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JAMA Pediatr. 2013 May;167(5):451-9. doi: 10.1001/jamapediatrics.2013.866.

Neurodevelopmental outcomes of extremely low-gestational-age neonates with low-grade periventricular-intraventricular hemorrhage.

Collaborators (193)

Caplan MS, Laptook AR, Hensman AM, Burke R, Caskey M, Johnson K, Alksninis B, Andrews D, Angela K, Leach TM, Watson VE, Ventura S, Fanaroff AA, Newman NS, Siner BS, Bhola M, Yalcinkaya G, Friedman HG, Schibler K, Donovan EF, Bridges K, Alexander B, Grisby C, Mincey HL, Hessling J, Gratton TL, Steichen JJ, Yolton K, Goldberg RN, Cotten C, Auten KJ, Fisher KA, Grimes S, Gustafson KE, Lohmeyer MB, Stoll BJ, Carlton DP, Hale EC, Higgins RD, Archer SW, Poindexter BB, Dusick AM, Wilson LD, Hamer F, Lytle C, Minnich HM, Das A, Poole W, Wallace D, Newman JE, Auman JO, Cunningham M, Huitema CM, Zaterka-Baxter KM, Van Meurs KP, Stevenson DK, Davis AS, Epi MS, Ball M, Palmquist AW, Proud MS, Bruno E, DeAnda ME, DeBattista AM, Kohn JG, Weiss HE, Frantz ID 3rd, Fiascone JM, MacKinnon BL, Furey A, Nylen E, McGowan EC, Carlo WA, Ambalavanan N, Peralta-Carcelen M, Collins MV, Cosby SS, Biasini FJ, Johnston KC, Nelson KG, Patterson CS, Phillips VA, Whitley S, Finer NN, Vaucher YE, Kaegi D, Rasmussen MR, Kaegi D, Arnell K, Demetrio C, Fuller MG, Rich W, West R, Bell EF, Acarregui MJ, Johnson KJ, Eastman DL, Duara S, Bauer CR, Everett-Thomas R, Hiriart-Fajardo S, Rigaud A, Calejo M, Eguaras SM, Berkowits MH, Garcia A, Pierre H, Stoerger A, Watterberg KL, Lowe JR, Fuller JF, Ohls RK, Lacy CB, Montman R, Phelps DL, Myers GJ, Reubens LJ, Burnell E, Hust D, Johnson JB, Jensen RL, Kushner E, Merzbach J, Yost K, Zwetsch L, Kennedy KA, Tyson JE, Alaniz NI, Evans PW, Green C, Harris BF, Jiminez M, Lis AE, Martin S, McDavid E, Morris BH, Poundstone M, Siddiki S, Simmons MC, Tate PL, Wright SL, Sánchez PJ, Heyne RJ, Salhab WA, Rosenfeld CR, Guzman A, Leps MH, Miller NA, Hensley G, Adams SS, Madden LA, Heyne E, Morgan JS, Boatman CT, Torres LE, Faix RG, Yoder BA, Osborne KA, Spencer C, Weaver-Lewis K, Baker S, Bird K, Burnett J, Steffen M, Zanetti K, O' Shea T, Dillard RG, Washburn LK, Jackson BG, Peters N, Chiu K, Allred DE, Goldstein DJ, Halfond R, Peterson C, Waldrep EL, Welch CD, Morris MW, Hounshell GW, Shankaran S, Pappas A, Bara R, Goldston LA, Ehrenkranz RA, Jacobs H, Butler CG, Cervone P, Greisman S, Konstantino M, Poulsen J, Taft J, Williams J, Romano E.

Author information

Departments of Pediatrics, Rainbow Babies and Children’s Hospital, Case Western ReserveUniversity, Cleveland, OH 44106, USA.



Low-grade periventricular-intraventricular hemorrhage is a common neurologic morbidity among extremely low-gestational-age neonates, yet the outcomes associated with this morbidity are not fully understood. In a contemporary multicenter cohort, we evaluated the impact of such hemorrhages on early (18-22 month) neurodevelopmental outcomes of extremely premature infants.


To compare neurodevelopmental outcomes at 18 to 22 months' corrected age for extremely low-gestational-age infants with low-grade (grade 1 or 2) periventricular-intraventricular hemorrhage with those of infants with either no hemorrhage or severe (grade 3 or 4) hemorrhage demonstrated on cranial ultrasonography.


Longitudinal observational study.


Sixteen centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network.


A total of 1472 infants born at less than 27 weeks' gestational age between January 1, 2006, and December 31, 2008, with ultrasonography results within the first 28 days of life and surviving to 18 to 22 months with complete follow-up assessments were eligible.


Low-grade periventricular-intraventricular hemorrhage.


Outcomes included cerebral palsy; gross motor functional limitation; cognitive and language scores according to the Bayley Scales of Infant Development, 3rd Edition; and composite measures of neurodevelopmental impairment. Regression modeling evaluated the association of hemorrhage severity with adverse outcomes while controlling for potentially confounding variables and center differences.


Low-grade hemorrhage was not associated with significant differences in unadjusted or adjusted risk of any adverse neurodevelopmental outcome compared with infants without hemorrhage. Compared with low-grade hemorrhage, severe hemorrhage was associated with decreased adjusted continuous cognitive (β, -3.91 [95% CI, -6.41 to -1.42]) and language (β, -3.19 [-6.19 to -0.19]) scores as well as increased odds of each adjusted categorical outcome except severe cognitive impairment (odds ratio [OR], 1.46 [0.74 to 2.88]) and mild language impairment (OR, 1.35 [0.88 to 2.06]).


At 18 to 22 months, the neurodevelopmental outcomes of extremely low-gestational-age infants with low-grade periventricular-intraventricular hemorrhage are not significantly different from those without hemorrhage. Additional study at school age and beyond would be informative.

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