Birth delivery mode alters perinatal cell death in the mouse brain

Significance The rate of cesarean section (C-section) delivery worldwide far exceeds the World Health Organization’s recommended rate. C-section delivery has been linked to behavioral effects in the offspring. This suggests effects on the brain, but human studies are confounded by the medical complications, altered birth timing, and maternal factors associated with C-section delivery. We addressed these limitations in a carefully controlled study in mice. Vaginally-born offspring exhibited an acute decrease in cell death across the brain that was absent in C-section–born mice. C-section delivery also was associated with softer vocalizations, as well as with a reduction in at least one neuronal cell type and increased body weight at weaning. Thus, birth mode has acute effects on neurodevelopment that may lead to lasting changes in the brain and behavior.