Background: Extremely-low-birth-weight (ELBW; ≤1,000 g) infants are at high risk for neurodevelopmental impairments. Conventional brain MRI at term-equivalent age is increasingly used for prediction of outcomes. However, optimal prediction models remain to be determined, especially for cognitive outcomes. Objective: The aim was to evaluate the accuracy of a data-driven MRI scoring system to predict neurodevelopmental impairments. Methods: 122 ELBW infants had a brain MRI performed at term-equivalent age. Conventional MRI findings were scored with a standardized algorithm and tested using a multivariable regression model to predict neurodevelopmental impairment, defined as one or more of the following at 18-24 months' corrected age: cerebral palsy, bilateral blindness, bilateral deafness requiring amplification, and/or cognitive/language delay. Results were compared with a commonly cited scoring system. Results: In multivariable analyses, only moderate-to-severe gyral maturational delay was a significant predictor of overall neurodevelopmental impairment (OR: 12.6, 95% CI: 2.6, 62.0; p < 0.001). Moderate-to-severe gyral maturational delay also predicted cognitive delay, cognitive delay/death, and neurodevelopmental impairment/death. Diffuse cystic abnormality was a significant predictor of cerebral palsy (OR: 33.6, 95% CI: 4.9, 229.7; p < 0.001). These predictors exhibited high specificity (range: 94-99%) but low sensitivity (30-67%) for the above outcomes. White or gray matter scores, determined using a commonly cited scoring system, did not show significant association with neurodevelopmental impairment. Conclusions: In our cohort, conventional MRI at term-equivalent age exhibited high specificity in predicting neurodevelopmental outcomes. However, sensitivity was suboptimal, suggesting additional clinical factors and biomarkers are needed to enable accurate prognostication.

Keywords:
Extremely-low-birth-weight infants, Prematurity, Magnetic resonance imaging, Neurodevelopmental outcome, Cerebral palsy, Brain development
1.
Hintz SR, Kendrick DE, Wilson-Costello DE, Das A, Bell EF, Vohr BR, Higgins RD; NICHD Neonatal Research Network: Early-childhood neurodevelopmental outcomes are not improving for infants born at <25 weeks' gestational age. Pediatrics 2011;127:62-70.
2.
Mercier CE, Dunn MS, Ferrelli KR, Howard DB, Soll RF; Vermont Oxford Network ELBW Infant Follow-Up Study Group: Neurodevelopmental outcome of extremely low birth weight infants from the Vermont Oxford Network: 1998-2003. Neonatology 2010;97:329-338.
3.
Wilson-Costello D, Friedman H, Minich N, Siner B, Taylor G, Schluchter M, Hack M: Improved neurodevelopmental outcomes for extremely low birth weight infants in 2000-2002. Pediatrics 2007;119:37-45.
4.
Mirmiran M, Barnes PD, Keller K, Constantinou JC, Fleisher BE, Hintz SR, Ariagno RL: Neonatal brain magnetic resonance imaging before discharge is better than serial cranial ultrasound in predicting cerebral palsy in very low birth weight preterm infants. Pediatrics 2004;114:992-998.
5.
Whitaker AH, Feldman JF, Van Rossem R, Schonfeld IS, Pinto-Martin JA, Torre C, Blumenthal SR, Paneth NS: Neonatal cranial ultrasound abnormalities in low birth weight infants: relation to cognitive outcomes at six years of age. Pediatrics 1996;98:719-729.
6.
Dyet LE, Kennea N, Counsell SJ, Maalouf EF, Ajayi-Obe M, Duggan PJ, Harrison M, Allsop JM, Hajnal J, Herlihy AH, Edwards B, Laroche S, Cowan FM, Rutherford MA, Edwards AD: Natural history of brain lesions in extremely preterm infants studied with serial magnetic resonance imaging from birth and neurodevelopmental assessment. Pediatrics 2006;118:536-548.
7.
Valkama AM, Paakko EL, Vainionpaa LK, Lanning FP, Ilkko EA, Koivisto ME: Magnetic resonance imaging at term and neuromotor outcome in preterm infants. Acta Paediatr 2000;89:348-355.
8.
Miller SP, Ferriero DM, Leonard C, Piecuch R, Glidden DV, Partridge JC, Perez M, Mukherjee P, Vigneron DB, Barkovich AJ: Early brain injury in premature newborns detected with magnetic resonance imaging is associated with adverse early neurodevelopmental outcome. J Pediatr 2005;147:609-616.
9.
Woodward LJ, Anderson PJ, Austin NC, Howard K, Inder TE: Neonatal MRI to predict neurodevelopmental outcomes in preterm infants. N Engl J Med 2006;355:685-694.
10.
Hintz SR, Barnes PD, Bulas D, Slovis TL, Finer NN, Wrage LA, Das A, Tyson JE, Stevenson DK, Carlo WA, Walsh MC, Laptook AR, Yoder BA, Van Meurs KP, Faix RG, Rich W, Newman NS, Cheng H, Heyne RJ, Vohr BR, Acarregui MJ, Vaucher YE, Pappas A, Peralta-Carcelen M, Wilson-Costello DE, Evans PW, Goldstein RF, Myers GJ, Poindexter BB, McGowan EC, Adams-Chapman I, Fuller J, Higgins RD; SUPPORT Study Group of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network: Neuroimaging and neurodevelopmental outcome in extremely preterm infants. Pediatrics 2015;135:e32-e42.
11.
Woodward LJ, Clark CA, Bora S, Inder TE: Neonatal white matter abnormalities an important predictor of neurocognitive outcome for very preterm children. PloS One 2012;7:e51879.
12.
Iwata S, Iwata O, Bainbridge A, Nakamura T, Kihara H, Hizume E, Sugiura M, Tamura M, Matsuishi T: Abnormal white matter appearance on term FLAIR predicts neuro-developmental outcome at 6 years old following preterm birth. Int J Dev Neurosci 2007;25:523-530.
13.
Pogribna U, Yu X, Burson K, Zhou Y, Lasky RE, Narayana PA, Parikh NA: Perinatal clinical antecedents of white matter microstructural abnormalities on diffusion tensor imaging in extremely preterm infants. PloS One 2013;8:e72974.
14.
McArdle CB, Richardson CJ, Nicholas DA, Mirfakhraee M, Hayden CK, Amparo EG: Developmental features of the neonatal brain: MR imaging. Part I. Gray-white matter differentiation and myelination. Radiology 1987;162:223-229.
15.
Horsch S, Hallberg B, Leifsdottir K, Skiold B, Nagy Z, Mosskin M, Blennow M, Aden U: Brain abnormalities in extremely low gestational age infants: a Swedish population based MRI study. Acta Paediatr 2007;96:979-984.
16.
Chi JG, Dooling EC, Gilles FH: Gyral development of the human brain. Ann Neurol 1977;1:86-93.
17.
Martin E, Kikinis R, Zuerrer M, Boesch C, Briner J, Kewitz G, Kaelin P: Developmental stages of human brain: an MR study. J Comput Assist Tomogr 1988;12:917-922.
18.
Bayley N: Bayley Scales of Infant and Toddler Development III. San Antonio, Pearson, 2005.
19.
Moore T, Johnson S, Haider S, Hennessy E, Marlow N: Relationship between test scores using the second and third editions of the Bayley Scales in extremely preterm children. J Pediatr 2012;160:553-558.
20.
Landis JR, Koch GG: The measurement of observer agreement for categorical data. Biometrics 1977;33:159-174.
21.
Rathbone R, Counsell SJ, Kapellou O, Dyet L, Kennea N, Hajnal J, Allsop JM, Cowan F, Edwards AD: Perinatal cortical growth and childhood neurocognitive abilities. Neurology 2011;77:1510-1517.
22.
Skiold B, Vollmer B, Bohm B, Hallberg B, Horsch S, Mosskin M, Lagercrantz H, Aden U, Blennow M: Neonatal magnetic resonance imaging and outcome at age 30 months in extremely preterm infants. J Pediatr 2012;160:559-566.e1.
23.
Eichenwald EC: Neuroimaging of extremely preterm infants: perils of prediction. Pediatrics 2015;135:e176-e177.
24.
Parikh NA, He L, Bonfante-Mejia E, Hochhauser L, Wilder PE, Burson K, Kaur S: Automatically quantified diffuse excessive high signal intensity on MRI predicts cognitive development in preterm infants. Pediatr Neurol 2013;49:424-430.
25.
Kidokoro H, Neil JJ, Inder TE: New MR imaging assessment tool to define brain abnormalities in very preterm infants at term. AJNR Am J Neuroradiol 2013;34:2208-2214.
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2016
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