Neuroimaging and Neurodevelopmental Outcome in Extremely Preterm Infants

Abstract

BACKGROUND: Extremely preterm infants are at risk for neurodevelopmental impairment (NDI). Early cranial ultrasound (CUS) is usual practice, but near-term brain MRI has been reported to better predict outcomes. We prospectively evaluated MRI white matter abnormality (WMA) and cerebellar lesions, and serial CUS adverse findings as predictors of outcomes at 18 to 22 months' corrected age.METHODS: Early and late CUS, and brain MRI were read by masked central readers, in a large cohort (n = 480) of infants ,28 weeks' gestation surviving to near term in the Neonatal Research Network. Outcomes included NDI or death after neuroimaging, and significant gross motor impairment or death, with NDI defined as cognitive composite score ,70, significant gross motor impairment, and severe hearing or visual impairment. Multivariable models evaluated the relative predictive value of neuroimaging while controlling for other factors.RESULTS: Of 480 infants, 15 died and 20 were lost. Increasing severity of WMA and significant cerebellar lesions on MRI were associated with adverse outcomes. Cerebellar lesions were rarely identified by CUS. In full multivariable models, both late CUS and MRI, but not early CUS, remained independently associated with NDI or death (MRI cerebellar lesions: odds ratio, 3.0 [95% confidence interval: 1.3-6.8]; late CUS: odds ratio, 9.8 [95% confidence interval: 2.8-35]), and significant gross motor impairment or death. In models that did not include late CUS, MRI moderate-severe WMA was independently associated with adverse outcomes.CONCLUSIONS: Both late CUS and near-term MRI abnormalities were associated with outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of near-term neuroimaging.WHAT'S KNOWN ON THIS SUBJECT: White matter abnormality (WMA) on neuroimaging is considered a crucial link with adverse neurodevelopmental outcome in preterm infants. Brain MRI is more sensitive in detecting WMA than cranial ultrasound (CUS), but questions remain about timing and prognostic value of modalities.WHAT THIS STUDY ADDS: Near-term CUS and MRI abnormalities were associated with adverse 18-to 22-month outcomes, independent of early CUS and other factors, underscoring the relative prognostic value of later neuroimaging in this large, extremely preterm cohort surviving to near-term. Trained research staff at each center collected maternal, demographic, perinatal, and neonatal data by using common definitions that were developed by NICHD NRN investigators and described in previous publications. [13][14][15][16] Data were transmitted to the NRN Data Coordinating Center at RTI International, which stored, managed, and analyzed all data. Neuroimaging: CUS and Brain MRI Cranial UltrasoundAn "early" CUS at 4 to 14 days, and a "late" CUS at 35 to 42 weeks' postmenstrual age (PMA) were obtained for NEURO study participants. CUS imaging was per local center clinical protocol. Mastoid, posterior fossa, or cine views were not specifically required. Central reader interpretat...

Neuroimaging of Extremely Preterm Infants: Perils of Prediction

“…First, CUS examinations in ELGANs should routinely include a mastoid view for visualization of the cerebellum; this view was included in less than half of the CUS scans performed in the current study. In Hintz et al 6 Lastly, in the current study a substantial proportion of surviving infants with severe abnormalities on either late CUS or MRI scans were only mildly impaired or unimpaired at 18 to 22 months (26.9% and 16.7%, respectively). These findings point out the perils of prediction for individual infants and our poor understanding of the impact of social or other factors on brain development.…”

“…[2][3][4] This observation has led to recommendations that a routine brain MRI examination at term postmenstrual age be performed for all extremely low gestational age newborns (ELGAN) as a way to better predict the risk for NDI. 5 In this issue of Pediatrics, Hintz et al 6 describe the first large prospective evaluation of early (4-14 days) and near-term (35-42 weeks postmenstrual age) CUS and near-term brain MRI scans in the prediction of NDI at 18 to 22 months. In a prospective cohort of 480 infants born at ,28 weeks' gestation who underwent all 3 scans, the primary outcome of NDI or death was assessed by certified examiners.…”

Early Conventional MRI for Prediction of Neurodevelopmental Impairment in Extremely-Low-Birth-Weight Infants

“…However, our study differs from those that have found associations of WM injury on near-term MRI with cognitive outcomes. Moderate-to-severe WM injury on structural MRI was a predictor of NDI in several relatively large cohorts[6, 8–10]. Woodward et al[9] studied 167 very preterm infants and observed that moderate-to-severe WM abnormality predicted severe cognitive delay, severe motor delay, CP, neurosensory impairment, and NDI at 2 years corrected age.…”

“…Not surprisingly, brain MRI has become increasingly utilized in this population. Early evidence with conventional MRI at term-equivalent age (TEA) suggests that MRI may improve prognostication and identification of those at highest risk for impairments when compared to cranial ultrasound[4, 6–10]. Yet, more objective and accurate models for predicting NDI, especially cognitive outcomes, remain to be determined.…”

Impact of Xenon on CLIC4 and Bcl-2 Expression in Lipopolysaccharide and Hypoxia-Ischemia-Induced Periventricular White Matter Damage

“…It accounts for 10% of the cerebral palsy cases and 25–50% of cognitive/behavioral deficits observed in VLBW preterm survivors [1]. Hintz et al [2] reported that 19.3 % of the surviving preterm infants developed cerebellar lesions. The pathogenesis of WMD primarily involves cerebral hypoxia-ischemia (HI) injury, systemic inflammation, and maternal or fetal infection.…”