Postpartum haemorrhage (PPH) remains a leading cause of maternal morbidity and mortality worldwide. While coagulation disorders are seldom the primary cause of PPH and are rare early in PPH, the incidence of coagulation abnormalities increases when blood loss escalates. Acute obstetric coagulopathy (AOC), with an incidence of one in 1000 deliveries, has emerged as a distinct coagulopathy in PPH, highlighting the need for timely coagulation testing and intervention. This narrative review examines the current evidence on the use of visco-elastic haemostatic assays (VHAs) to guide treatment in PPH, and further explores the prophylactic and therapeutic roles of fibrinogen and tranexamic acid (TXA).VHAs have shown potential in PPH management, with large prospective and retrospective cohort studies demonstrating reductions in transfusions and transfusion-related complications. However, these findings have not been consistently replicated, possibly due to variations in study design and statistical power. This review explores the benefits and limitations of VHAs in the context of PPH management. Until large, well designed studies suggest otherwise, women with PPH might benefit from access to VHAs, given their potential to improve clinical outcomes in large cohorts without evidence of associated harm.Fibrinogen replacement is essential in PPH management. VHAs have been shown to be as effective as the Clauss fibrinogen assay in guiding fibrinogen substitution during PPH. Recent updates to ROTEM Sigma cartridges have led to new FIBTEM A5 thresholds, with the Obstetric Bleeding Strategy (OBS) group of Wales proposing a FIBTEM A5 of 8 mm or less as the new trigger for fibrinogen replacement in PPH. Fibrinogen concentrate offers advantages over cryoprecipitate and may be preferred when both are available. Effective fibrinogen substitution not only corrects VHA results but also helps to control bleeding.TXA is a cornerstone in the treatment of PPH and should be administered promptly at a dose of 1 g as soon as PPH is diagnosed, regardless of VHA results, and always within three hours of onset. A second dose may be given if bleeding persists or recurs. However, high-quality randomised trials have consistently shown no benefit from prophylactic TXA in low-risk caesarean section or in vaginal births across all risk groups. Data on the prophylactic use of TXA in high-risk caesarean section are limited and its use in these cases should be based on clinical judgement and individual risk assessment.

Neuraxial labour analgesia is considered the 'gold-standard' technique for the provision of analgesia during vaginal birth. Recently, there has been growing interest in the potential impacts of labour epidural analgesia beyond pain relief. One particular concern is its association with the development of maternal fever, so-called epidural-related maternal fever (ERMF). Hyperthermia during labour is a significant clinical concern, as it can impact both maternal and neonatal outcomes. This narrative review explores the association between epidural analgesia and maternal fever, outlines its suggested pathophysiological mechanisms, examines its potential implications and considers the management of neuraxial analgesia in the context of existing maternal fever. The two main theories explaining the development of ERMF are the sterile inflammation hypothesis, and the altered thermoregulation hypothesis. Patient characteristics, features of pregnancy and labour, midwifery and/or obstetric interventions and epidural-related factors can all contribute to an increased risk of developing ERMF. Although these factors may be manipulated to reduce ERMF incidence, there is no clear evidence that supports the recommendation of any intervention to prevent ERMF development. The associated detrimental effects of maternal fever on the woman, foetus, and newborn are highlighted, although many of these adverse outcomes have not been definitively established when ERMF has been the focus of study. There remains a significant need to further understand the pathophysiology, clinical significance, preventive strategies and treatment modalities of ERMF. It is crucial that future studies distinguish ERMF as a distinct category within maternal intrapartum fever.

Postpartum haemorrhage (PPH) remains a leading cause of maternal morbidity and mortality worldwide. While coagulation disorders are seldom the primary cause of PPH and are rare early in PPH, the incidence of coagulation abnormalities increases when blood loss escalates. Acute obstetric coagulopathy (AOC), with an incidence of one in 1000 deliveries, has emerged as a distinct coagulopathy in PPH, highlighting the need for timely coagulation testing and intervention. This narrative review examines the current evidence on the use of visco-elastic haemostatic assays (VHAs) to guide treatment in PPH, and further explores the prophylactic and therapeutic roles of fibrinogen and tranexamic acid (TXA). VHAs have shown potential in PPH management, with large prospective and retrospective cohort studies demonstrating reductions in transfusions and transfusion-related complications. However, these findings have not been consistently replicated, possibly due to variations in study design and statistical power. This review explores the benefits and limitations of VHAs in the context of PPH management. Until large, well designed studies suggest otherwise, women with PPH might benefit from access to VHAs, given their potential to improve clinical outcomes in large cohorts without evidence of associated harm. Fibrinogen replacement is essential in PPH management. VHAs have been shown to be as effective as the Clauss fibrinogen assay in guiding fibrinogen substitution during PPH. Recent updates to ROTEM Sigma cartridges have led to new FIBTEM A5 thresholds, with the Obstetric Bleeding Strategy (OBS) group of Wales proposing a FIBTEM A5 of 8 mm or less as the new trigger for fibrinogen replacement in PPH. Fibrinogen concentrate offers advantages over cryoprecipitate and may be preferred when both are available. Effective fibrinogen substitution not only corrects VHA results but also helps to control bleeding. TXA is a cornerstone in the treatment of PPH and should be administered promptly at a dose of 1 g as soon as PPH is diagnosed, regardless of VHA results, and always within three hours of onset. A second dose may be given if bleeding persists or recurs. However, high-quality randomised trials have consistently shown no benefit from prophylactic TXA in low-risk caesarean section or in vaginal births across all risk groups. Data on the prophylactic use of TXA in high-risk caesarean section are limited and its use in these cases should be based on clinical judgement and individual risk assessment.

Neuraxial labour analgesia is considered the 'gold-standard' technique for the provision of analgesia during vaginal birth. Recently, there has been growing interest in the potential impacts of labour epidural analgesia beyond pain relief. One particular concern is its association with the development of maternal fever, so-called epidural-related maternal fever (ERMF). Hyperthermia during labour is a significant clinical concern, as it can impact both maternal and neonatal outcomes. This narrative review explores the association between epidural analgesia and maternal fever, outlines its suggested pathophysiological mechanisms, examines its potential implications and considers the management of neuraxial analgesia in the context of existing maternal fever. The two main theories explaining the development of ERMF are the sterile inflammation hypothesis, and the altered thermoregulation hypothesis. Patient characteristics, features of pregnancy and labour, midwifery and/or obstetric interventions and epidural-related factors can all contribute to an increased risk of developing ERMF. Although these factors may be manipulated to reduce ERMF incidence, there is no clear evidence that supports the recommendation of any intervention to prevent ERMF development. The associated detrimental effects of maternal fever on the woman, foetus, and newborn are highlighted, although many of these adverse outcomes have not been definitively established when ERMF has been the focus of study. There remains a significant need to further understand the pathophysiology, clinical significance, preventive strategies and treatment modalities of ERMF. It is crucial that future studies distinguish ERMF as a distinct category within maternal intrapartum fever.

Nowadays, widespread antenatal ultrasound screenings detect congenital anomalies earlier and more frequently. This has sparked research into foetal surgery, offering treatment options for various conditions. These surgeries aim to correct anomalies or halt disease progression until after birth. Minimally invasive procedures can be conducted under local anaesthesia (with/without maternal sedation), while open mid-gestational procedures necessitate general anaesthesia. Anaesthesia serves to prevent maternal and foetal pain, to provide immobilization, and to optimize surgical conditions by ensuring uterine relaxation. As early as 12 weeks after conception, the foetus may experience pain. Thus, in procedures involving innervated foetal tissue or requiring foetal immobilization, anaesthetic drugs can be administered directly to the foetus (intramuscular or intravenous) or indirectly (transplacental) to the mother. However, animal studies have indicated that exposure to prenatal anaesthesia might impact foetal brain development, translating these findings to the clinical setting remains difficult.

In 2020, the publication of work reporting a 37% relative increase in the risk of autism spectrum disorder (ASD) in the offspring of mothers who had received labour epidural analgesia (LEA)1 led to widespread scrutiny in the lay press and social media, potentially influencing maternal decision-making all over the world. However, it remains imperative to approach this matter critically, appreciating the complexity of association and causation and the need for a balanced interpretation of the available evidence. Currently, within the developed world, LEA stands as the benchmark for managing labour pain. The technique is widely acknowledged as safe and beneficial to both the mother and the foetus and consistently yields high patient satisfaction. The WHO recommends LEA in healthy women depending on a woman's preferences.2 However, the long-term effects, and more specifically the neurodevelopmental effects of LEA on the offspring have recently been a subject of inquiry. ASD is a neurodevelopmental condition characterised by challenges in social communication and the manifestation of restricted, repetitive behaviours or interests. Epidemiologically, ASD is observed in approximately 2 to 3% of the United States' population. The observation of an apparent upward trend in prevalence over recent years has been attributed, at least in part, to heightened ascertainment practices but environmental factors might also bear a degree of responsibility.3 Various factors identified in epidemiological studies have been associated with ASD, yet none exhibit absolute specificity for ASD development. The complex, poorly understood, cause of ASD appears to be intertwined with a convergence of heterogeneous genetic and environmental factors, including maternal health, infectious and pharmacological causes, social influences and environmental exposures. Maternal factors, including gestational hypertension, maternal overweight status before or during pregnancy, pre-eclampsia and maternal age of 35 years or older, have been identified as correlating with elevated rates of ASD in the offspring. Other cohort and case–control studies have reported an association between the incidence of ASD in the offspring and advanced paternal age, medication use during pregnancy, and both short (<12 months) and prolonged (72 months) interpregnancy intervals. Concerning the relationship between medication use during pregnancy and ASD risk, exposure to valproic acid and the utilisation of selective serotonin reuptake inhibitors (SSRIs) during pregnancy have also been associated with an increased risk for ASD. An observational, retrospective cohort study by Qiu et al.1 reported a 37% relative increase in the risk of ASD in the offspring of mothers who had received LEA. In addition, they delineated a discernible dose–response relationship between LEA and the likelihood of ASD.4,5 The study had some significant limitations. There was a lack of data about labour complications (e.g. prolonged labour, foetal distress and malposition), which are known to increase the risk of ASD. These factors are, in turn, associated with increased LEA and are important confounders. Women who delivered by caesarean section (itself an important association with autism) were excluded. Additionally, children not enrolled with the health insurance scheme by 1 year of age were excluded. It is possible that these children were from lower socio-economic groups, who are historically subject to underdiagnosis of autism, and who were also over-represented in the nonepidural cohort. Despite these limitations, the study raised substantial concerns regarding the safety of LEA and implications for public health. Following this initial study, various epidemiological cohort studies have sought to explore the suggested association between LEA and the increased prevalence of ASD in the offspring. In this European Journal of Anaesthesiology issue, Zamstein and co-workers (pp. 282–287) report the results of their retrospective population-based cohort study, which shows that LEA was not independently associated with ASD after adjusting for confounding factors. This conclusion corroborates the findings of other retrospective cohort studies.6–11 Furthermore, several studies employing a sibling-matched retrospective cohort design revealed in the preliminary unmatched analysis an elevated hazard ratio, which dissipated after sibling-matching, culminating in an adjusted hazard ratio that did not exhibit an increase.6,7,9–11 This adds complexity to the debate, underscoring the challenges of isolating specific variables in observational studies. Sibling matching offers a distinct advantage over other observational studies by mitigating bias from residual confounding attributed to unmeasurable variables that persist consistently within families. Similarly, the only prospective observational birth cohort study found no statistically significant correlation between maternal LEA and autistic traits. The assessment was conducted prospectively using a battery of ASD screening tests up to the age of 7 years.12 These important results address the existing gap in the literature by employing a standardised prospective neurobehavioral battery for all participants (and not depending on a clinical diagnosis of ASD) as primary outcome. This holds paramount significance as there is a growing acknowledgement that subclinical autistic traits manifest to diverse extents within the general population, with a clinical diagnosis being established only when individuals exhibit substantial functional impairment and psychological or social distress. Studies employing administrative databases, such as those focused on particular education data and health records, generally tend to underestimate the prevalence of ASD when juxtaposed with investigations utilising more meticulous methodologies for case identification. Meta-analyses conducted on this topic present an intriguing picture.13–16 On one hand, they reveal an association between neuraxial labour analgesia and autism when no confounding variables are considered. However, a critical turning point emerges when confounders are pondered, resulting in a very weak association. Moreover, this association was also based on low-quality evidence.14 A recent systematic review by Fang and co-workers, revealed a notably elevated risk of ASD when the influence of confounding variables was disregarded [hazard ratio 1.3, 95% confidence interval (CI), 1.25 to 1.3521, and hazard ratio 1.24, 95% CI 1.14 to 1.345]. However, upon accounting for potential confounders, the effect diminished, yet remained statistically significant [hazard ratio 1.13, 95% CI, 1.03 to 1.25, and hazard ratio 1.11, 95% CI, 1.06 to 1.165].16 Nevertheless, when only studies using a sibling-matched design were analysed, this meta-analysis concluded that there was no significant association (hazard ratio 1.07, 95% CI, 0.99 to 1.16),13,16 whereas another demonstrated a significant association in sibling-matched designed studies [hazard ratio 1.10, 95% CI, 1.02 to 1.18],13 with, however, no dose–response effect. It was concluded that the small statistically significant association between LEA and ASD may be elucidated by selection bias and residual (unmeasured) confounders, such as genetic factors.16 A final but critical consideration is the role of the biological plausibility of the potential role of LEA in the development of ASD. Qui et al. speculated that the local anaesthetic used in the mother's epidural space may have a neurotoxic effect on the foetal brain, increasing the risk of autism. However, while epidurally administered local anaesthetics can cross the placenta easily because of their low molecular weight, studies in humans indicate negligible systemic absorption with low concentrations in the neonatal bloodstream17,18 and evidence of foetal local anaesthetic metabolism8,19; therefore, any argument for causation is severely weakened. The lack of a consistent dose–response effect further complicates matters, making it challenging to establish a straightforward relationship between neuraxial labour analgesia and autism. It is, therefore, crucial to approach the findings of Qiu et al.1 and related meta-analyses13–16 with caution. The presence of an association without confounders does not imply causation. The intricacies of human biology and the myriad factors influencing neurodevelopment demand a meticulous examination of the evidence. The concern surrounding LEA and autism, initially fuelled by the Qiu article and subsequent media coverage, requires a tempered response. The strength of evidence hinges on the robustness of its underlying data. Although systematically reviewing the available evidence suggests a weak association, the significance of this association is contingent on the consideration of (unmeasured) confounding variables. The inconclusive results of sibling matching, the absence of an apparent dose–response effect and the first negative prospective observational study emphasise the need for continued research before drawing definitive conclusions. As we navigate the delicate balance between scientific inquiry and public perception, it is paramount to communicate clearly. For now, the available evidence should provide reassurance to prospective parents, enabling them to make informed and personalised decisions regarding labour analgesia, free from anxiety and guilt associated with the choice of LEA.

BackgroundAnaesthetists of all grades who work on a labour ward are likely to be involved in the insertion or management of an intrathecal catheter after inadvertent dural puncture at some point in their careers. Although the use of intrathecal catheters after inadvertent dural puncture in labour has increased in popularity over recent decades, robust evidence on best practice has been lacking.MethodsThe Obstetric Anaesthetists' Association set up an expert working party to review the literature. A modified Delphi approach was used to produce statements and recommendations on insertion and management of intrathecal catheters for labour and operative delivery following inadvertent dural puncture during attempted labour epidural insertion. Statements and recommendations were graded according to the US Preventive Services Task Force grading methodology.ResultsA total of 296 articles were identified in the initial literature search. Further screening identified 111 full text papers of relevance. A structured narrative review was produced which covered insertion of an intrathecal catheter; initial dosing; maintenance of labour analgesia; topping-up for operative delivery; safety features; complications; and recommended follow-up. The working party agreed on 17 statements and 26 recommendations. These were generally assigned a low or moderate level of certainty. The safety of mother and baby were a key priority in producing these guidelines.ConclusionsWith careful management, intrathecal catheters can provide excellent labour analgesia and may also be topped-up to provide anaesthesia for caesarean or operative vaginal delivery. The use of intrathecal catheters, however, also carries the risk of significant drug errors which may result in high- or total-spinal anaesthesia, or even cardiorespiratory arrest. It is vital that all labour wards have clear guidelines on the use of these catheters, and that staff are educated as to their potential complications.

Up to 1% of pregnant women require general anesthesia and maternal non-obstetric surgery during pregnancy, of which urgent abdominal procedures are most commonly indicated. This narrative review summarizes several dogmas and myths on the management of general anesthesia during pregnancy and the corresponding evidence. While historical studies found delayed gastric emptying during pregnancy, recent evidence concluded that gastric emptying remains nearly normal during the entire pregnancy until the onset of labor. To correctly estimate the aspiration risk, gastric ultrasound should be increasingly performed. Based on the available evidence, the application of cricoid pressure should be discouraged during rapid sequence induction of pregnant women. A cuffed endotracheal tube is traditionally recommended, but laryngeal masks have been used in > 9000 patients undergoing cesarean section without observation of aspiration. All material to manage a difficult airway should be available as difficult intubation remains an ongoing concern in obstetrics. Risk factors for difficult intubation are nonobstetric in nature. Due to the lack of evidence for hemodynamic management, it is not possible to make an evidence-based recommendation. We recommend to adhere to the expert opinion of maintaining maternal blood pressure close to the normal physiologic value by using (15°-)30° left lateral tilt position, intravenous fluids and noradrenaline or phenylephrine. Most recent clinical observational studies suggested to consider laparoscopic over open surgery as a standard treatment for abdominal surgery. While animal studies observed impaired fetal brain development after prenatal anesthesia exposure, this could not be confirmed by an observational clinical study.

( BMJ . 2024;385:q1053. http://dx.doi.org/10.1136/bmj.q1053) The World Health Organization (WHO) suggests using epidural analgesia (EA) for healthy pregnant women who desire pain relief during childbirth, taking into account personal preferences. Yet, a prevalent worry while obtaining consent is the potential adverse impacts of EA on the mother, the baby, or the delivery. Limited evidence is still available to handle these concerns. Kearns and colleagues researched to investigate the impact of EA on severe maternal morbidity (SMM). The results showed a notable correlation, as EA was connected to a 35% decrease in SMM, especially in women with a medical reason for using EA and those with preterm deliveries. These results have significant consequences for anesthetic care during childbirth and women’s health, underscoring the importance of additional research.

( Eur J Anaesthesiol . 2024;41(4):257–259. doi:10.1097/EJA.0000000000001965) Widespread use of labor epidural analgesia (LEA) in developed countries as the leading pain management technique during pregnancy without many adverse perinatal events should suggest its efficacy and safety. However, various researchers and some in the general public have begun to question the lasting effects in children born in the setting of maternal LEA use. One such neurodevelopmental disorder being examined is autism spectrum disorder (ASD). A 2020 study claimed a 37% risk increase for ASD diagnoses in children whose mother used LEA during the birthing process. Although this and other similar publications have received widespread attention, in this editorial, authors caution mothers and providers to carefully consider the complexity of the neurodevelopmental disorder etiology.

The aim of this pragmatic approach to retrospective observational study was to identify the end-tidal concentration of sevoflurane which was associated with optimal surgical conditions (i.e., absence of any movement, coughing and straining) in 127 pregnant sheep. Optimal surgical conditions were observed in 90% of the ewes with an end-tidal concentration of sevoflurane of 2.4 Vol-% [95% CI: 2.2; 2.8] during minimal-mild nociceptive stimuli (placement of arterial catheter, bladder catheter, shaving), with 4.4 Vol-% [95% CI: 4.0; 5.2] during maternal laparotomy and hysterotomy and with 4.4 Vol-% [95% CI: 3.9; 5.8] during subsequent manipulation of the uterus and fetal surgery.

Translational research on obstetric diseases and foetal surgery is frequently performed in pregnant sheep ( Basurto et al., 2021 Basurto D. Sananès N. Bleeser T. et al. Safety and efficacy of smart tracheal occlusion device in diaphragmatic hernia lamb model. Ultrasound Obstet Gynecol. 2021; 57: 105-112 Crossref PubMed Scopus (19) Google Scholar ; Joyeux et al., 2022 Joyeux L. Basurto D. Bleeser T. et al. Fetoscopic insufflation of heated-humidified carbon dioxide during simulated spina bifida repair is safe under controlled anesthesia in the fetal lamb. Prenat Diagn. 2022; 42: 180-191 Crossref Scopus (1) Google Scholar ; Bleeser et al., 2023 Bleeser T. Basurto D. Russo F. et al. Effects of cumulative duration of repeated anaesthesia exposure on foetal brain development in the ovine model. J Clin Anesth. 2023; 85111050 Crossref PubMed Scopus (2) Google Scholar ). Usually, at least two anaesthetics are required in these models: one at a gestational age of +70 days and one at +100 days. During general anaesthesia in pregnancy, it is important to maintain maternal physiological homeostasis to ensure foetal viability e.g., by adjusting maternal ventilation to achieve a physiological maternal arterial carbon dioxide partial pressure (PaCO2), maintaining maternal blood pressure close to the conscious values, ( Bleeser et al., 2022 Bleeser T. Vally J. Van de Velde M. et al. General anaesthesia for non-obstetric surgery during pregnancy: A narrative review. European Journal of Anaesthesiology and Intensive Care. 2022; 1: 1-11 Crossref Google Scholar ). Therefore, physiological values of the cardiopulmonary variables in pregnant sheep are needed. Currently, only two studies have reported these values ( Cissik et al., 1991 Cissik J.H. Ehler W.J. Hankins G.D. et al. Cardiopulmonary reference standards in the pregnant sheep (Ovis aries): a comparative study of ovine and human physiology in obstetrics. Comp Biochem Physiol A Comp Physiol. 1991; 100: 877-880 Crossref PubMed Scopus (14) Google Scholar ; Okutomi et al., 2009 Okutomi T. Whittington R.A. Stein D.J. et al. Comparison of the effects of sevoflurane and isoflurane anesthesia on the maternal-fetal unit in sheep. J Anesth. 2009; 23: 392-398 Crossref PubMed Scopus (65) Google Scholar ). However, both studies were conducted at a gestational age of +130 days, and it has been established that cardiopulmonary variables change with advancing pregnancy ( Bleeser et al., 2022 Bleeser T. Vally J. Van de Velde M. et al. General anaesthesia for non-obstetric surgery during pregnancy: A narrative review. European Journal of Anaesthesiology and Intensive Care. 2022; 1: 1-11 Crossref Google Scholar ). Moreover, one of these studies investigated these reference values during light halothane anaesthesia (defined as a level of anaesthesia maintaining spontaneous respiration but preventing spontaneous movements) ( Cissik et al., 1991 Cissik J.H. Ehler W.J. Hankins G.D. et al. Cardiopulmonary reference standards in the pregnant sheep (Ovis aries): a comparative study of ovine and human physiology in obstetrics. Comp Biochem Physiol A Comp Physiol. 1991; 100: 877-880 Crossref PubMed Scopus (14) Google Scholar ), which may have affected the accuracy and reliability of the results. Therefore, the aim of the present study was to determine haemodynamic variables and blood gas values in conscious pregnant ewes at a gestational age of approximately 70 and 100 days.

BACKGROUND:Anesthesia-associated hypotension in pregnant women is frequently managed with vasoactive drugs to avoid uterine hypoperfusion. We systematically reviewed the effect direction of these drugs on uterine hemodynamic parameters (improved/unchanged/worsened). As the uterus lacks autoregulation, we hypothesized improved uterine hemodynamics after administration of vasoactive drugs. METHODS:Databases were searched from inception until November 2023. Clinical studies and animal studies in species with hemochorial placentas were eligible. The primary outcome was uterine hemodynamics (uterine blood flow or uterine resistance). Meta-analyses were performed on standardized mean differences (SMDs). Risk of bias was assessed using ROBINS-I and SYRCLE tools. RESULTS:Twelve clinical studies involving 368 patients and 21 preclinical studies involving 206 animals were included in the analysis, investigating thirteen different drugs. Apart from three randomized controlled preclinical trials, all other studies used a before-after (impact) design. Both clinical and preclinical data showed unchanged or worsened uterine hemodynamics with ephedrine, phenylephrine, and norepinephrine. The only drug with improved uterine hemodynamics was angiotensin II, but only in preclinical studies (standardized mean difference 0.66; 95% confidence interval, 0.02 to 1.30). There was considerable heterogeneity in both clinical and preclinical studies. Risk of bias was low to moderate in clinical studies. The before-after design of preclinical studies is inherently susceptible to bias. CONCLUSION:These findings suggest that vasoactive drugs do not improve uterine hemodynamics. Further research is warranted to investigate the clinical relevance of worsened uterine hemodynamics, especially in prolonged maternal and fetal surgery under general anesthesia, during laparoscopy, and in pregnancies with compromised fetal perfusion.

BACKGROUND:General anesthesia during pregnancy is not uncommon, for example, for trauma surgery, cerclage, or cesarean delivery. Current recommendations are to maintain maternal partial pressure of carbon dioxide in arterial blood (paCO2) at 30 mm Hg, which is based solely on the average maternal paCO2 in awake pregnant women. However, there is no evidence that this target, compared to other targets, would enable optimal conditions for the fetus during general anesthesia. Maternal paCO2 can affect uterine blood flow, affinity of hemoglobin for oxygen, and fetal CO2 elimination. In this study, a range of potential targets of maternal paCO2 was investigated in the ovine model, aiming to determine which target is most conducive to physiological fetal blood gas values during laparotomy with general anesthesia. METHODS:Ten time-mated pregnant Swifter ewes with a gestational age of 93 to 104 days were used. During the first phase of the experiment, anesthesia was induced, all ewes were ventilated to target a physiological maternal paCO2 of 30 mm Hg, a maternal laparotomy was performed, and a fetal microcatheter was inserted surgically to enable blood sampling from the fetal aorta. Thereafter, in the second phase of the experiment, the 10 pregnant ewes were randomized to 10 different targets of maternal paCO2 between 27 and 50 mm Hg (1 target for each ewe), and maternal ventilation was adjusted accordingly. Forty-five minutes later, maternal and fetal arterial blood gas samples were analyzed. Linear regression models were used to estimate maternal paCO2 enabling physiologic fetal parameters, including fetal paCO2 (primary outcome). RESULTS:A maternal paCO2 of 27.4 mm Hg (95% confidence interval, 23.1-30.3) enabled physiological fetal paCO2. Each increase in maternal paCO2 by 1 mm Hg, on average, increased fetal paCO2 by 0.94 mm Hg (0.69-1.19). This relationship had a strong correlation (r² = 0.906). No fetuses died during the experiment. CONCLUSIONS:This study provides experimental support for the clinical recommendation to maintain maternal paCO2 close to the physiologic value of 30 mm Hg during general anesthesia for maternal laparotomy in pregnancy as it is conducive to physiological fetal blood gas values. Given the lower bound of the 95% confidence interval, the possibility that a lower maternal paCO2 would improve fetal gas exchange cannot be excluded.

Up to 1% of pregnant women undergo anaesthesia for surgery (e.g. appendicectomy) [1]. The US Food and Drug Administration warned that repeated or prolonged use of general anaesthesia in pregnant women may impair fetal neurodevelopmental outcomes [2, 3]. Recently, we reported the neurodevelopmental outcomes of children aged 2–18 y that had been prenatally exposed to anaesthesia for maternal surgery [4]. The primary outcome of this bidirectional cohort study was the t-score of the global executive composite of the Behaviour Rating Inventory of Executive Function (BRIEF-GEC). In the entire study population (which included all modes of anaesthesia and all surgery types), there was no evidence for impaired neurodevelopment, with a weighted mean difference (wMD) (95%CI) for BRIEF-GEC of exposed minus unexposed children of 1.9 (−0.4 to 4.2). In contrast, exploratory analyses showed significant impairments in the subgroups of children prenatally exposed to general anaesthesia, wMD 3.1 (0.7 to 5.5); intra-abdominal surgery, wMD 4.3 (1.4 to 7.2); prolonged anaesthesia (> 1 h), wMD 3.7 (0.7 to 6.7) and laparoscopic surgery, wMD 4.5 (1.0 to 7.9). Except for experts in the field, these effect sizes, as represented by wMD, may be considered to have limited clinical utility. Therefore, the aim of this study was to compare and contextualise the effect sizes of prenatal anaesthesia exposure with those of other risk factors and conditions potentially affecting neurodevelopment. PubMed, EMBASE and Web of Science were searched systematically to identify all studies reporting BRIEF-GEC effect sizes (online Supporting Information Appendix S1). After deduplication, screening for eligible articles (title, abstract and full text) was done independently by two authors (TB and JB) using Rayyan. Eligible studies reported the BRIEF-GEC of children exposed to a potential risk factor, or suffering from a condition potentially affecting neurodevelopment, vs. children not exposed to this risk factor or absence of the condition (online Supporting Information Appendix S2 and Fig. 1). Data were extracted using a standardised table. The (adjusted) mean differences of BRIEF-GEC of the risk factors/conditions and prenatal anaesthesia exposure were displayed graphically. In all, 24 studies and 33 risk factors/conditions were included. The effect size of prenatal exposure to anaesthesia, reported as the primary outcome in our previous study [4], is comparable to the effect of a child spending ≥ 2 h per day in front of a screen (tablet, computer, television), or of maternal paracetamol intake (≥ 15 times) during pregnancy, or of > 2 h weekend catch-up sleep of a child (Fig. 1). The neurodevelopmental effects of prenatal exposure to general anaesthesia, prolonged anaesthesia, intra-abdominal surgery and laparoscopic surgery (exploratory outcomes in our previous study) were comparable with the effects of prenatal exposure to pesticides, a silent cerebral infarct in the child, < 9 h sleep per day, more green vegetation in the natural environment during childhood and a very low birthweight of the child. Neurodevelopmental effects of prenatal anaesthesia exposure were smaller than the effects of maternal opioid maintenance therapy during pregnancy, traumatic brain injury, dyslexia, autism spectrum disorder and attention deficit-hyperactivity disorder. In our previous study [4], 90% of exposed children were exposed prenatally a single time to an average duration of 91 min of anaesthesia for maternal surgery. The magnitude of these neurodevelopmental effects is comparable with those associated with factors frequently encountered during pregnancy and childhood in any child. We previously reported that in the general population, the neurodevelopmental effects of prenatal exposure to anaesthesia were comparable to the effects caused by the parents’ university level, maternal age and ownership of the family residence. Similarly, it has been reported that the neurodevelopmental effects of postnatal anaesthesia are smaller than the effects associated with the gender of the child, birth month, maternal education level and intelligence, prematurity and smoking during pregnancy [5, 6]. In the subgroups of general anaesthesia, prolonged anaesthesia, intra-abdominal surgery and laparoscopic surgery, we reported statistically significant effect sizes that were in the range of up to half a standard deviation of the unexposed children and corresponding in this analysis with the effects associated with a very low birthweight. Caution is required for this interpretation as our analyses were only exploratory. In addition, it remains unknown to which factor these effects can most likely be attributed: anaesthesia, surgery, the underlying disease, other (unknown) factors or a combination of them all. The contextualisation of observed effect sizes may be helpful to clinicians when explaining and construing the effects of prenatal anaesthesia to patients, for example during a consent discussion. We included only recent studies in which the confounding effect of socio-economic status was considered. For the limitations of this analysis and the need for further study, we refer to our previous study [4]. In summary, the findings of the present systematic review corroborate the conclusions of our previous study: overall, the neurodevelopmental effects of prenatal exposure to anaesthesia are comparable with those of ‘innocent’ risk factors. TB, SD and SR are funded by the European Society of Anaesthesiology and Intensive Care Young Investigator Start-up Grant 2021, the Society for Anaesthesia and Resuscitation of Belgium research grant 2019 and the Obstetric Anaesthetists’ Association International Grant 2019. No other competing interests declared. Appendix S1. Search string. Appendix S2. Eligibility criteria. Appendix S3. References for Figure 1. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.

( J Clin Anesth . 2023;85:111050) This study examines the impact of repeated and prolonged exposure to sevoflurane anesthesia on fetal neurodevelopment in pregnant sheep. The rationale behind this research lies in the concern over the possible negative effects of long or repeated exposure to anesthesia during pregnancy on fetal brain development, particularly based on findings in animal studies. The experiment involves exposing pregnant sheep to different anesthesia regimens and conducting neurobehavioral assessments of their offspring. It aims to determine whether repeated exposure results in neurodevelopmental impairments. The study follows ethical guidelines designed to align with principles promoting humane animal research.

ABSTRACTObjectivesTo define and grade fetal and maternal adverse events following fetal surgery for spina bifida and to report on the impact of engaging patients in collecting follow‐up data.MethodsThis prospective single‐center audit included 100 consecutive patients undergoing fetal surgery for spina bifida between January 2012 and December 2021. In our setting, patients return to their referring unit for further pregnancy care and delivery. On discharge, referring hospitals were requested to return outcome data. For this audit, we prompted patients and referring hospitals to provide data in cases of missing outcomes. Outcomes were categorized as missing, returned spontaneously or returned following additional request, by the patient and/or referring center. Postoperative maternal and fetal complications until delivery were defined and graded according to Maternal and Fetal Adverse Event Terminology (MFAET) and the Clavien–Dindo classification.ResultsThere were no maternal deaths, but severe maternal complications occurred in seven women (anemia in pregnancy, postpartum hemorrhage, pulmonary edema, lung atelectasis, urinary tract obstruction and placental abruption). No cases of uterine rupture were reported. Perinatal death occurred in 3% of fetuses and other severe fetal complications in 15% (perioperative fetal bradycardia/cardiac dysfunction, fistula‐related oligohydramnios, chorioamnionitis and preterm prelabor rupture of membranes (PPROM) before 32 weeks). PPROM occurred in 42% of patients and, overall, delivery took place at a median gestational age of 35.3 weeks (interquartile range, 34.0–36.6 weeks). Information provided following additional request, from both centers and patients but mainly from the latter, reduced missing data by 21% for gestational age at delivery, 56% for uterine‐scar status at birth and 67% for shunt insertion at 12 months. Compared with the generic Clavien–Dindo classification, the MFAET system ranked complications in a more clinically relevant way.ConclusionsThe nature and rate of severe complications following fetal surgery for spina bifida were similar to those reported in other large series. Spontaneous return of outcome data by referring centers was low, yet patient empowerment improved data collection. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.