Introduction: This retrospective, matched case-control cohort study describes the incidence, indications, anesthesia techniques and outcomes of pregnancies complicated by surgery in a single tertiary-referral hospital. Methods: Retrospective review of the hospital records of 171 patients who had non-obstetric surgery in the current pregnancy, between 2001 and 2016. Pregnancy outcomes of these women were firstly compared with all contemporary non-exposed patients (n=35 411), and secondly with 684 non-exposed control patients, matched for age, time of delivery and parity. Results: The incidence of non-obstetric surgery during pregnancy was 0.48%, mostly performed during the second trimester (44%) and under general anesthesia (81%). Intra-abdominal surgery (44%) was the most commonly performed procedure, predominantly using laparoscopy (79%). Women undergoing surgery delivered earlier and more frequently preterm (25% vs. 17%, P=0.018); and birth weight was significantly lower [median (95% CI) 3.16 (3.06 to 3.26) vs. 3.27 (3.22 to 3.32) kg, P=0.044]. When surgery was performed under general anesthesia, low birth weight was more frequent (22% vs. 6%, P=0.046). Overall pregnancy outcomes were neither influenced by trimester nor location (intra-vs. extra-abdominal) of surgery. However, preterm birth rate secondary to surgery was higher for interventions during the third trimester, compared with other trimesters (10% vs. 0, P <0.001). Conclusion: Pregnant women who underwent surgery delivered preterm more frequently and their babies had lower birth weights. Laparoscopic surgery did not increase the incidence of adverse pregnancy outcomes. General anesthesia was associated with low birth weight. Whether these associations suggest causation or reflect the severity of the underlying condition remains speculative.

Maternal surgery during pregnancy has a negative effect on fetal brain development both histologic and neurobehavioral but with time these differences fade out.

Histone deacetylase 6 (HDAC6) is a multifunctional cytoplasmic enzyme involved in diverse cellular processes such as intracellular transport and protein quality control. Inhibition of HDAC6 can alleviate defects in cell and rodent models of certain diseases, particularly neurodegenerative disorders, including Alzheimer's disease and amyotrophic lateral sclerosis. However, while HDAC6 represents a potentially powerful therapeutic target, development of effective brain-penetrant HDAC6 inhibitors remains challenging. Recently, [ 18 F]EKZ-001 ([ 18 F]Bavarostat), a brain-penetrant positron emission tomography (PET) radioligand with high affinity and selectivity toward HDAC6, was developed and evaluated preclinically for its ability to bind HDAC6. Herein, we describe the efficient and robust fully automated current Good Manufacturing Practices (cGMP) compliant production method. [ 18 F]EKZ-001 quantification methods were validated in nonhuman primates (NHP) using full kinetic modeling, and [ 18 F]EKZ-001 PET was applied to compare dose-occupancy relationships between two HDAC6 inhibitors, EKZ-317 and ACY-775. [ 18 F]EKZ-001 is cGMP produced with an average decay-corrected radiochemical yield of 14% and an average molar activity of 204 GBq/μmol. We demonstrate that a two-tissue compartmental model and Logan graphical analysis are appropriate for [ 18 F]EKZ-001 PET quantification in NHP brain. Blocking studies show that the novel compound EKZ-317 achieves higher target occupancy than ACY-775. This work supports the translation of [ 18 F]EKZ-001 PET for first-in-human studies.

No abstract

Up to 1% of pregnant women undergo anaesthesia for non-obstetric surgery. This study investigated neurodevelopmental outcomes after prenatal anaesthesia for maternal surgery. A bidirectional cohort study of children born between 2001 and 2018 was performed: neurodevelopmental outcomes of children who had received prenatal anaesthesia for maternal surgery were prospectively compared with unexposed children, with exposure status being assessed retrospectively. Children exposed to anaesthesia for obstetric and fetal surgery were excluded. The primary outcome was the global executive composite of the behaviour rating inventory of executive function score. Our secondary outcomes were: total problems; internalising problems and externalising problems derived from the child behaviour checklist; psychiatric diagnoses; and learning disorders. In 90% of exposed children, there was a single mean (SD) antenatal anaesthesia exposure lasting 91 (94) min. There was a broad spectrum of indications, with abdominal surgery being most frequent. Parents of 129 exposed (response rate 68%) and 453 unexposed (response rate 63%) children participated. There were no arguments for non-response bias. After propensity weighting, there were no statistically significant differences in primary outcome, with a weighted mean difference (95%CI) of exposed minus unexposed children of 1.9 (À0.4-4.2), p = 0.10; or any of the secondary outcomes. Sensitivity analyses confirmed the robustness. Exploratory analyses, however, showed significant differences in certain subgroups for the primary outcome, (e.g. for intra-abdominal surgery, exposure duration > 1 h) and some cognitive subdomains (e.g. working memory and attention). This bidirectional cohort study, the largest investigation on the subject to date, has found no evidence in the general population for an association between prenatal exposure to anaesthesia and impaired neurodevelopmental outcomes.