The article by Dr. Isabella Panfoli and colleagues is
published in Current Pediatric Reviews, Volume 18, Issue 2, 2022The article by
Dr. Isabella Panfoli and colleagues is published in Current Pediatric Reviews,
Volume 18, Issue 2, 2022
NEWS RELEASE 13-MAY-2022
Prematurity affects about 10% of
pregnancies worldwide each year. In about 20% of very low birth weight (VLBW)
premature infants, punctate white matter lesions (PWML) can be diagnosed at MRI
at term equivalent age. PWML is accompanied by mild impairment in the
development of white matter tracts, that can affect both long-term motor and
cognitive performance. The principal factors involved in the pathophysiology of
white matter lesions are intrinsic vulnerability, inflammation, and oxidative
stress.
Aiming at early identification of
preterm infants at risk for developing clinical complications, this
retrospective study correlated blood adenosine levels to the development of
complications or prematurity, especially those related to brain injury, in 56
VLBW infants admitted at the Neonatal Intensive Care Unit of Gaslini Pediatric
Hospital. The blood adenosine content in the cohort, assayed by Mass
Spectrometry on dried blood spots collected for newborn screening program for
congenital disease, showed that Ado levels at 15 days of life positively
correlated to the white matter lesions at MRI performed at term equivalent age
(OR [95%CI] of 50.0 [3.6-688.3], p-value < 0.001), with a cut-off value of
1.58 μM. Adenosine was higher (2.50 μM vs. 0.96 μM) in those infants who
developed brain white matter lesions. Neurodevelopmental outcome of the same
infants, measured with Griffiths Mental Development Scales (GMDS) at 12 ± 2
months corrected age, was slight negatively correlated with adenosine blood
levels at 15 days of life. This result appears confirmative of our previous
finding of elevated Ado blood levels in VLBW, negatively correlated with birth
weight.
It has been supposed that the
brain sensory overstimulation caused by premature birth, together with multi
drug exposure (affecting adenosine clearance) further compounded by the ambient
higher oxygen levels may promote adenosine persistence in the circulation. In
some VLBW predisposed premature infants a higher adenosine release from
unmyelinated axons, typical of an immature brain, may occur. Immature adenosine
clearance represents a further possible source of elevated blood adenosine. In
turn, adenosine may induce the differentiation of Oligodendrocyte Progenitor
Cells (OPC) to mature oligodendrocytes. This would result in a critical reduction
in the absolute number of myelinizing oligodendrocytes at a later stage,
potentially related to the impaired white matter maturation. These disturbances
of neuronal maturation appear consistent with the typical “primary cerebral
dysmaturation disorder” of prematurity. It has been supposed that such
white matter vulnerability may be further accentuated from the interruption of
fetal supply of ideal nutrients, in particular key lipids. Different
complications of prematurity were also found consistent with Ado levels
changes, but a major finding relates to PVWM. Notably, white matter lesions
show a positive correlation also to retinopathy of prematurity (ROP), a
condition in which inflammation and oxidative stress play a pivotal pathogenic
role.
It remains to be investigated why
some babies at 15 days have a significantly higher levels of adenosine compared
to other not developing PVWM. Nonetheless, the present work suggested the
reliability, confirmed by multivariate analysis, of blood adenosine levels at day
15 post birth as the major predictor of brain injury occurrence. A potential
role of blood adenosine as a biomarker of complications of prematurity,
especially brain injury, and of poor long-term outcome in VLBW infants, may
pose the basis for the stratification of strategic early postnatal
neuroprotective interventions.
For more information, please
visit: https://www.eurekaselect.com/article/120485
Current Pediatric Reviews
10.2174/1573396318666220127155943
Adenosine Blood Level: A Biomarker of White Matter
Damage in Very Low Birth Weight Infants
11-Mar-2022
