TY - JOUR
T1 - Examination of the pattern of growth of cerebral tissue volumes from hospital discharge to early childhood in very preterm infants
AU - Monson, Brian B.
AU - Anderson, Peter J.
AU - Matthews, Lillian G.
AU - Neil, Jeffrey J.
AU - Kapur, Kush
AU - Cheong, Jeanie L.Y.
AU - Doyle, Lex W.
AU - Thompson, Deanne K.
AU - Inder, Terrie E.
N1 - Funding Information:
This work was supported by Australia's National Health and Medical Research Council, including Centre for Clinical Research Excellence grant 546519 (Drs Anderson, Cheong, Doyle, and Inder), Centre for Research Excellence grant 1060733 (Drs Anderson, Cheong, Doyle, and Thompson), project grant 237117 (Dr Doyle), project grant 491209 (Dr Anderson), Senior Research Fellowship 1081288 (Dr Anderson), Career Development Fellowship 1085754 (Dr Thompson), Early Career Fellowship 1012236 (Dr Thompson), and Early Career Fellowship 1053787 (Dr Cheong). The study was also supported by the Victorian Government's Operational Infrastructure Support Program, as well as by the following US funders: grant HD058056 from the National Institutes of Health, the United Cerebral Palsy Foundation, The G. Harold & Leila Y. Mathers Charitable Foundation, and The Brown Foundation.
Publisher Copyright:
© 2016 American Medical Association. All rights reserved.
PY - 2016/8
Y1 - 2016/8
N2 - Importance: Smaller cerebral volumes at hospital discharge in very preterm (VPT) infants are associated with poor neurobehavioral outcomes. Brain growth from the newborn period to middle childhood has not been explored because longitudinal data have been lacking. Objectives: To examine the pattern of growth of cerebral tissue volumes from hospital discharge to childhood in VPT infants and to determine perinatal risk factors for impaired brain growth and associations with neurobehavioral outcomes at 7 years. Design, setting, and participants: Prospective cohort study of VPT infants (<30 weeks' gestation or <1250 g) born between April 11, 2001, and April 26, 2004, and followed up at 7 years' corrected age. The setting was The Royal Women's Hospital and The Royal Children's Hospital, Melbourne, Australia. Of 224 VPT infants and 46 full-term (FT) infants, usable magnetic resonance imaging data at either infancy or 7 years were collected for 214 VPT children (95.5%) and 46 FT children (100%), while 126 VPT children (56.3%) and 31 FT children (67.4%) had usable magnetic resonance imaging data at both time points. Follow-up was conducted from April 28, 2008, to August 9, 2011. Our final analysis was on March 3, 2016. Exposure: Prematurity. Main outcomes and measures: Absolute tissue growth, defined as change in absolute tissue volume, between infancy and 7 years was calculated for cortical gray matter volume (GMV), white matter volume (WMV), and subcortical GMV. IQ, language, and motor function were measured at 7 years. Results: The study cohort comprised 260 participants. Their mean (SD) age was 7.5 (0.2) years, and 49.2%(128 of 260) were female. Early GMV deficits in VPT infants were magnified by 7 years, with less growth than FT controls. Growth differences were 31.4 (95%CI, 14.8-48.1) cm3 for cortical GMV and 1.7 (95%CI, 0.5-2.8) cm3 for subcortical GMV. Within the VPT group, greater growth was observed in boys for cortical GMV (31.9; 95%CI, 16.8-46.9 cm3), WMV (31.7; 95%CI, 19.7-43.7 cm3), and subcortical GMV (1.8; 95%CI, 0.8-2.8 cm3). After controlling for sex and maternal education, all tissue volumes in infancy correlated with IQ (r ≥ 0.35, P < .05) and language (r ≥ 0.29, P < .05). Seven-year volumes correlated with IQ (r = 0.28, P = .04 for cortical GMV), language (r = 0.29, P = .04 for cortical GMV), and motor functioning (r ≥ 0.29, P < .05 for all tissues). There was no evidence of any association between brain growth during childhood and outcomes in VPT infants. Conclusions and relevance: Low brain volumes observed in VPT infants are exaggerated at 7 years. Low brain volume in infancy is associated with long-term functional outcomes, emphasizing the persisting influence of early brain development on subsequent growth and outcomes.
AB - Importance: Smaller cerebral volumes at hospital discharge in very preterm (VPT) infants are associated with poor neurobehavioral outcomes. Brain growth from the newborn period to middle childhood has not been explored because longitudinal data have been lacking. Objectives: To examine the pattern of growth of cerebral tissue volumes from hospital discharge to childhood in VPT infants and to determine perinatal risk factors for impaired brain growth and associations with neurobehavioral outcomes at 7 years. Design, setting, and participants: Prospective cohort study of VPT infants (<30 weeks' gestation or <1250 g) born between April 11, 2001, and April 26, 2004, and followed up at 7 years' corrected age. The setting was The Royal Women's Hospital and The Royal Children's Hospital, Melbourne, Australia. Of 224 VPT infants and 46 full-term (FT) infants, usable magnetic resonance imaging data at either infancy or 7 years were collected for 214 VPT children (95.5%) and 46 FT children (100%), while 126 VPT children (56.3%) and 31 FT children (67.4%) had usable magnetic resonance imaging data at both time points. Follow-up was conducted from April 28, 2008, to August 9, 2011. Our final analysis was on March 3, 2016. Exposure: Prematurity. Main outcomes and measures: Absolute tissue growth, defined as change in absolute tissue volume, between infancy and 7 years was calculated for cortical gray matter volume (GMV), white matter volume (WMV), and subcortical GMV. IQ, language, and motor function were measured at 7 years. Results: The study cohort comprised 260 participants. Their mean (SD) age was 7.5 (0.2) years, and 49.2%(128 of 260) were female. Early GMV deficits in VPT infants were magnified by 7 years, with less growth than FT controls. Growth differences were 31.4 (95%CI, 14.8-48.1) cm3 for cortical GMV and 1.7 (95%CI, 0.5-2.8) cm3 for subcortical GMV. Within the VPT group, greater growth was observed in boys for cortical GMV (31.9; 95%CI, 16.8-46.9 cm3), WMV (31.7; 95%CI, 19.7-43.7 cm3), and subcortical GMV (1.8; 95%CI, 0.8-2.8 cm3). After controlling for sex and maternal education, all tissue volumes in infancy correlated with IQ (r ≥ 0.35, P < .05) and language (r ≥ 0.29, P < .05). Seven-year volumes correlated with IQ (r = 0.28, P = .04 for cortical GMV), language (r = 0.29, P = .04 for cortical GMV), and motor functioning (r ≥ 0.29, P < .05 for all tissues). There was no evidence of any association between brain growth during childhood and outcomes in VPT infants. Conclusions and relevance: Low brain volumes observed in VPT infants are exaggerated at 7 years. Low brain volume in infancy is associated with long-term functional outcomes, emphasizing the persisting influence of early brain development on subsequent growth and outcomes.
UR - http://www.scopus.com/inward/record.url?scp=84980328058&partnerID=8YFLogxK
U2 - 10.1001/jamapediatrics.2016.0781
DO - 10.1001/jamapediatrics.2016.0781
M3 - Article
C2 - 27368090
AN - SCOPUS:84980328058
SN - 2168-6203
VL - 170
SP - 772
EP - 779
JO - JAMA Pediatrics
JF - JAMA Pediatrics
IS - 8
ER -