indicator of disease severity in transient abnormal myelopoiesis associated with Down syndrome
Article References: Eto, E., Inoue, M., Goto, H. et al. “Serum hyaluronic acid as an early indicator of disease severity in transient abnormal myelopoiesis associated with Down syndrome.” Journal of Perinatology (2026). https://doi.org/10.1038/s41372-026-02877-6
Image Credits: AI Generated
DOI: 10.1038/s41372-026-02877-6
Keywords: Down syndrome, transient abnormal myelopoiesis, serum hyaluronic acid, neonatal medicine, myeloid disorders, biomarkers, disease severity, liver injury, hematology
Tags: connective tissue biomarkersDown syndromeearly diagnosis of TAMearly intervention in TAMGATA1 gene mutationshyaluronic acidinfant liver and lung complicationsnewborn blood disorder predictionprenatal blood testsrisk assessment in newbornsseverity markers in Down syndrometransient abnormal myelopoiesis
