Neurodevelopmental outcomes after prenatal exposure to anaesthesia for maternal surgery: a propensity‐score weighted bidirectional cohort study

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.

Prenatal Sevoflurane Exposure Impairs the Learning and Memory of Rat Offspring via HMGB1-Induced NLRP3/ASC Inflammasome Activation

“…Unfortunately, clinical evidence was somewhat little. A recent clinical study indicated that prenatal anesthesia exposure for non-obstetric surgery may not result in clinically significant neurodevelopmental outcomes abnormalities . The subjective psychosocial problem questionnaires assess, effects of surgery, and underlying pathology may be closely related to this result.…”

Non‐obstetric surgery and later childhood development: optimal anaesthesia for the mother–infant dyad

“…In this issue of Anaesthesia, showed an increased risk with general anaesthesia, intraabdominal, laparoscopic or prolonged (> 1 h) surgery for executive function alone, with estimates for the weighted mean difference of t-scores in these subgroups ranging from 3.2 to 4.5, an effect size explained by the authors as being of similar magnitude to a parental university level education [8].…”

“…The findings were similar with alternative statistical methodology including propensity score adjustment and matching, and in sensitivity analyses with age strata, or after exclusion of fetuses exposed to important confounders such as chemo‐ or radiotherapy and illicit drugs. Exploratory analyses showed an increased risk with general anaesthesia, intra‐abdominal, laparoscopic or prolonged (> 1 h) surgery for executive function alone, with estimates for the weighted mean difference of t‐scores in these subgroups ranging from 3.2 to 4.5, an effect size explained by the authors as being of a similar magnitude to a parental university level education [8].…”

“…This study represents the largest study in this field to date and provides useful information and reassurance to parents and healthcare staff [8]. Given that a randomised controlled trial to assess potential causality of neurotoxicity secondary to fetal exposure to general anaesthesia is not feasible, only observational studies with their inherent biases can estimate potential treatment effects.…”

Prenatal anesthetic exposure and offspring neurodevelopmental outcomes—A narrative review

“…It has been reported that the effect values for anesthesia are even smaller than those for other factors such as demographics (25). It is not difficult to understand how a child's good postnatal upbringing may offset a single, small exposure to prenatal anesthesia.…”