Brain chemical ratios may forecast developmental delays in preterm infants

The combination of choline (Cho)/creatine (Cr) and N-acetylaspartate (NAA)/Cho ratios measured in the posterior periventricular white matter at term-equivalent age is predictive of motor outcome at one year in infants born at less than 32 weeks gestation, according to a study published online Dec. 17 in Radiology.

Preterm infants are susceptible to white matter injury, which is the most common cause of chronic neurologic disability in children with cerebral palsy. Advancements in neonatal intensive care and neuroimaging have revealed that while incidences of periventricular leukomalacia with large necrotic lesions have decreased, milder diffuse nondestructive white matter lesions have taken reign in preterm infants.

“The area most vulnerable to injury is the posterior periventricular white matter; this spatial vulnerability relates to the relative density of susceptible developing ogliodendrocytes in this region,” wrote the study’s lead author, Giles S. Kendall, MRCPH, PhD, of the University College London, and colleagues.

Kendall and colleagues designed their study to determine if diffuse white matter injury of prematurity is associated with an increased Cho/Cr ratio and a reduced NAA/Cho ratio, whether these measures can be used as biomarkers of outcome, and if changes in peak area metabolite ratios at MR spectroscopy (MRS) are associated with changes in T2 and fractional anisotropy (FA) at MRI.

The study included 43 infants who were born before 32 weeks gestation and were admitted to the neonatal intensive care unit at the University College London between 2007 and 2010. The authors performed MRI and MRS on the infants at their approximate expected due dates. After a year, 40 of the 43 infants were evaluated using the Bayley Scales of Infant and Toddler Development. These scales evaluate fine motor, gross motor, and communication abilities. Of the infants assessed, 15 had abnormal composite motor skills and four demonstrated cognitive impairment.

Upon performing statistical analysis of the MRS results and the Bayley Scales scores, the researchers discovered that an increased chemical ratio of Cho/Cr and a decreased ratio of NAA/Cho at birth were significantly correlated with developmental delays a year later. Low NAA/Cho and rising Cho/Cr ratios seen during MRS at the expected due date predicted with 70 percent certainty which babies would be at a high risk for motor development problems at one year.

“Such MR spectroscopy biomarkers of functional outcome may facilitate the targeting of late neonatal therapeutic and interventional strategies and may have a role as outcome markers for future neuroprotection trials in the early neonatal period,” concluded the authors.

Recent research presented at the annual meeting of the Radiological Society of North America in Chicago found that MRS reveals a false start of white matter maturation in preterm infants, potentially leading to behavioral problems and other issues later in life. To learn more, click here.