Urinary β-2-microglobulin as an alternative marker for fetal inflammatory response and development of BPD in preterm infants

There is mounting evidence suggesting that inflammation plays a key role in the etiology of preterm birth and its consequences on neonatal outcomes. Elevated inflammatory mediators such as interleukin-6, interleukin-8 and tumor necrosis factor- in the umbilical cord plasma or amniotic fluid have already been reported to be sensitive indicators of chorioamnionitis (CAM) and independent risk factors for the development of bronchopulmonary dysplasia (BPD). However, a direct assay of proinflammatory cytokines, which is both expensive and time consuming, is not suitable for routine laboratory testing in neonatal intensive care practice. ?-2-Microglobulin (B2M) could represent a surrogate marker of inflammatory response, as it is expressed on the surface of most nucleated cells as a subunit of the class I major histocompatibility complex (MHC) and is upregulated by systemic immuneactivation. Multiple studies have shown that elevated B2M levels in the serum and urine are nonspecific but sensitive indicators of various conditions, which include infectious, lymphoproliferative, autoimmune and chronic inflammatory disorders.
Moreover, the potential role of B2M in perinatal medicine is particularly appealing because B2M does not cross the placenta.
On this basis, a Japanese group has examined urinary levels of B2M at birth in 96 premature infants (24-28 weeks), and assessed whether B2M levels can be used as an indicative marker of fetal inflammatory response and subsequent adverse pulmonary outcomes.
In total, BPD was diagnosed in 34% (33/96) of the infants. The urinary B2M levels were greater at any gestational age in neonates with BPD than in those without BPD. However, there was no significant correlation between urinary B2M level and gestational age, suggesting that elevation of B2M at birth was not simply caused by prematurity but mainly by the influence of intrauterine inflammatory response. No correlation was observed between the levels of urinary B2M and BPD severity. After adjusting for variables that are significantly associated with occurrence of BPD, elevated urinary B2M at birth still remained significantly associated with higher risk of BPD (OR 10.4, 95% CI 3.7-32.4; p<0.0001). Urinary B2M levels at birth were significantly greater in neonates from mothers with CAM, while no association was found between neonates who received antenatal glucocorticoid treatment and those who did not.
In conclusion, these findings suggest that elevated urinary B2M levels at birth may be a timely indicator of fetal inflammatory response and subsequent BPD risk. A better definition of the physiological mechanisms that are responsible for higher urine levels of B2M at birth and that lead to BPD, and the development of strategies that safely and effectively modify this pathophysiology, will likely improve outcomes for preterm infants.

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