Supplementary Material for: Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model

<b><i>Introduction:</i></b> Anesthesia during pregnancy can impair fetal neurodevelopment, but effects of surgery remain unknown. The aim is to investigate effects of abdominal surgery on fetal brain development. Hypothesis is that surgery impairs outcome. <b><i>Methods:</i></b> Pregnant rabbits were randomized at 28 days of gestation to 2 h of general anesthesia (sevoflurane group, <i>n</i> = 6) or to anesthesia plus laparoscopic appendectomy (surgery group, <i>n</i> = 13). On postnatal day 1, neurobehavior of pups was assessed and brains harvested. Primary outcome was neuron density in the frontal cortex, and secondary outcomes included neurobehavioral assessment and other histological parameters. <b><i>Results:</i></b> Fetal survival was lower in the surgery group: 54 versus 100% litters alive at birth (<i>p</i> = 0.0442). In alive litters, pup survival until harvesting was 50 versus 69% (<i>p</i> = 0.0352). No differences were observed for primary outcome (<i>p</i> = 0.5114) for surviving pups. Neuron densities were significantly lower in the surgery group in the caudate nucleus (<i>p</i> = 0.0180), but not different in other regions. No differences were observed for secondary outcomes. Conclusions did not change after adjustment for mortality. <b><i>Conclusion:</i></b> Abdominal surgery in pregnant rabbits at a gestational age corresponding to the end of human second trimester results in limited neurohistological changes but not in neurobehavioral impairments. High intrauterine mortality limits translation to clinical scenario, where fetal mortality is close to zero.