Athina Pappas1, Ira Adams-Chapman2, Seetha Shankaran1, Scott A McDonald3, Barbara J Stoll4, Abbot R Laptook5, Waldemar A Carlo6, Krisa P Van Meurs7, Susan R Hintz7, Martha D Carlson8, Jane E Brumbaugh9,10, Michele C Walsh11, Myra H Wyckoff12, Abhik Das13, Rosemary D Higgins14. 1. Department of Pediatrics, Wayne State University, Detroit, Michigan. 2. Emory University School of Medicine, Department of Pediatrics, Children's Healthcare of Atlanta, Atlanta, Georgia. 3. Social, Statistical and Environmental Sciences Unit, RTI International, Research Triangle Park, North Carolina. 4. Department of Pediatrics, McGovern Medical School at The University of Texas Health Science Center, Houston. 5. Department of Pediatrics, Women and Infants Hospital, Brown University, Providence, Rhode Island. 6. Division of Neonatology, University of Alabama, Birmingham. 7. Division of Neonatal and Developmental Medicine, Department of Pediatrics, Stanford University School of Medicine and Lucile Packard Children's Hospital, Palo Alto, California. 8. Department of Pediatrics, University of Michigan, Ann Arbor. 9. Department of Pediatrics, University of Iowa, Iowa City. 10. Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, Minnesota. 11. Department of Pediatrics, Rainbow Babies and Children's Hospital, Case Western Reserve University, Cleveland, Ohio. 12. Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas. 13. Social, Statistical, and Environmental Sciences Unit, RTI International, Rockville, Maryland. 14. Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland.
Abstract
Importance: Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood. Objective: To characterize the outcomes of extremely preterm neonates younger than 27 weeks' gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks' postmenstrual age. Design, Setting, and Participants: This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks' gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks' postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017. Main Outcomes and Measures: The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes. Results: Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ. Conclusions and Relevance: Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.
Importance: Studies of cranial ultrasonography and early childhood outcomes among cohorts of extremely preterm neonates have linked periventricular-intraventricular hemorrhage and cystic periventricular leukomalacia with adverse neurodevelopmental outcomes. However, the association between nonhemorrhagic ventriculomegaly and neurodevelopmental and behavioral outcomes is not fully understood. Objective: To characterize the outcomes of extremely preterm neonates younger than 27 weeks' gestational age who experienced nonhemorrhagic ventriculomegaly that was detected prior to 36 weeks' postmenstrual age. Design, Setting, and Participants: This longitudinal observational study was conducted at 16 centers of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network. Infants born prior to 27 weeks' gestational age in any network facility between July 1, 2006, and June 30, 2011, were included if they had a cranial ultrasonogram performed prior to 36 weeks' postmenstrual age. Comparisons were made between those with ventriculomegaly and those with normal cranial sonograms. Data analysis was completed from August 2013 to August 2017. Main Outcomes and Measures: The main outcome was neurodevelopmental impairment, defined as a Bayley Scales of Infant and Toddler Development III cognitive score less than 70, moderate/severe cerebral palsy, a Gross Motor Function Classification System score of level 2 or more, vision impairment, or hearing impairment. Secondary outcomes included Bayley Scales of Infant and Toddler Development III subscores, components of neurodevelopmental impairment, behavioral outcomes, and death/neurodevelopmental impairment. Logistic regression was used to evaluate the association of ventriculomegaly with adverse outcomes while controlling for potentially confounding variables and center differences as a random effect. Linear regression was used similarly for continuous outcomes. Results: Of 4193 neonates with ultrasonography data, 300 had nonhemorrhagic ventriculomegaly (7%); 3045 had normal cranial ultrasonograms (73%), 775 had periventricular-intraventricular hemorrhage (18.5%), and 73 had cystic periventricular leukomalacia (1.7%). Outcomes were available for 3008 of 3345 neonates with ventriculomegaly or normal scans (90%). Compared with normal cranial ultrasonograms, ventriculomegaly was associated with lower gestational age, male sex, and bronchopulmonary dysplasia, late-onset sepsis, meningitis, necrotizing enterocolitis, and stage 3 retinopathy of prematurity. After adjustment, neonates with ventriculomegaly had higher odds of neurodevelopmental impairment (odds ratio [OR], 3.07; 95% CI, 2.13-4.43), cognitive impairment (OR, 3.23; 95% CI, 2.09-4.99), moderate/severe cerebral palsy (OR, 3.68; 95% CI, 2.08-6.51), death/neurodevelopmental impairment (OR, 2.17; 95% CI, 1.62-2.91), but not death alone (OR, 1.09; 95% CI, 0.76-1.57). Behavioral outcomes did not differ. Conclusions and Relevance: Nonhemorrhagic ventriculomegaly is associated with increased odds of neurodevelopmental impairment among extremely preterm neonates.
Authors: T Michael O'Shea; Bhavesh Shah; Elizabeth N Allred; Raina N Fichorova; Karl C K Kuban; Olaf Dammann; Alan Leviton Journal: Brain Behav Immun Date: 2013-01-04 Impact factor: 7.217
Authors: Shannon E G Hamrick; Steven P Miller; Carol Leonard; David V Glidden; Ruth Goldstein; Vijay Ramaswamy; Robert Piecuch; Donna M Ferriero Journal: J Pediatr Date: 2004-11 Impact factor: 4.406
Authors: L R Ment; H S Bada; P Barnes; P E Grant; D Hirtz; L A Papile; J Pinto-Martin; M Rivkin; T L Slovis Journal: Neurology Date: 2002-06-25 Impact factor: 9.910
Authors: Barbara J Stoll; Nellie I Hansen; Edward F Bell; Michele C Walsh; Waldemar A Carlo; Seetha Shankaran; Abbot R Laptook; Pablo J Sánchez; Krisa P Van Meurs; Myra Wyckoff; Abhik Das; Ellen C Hale; M Bethany Ball; Nancy S Newman; Kurt Schibler; Brenda B Poindexter; Kathleen A Kennedy; C Michael Cotten; Kristi L Watterberg; Carl T D'Angio; Sara B DeMauro; William E Truog; Uday Devaskar; Rosemary D Higgins Journal: JAMA Date: 2015-09-08 Impact factor: 56.272
Authors: Karl C K Kuban; Elizabeth N Allred; T Michael O'Shea; Nigel Paneth; Marcello Pagano; Olaf Dammann; Alan Leviton; Adré Du Plessis; Sjirk J Westra; Cindy R Miller; Haim Bassan; Kalpathy Krishnamoorthy; Joseph Junewick; Nicholas Olomu; Elaine Romano; Joanna Seibert; Steve Engelke; Padmani Karna; Daniel Batton; Sunila E O'Connor; Cecelia E Keller Journal: J Child Neurol Date: 2009-01 Impact factor: 1.987
Authors: Pilar Medina-Alva; Kevin R Duque; Alonso Zea-Vera; Sicilia Bellomo; César Cárcamo; Daniel Guillen-Pinto; Maria Rivas; Alfredo Tori; Jaime Zegarra; Luis Cam; Anne Castañeda; Aasith Villavicencio; Theresa J Ochoa Journal: Early Hum Dev Date: 2019-02-08 Impact factor: 2.079
Authors: Vivek V Shukla; Andrew Klinger; Siamak Yazdi; A K M Fazlur Rahman; Sydney Wright; Angela Barganier; Namasivayam Ambalavanan; Waldemar A Carlo; Manimaran Ramani Journal: J Perinatol Date: 2022-07-01 Impact factor: 3.225
Authors: Rebecca A Dorner; Vera Joanna Burton; Marilee C Allen; Shenandoah Robinson; Bruno P Soares Journal: J Perinatol Date: 2018-08-30 Impact factor: 2.521
Authors: Shenandoah Robinson; Fatu S Conteh; Akosua Y Oppong; Tracylyn R Yellowhair; Jessie C Newville; Nagat El Demerdash; Christine L Shrock; Jessie R Maxwell; Stephen Jett; Frances J Northington; Lauren L Jantzie Journal: Front Cell Neurosci Date: 2018-09-25 Impact factor: 5.505
Authors: S Arulkumaran; N Tusor; A Chew; S Falconer; N Kennea; P Nongena; J V Hajnal; S J Counsell; M A Rutherford; A D Edwards Journal: AJNR Am J Neuroradiol Date: 2020-08 Impact factor: 3.825