Fetally‐injected drugs for immobilization and analgesia do not modify fetal brain development in a rabbit model

Objective During fetal surgery, fetuses receive medication (atropine‐fentanyl‐curare) to prevent fetal pain, movement and bradycardia. Although essential there has been no detailed review of potential side effects. Herein we aimed to assess the effects of this medication cocktail on fetal brain development in a rabbit model. Methods Pregnant does underwent laparotomy at 28 days of gestation. Two pups of each horn were randomized to an ultrasound guided injection with medication (atropine‐cisatracurium‐fentanyl, as clinically used) or saline (sham). The third pup was used as control. At term, does were delivered by cesarean. Outcome measures were neonatal biometry, neuromotoric functioning and neuro‐histology (neuron density, synaptic density and proliferation). Results Maternal vital parameters remained stable during surgery. Fetal heart rates did not differ before and after injection, and were comparable for the three groups. At birth, neonatal body weights and brain‐to‐body weight ratios were also comparable. Both motor and sensory neurobehavioral scores were comparable. There were no differences in neuron density or proliferation. Sham pups, had a lower synaptic density in the hippocampus as compared to the medication group, however there was no difference in the other brain areas. Conclusion In the rabbit model, fetal medication does not appear to lead to short‐term neurocognitive effects. Key points What's already known about this topic? During fetal surgery, fetuses receive medication (atropine‐fentanyl‐curare) to prevent fetal pain, movement and bradycardia. Maternal anesthesia can cause impaired brain development There are no reports on neurodevelopmental effects of direct fetal anesthesia What does this study add? This is the first study investigating the effects of fetal medication Many centers still rely on the transplacental transfer of maternal anesthesia to achieve fetal analgesia. Based on these findings, a direct fetal injection with medication would be preferred.