Long-term influence of normal variation in neonatal characteristics on human brain development
- aDepartment of Psychology, University of Oslo, 0373 Oslo, Norway;
- bMultimodal Imaging Laboratory,
- Departments of cNeurosciences,
- dRadiology,
- fPsychiatry, and
- pCognitive Science, and
- eCenter for Human Development, University of California at San Diego, La Jolla, CA 92037;
- gDepartment of Psychiatry and Behavioral Sciences, University of California, Davis, CA 95817;
- hScripps Genomic Medicine, Scripps Translational Science Institute and Scripps Health, La Jolla, CA 92037;
- iSackler Institute for Developmental Psychobiology, Weil Cornell Medical College, New York, NY 10065;
- jDepartment of Medicine, University of Hawaii and Queen's Medical Center, Honolulu, HI 96813;
- kDepartment of Psychiatry, University of Massachusetts Medical School, Boston, MA 01655;
- lDepartments of Pediatrics and Genetics, Yale University School of Medicine, New Haven, CT 06520;
- mKennedy Krieger Institute and
- oF. M. Kirby Research Center, Kennedy Krieger Institute and Department of Radiology, Johns Hopkins University School of Medicine, Baltimore, MD 21205; and
- nChildren's Hospital Boston, Harvard Medical School, Boston, MA 02115
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Edited by Marcus E. Raichle, Washington University, St. Louis, MO, and approved October 2, 2012 (received for review May 16, 2012)

Abstract
It is now recognized that a number of cognitive, behavioral, and mental health outcomes across the lifespan can be traced to fetal development. Although the direct mediation is unknown, the substantial variance in fetal growth, most commonly indexed by birth weight, may affect lifespan brain development. We investigated effects of normal variance in birth weight on MRI-derived measures of brain development in 628 healthy children, adolescents, and young adults in the large-scale multicenter Pediatric Imaging, Neurocognition, and Genetics study. This heterogeneous sample was recruited through geographically dispersed sites in the United States. The influence of birth weight on cortical thickness, surface area, and striatal and total brain volumes was investigated, controlling for variance in age, sex, household income, and genetic ancestry factors. Birth weight was found to exert robust positive effects on regional cortical surface area in multiple regions as well as total brain and caudate volumes. These effects were continuous across birth weight ranges and ages and were not confined to subsets of the sample. The findings show that (i) aspects of later child and adolescent brain development are influenced at birth and (ii) relatively small differences in birth weight across groups and conditions typically compared in neuropsychiatric research (e.g., Attention Deficit Hyperactivity Disorder, schizophrenia, and personality disorders) may influence group differences observed in brain parameters of interest at a later stage in life. These findings should serve to increase our attention to early influences.
Footnotes
- ↵1To whom correspondence should be addressed. E-mail: k.b.walhovd{at}psykologi.uio.no.
↵2Data used in preparation of this study were obtained from the Pediatric Imaging, Neurocognition, and Genetics Study (PING) database. As such, the investigators within PING contributed to the design and implementation of PING and/or provided data but did not participate in the analysis or writing of this report. A complete listing of PING investigators can be found in the Supporting Information.
Author contributions: K.B.W., A.M.F., T.T.B., N.A., D.G.A., C.S.B., N.J.S., B.J.C., L.C., T.M.E., J.F., J.R.G., W.E.K., S.S.M., P.Z., S.M., and A.M.D. designed research; K.B.W., A.M.F, T.T.B., C.M., N.A., D.G.A., C.S.B., N.J.S., B.F.D., B.J.C., L.C., T.M.E., J.F., J.R.G., W.E.K., S.S.M., P.Z., S.M., and A.M.D. performed research; P.I.N.G. contributed new reagents/analytic tools; K.B.W., A.M.F., J.M.K., Y.C., D.J.H., J.C.R., M.E., O.L., and A.M.D. analyzed data; K.B.W. and A.M.F. wrote the paper; and P.I.N.G. provided phenotype and genotype data.
Conflict of interest statement: A.M.D. is a founder of and holds equity interest in CorTechs Labs, La Jolla, CA and serves on its scientific advisory board. The terms of this arrangement have been reviewed and approved by the University of California at San Diego, in accordance with its conflict of interest policies.
This article is a PNAS Direct Submission.
This article contains supporting information online at www.pnas.org/lookup/suppl/doi:10.1073/pnas.1208180109/-/DCSupplemental.