We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Structural Growth Trajectories and Rates of Change in the First 3 Months of Infant Brain Development

Dominic Holland, PhD1,2; Linda Chang, MD3; Thomas M. Ernst, PhD3; Megan Curran2; Steven D. Buchthal, PhD3; Daniel Alicata, MD3; Jon Skranes, MD3,4; Heather Johansen3; Antonette Hernandez3; Robyn Yamakawa3; Joshua M. Kuperman, PhD2,5; Anders M. Dale, PhD1,2,5
[+] Author Affiliations
1Department of Neurosciences, University of California, San Diego, La Jolla
2Multimodal Imaging Laboratory, University of California, San Diego, La Jolla
3Department of Medicine, John A. Burns School of Medicine, University of Hawaii, Honolulu
4Department of Laboratory Medicine, Children’s and Women’s Health, Norwegian University of Science and Technology, Trondheim, Norway
5Department of Radiology, University of California, San Diego, La Jolla
JAMA Neurol. 2014;71(10):1266-1274. doi:10.1001/jamaneurol.2014.1638.
Text Size: A A A
Published online

Importance  The very early postnatal period witnesses extraordinary rates of growth, but structural brain development in this period has largely not been explored longitudinally. Such assessment may be key in detecting and treating the earliest signs of neurodevelopmental disorders.

Objective  To assess structural growth trajectories and rates of change in the whole brain and regions of interest in infants during the first 3 months after birth.

Design, Setting, and Participants  Serial structural T1-weighted and/or T2-weighted magnetic resonance images were obtained for 211 time points from 87 healthy term-born or term-equivalent preterm-born infants, aged 2 to 90 days, between October 5, 2007, and June 12, 2013.

Main Outcomes and Measures  We segmented whole-brain and multiple subcortical regions of interest using a novel application of Bayesian-based methods. We modeled growth and rate of growth trajectories nonparametrically and assessed left-right asymmetries and sexual dimorphisms.

Results  Whole-brain volume at birth was approximately one-third of healthy elderly brain volume, and did not differ significantly between male and female infants (347 388 mm3 and 335 509 mm3, respectively, P = .12). The growth rate was approximately 1%/d, slowing to 0.4%/d by the end of the first 3 months, when the brain reached just more than half of elderly adult brain volume. Overall growth in the first 90 days was 64%. There was a significant age-by-sex effect leading to widening separation in brain sizes with age between male and female infants (with male infants growing faster than females by 200.4 mm3/d, SE = 67.2, P = .003). Longer gestation was associated with larger brain size (2215 mm3/d, SE = 284, P = 4×10−13). The expected brain size of an infant born one week earlier than average was 5% smaller than average; at 90 days it will not have caught up, being 2% smaller than average. The cerebellum grew at the highest rate, more than doubling in 90 days, and the hippocampus grew at the slowest rate, increasing by 47% in 90 days. There was left-right asymmetry in multiple regions of interest, particularly the lateral ventricles where the left was larger than the right by 462 mm3 on average (approximately 5% of lateral ventricular volume at 2 months). We calculated volume-by-age percentile plots for assessing individual development.

Conclusions and Relevance  Normative trajectories for early postnatal brain structural development can be determined from magnetic resonance imaging and could be used to improve the detection of deviant maturational patterns indicative of neurodevelopmental disorders.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1.
Infant Atlas and Automatically Segmented Magnetic Resonance Images

A, Cross-sections through T1 (upper) and T2 (lower) atlas images. B, Examples of automatic segmentation. Upper row: 5-day-old male neonate (brain volume, 3.1 × 105 mm3; 30% of elderly adult brain volume); lower row, 117-day-old male infant with a brain more than twice as large (brain volume, 6.6 × 105 mm3; 65% of adult brain volume). Color key: yellow, hippocampus; pink, putamen; light blue, caudate; medium blue, pallidum; light green, thalamus; purple, ventricles; dark green, cerebellum; gray, brain stem; brown, rest of whole-brain parenchyma.

Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Whole-Brain Growth Trajectories, Daily Growth Rates, and Volume-for-Age Percentile Plots

A, Spaghetti plot showing whole-brain volume for 39 male and 48 female infants (94 and 117 time points, respectively) during the first 3 months of postnatal life, along with generalized additive mixed model (GAMM) fits to the data (dark lines, from the Equation), and 95% CIs (shaded regions); see also eFigure 2 in the Supplement. B, Daily growth rate for the whole brain during the first 3 months of postnatal life (for male and female infants combined). The dashed line is the gradient of a GAMM fit for whole-brain volume trajectory; the solid line is a GAMM fit to centered linear estimates of the growth rates (between each subject’s neighboring data points) from the longitudinal data only. Whole-brain volume-by age percentile plots for boys (C) and girls (D) (see also eFigure 3B and 3D in the Supplement); these plots can be used when controlling for an infant’s head circumference and gestational age at birth.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.
Submit a Comment


Some tools below are only available to our subscribers or users with an online account.

2 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections
PubMed Articles

Users' Guides to the Medical Literature
Clarifying Your Question

Users' Guides to the Medical Literature
Three Examples of Question Clarification