Prognostic value of neonatal brain imaging for very low birthweight preterm infants

Very low birthweight (VLBW) preterm infants are at high risk of developing neurological disabilities including cerebral palsy, neurosensory impairment, and language and cognitive deficit. The type and severity of these neurodevelopmental deficits depend on the region and extent of perinatal and/or neonatal brain injury. Brain injuries in preterm infants include parenchymal infarction, germinal matrix and intraventricular hemorrhage, and white matter injury. The injury may be a focal necrosis/ cyst (5%); however, it is commonly a diffuse periventricular white matter injury that results in white matter loss and consequent ventricular enlargement. The diffuse white matter injury may particularly affect vulnerable oligodendrocytes. Neonatal brain imaging, using serial cranial ultrasound and magnetic resonance imaging (MRI), is an early predictor of VLBW preterm infants at risk of neurodevelopmental impairment. Although a normal scan is reassuring, the predictive value of abnormal images is variable. This variability may be due to any of a number of factors: the low intensity of ultrasound or MRI scanner used, motion artifacts, the level of experience of the person performing and/or reading VLBW preterm infant brain images, type of the injury, and individual differences in the level of brain plasticity. The paper by de Bru€ıne et al. is interesting for several reasons: (1) They used higher intensity neonatal MRI, 3T instead of commonly used 1.5T; (2) Diffusion tensor imaging (DTI)/ tractography data are quantified; (3) A high percentage of the children were followed-up to 2 years of age; and (4) DTI results, independent from other clinical factors in the neonatal period, accurately predicted neurodevelopmental outcome. Although the relationship between perinatal/neonatal brain injury and subsequent neurological deficits in preterm infants is well established, there are exceptions. Some infants with brain injury develop normally while others without visible brain injury have neurological deficits. Although these false positive and false negative cases are uncommon, they have been used by health policy makers to argue against universal neonatal brain imaging (particularly MRI) in VLBW preterm infants. The number of these cases varies from center to center. On average, one of every four infants with neurological deficits will not be identified, and the chance of misdiagnosis of a normal case is 1 in 10. It is also very important to define not only the extent of the given brain injury but its localization. A small reduction in the number and/or diameter of axons in the posterior limb of the internal capsule, discernible by diffusion tensor MRI, can induce cerebral palsy. On the other hand, a large cranial cyst may spare connecting neuronal fibers involved in motor control or language development and result in minimal or no neurodevelopmental abnormalities. The cost of brain MRI is high and is not available in every hospital. Moreover, the expertize for reading and analyzing VLBW preterm infant neonatal brain images is not yet widely available. However, the benefit of early diagnosis outweighs the disadvantages and costs of neonatal neuroimaging. In the case of cerebral palsy, early diagnosis and intervention can prevent the development of neuro-musculoskeletal deformities and the need for orthopedic surgery. Early detection and intervention in cases of language impairment can have tremendous long-term benefits. The implications of de Bru€ıne et al. and other related studies for clinical practice are as follows: (1) Serial cranial ultrasound and MRI around corrected term age are recommended; (2) A neuroradiologist and neonatologist familiar with the VLBW preterm infant brain should review the images; (3) The use of good quality images and advanced quantitative analysis is essential; (4) A large multi-center trial is needed to standardize the method of neonatal neuroimaging and post hoc quantitative image analysis for the prediction of neurodevelopmental outcomes; and (5) More importantly, we need early interventional studies to prevent/treat brain injury and refer these very vulnerable children to the right clinical services.