Cesarean Delivery Impacts Infant Brain Development

S.C. Deoni; S.H. Adams; X. Li; T.M. Badger; R.T. Pivik; C.M. Glasier; R.H. Ramakrishnaiah; A.C. Rowell; X. Ou

doi:10.3174/ajnr.A5887

Abstract

BACKGROUND AND PURPOSE: The cesarean delivery rate has increased globally in the past few decades. Neurodevelopmental outcomes associated with cesarean delivery are still unclear. This study investigated whether cesarean delivery has any effect on the brain development of offspring.

MATERIALS AND METHODS: A total of 306 healthy children were studied retrospectively. We included 3 cohorts: 2-week-old neonates (cohort 1, n = 32/11 for vaginal delivery/cesarean delivery) and 8-year-old children (cohort 2, n = 37/23 for vaginal delivery/cesarean delivery) studied at Arkansas Children's Hospital, and a longitudinal cohort of 3-month to 5-year-old children (cohort 3, n = 164/39 for vaginal delivery/cesarean delivery) studied independently at Brown University. Diffusion tensor imaging, myelin water fraction imaging, voxel-based morphometry, and/or resting-state fMRI data were analyzed to evaluate white matter integrity, myelination, gray matter volume, and/or functional connectivity, respectively.

RESULTS: While not all MR imaging techniques were shared across the institutions/cohorts, post hoc analyses showed similar results of potential effects of cesarean delivery. The cesarean delivery group in cohort 1 showed significantly lower white matter development in widespread brain regions and significantly lower functional connectivity in the brain default mode network, controlled for a number of potential confounders. No group differences were found in cohort 2 in white matter integrity or gray matter volume. Cohort 3 had significantly different trajectories of white matter myelination between groups, with those born by cesarean delivery having reduced myelin in infancy but normalizing with age.

CONCLUSIONS: Cesarean delivery may influence infant brain development. The impact may be transient because similar effects were not observed in older children. Further prospective and longitudinal studies may be needed to confirm these novel findings.

ABBREVIATIONS:

BMI: body mass index
DMN: default mode network
FA: fractional anisotropy
ICA: independent component analysis
IQ: intelligence quotient
MWF: myelin water fraction
RS-fMRI: resting-state fMRI
TFCE: threshold-free cluster enhancement
TBSS: Tract-Based Spatial Statistics
VBM: voxel-based morphometry

Footnotes

Disclosures: Sean C. Deoni—RELATED: National Institutes of Health, Comments: National Institute of Mental Health award as listed in the funding section*; UNRELATED: Consultancy: Nestlé Nutrition, Comments: consultant fees associated with nutritional impacts on neurodevelopment; Grants/Grants Pending: Nestlé Nutrition, Comments: study of nutritional impact on brain development*; Payment for Lectures Including Service on Speakers Bureaus: Wyeth Nutrition, Nestlé Nutrition, Comments: speaking fees for lectures on early brain development. Sean H. Adams—RELATED: Grant: US Department of Agriculture–Agricultural Research Service, Comments: The Arkansas Children's Nutrition Center is funded as a national research center by the US Department of Agriculture–Agricultural Research Service*; Support for Travel to Meetings for the Study or Other Purposes: US Department of Agriculture–Agricultural Research Service, Comments: The Arkansas Children's Nutrition Center is funded as a national research center by the US Department of Agriculture–Agricultural Research Service; the Center has travel support for its investigators to attend scientific conferences*; Provision of Writing Assistance, Medicines, Equipment, or Administrative Support: US Department of Agriculture–Agricultural Research Service, Comments: The Arkansas Children's Nutrition Center is funded as a national research center by the US Department of Agriculture–Agricultural Research Service. The Center has administrative support for its investigators*; UNRELATED: Consultancy: roundtable participant (eg, International Life Sciences Institute) and meeting organizer (eg, for the National Dairy Council); Employment: University of Arkansas for Medical Sciences; Grants/Grants Pending: US Department of Agriculture–Agricultural Research Service, Comments: The Arkansas Children's Nutrition Center is funded as a national research center by the US Department of Agriculture–Agricultural Research Service. This is not in conflict with the current article; Payment for Lectures Including Service on Speakers Bureaus, Comments: Various honoraria for invited seminars at universities or giving talks at national scientific conferences are not in conflict; topic areas have nothing to do with brain function or the subject matter of the current article; Travel/Accommodations/Meeting Expenses Unrelated to Activities Listed: The Arkansas Children's Nutrition Center is funded as a national research center by the US Department of Agriculture–Agricultural Research Service; the Center has travel support for its investigators to attend scientific conferences.* Thomas M. Badger—RELATED: Grant: National Institutes of Health and US Department of Agriculture*. Rudolph T. Pivik—RELATED: Grant: US Department of Agriculture–Agricultural Research Service Project 6026-51000-010-05S*; UNRELATED: Employment: University of Arkansas for Medical Sciences, Comments: only my salary as Research Professor, Department of Pediatrics. Charles M. Glasier—RELATED: Grant: Arkansas Children's Hospital; UNRELATED: Expert Testimony: medicolegal cases; Payment for Lectures Including Service on Speakers Bureaus: Cincinnati Children's Hospital. Amy C. Rowell—RELATED: Grant: US Department of Agriculture.* Xiawei Ou—RELATED: Grant: US Department of Agriculture–Agricultural Research Service Project 6026-51000-010-05S.* *Money paid to the institution.
The studies were supported, in part, by the US Department of Agriculture–Agricultural Research Service Project (6026-51000-010-05S) at the Arkansas Children's Nutrition Center, the Marion B. Lyon Award at the Arkansas Children's Research Institute, and grants from the National Institute of Mental Health (R01MH087510) and the Bill and Melinda Gates Foundation. Dr Xiawei Ou is also supported by National Institutes of Health Centers of Biomedical Research Excellence grants P20GM121293 (Center for Translational Pediatric Research at Arkansas Children's Research Institute) and P30GM110702 (Center for Translational Neuroscience at University of Arkansas for Medical Sciences).