Effects of Maternal Abdominal Surgery on Fetal Brain Development in the Rabbit Model

Abstract

Introduction: 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.

Methods: Pregnant rabbits were randomized at 28 days of gestation to 2 h of general anesthesia (sevoflurane group, n = 6) or to anesthesia plus laparoscopic appendectomy (surgery group, n = 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.

Results: Fetal survival was lower in the surgery group: 54 versus 100% litters alive at birth (p = 0.0442). In alive litters, pup survival until harvesting was 50 versus 69% (p = 0.0352). No differences were observed for primary outcome (p = 0.5114) for surviving pups. Neuron densities were significantly lower in the surgery group in the caudate nucleus (p = 0.0180), but not different in other regions. No differences were observed for secondary outcomes. Conclusions did not change after adjustment for mortality.

Conclusion: 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.

Keywords: Fetus; Neurobehavior; Neuron density; Pregnancy; Surgery.

Fig. 1. Neuron density.

a The brains were cut to obtain 2 sets of 3 consecutive slides (distance: 100 μm between the slides). b Neuron densities counted manually on NeuN-stained slides. Data are shown as individual data points, and bars represent mean and standard deviation. NeuN, neuronal nuclei.

Fig. 2

Biometrics. Biometrics of the pups: the weight of the pups 1 day after birth, the weight and volume of the brains of the pups after harvesting, and the brain to body weight ratio. Data are shown as individual data points, and bars represent mean and standard deviation.

Fig. 3

Neurobehavioral assessment. The motoric scores, sensoric scores, number of hops, and number of falling overs of the pups 1 day after birth. Data are shown as individual data points, and bars represent mean and standard deviation. Pictures from left to right: open field test, facial/whisker touch response, sucking and swallowing, surface righting reflex, odor aversion, pain sensation, synchronous hop, and falling over.

Fig. 4

Proliferation. Proliferation in the brains of the pups measured using the Ki67 marker. Data are shown as individual data points, and bars represent mean and standard deviation.

Fig. 5

Synaptogenesis. Synaptophysin levels in the brains, measured as the mean gray value. Data are shown as individual data points, and bars represent mean and standard deviation.