Maternal "mirror" syndrome: Evaluating the benefits of fetal therapy.

OBJECTIVE: To evaluate maternal and perinatal outcomes following fetal intervention in the context of maternal "mirror" syndrome. STUDY DESIGN: A multicenter retrospective study of all cases of fetal hydrops complicated by maternal "mirror" syndrome and treated by any form of fetal therapy between 1995 and 2022. Medical records and ultrasound images of all cases were reviewed. "Mirror" syndrome was defined as fetal hydrops and/or placentomegaly associated with the maternal development of pronounced edema, with or without pre-eclampsia. Fetal hydrops was defined as the presence of abnormal fluid collections in ≥2 body cavities. RESULTS: Twenty-one pregnancies met the inclusion criteria. Causes of fetal hydrops and/or placentomegaly included fetal lung lesions (n = 9), twin-twin transfusion syndrome (n = 6), severe fetal anemia (n = 4), and others (n = 2). Mean gestational age at "mirror" presentation was 27.0 ± 3.8 weeks. Maternal "mirror" syndrome was identified following fetal therapeutic intervention in 14 cases (66.6%). "Mirror" symptoms resolved or significantly improved before delivery in 8 (38.1%) cases with a mean interval from fetal intervention to maternal recovery of 13.1 days (range 4-35). Three women needed to be delivered because of worsening "mirror" syndrome. Of the 21 pregnancies treated (27 fetuses), there were 15 (55.5%) livebirths, 7 (25.9%) neonatal deaths and 5 (18.5%) intra-uterine deaths. CONCLUSION: Following successful treatment and resolution of fetal hydrops, maternal "mirror" syndrome can improve or sometimes completely resolve before delivery. Furthermore, the recognition that "mirror" syndrome may arise only after fetal intervention necessitates hightened patient maternal surveillance in cases of fetal hydrops.

Intravenous immunoglobulin in the management of severe early onset red blood cell alloimmunisation.

Our objective was to assess the effect of maternal intravenous immunoglobulin (IVIG) administration for severe red blood cell (RBC) alloimmunisation on fetal outcomes. This is a case-control study. Women with a history of severe early onset alloimmunisation resulting in fetal loss in a previous pregnancy and high anti-D or anti-K antibody titres received IVIG in a subsequent pregnancy. We assessed gestational age at first transfusion and fetal outcomes in the subsequent pregnancy and compared these with the outcomes in the previous pregnancy. The most responsible antibody was anti-D in 17 women and anti-K in two others, whilst seven had more than one antibody. In all, 19 women received IVIG in 22 pregnancies, two of which did not even need an intrauterine transfusion (IUT). For previous early losses despite transfusion, IVIG was associated with a relative increase in fetal haemoglobin between treated and untreated pregnancies of 36.5 g/L (95% confidence interval 19.8-53.2, p = 0.0013) and improved perinatal survival (eight of eight vs. none of six, p = 0.001). For previous losses at <20 weeks, it enabled first transfusion deferral in subsequent pregnancies to at least 19.9 weeks (mean 23.2 weeks). Overall, IVIG decreases the severity of haemolytic disease of the fetus and newborn and allows deferral of the first IUT to a safer gestation in severe early-onset RBC alloimmunisation and rarely may even avoid the need for IUT entirely.

Development of a Training Model for Teaching Intrauterine Fetal Blood Transfusion.

This article describes an inexpensive simulator developed for teaching intrauterine blood transfusion. The model is constructed from a boneless chicken thigh folded over a Penrose drain placed in a water-filled snap-lock lid container and covered by melted ballistic gel to simulate the fetal intrahepatic vessel. Participants valued this educational tool and reported feeling the model was practical and realistic. This low-cost, high-fidelity model provides realistic tissue resistance and represents a sonographically accurate intrahepatic fetal blood transfusion training tool.

Monochorionic monoamniotic twin pregnancies.

Monoamniotic twin pregnancies are rare, but early diagnosis of such pregnancies is critical, as the incidence of complications in these pregnancies is much higher than in diamniotic or dichorionic twin pregnancies. Overall, only 70% of all monoamniotic twins will survive. Furthermore, approximately half of fetal deaths in these pregnancies are because of the high incidence of fetal anomalies (15%-25%), such as twin reversed arterial perfusion sequence and conjoined twinning. Therefore, early anatomy screening in the first trimester of pregnancy is recommended. Other causes of fetal death in these pregnancies include twin-twin transfusion syndrome, tight cord entanglement, or acute hemodynamic imbalances through the large placental vascular anastomoses. After viability, fetal surveillance can be intensified, as this decreases the risk of in utero death. Both inpatient and outpatient surveillance are reasonable. If otherwise uncomplicated, monoamniotic twins should be delivered at 33 to 34 weeks' gestation. Most centers will deliver by cesarean delivery, but some continue to advocate for vaginal delivery. Lastly, neonatal morbidity is high in monoamniotic twin pregnancies and is mainly related to prematurity.

Outcome predictors for maternal red blood cell alloimmunisation with anti-K and anti-D managed with intrauterine blood transfusion.

Red blood cell (RBC) alloimmunisation with anti-D and anti-K comprise the majority of cases of fetal haemolytic disease requiring intrauterine red cell transfusion (IUT). Few studies have investigated which haematological parameters can predict adverse fetal or neonatal outcomes. The aim of the present study was to identify predictors of adverse outcome, including preterm birth, intrauterine fetal demise (IUFD), neonatal death (NND) and/or neonatal transfusion. We reviewed the records of all pregnancies alloimmunised with anti-K and anti-D, requiring IUT over 27 years at a quaternary fetal centre. We reviewed data for 128 pregnancies in 116 women undergoing 425 IUTs. The median gestational age (GA) at first IUT was significantly earlier for anti-K than for anti-D (24·3 vs. 28·7 weeks, P = 0·004). Women with anti-K required more IUTs than women with anti-D (3·84 vs. 3·12 mean IUTs, P = 0·036) and the fetal haemoglobin (Hb) at first IUT was significantly lower (51.0 vs. 70.5 g/l, P = 0·001). The mean estimated daily decrease in Hb did not differ between the two groups. A greater number of IUTs and a slower daily decrease in Hb (g/l/day) between first and second IUTs were predictive of a longer period in utero. Earlier GA at first IUT and a shorter interval from the first IUT until delivery predicted IUFD/NND. Earlier GA and lower Hb at first IUT significantly predicted need for phototherapy and/or blood product use in the neonate. In the anti-K group, a greater number of IUTs was required in women with a higher titre. Furthermore, the higher the titre, the earlier the GA at which an IUT was required in both groups. The rate of fall in fetal Hb between IUTs decreased, as the number of transfusions increased. Our present study identified pregnancies at considerable risk of an unfavourable outcome with anti-D and anti-K RBC alloimmunisation. Identifying such patients can guide pregnancy management, facilitates patient counselling, and can optimise resource use. Prospective studies can also incorporate these characteristics, in addition to laboratory markers, to further identify and improve the outcomes of these pregnancies.

Prophylactic Administration of Uterotonics to Prevent Postpartum Hemorrhage in Women Undergoing Cesarean Delivery for Arrest of Labor: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether prophylactic administration of oxytocin plus ergonovine or oxytocin plus carboprost is more effective than oxytocin alone in reducing the need for additional uterotonics among women undergoing cesarean delivery for labor arrest. METHODS: In this double-blind, three-arm randomized controlled trial, participants were assigned to receive either oxytocin 5 units intravenous alone, or with ergonovine 0.25 mg intravenous or carboprost 0.25 mg intramuscular immediately after delivery, followed with maintenance infusion of oxytocin 40 milliunits/minute in all groups. Uterine tone was assessed at 3, 5, and 10 minutes after delivery, and additional uterotonics were administered if deemed necessary. The primary outcome was intraoperative need for additional uterotonics. Secondary outcomes included uterine tone, calculated blood loss, and side effects. A sample size of 34 per group (n=102), based on the null hypothesis that there is no association between treatment assignment and the need for additional uterotonics, permitted independent post hoc pairwise comparisons between oxytocin plus ergonovine, oxytocin plus carboprost, and oxytocin alone using an adjusted P-value of .025. The association between the need for additional uterotonics and treatment group was assessed using the χ2 test. RESULTS: From June 2013 through July 2019, 105 participants were randomized (35 per group) and data from 100 participants were analyzed: oxytocin (n=35), oxytocin plus ergonovine (n=33), and oxytocin plus carboprost (n=32). There was no difference in the requirement of additional intraoperative uterotonics across groups (oxytocin [37%] vs oxytocin plus ergonovine [33%] vs oxytocin plus carboprost [34%], P=.932). Uterine tone and calculated blood loss were similar across groups. Incidence of nausea or vomiting was higher in oxytocin plus ergonovine (85%; odds ratio [OR] 5.3, 95% CI 1.7-16.9, P=.003) and oxytocin plus carboprost (72%; OR 2.4, 95% CI 0.9-6.7, P=.086) compared with the oxytocin (51%) group. CONCLUSION: Compared with oxytocin alone, prophylactic use of a combination of uterotonic drugs did not reduce the need for additional uterotonics at cesarean delivery for labor arrest. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT01869556.

Selective fetal reduction in complicated monochorionic twin pregnancies: A comparison of techniques.

OBJECTIVE: To compare perinatal outcomes associated with three methods of selective reduction in complicated monochorionic (MC) twin pregnancies: bipolar cord coagulation (BC), fetoscopic or ultrasound guided laser cord occlusion and radiofrequency ablation (RFA). METHODS: Retrospective cohort study of complicated MC twin pregnancies undergoing selective fetal reduction at a tertiary fetal center over a 20-year period. Obstetric and perinatal outcomes were compared. RESULTS: 105 procedures met inclusion criteria: 74 RFAs, 17 lasers and 14 BCs. Procedure duration was significantly shorter for RFA (27.4 ± 15.8 minutes) compared to BC (91.7 ± 38.7 minutes) and laser (83.4 ± 40.4 minutes), P < .0001). The incidence of preterm prelabor rupture of membranes (PPROM) and co-twin demise did not differ between groups, however preterm delivery <34 weeks occurred less frequently following RFA (29.7%), compared to laser (64.7%) or BC (42.9%) (P = .02); delivery <37 weeks was also less frequent following RFA (45.9%), compared to laser (76.5%) or BC (78.6%)(P = .01). The difference in preterm birth<34 weeks between RFA and laser was maintained after adjusting for cord occlusion indication and amnionicity (OR 3.96, 95% CI 1.27-12.31). CONCLUSIONS: In our experience, RFA procedures were simpler, faster and associated with a lower risk of preterm delivery <34 and <37 weeks, compared to laser or BC.

Outcomes of haemoglobin Bart's hydrops fetalis following intrauterine transfusion in Ontario, Canada.

OBJECTIVES: With improved access to intrauterine transfusion (IUT), more fetuses with haemoglobin Bart's hydrops fetalis (HBHF; homozygous α0-thalassaemia) will survive. DESIGN: To evaluate the long-term outcome of affected fetuses with and without IUT in Ontario, Canada, we retrospectively collected data on IUTs and pregnancy outcomes in all cases of HBHF, from 1989 to 2014. Clinical outcome and neurocognitive profiles of long-term survivors were also collected and compared with data from 24 patients with transfusion-dependent ß-thalassaemia (TDT-ß). RESULTS: Of the 99 affected pregnancies (93 prenatally diagnosed), 68 resulted in miscarriage or elective termination of pregnancy. Twelve mothers (12%) continued their pregnancies without IUT, and none of those newborns survived the first week of life. All 13 fetuses that received IUT(s) were live-born, but 3 died due to severe hydrops at birth and 1 died due to infection. The remaining nine survivors, in comparison with TDT-ß patients, had earlier iron overload requiring iron chelation therapy. Endocrinopathies and short stature were more frequent in these patients. Neurocognitive outcome was not significantly affected in five patients who were assessed, and none were diagnosed with intellectual impairment. In three patients, MRI studies demonstrated brain white matter changes in keeping with 'silent' ischaemic infarcts. CONCLUSIONS: In patients with HBHF, IUT is associated with improved survival. While acceptable neurocognitive outcome can be expected, these patients have more clinical complications compared with their TDT-ß counterparts. The clinical and neurocognitive outcomes of HBHF should be discussed in detail when counselling and offering IUT for patients.

Homozygous GLUL deletion is embryonically viable and leads to glutamine synthetase deficiency.

Glutamine synthetase (GS) is the enzyme responsible for the biosynthesis of glutamine, providing the only source of endogenous glutamine necessary for several critical metabolic and developmental pathways. GS deficiency, caused by pathogenic variants in the glutamate-ammonia ligase (GLUL) gene, is a rare autosomal recessive inborn error of metabolism characterized by systemic glutamine deficiency, persistent moderate hyperammonemia, and clinically devastating seizures and multi-organ failure shortly after birth. The four cases reported thus far were caused by homozygous GLUL missense variants. We report a case of GS deficiency caused by homozygous GLUL gene deletion, diagnosed prenatally and likely representing the most severe end of the spectrum. We expand the known phenotype of this rare condition with novel dysmorphic, radiographic and neuropathologic features identified on post-mortem examination. The biallelic deletion identified in this case also included the RNASEL gene and was associated with immune dysfunction in the fetus. This case demonstrates that total absence of the GLUL gene in humans is viable beyond the embryonic period, despite the early embryonic lethality found in GLUL animal models.

Natural History of Ventriculomegaly in Fetal Agenesis of the Corpus Callosum.

OBJECTIVES: To assess the natural evolution of the size of the fetal lateral ventricles throughout pregnancy in fetuses with callosal anomalies. METHODS: Cases of fetal callosal anomalies were retrospectively classified as isolated or complex based on the presence of other structural or genetic anomalies. Longitudinal ultrasound studies were reviewed, and postnatal outcomes were retrieved for isolated cases. RESULTS: In 135 fetuses, those who first presented after 24 weeks' gestation were more likely to have ventriculomegaly (n = 58 of 68 [85%]) than those who presented before 24 weeks (n = 39 of 67 [58%]; P < .001). In 79 cases that had longitudinal follow-up, the mean increase in ventricular width was 0.6 mm/wk, without a significant difference between isolated and complex cases (mean ± SD, 0.6 ± 1.5 versus 0.6 ± 1.1 mm; P = .45). CONCLUSIONS: Callosal anomalies are associated with progressive ventriculomegaly on prenatal ultrasound imaging, without a difference between isolated and complex anomalies. This feature should be considered part of the disease spectrum. The consequence of progressive ventriculomegaly on the long-term neurodevelopmental outcome is still unknown, and further studies should be aimed at obtaining long-term follow-up of these cases.

Fetal Sclerotherapy for Hydropic Congenital Cystic Adenomatoid Malformations of the Lung Refractory to Steroids: A Case Report and Review of the Literature.

Microcystic congenital cystic adenomatoid malformations (CCAM), when associated with hydrops, carry a dismal prognosis. Options for treatment are limited and experimental, including antenatal corticosteroids, open fetal surgery, laser ablation and, more recently, sclerotherapy. We describe a case of a large, predominantly microcystic CCAM in a hydropic fetus treated successfully with direct interstitial injection of a sclerosant agent (3% sodium tetradecyl sulfate) at 23+3 weeks gestation, after multiple failed courses of steroids. Elective thoracoscopic right lower lobectomy was performed at 1 year of life and there have been no respiratory or other medical morbidities since. A literature review of fetal lung masses treated with sclerosants antenatally reveals that sclerotherapy may represent a novel treatment option for large hydropic microcystic CCAMs, which are unresponsive to corticosteroids. Further studies are required to evaluate the utility and safety of fetal sclerotherapy, as this may represent an alternative minimally invasive treatment option to fetal lobectomy.

Variability in intensive care unit admission among pregnant and postpartum women in Canada: a nationwide population-based observational study.

BACKGROUND: Pregnancy-related critical illness results in approximately 300,000 deaths globally each year. The objective was to describe the variation in ICU admission and the contribution of patient- and hospital-based factors in ICU admission among acute care hospitals for pregnant and postpartum women in Canada. METHODS: A nationwide cohort study between 2004 and 2015, comprising all pregnant or postpartum women admitted to Canadian hospitals. The primary outcome was ICU admission. Secondary outcomes were severe maternal morbidity (a potentially life-threatening condition) and maternal death (during and within 6 weeks after pregnancy). The proportion of total variability in ICU admission rates due to the differences among hospitals was described using the median odds ratio from multi-level logistic regression models, adjusting for individual hospital clusters. RESULTS: There were 3,157,248 identifiable pregnancies among women admitted to 342 Canadian hospitals. The overall ICU admission rate was 3.2 per 1000 pregnancies. The rate of severe maternal morbidity was 15.8 per 1000 pregnancies, of which 10% of women were admitted to an ICU. The most common severe maternal morbidity events included postpartum hemorrhage (n = 16,364, 0.52%) and sepsis (n = 11,557, 0.37%). Of the 195 maternal deaths (6.2 per 100,000 pregnancies), only 130 (67%) were admitted to ICUs. Patients dying in hospital, without admission to ICU, included those with cardiovascular compromise, hemorrhage, and sepsis. For 2 pregnant women with similar characteristics at different hospitals, the average (median) odds of being admitted to ICU was 1.92 in 1 hospital compared to another. Hospitals admitting the fewest number of pregnant patients had the highest incidence of severe maternal morbidity and mortality. Patient-level factors associated with ICU admission were maternal comorbidity index (OR 1.88 per 1 unit increase, 95%CI 1.86-1.99), urban residence (OR 1.09, 95%CI 1.02-1.16), and residing at the lowest income quintile (OR 1.44, 95%CI 1.34-1.55). CONCLUSIONS: Most women who experience severe maternal morbidity are not admitted to an ICU. There exists a wide hospital-level variability in ICU admission, with patients living in urban locations and patients of lowest income levels most likely to be admitted to ICU. Cardiovascular compromise, hemorrhage, and sepsis represent an opportunity for improved patient care and outcomes.

Association of Maternal Age With Severe Maternal Morbidity and Mortality in Canada.

Importance: Over the past 2 decades, there has been a trend toward increasing maternal age in many high-income countries. Maternal age may lead to greater attendant morbidity and mortality for Canadian mothers. Objective: To investigate the association of maternal age, adjusting for patient-level and hospital-level factors, with severe maternal morbidity (SMM) and maternal death in Canada. Design, Setting, and Participants: A nationwide population-based cohort study of all antepartum, peripartum, and postpartum women and adolescents seen at Canadian acute care hospitals from April 1, 2004, to March 31, 2015. All analyses were completed on September 13, 2018. Exposures: Maternal age at the index delivery. Main Outcomes and Measures: Severe maternal morbidity and maternal death during pregnancy and within 6 weeks after termination of pregnancy. Results: During the study period, there were 3 162 303 new pregnancies (mean [SD] maternal age, 29.5 [5.6] years) and 3 533 259 related hospital admissions. There were 54 219 episodes of SMM (17.7 cases per 1000 deliveries) in the entire study period, with a 9.8% relative increase from 2004-2005 to 2014-2015, in addition to an increasing proportion of pregnancies to older mothers. Independent patient-level factors associated with SMM included increasing Maternal Comorbidity Index; maternal age 19 years or younger and 30 years or older, with the greatest risk experienced by women 45 years or older (odds ratio [OR], 2.69; 95% CI, 2.34-3.06 compared with maternal age 20-24 years); and lowest income quintile (OR, 1.19; 95% CI, 1.14-1.22 compared with highest income quintile). Hospital-level factors associated with SMM included specific provinces. Independent patient-level factors associated with maternal mortality included increasing Maternal Comorbidity Index, age 40 to 44 years (OR, 3.39; 95% CI, 1.68-6.82 compared with age 20-24 years), age 45 years or older (OR, 4.39; 95% CI, 1.01-19.10 compared with age 20-24 years), and lowest income quintile (OR, 4.14; 95% CI, 2.03-8.50 compared with highest income quintile). Hospital-level factors associated with maternal mortality included lowest hospital pregnancy volume. Conclusions and Relevance: In Canada, maternal age and SMM have increased over the past decade. Results of this study suggest that province of residence, maternal comorbidity, residence income quintile, and extremes of maternal age, especially those 45 years or older, were associated with SMM and mortality. These findings are relevant to prospective parents, their health care team, and public health planning.

Impact of introduction of noninvasive prenatal testing on uptake of genetic testing in fetuses with central nervous system anomalies.

OBJECTIVE: To evaluate the impact of introduction of noninvasive prenatal testing (NIPT) on the uptake of invasive testing in pregnancies complicated by fetal central nervous system (CNS) anomalies. METHODS: Retrospective review of all singleton pregnancies complicated by fetal CNS anomalies seen at a single tertiary center between 2010 and 2017. Cases who had undergone invasive testing or NIPT prior to the diagnosis of the CNS anomaly were excluded. Cases were segregated according to whether they were seen prior to introduction of NIPT (group A, 2010-2013) or thereafter (group B, 2014-2017). We examined the rate of invasive and noninvasive genetic testing in each group. RESULTS: We retrieved 500 cases: 308 (62%) were isolated CNS anomalies, and 192 (38%) had additional structural anomalies. In the total cohort, 165 women (33%) underwent expectant management with no further prenatal genetic testing, 166 (33%) had invasive testing, 52 (10%) had NIPT, and 117 pregnancies (23%) were terminated without further prenatal investigations. The introduction of NIPT significantly decreased the number of pregnancies having no testing (44% group A vs 22% in group B, p < .0001), particularly in the group presenting with isolated ventriculomegaly, but did not affect the uptake of invasive testing (34% vs 32%, respectively; p = .61). NIPT would have missed 4% of pathogenic copy number variants (CNVs) in the group of cases with isolated brain anomalies and 11% of CNVs in cases with complex anomalies. CONCLUSIONS: Uptake of invasive prenatal testing in fetuses with brain anomalies was not affected by NIPT. However, the incidence of no genetic testing was significantly reduced. NIPT was a suboptimal testing strategy in this population as it missed a significant number of subchromosomal genetic anomalies.

Risk prediction models for maternal mortality: A systematic review and meta-analysis.

PURPOSE: Pregnancy-related critical illness leads to death for 3-14% of affected women. Although identifying patients at risk could facilitate preventive strategies, guide therapy, and help in clinical research, no prior systematic review of this literature exploring the validity of risk prediction models for maternal mortality exists. Therefore, we have systematically reviewed and meta-analyzed risk prediction models for maternal mortality. METHODS: Search strategy: MEDLINE, EMBASE and Scopus, from inception to May 2017. Selection criteria: Trials or observational studies evaluating risk prediction models for maternal mortality. Data collection and analysis: Two reviewers independently assessed studies for eligibility and methodological quality, and extracted data on prediction performance. RESULTS: Thirty-eight studies that evaluated 12 different mortality prediction models were included. Mortality varied across the studies, with an average rate 10.4%, ranging from 0 to 41.7%. The Collaborative Integrated Pregnancy High-dependency Estimate of Risk (CIPHER) model and the Maternal Severity Index had the best performance, were developed and validated from studies of obstetric population with a low risk of bias. The CIPHER applies to critically ill obstetric patients (discrimination: area under the receiver operating characteristic curve (AUC) 0.823 (0.811-0.835), calibration: graphic plot [intercept-0.09, slope 0.92]). The Maternal Severity Index applies to hospitalized obstetric patients (discrimination: AUC 0.826 [0.802-0.851], calibration: standardized mortality ratio 1.02 [0.86-1.20]). CONCLUSIONS: Despite the high heterogeneity of the study populations and the limited number of studies validating the finally eligible prediction models, the CIPHER and the Maternal Severity Index are recommended for use among critically ill and hospitalized pregnant and postpartum women for risk adjustment in clinical research and quality improvement studies. Neither index has sufficient discrimination to be applicable for clinical decision making at the individual patient level.

Teaching an Experienced Multidisciplinary Team About Postpartum Hemorrhage: Comparison of Two Different Methods.

OBJECTIVE: Morbidity from postpartum hemorrhage (PPH) affects 20% of pregnancies worldwide and remains a significant cause of maternal mortality. This study compared the impressions of experienced clinicians on the effect of two methods of educational interventions in a MoreOB training program designed to improve recognition and management of PPH. METHODS: Participants were exposed to a traditional didactic lecture and an interactive clinical intervention exercise incorporating video simulation of a PPH event with opportunities for feedback and discussion of how to proceed. They were then invited to respond to a questionnaire regarding their impressions of both methods. RESULTS: Of 150 participants, 110 completed the questionnaire. Respondents considered the interactive format to be more effective (55%) and enjoyable (72%) than the traditional didactic format. The majority (81%), however, still recommended a mixture of both interactive and didactic formats in future events, supported by a multidisciplinary drill. CONCLUSION: Clinical learners value interactivity and mutual reinforcement among varied learning exercises in their educational experiences. Future educational programs may consider incorporating similar methods in order to maximize participants' receptiveness.

Objectif : La morbidité attribuable à l'hémorragie postpartum (HPP) affecte 20 % des grossesses à l'échelle mondiale et demeure une cause importante de mortalité maternelle. Cette étude a comparé les impressions de cliniciens expérimentés quant aux effets de deux méthodes d'intervention pédagogique (dans le cadre d'un programme de formation AMPROOB) conçues pour améliorer la reconnaissance et la prise en charge de l'HPP. Méthodes : Les participants ont pris part à un exposé magistral traditionnel et à un exercice interactif d'intervention clinique alliant la simulation vidéo d'un événement d'HPP à des occasions de formuler des commentaires et de participer à des discussions sur la façon de procéder. Nous les avons par la suite conviés à répondre à un questionnaire au sujet de leurs impressions quant à ces deux méthodes. Résultats : Cent dix des 150 participants ont rempli le questionnaire. Les répondants étaient d'avis que le format interactif était plus efficace (55 %) et plaisant (72 %) que le format magistral traditionnel. La majorité d'entre eux (81 %) ont cependant recommandé l'offre d'une approche mixte intégrant les deux formats dans le cadre des événements à venir, le tout devant alors être soutenu par la tenue d'un exercice d'entraînement multidisciplinaire. Conclusion : Dans le domaine clinique, les apprenants accordent de l'importance à l'interactivité et au renforcement mutuel de divers exercices d'apprentissage dans le cadre de leurs expériences pédagogiques. Les futurs programmes pédagogiques pourraient envisager l'intégration de méthodes semblables afin de maximiser la réceptivité des participants.

Carbetocin at Cesarean delivery for labour arrest: a sequential allocation trial to determine the effective dose.

PURPOSE: The aim of this study was to estimate the effective dose 90% (ED90) of carbetocin to provide adequate uterine tone at Cesarean delivery (CD) for labour arrest. METHODS: We conducted a double-blind dose-finding study of carbetocin using a biased-coin up-and-down design in women undergoing CD for labour arrest under epidural anesthesia. Forty healthy term pregnant women who had received at least three hours of oxytocin infusion during labour were recruited for the study. Carbetocin was administered intravenously upon delivery of the anterior shoulder of the fetus. The first patient received 20 µg, and the dose for the subsequent patient was determined according to the response of the previous patient as per the biased-coin allocation scheme using increments or decrements of 20 µg (maximum 140 µg). Uterine tone was assessed by the obstetrician and rated as satisfactory or unsatisfactory throughout the intraoperative period. The primary outcome was satisfactory uterine tone with no need for additional uterotonic drugs intraoperatively. Secondary outcomes included use of additional uterotonic drugs postoperatively in the first 24 hr, estimated blood loss, and adverse effects. RESULTS: The ED90 of carbetocin to produce adequate uterine tone was estimated at 121 µg (95% confidence interval [CI]: 111 to 130; 99% CI: 108 to 133) using the truncated Dixon and Mood (DM) method. The isotonic estimator of ED90 was 140 µg; however, the observed response rate across all doses was < 90%. Also, the 95% CI of the DM estimator is likely to have lower than expected coverage, while the 99% CI may have about 90% coverage. Therefore, these results should be interpreted with caution. The overall median (range) estimated blood loss was 1,014 (104-2,436) mL. The overall incidence of hypotension and tachycardia were 45% and 57.5%, respectively. At a dose of 140 µg, the incidence of tachycardia and intraoperative arrhythmias was 76% and 14%, respectively. CONCLUSION: The ED90 of carbetocin at CD for labour arrest, as determined in our study, should be interpreted with caution since it may be underestimated. This dose is higher than the currently recommended dose of 100 µg at elective CD and should not be used routinely given the uncertainty regarding its efficacy and the high incidence of arrhythmias at higher doses. This trial was registered at ClinicalTrials.gov, number: NCT01725243.

Carbetocin at elective Cesarean delivery: a sequential allocation trial to determine the minimum effective dose.

PURPOSE: The purpose of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 90% of females (ED90) undergoing elective Cesarean delivery (CD) under spinal anesthesia. METHODS: We conducted a double-blind dose-finding study of carbetocin. Forty females undergoing elective CD received carbetocin intravenously upon delivery of the fetus. The dose of carbetocin for each patient was determined according to a biased-coin up-and-down sequential allocation scheme designed to cluster doses close to ED90. The initial dose was 10 µg, with increments/decrements of 5 µg. The anesthesiologist, obstetrician, and patient were blinded to the dose. The obstetrician assessed the uterine tone at one-minute intervals for five minutes after carbetocin administration. In case of unsatisfactory tone, additional uterotonics were administered. The primary outcome was requirement for additional intraoperative uterotonics. Secondary outcomes were postoperative requirement for additional uterotonics within 24 hr of delivery, estimated blood loss and side effects. RESULTS: The ED90 of carbetocin was 14.8 µg (95% confidence interval 13.7 to 15.8). Thirty-seven patients (92.5%) had adequate uterine tone with no requirement of additional intraoperative uterotonics. Two patients (5%) required postoperative uterotonics within 24 hr. The overall mean (SD) estimated blood loss was 786 (403) mL and the overall incidence of hypotension (decrease in systolic blood pressure ≥ 20% baseline) was 37.5%. CONCLUSION: Based on our study, the ED90 of carbetocin at elective CD is less than one-fifth the currently recommended dose of 100 µg. This study was registered at clinicaltrials.gov (NCT-01651130).

Carbetocin at elective Cesarean delivery: a randomized controlled trial to determine the effective dose, part 2.

PURPOSE: The aim of this study was to determine the intravenous dose of carbetocin required to produce effective uterine contraction in 95% of women (ED95) undergoing elective Cesarean delivery under spinal anesthesia. METHODS: One hundred and twenty term pregnant women at low risk for postpartum hemorrhage (PPH) undergoing elective Cesarean delivery under spinal anesthesia were randomly allocated to receive carbetocin in doses of 20, 40, 60, 80, or 100 µg iv upon delivery of the fetus. The obstetrician evaluated the efficacy of uterine tone as satisfactory or unsatisfactory, and in case of unsatisfactory tone, additional uterotonics were administered as per routine institutional practice. The primary outcome measure was satisfactory uterine tone at two minutes after carbetocin administration, and the secondary outcomes were the estimated blood loss, need for additional uterotonic agents within 24 hr, and side effects. RESULTS: Overall satisfactory uterine tone at two minutes was observed in 94.2% (113/120) of the women, and there was no difference across the different study groups. It was not possible to calculate the ED95 of carbetocin due to the even distribution of women with unsatisfactory uterine tone at two minutes across all dose groups (P = 0.60). Additional uterotonics within 24 hr were required in 13% (16/120) of the women. Side effects were similar across all dose groups, with an overall 42.5% incidence of hypotension following the administration of carbetocin. CONCLUSIONS: In women at low risk for PPH undergoing elective Cesarean delivery under spinal anesthesia, carbetocin is similarly effective in doses of 20-100 µg. There is a high incidence of hypotension associated with carbetocin in these doses. Further dose-finding studies are warranted, including doses lower than 20 µg. This trial was registered at www.clinicaltrials.gov (NCT01428817).