Location: Arkansas Children's Nutrition CenterTitle: Caesarean section delivery impacts infant brain development
|DEONI, S - Brown University|
|Ferruzzi, Mario - Arkansas Children'S Nutrition Research Center (ACNC)|
|LI, XUEHUA - Arkansas Children'S Nutrition Research Center (ACNC)|
|PIVIK, TERRY - Arkansas Children'S Nutrition Research Center (ACNC)|
|GLASIER, CHARLES - Arkansas Children'S Hospital|
|RAMAKRISHNAIAH, RAGHU - Arkansas Children'S Hospital|
|ROWELL, A - Arkansas Children'S Hospital|
|OU, XIAWEI - Arkansas Children'S Nutrition Research Center (ACNC)|
Submitted to: American Journal of Neuroradiology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/6/2018
Publication Date: 11/22/2018
Citation: Deoni, S.C., Adams, S.H., Li, X., Badger, T.M., Pivik, T., Glasier, C.M., Ramakrishnaiah, R.H., Rowell, A.C., Ou, X. 2018. Caesarean section delivery impacts infant brain development. American Journal of Neuroradiology. https://doi.org/10.3174/ajnr.A5887.
Interpretive Summary: The in utero environment and postnatal exposures such as infant diet impact long-term growth and development of children, and can contribute to later-life disease risk. For instance, maternal obesity increases the odds that offspring will develop obesity, and studies have shown that brain structure and neurodevelopment differ in babies born to obese mothers. Research is testing the effects of improved maternal physical activity and metabolic health on thwarting of obesity-associated outcomes in brain development. Understanding the efficacy and mechanisms of these interventions may be confounded by variables that differ among women during the pre-natal and peri-natal period, such as mode of delivery (C-section or natural birth). This is important to consider since the rate of C-section delivery in the US has rapidly increased during the past two decades, and it is unclear whether C-section birth impacts long-term neurodevelopment of children. We analyzed brain MRI data in two cohorts of healthy children previously studied at ACNC: 2-week-old infants from the Glowing project, and 8-year-old children from the Brain Power project. We found that for 2-week-old healthy term infants, those born by vaginal delivery have higher integrity of brain white matter (which is one of the two major components in the brain and facilitates neural signal transfer) than those born by C-section. In addition, those born by vaginal delivery also have better-developed functional connectivity (when brain is at rest, certain regions of the brain tissues are regarded as functionally connected as measured by region-specific brain oxygen use) in certain brain networks. These differences are significant even after excluding potential confounding factors. However, these differences were not observed for 8-year-old children. Findings were confirmed by another independently-conducted study at a collaborating institution: i.e., different brain myelination patterns in infants born by C-section compared to infants born by vaginal delivery, with differences dissipated with age. Thus, C-section delivery impacts infant brain development as an independent, early-life factor. This important finding has implications for clinical decisions related to voluntary C-section procedures, and highlights that in studies examining developmental programming of the brain, birth mode is a critical variable to consider when interpreting results.
Technical Abstract: 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. 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. 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. 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.