Severe Maternal Morbidity and Maternal Mortality Associated with Assisted Reproductive Technology.

OBJECTIVE: To assess the association between use of assisted reproductive technologies (ART) and severe maternal morbidity and maternal mortality (SMM). METHODS: We carried out a cohort study that included all hospital deliveries at ≥20 weeks gestation in Canada (excluding Québec) between April 2009 and March 2018. Outcomes of interest included composite SMM and SMM types (e.g., severe preeclampsia, HELLP syndrome, and eclampsia; severe hemorrhage; acute renal failure). Multivariable regression was used to estimate crude and adjusted rate ratios (RR and aRR) and 95% confidence intervals (CI). RESULTS: The study included 2 535 056 women, of whom 72 023 (2.8%) delivered following the use of ART. The composite SMM rate for women who used ART was 34.7 per 1000 deliveries (95% CI 33.0-36.0) versus 11.5 per 1000 deliveries (95% CI 11.4-11.6) for women who did not use ART (RR 3.01; 95% CI 2.89-3.14). ART use was associated with SMM types such as severe preeclampsia, HELLP syndrome, and eclampsia (RR 3.50; 95% CI 3.27-3.73), severe hemorrhage (RR 3.58, 95% CI 3.27-3.92), and acute renal failure (RR 6.79; 95% CI 5.78-7.98). Associations between ART and composite SMM were attenuated but remained elevated after adjusting for maternal characteristics (aRR 2.34; 95% CI 2.24-2.45). Women who used ART and had a multi-fetal pregnancy had a 4.7 times higher rate of composite SMM compared with women who did not use ART and delivered singletons. CONCLUSION: Women who deliver following the use of ART have increased risks of SMM and require counselling that includes mention of the lower risks of SMM associated with ART-conceived singleton pregnancy.

Anxiety among women experiencing medically complicated pregnancy: A systematic review and meta-analysis.

BACKGROUND: Symptoms of anxiety are common among pregnant and postpartum women, and 15%-20% of pregnancies are affected by medical complications. Despite this, little is known about the relationship of medical complications in pregnancy and women's experience of anxiety. The purpose of this research was to conduct a systematic review and meta-analysis of differences in anxiety symptom severity among women experiencing a medically complicated versus a medically uncomplicated pregnancy. METHODS: This work was guided by the PRISMA reporting process. Electronic databases MEDLINE and PsycINFO were searched to identify studies that met the inclusion criteria. An adaptation of the Newcastle-Ottawa Quality Assessment Scale for case-control studies was used to perform a quality assessment review. A random-effects meta-analysis was used to calculate the estimated average standardized mean differences. RESULTS: Based on the five studies which met our inclusion criteria, findings provide evidence of higher levels of anxiety symptoms among pregnant women experiencing a medically complicated versus a medically uncomplicated pregnancy. Despite considerable heterogeneity, all mean difference estimates are in the direction of greater anxiety in the high-risk groups. CONCLUSIONS: Women experiencing a medically complex pregnancy report higher levels of anxiety symptoms compared to women experiencing a medically uncomplicated pregnancy.

Episiotomy use among vaginal deliveries and the association with anal sphincter injury: a population-based retrospective cohort study.

BACKGROUND: The rate of obstetric anal sphincter injury has increased in recent years, particularly among operative vaginal deliveries. We sought to characterize temporal trends in episiotomy use and to quantify the association between episiotomy and obstetric anal sphincter injury. METHODS: Using a population-based retrospective cohort study design of hospital data from 2004 to 2017, we studied all vaginal deliveries of singleton infants at term gestation in Canada (excluding Quebec). Rates of obstetric anal sphincter injury were contrasted between women who had an episiotomy and those who did not. Log-binomial regression was used to estimate the association between episiotomy and obstetric anal sphincter injury among women with spontaneous and operative vaginal deliveries after controlling for confounders. RESULTS: The study population included 2 570 847 deliveries. Episiotomy use declined significantly among operative vaginal deliveries (53.1% in 2004 to 43.2% in 2017, p < 0.0001) and spontaneous vaginal deliveries (13.5% in 2004 to 6.5% in 2017, p < 0.0001). Episiotomy was associated with higher rates of obstetric anal sphincter injury among spontaneous vaginal deliveries (4.8 with episiotomy v. 2.4% without; adjusted rate ratio [RR] 2.06, 95% confidence interval [CI] 2.00-2.11) and this association remained after stratification by parity and obstetric history. In contrast, episiotomy was associated with lower rates of obstetric anal sphincter injury among forceps deliveries in nulliparous women (adjusted RR 0.63, 95% CI 0.61-0.66), and women with vaginal birth after cesarean (adjusted RR 0.71, 95% CI 0.60-0.85), but not among parous women without a previous cesarean (adjusted RR 1.16, 95% CI 1.00-1.34). INTERPRETATION: Episiotomy use has declined in Canada for all vaginal deliveries. The protective association between episiotomy and obstetric anal sphincter injury among women who gave birth by operative vaginal delivery (especially forceps) warrants reconsideration of clinical practice among nulliparous women and those attempting vaginal birth after cesarean.

Morbidity and Mortality Associated With Forceps and Vacuum Delivery at Outlet, Low, and Midpelvic Station.

OBJECTIVE: This study sought to quantify perinatal and maternal morbidity and mortality associated with forceps and vacuum delivery compared with Caesarean delivery in the second stage of labour and to estimate whether these associations differed by pelvic station. METHODS: The investigators conducted a population-based, retrospective cohort study of term singleton deliveries by operative delivery with prolonged second stage of labour in Canada (2003-2013) using national hospitalization data. The primary study outcomes were severe perinatal morbidity and mortality (i.e., seizures, assisted ventilation, severe birth trauma, and perinatal death) and severe maternal morbidity and mortality (i.e., severe postpartum hemorrhage, cardiac complication, and maternal death). Logistic regression was used to estimate adjusted odds ratios (aOR) and 95% confidence intervals (CI) after stratifying by indication (dystocia or fetal distress). The Breslow-Day chi-square test for heterogeneity in ORs was used to test effect modification by pelvic station (outlet, low, or midpelvic). RESULTS: There were 61 106 deliveries included in the study. Among women with dystocia, forceps and vacuum deliveries were associated with higher rates of perinatal morbidity and mortality compared with Caesarean delivery (forceps: aOR 1.56; 95% CI 1.13-2.17; vacuum: aOR 1.44; 95% CI 1.06-1.97). Vacuum delivery was associated with lower rates of maternal morbidity and mortality compared with Caesarean delivery (dystocia: aOR 0.64; 95% CI 0.51-0.81; fetal distress: aOR 0.43; 95% CI 0.32-0.57). Pelvic station did not significantly modify the associations between forceps or vacuum and perinatal or maternal morbidity and mortality. CONCLUSION: Forceps and vacuum delivery is associated with increased rates of severe perinatal morbidity and mortality compared with Caesarean delivery among women with dystocia, whereas vacuum delivery is associated with decreased rates of severe maternal morbidity and mortality.

Severe hemolytic disease of the fetus and newborn due to allo-anti-D in a patient with a partial DEL phenotype arising from the variant allele described as RHD*148+1T (RHD*01EL.31).

BACKGROUND: RhD DEL variants may show complete or partial expression of RhD epitopes. There have been only rare reports of anti-D causing hemolytic disease of the fetus and newborn (HDFN) in this context. We report a case of severe HDFN associated with a recently described DEL variant. CASE REPORT: A multiparous woman presented with an allo-anti-D and showed incongruent phenotyping and genotyping results on initial study. Further investigations identified the RHD mutation, defined as RHD*148+1T and named RHD*01EL.31, which had been previously associated with a DEL phenotype. Extended RhD phenotyping by adsorption-elution showed that there was reactivity with four of nine monoclonal anti-D antibodies, suggesting a partial DEL phenotype. The first child showed no clinical evidence of HDFN, although the cord direct antiglobulin test was positive. The second child developed fetal anemia treated with intrauterine transfusion, and neonatal hyperbilirubinemia requiring exchange transfusion. CONCLUSION: The RHD allele, RHD*148+1T, results in a partial Del phenotype, and the anti-D formed in pregnant women with this phenotype is capable of causing severe HDFN.

Ecological association between operative vaginal delivery and obstetric and birth trauma.

BACKGROUND: Increased use of operative vaginal delivery (use of forceps, vacuum or other device) has been recommended to address high rates of cesarean delivery. We sought to determine the association between rates of operative vaginal delivery and obstetric trauma and severe birth trauma. METHODS: We carried out an ecological analysis of term, singleton deliveries in 4 Canadian provinces (2004-2014) using data from the Canadian Institute for Health Information. The primary exposure was mode of delivery. The primary outcomes were obstetric trauma and severe birth trauma. RESULTS: Data on 1 938 913 deliveries were analyzed. The rate of obstetric trauma was 7.2% in nulliparous women, and 2.2% and 2.7% among parous women without and with a previous cesarean delivery, respectively, and rates of severe birth trauma were 2.1, 1.7 and 0.7 per 1000, respectively. Each 1% absolute increase in rates of operative vaginal delivery was associated with a higher frequency of obstetric trauma among nulliparous women (adjusted rate ratio [ARR] 1.06, 95% confidence interval [CI] 1.05-1.06), parous women without a previous cesarean delivery (ARR 1.10, 95% CI 1.08-1.13) and parous women with a previous cesarean delivery (ARR 1.11, 95% CI 1.07-1.16). Operative vaginal delivery was associated with more frequent severe birth trauma, but only in nulliparous women (ARR 1.05, 95% CI 1.03-1.07). In nulliparous women, sequential vacuum and forceps instrumentation was associated with the largest increase in obstetric trauma (ARR 1.44, 95% CI 1.35-1.55) and birth trauma (ARR 1.53, 95% CI 1.03-2.27). INTERPRETATION: Increases in population rates of operative vaginal delivery are associated with higher population rates of obstetric trauma, and in nulliparous women with severe birth trauma.

A Common Language: What Exactly Does 34 Weeks Gestation Mean?

There are multiple conventions for gestational age notation, which lead to different interpretations of completed weeks. This variability is exemplified by the different gestational age ranges recommended for administration of antenatal corticosteroid prophylaxis. Antenatal corticosteroid prophylaxis is widely recommended for women at risk of preterm delivery up to 34 completed weeks gestation. According to the World Health Organization, 34 completed weeks refers to the time period from the first day of the last menstrual period (day zero) to 34 weeks and 6 days of gestation (i.e., to 34+6 34 weeks, or 244 days gestation). However, an alternative convention interprets 34 completed weeks as the period from the first day of the last menstrual period to 33+6 36 weeks' gestation (i.e., 237 days' gestation). These inconsistencies in gestational age notation may have led to different practice recommendations for antenatal corticosteroid prophylaxis worldwide. Agreeing on the World Health Organization notation and interpretation of completed weeks may help promote clear communication within our discipline and more precise and effective knowledge dissemination.

No. 364-Antenatal Corticosteroid Therapy for Improving Neonatal Outcomes.

OBJECTIVE: To assess the benefits and risks of antenatal corticosteroid therapy for women at risk of preterm birth or undergoing pre-labour Caesarean section at term and to make recommendations for improving neonatal and long-term outcomes. OPTIONS: To administer or withhold antenatal corticosteroid therapy for women at high risk of preterm birth or women undergoing pre-labour Caesarean section at term. OUTCOMES: Perinatal morbidity, including respiratory distress syndrome, intraventricular hemorrhage, bronchopulmonary dysplasia, infection, hypoglycemia, somatic and brain growth, and neurodevelopment; perinatal mortality; and maternal morbidity, including infection and adrenal suppression. INTENDED USERS: Maternity care providers including midwives, family physicians, and obstetricians. TARGET POPULATION: Pregnant women. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to September 2017. Medical Subject Heading (MeSH) terms and key words related to pregnancy, prematurity, corticosteroids, and perinatal and neonatal mortality and morbidity were used. Statements from professional organizations including that of the National Institutes of Health, the American College of Obstetricians and Gynecologists, the Society for Maternal Fetal Medicine, the Royal College of Obstetricians and Gynaecologists, and the Canadian Pediatric Society were reviewed for additional references. Randomized controlled trials conducted in pregnant women evaluating antenatal corticosteroid therapy and previous systematic reviews on the topic were eligible. Evidence from systematic reviews of non-experimental (cohort) studies was also eligible. VALIDATION METHODS: This Committee Opinion has been reviewed and approved by the Maternal-Fetal Medicine Committee of the SOGC and approved by SOGC Council. BENEFITS, HARMS, AND/OR COSTS: A course of antenatal corticosteroid therapy administered within 7 days of delivery significantly reduces perinatal morbidity/mortality associated with preterm birth between 24 + 0 and 34 + 6 weeks gestation. When antenatal corticosteroid therapy is given more than 7 days prior to delivery or after 34 + 6 weeks gestation, the adverse effects may outweigh the benefits. Evidence on long-term effects is scarce, and potential neurodevelopment harms are unquantified in cases of late preterm, term, and repeated exposure to antenatal corticosteroid therapy. GUIDELINE UPDATE: Evidence will be reviewed 5 years after publication to evaluate the need for a complete or partial update of the guideline. If important evidence is published prior to the 5-year time point, an update will be issued to reflect new knowledge and recommendations. SPONSORS: The guideline was developed with resources provided by the Society of Obstetricians and Gynaecologists of Canada with support from the Canadian Institutes of Health Research (APR-126338). SUMMARY STATEMENTS: RECOMMENDATIONS: Gestational Age Considerations Agents, Dosage, Regimen, and Target Timing Subpopulations and Special Consideration.

N° 364 - La Corticothérapie Prénatale Pour Améliorer Les Issues Néonatales.

OBJECTIF: Évaluer les avantages et les risques de la corticothérapie prénatale chez les femmes qui présentent un risque d'accouchement prématuré ou qui subissent une césarienne à terme avant début de travail, et formuler des recommandations visant l'amélioration des issues néonatales et des issues à long terme. OPTIONS: Administrer ou ne pas administrer une corticothérapie prénatale aux femmes qui présentent un risque élevé d'accouchement prématuré ou qui subissent une césarienne avant travail à terme. RéSULTATS: Morbidité périnatale, notamment le syndrome de détresse respiratoire, l'hémorragie intraventriculaire, la dysplasie bronchopulmonaire, l'infection, l'hypoglycémie, ainsi que les troubles de la croissance somatique et cérébrale et du neurodéveloppement; mortalité périnatale; et morbidité maternelle, notamment l'infection et la suppression surrénalienne. UTILISATEURS CIBLES: Fournisseurs de soins de maternité, notamment les sages-femmes, les médecins de famille et les obstétriciens. POPULATION CIBLE: Femmes enceintes. ÉVIDENCE: Nous avons interrogé les bases de données Medline, PubMed et Embase ainsi que la Bibliothèque Cochrane, de leur création au mois de septembre 2017. Nous nous sommes servis de Medical Subjet Headings (MeSH) et de mots clés en lien avec la grossesse, la prématurité, les corticostéroïdes ainsi que la mortalité et la morbidité périnatales et néonatales. Nous avons également consulté les déclarations d'organismes professionnels tels que les National Institutes of Health, l'American College of Obstetricians and Gynecologists, la Society for Maternal-Fetal Medicine, le Royal College of Obstetricians and Gynaecologists et la Société canadienne de pédiatrie pour obtenir des références additionnelles. Les essais cliniques randomisés évaluant la corticothérapie prénatale menés sur des femmes enceintes et les revues systématiques antérieures sur le sujet étaient admissibles, tout comme les données venant de revues systématiques d'études non expérimentales (études de cohorte). VALEURS: La présente opinion de comité a été révisée et approuvée par le Comité de médecine fœto-maternelle de la SOGC, et approuvée par le Conseil de la SOGC. AVANTAGES, INCONVéNIENTS ET COûTS: L'administration d'une corticothérapie prénatale dans les sept jours précédant l'accouchement réduit significativement la morbidité et la mortalité périnatales associées à la naissance prématurée survenant entre 24+0 et 34+6 semaines de grossesse. Si la corticothérapie prénatale est administrée plus de sept jours avant l'accouchement ou après 34+6 semaines de grossesse, les effets indésirables peuvent surpasser les avantages. Les données probantes sur l'impact à long terme de la corticothérapie prénatale sont rares. Par ailleurs, les effets neurodéveloppementaux néfastes potentiels de l'exposition répétée à la corticothérapie prénatale ou de l'administration de corticostéroïdes en période préterme tardive ou à terme n'ont pas été quantifiés. MIS-à-JOUR à LA DIRECTIVE: Une revue des données probantes sera menée cinq ans après la publication de la présente directive clinique afin d'évaluer si une mise à jour complète ou partielle s'impose. Si de nouvelles données probantes importantes sont publiées avant la fin de ces cinq ans, une mise à jour tenant compte des nouvelles connaissances et recommandations sera publiée. COMMANDITAIRES: La présente directive clinique a été élaborée à l'aide de ressources fournies par la Société des obstétriciens et gynécologues du Canada et avec l'appui des Instituts de recherche en santé du Canada (APR-126338). MOTS CLéS: Corticothérapie prénatale, maturation fœtale, prématurité, période préterme tardive, césarienne avant travail DÉCLARATION SOMMAIRES: RECOMMANDATIONS: Considérations relatives à l'âge gestationnel.

Perinatal and maternal morbidity and mortality after attempted operative vaginal delivery at midpelvic station.

BACKGROUND: Increased use of operative vaginal delivery (i.e., forceps or vacuum application), of which 20% occurs at midpelvic station, has been advocated to reduce the rate of cesarean delivery. We aimed to quantify severe perinatal and maternal morbidity and mortality associated with attempted midpelvic operative vaginal delivery. METHODS: We studied all term singleton deliveries in Canada between 2003 and 2013, by attempted midpelvic operative vaginal or cesarean delivery with labour (with and without prolonged second stage). The primary outcomes were composite severe perinatal morbidity and mortality (e.g., convulsions, assisted ventilation, severe birth trauma and perinatal death), and composite severe maternal morbidity and mortality (e.g., severe postpartum hemorrhage, shock, sepsis, cardiac complications, acute renal failure and death). RESULTS: The study population included 187 234 deliveries. Among women with dystocia and prolonged second stage of labour, midpelvic operative vaginal delivery was associated with higher rates of severe perinatal morbidity and mortality compared with cesarean delivery (forceps, adjusted odds ratio [AOR] 1.81, 95% confidence interval [CI] 1.24 to 2.64; vacuum, AOR 1.81, 95% CI 1.17 to 2.80; sequential instruments, AOR 3.19, 95% CI 1.73 to 5.88), especially with higher rates of severe birth trauma. Rates of severe maternal morbidity and mortality were not significantly different after operative vaginal delivery, although rates of obstetric trauma were higher (forceps, AOR 4.51, 95% CI 4.04 to 5.02; vacuum, AOR 2.70, 95% CI 2.35 to 3.09; sequential instruments, AOR 4.24, 95% CI 3.46 to 5.19). Among women with fetal distress, similar associations were seen for severe birth trauma and obstetric trauma, although vacuum was associated with lower rates of severe maternal morbidity and mortality (AOR 0.52, 95% CI 0.33 to 0.80). Associations tended to be stronger among women without a prolonged second stage. INTERPRETATION: Midpelvic operative vaginal delivery is associated with higher rates of severe birth trauma and obstetric trauma, whereas overall rates of severe perinatal and maternal morbidity and mortality vary by indication and operative instrument.

No. 343-Routine Non-invasive Prenatal Prediction of Fetal RHD Genotype in Canada: The Time is Here.

The optimal management of the D-negative pregnant woman is now based on the non-invasive antenatal prediction of fetal D-blood group by cell-free DNA (cfDNA) in maternal plasma, with targeted prophylaxis for women carrying RHD-positive fetuses. This provides the optimal care for D-negative pregnant women and has been adopted as the standard approach in a growing number of countries around the world. This paper is the result of a consensus meeting of the Canadian National Rh Working Group, an interdisciplinary group formed to review the current status of fetal RHD genotyping based on cfDNA in Canada. The group, in collaboration with the SOGC Genetics committee, reviewed the benefits and challenges of implementing RHD genotyping with targeted prophylaxis in the context of the existing routine antenatal anti D prophylaxis program in Canada. The following summary statements and recommendations are based on this review. SUMMARY STATEMENTS: RECOMMENDATIONS.

No 343-Prédiction du génotype RHD fœtal par test prénatal non invasif de routine au Canada : l'heure est venue.

Actuellement, la meilleure façon de prendre en charge les femmes enceintes Rh négatives consiste à prédire la présence ou l'absence de l'antigène D chez le fœtus au moyen d'un test non invasif analysant l'ADN acellulaire (ADNa) dans le plasma maternel, et à administrer une prophylaxie à celles dont l'enfant est RHD positif. Cette approche, prise pour norme dans un nombre croissant de pays, assure aux femmes enceintes Rh négatives des soins optimaux. La présente directive est le fruit d'une réunion de consensus du groupe de travail national sur le facteur Rh du Canada, un groupe interdisciplinaire formé pour examiner la situation nationale actuelle du génotypage RHD fœtal effectué sur l'ADNa. En collaboration avec le Comité de génétique de la SOGC, le groupe s'est penché sur les avantages et les difficultés associés au génotypage RHD combiné à une prophylaxie ciblée dans le contexte du programme de prophylaxie anténatale anti-D de routine canadien existant. De ce travail ont émergé les déclarations sommaires et recommandations suivantes. DéCLARATIONS SOMMAIRES: RECOMMANDATIONS.

Association Between Prepregnancy Body Mass Index and Severe Maternal Morbidity.

Importance: Although high body mass index (BMI) is associated with adverse birth outcomes, the association with severe maternal morbidity is unclear. Objective: To examine the association between prepregnancy BMI and severe maternal morbidity. Design, Setting, and Participants: Retrospective population-based cohort study including all singleton hospital births in Washington State, 2004-2013. Demographic data and morbidity diagnoses were obtained from linked birth certificates and hospitalization files. Exposures: Prepregnancy BMI (weight in kilograms divided by height in meters squared) categories included underweight (<18.5), normal BMI (18.5-24.9), overweight (25.0-29.9), obesity class 1 (30.0-34.9), obesity class 2 (35.0-39.9), and obesity class 3 (≥40). Main Outcomes and Measures: Composite severe maternal morbidity or mortality included life-threatening conditions and conditions leading to serious sequelae (eg, amniotic fluid embolism, hysterectomy), complications requiring intensive care unit admission, and maternal death. Logistic regression was used to obtain adjusted odds ratios (ORs) and adjusted rate differences with 95% confidence intervals, adjusted for confounders (eg, maternal age and parity). Results: Overall, 743 630 women were included in the study (mean age, 28.1 [SD, 6.0] years; 41.4% nulliparous). Prepregnancy BMI was distributed as follows: underweight, 3.2%; normal weight, 47.5%; overweight, 25.8%; obesity class 1, 13.1%; obesity class 2, 6.2%; and obesity class 3, 4.2%. Rates of severe maternal morbidity or mortality were 171.5, 143.2, 160.4, 167.9, 178.3 and 202.9 per 10 000 women, respectively. Adjusted ORs were 1.2 (95% CI, 1.0-1.3) for underweight women; 1.1 (95% CI, 1.1-1.2) for overweight women; 1.1 (95% CI, 1.1-1.2) for women with class 1 obesity; 1.2 (95% CI, 1.1-1.3) for women with class 2 obesity; and 1.4 (95% CI, 1.3-1.5) for women with class 3 obesity compared with women with normal BMI. Absolute risk increases (adjusted rate differences per 10 000 women, compared with women with normal BMI) were 28.8 (95% CI, 12.2-47.2) for underweight women, 17.6 (95% CI, 10.5-25.1) for overweight women, 24.9 (95% CI, 15.7-34.6) for women with class 1 obesity, 35.8 (95% CI, 23.1-49.5) for women with class 2 obesity, and 61.1 (95% CI, 44.8-78.9) for women with class 3 obesity. Conclusions and Relevance: Among pregnant women in Washington State, low and high prepregnancy BMI, compared with normal BMI, were associated with a statistically significant but small absolute increase in severe maternal morbidity or mortality.

Impaired NLRP3 inflammasome activity during fetal development regulates IL-1ß production in human monocytes.

Interleukin-1ß (IL-1ß) production is impaired in cord blood monocytes. However, the mechanism underlying this developmental attenuation remains unclear. Here, we analyzed the extent of variability within the Toll-like receptor (TLR)/NLRP3 inflammasome pathways in human neonates. We show that immature low CD14 expressing/CD16(pos) monocytes predominate before 33 weeks of gestation, and that these cells lack production of the pro-IL-1ß precursor protein upon LPS stimulation. In contrast, high levels of pro-IL-1ß are produced within high CD14 expressing monocytes, although these cells are unable to secrete mature IL-1ß. The lack of secreted IL-1ß in these monocytes parallels a reduction of NLRP3 induction following TLR stimulation resulting in a lack of caspase-1 activity before 29 weeks of gestation, whereas expression of the apoptosis-associated speck-like protein containing a CARD and function of the P2×7 receptor are preserved. Our analyses also reveal a strong inhibitory effect of placental infection on LPS/ATP-induced caspase-1 activity in cord blood monocytes. Lastly, secretion of IL-1ß in preterm neonates is restored to adult levels during the neonatal period, indicating rapid maturation of these responses after birth. Collectively, our data highlight important developmental mechanisms regulating IL-1ß responses early in gestation, in part due to a downregulation of TLR-mediated NLRP3 expression. Such mechanisms may serve to limit potentially damaging inflammatory responses in a developing fetus.

Competence by Design: The Role of High-Stakes Examinations in a Competence Based Medical Education System.

Competency based medical education is developed utilizing a program of assessment that ideally supports learners to reflect on their knowledge and skills, allows them to exercise a growth mindset that prepares them for coaching and eventual lifelong learning, and can support important progression and certification decisions. Examinations can serve as an important anchor to that program of assessment, particularly when considering their strength as an independent, third-party assessment with evidence that they can predict future physician performance and patient outcomes. This paper describes the aims of the Royal College of Physicians and Surgeons of Canada's ("the Royal College") certification examinations, their future role, and how they relate to the Competence by Design model, particularly as the culture of workplace assessment and the evidence for validity evolves. For example, high-stakes examinations are stressful to candidates and focus learners on exam preparation rather than clinical learning opportunities, particularly when they should be developing greater autonomy. In response, the Royal College moved the written examination earlier in training and created an exam quality review, by a specialist uninvolved in development, to review the exam for clarity and relevance. While learners are likely to continue to focus on the examination as an important hurdle to overcome, they will be preparing earlier in training, allowing them the opportunity to be more present and refine their knowledge when discussing clinical cases with supervisors in the Transition to Practice phase. The quality review process better aligns the exam to clinical practice and can improve the educational impact of the examination preparation process.