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Higher rates of postpartum hemorrhage (PPH) have been reported for women with von Willebrand disease (VWD). Comprehensive multidisciplinary care reduces these rates; thus PPH may not be secondary to VWD.We conducted a retrospective review for the period of 2009-2018, including all VWD pregnancies at 2 tertiary care academic hospitals to determine rates, etiology, and timing of PPH.A total of 63 women with 80 pregnancies were included. Three women had twin pregnancies. Sixty-six pregnancies (82.5%) involved type 1 VWD; 4 (5.0%), type 2 (unclear subtype); 3 (3.8%) type 2A; 3 (3.8%) type 2B; and 2 (2.5%), type 2M. Median age of patients was 32.9 years (range 19-43 y). Most patients were blood type O (65%), and 33 of 80 pregnancies (41.3%) were nulliparous. The mean bleeding assessment score was 8 (range 0-16). Thirty-seven pregnancies (46.3%) received prophylactic hemostatic treatment prior to delivery. Seventy-four percent of pregnancies were delivered vaginally, and 88% received epidural anaesthesia. The majority of pregnancies (78.8%) had von Willebrand factor (VWF) levels assessed during the third trimester, with most (71.3%) achieving VWF levels above 1.00 IU/mL. Four pregnancies (5.2%) were complicated by primary PPH; uterine atony in 2 and placenta previa in 1. Delayed postpartum bleeding occurred in 5 pregnancies (6.3%).Multidisciplinary care of pregnancies with VWD improves outcomes. Rates of primary and delayed PPH in this study are lower than previously described and are similar to those of women without VWD. In women with VWD, uterine etiologies for primary PPH need to be considered, in a manner similar to the assessment of women without VWD, to ensure hemostasis is achieved.

For over a year, the world has been gripped by the coronavirus disease 2019 (COVID-19) pandemic, which has had far-reaching effects on society. The integrity of national health care systems has also been challenged, owing to shifts in guidance and misinformation. While initial reports suggested that pregnant people were not at increased risk of severe COVID-19 disease, current data arising from the "third wave" paint a much more concerning picture. Additionally, pregnant and lactating people were excluded from vaccine trials, which has hindered the ability of health care professionals to provide evidence-based counselling regarding the safety and efficacy of the available vaccines in these populations. This commentary reviews the current data on the safety of COVID-19 vaccines in pregnancy. The evidence is clear that the risks of hospitalization and severe maternal and potentially fetal morbidity from COVID-19 in pregnancy far outweigh the very minimal risks of COVID-19 vaccination in pregnancy.

Background Coronavirus disease 2019 (COVID‐19) occurs following infection with the potentially fatal, severe acute respiratory syndrome coronavirus‐2 (SARS‐CoV‐2) virus. Infection can be complicated by coagulopathy, at times featuring thrombocytopenia and thrombosis alongside other coagulation abnormalities, also termed COVID‐19‐associated coagulopathy (CAC). Data concerning CAC in pregnancy are limited. Better understanding of physician experiences is essential to identify current practice patterns and knowledge gaps. Objectives To determine physician experiences and practice patterns regarding CAC in pregnancy. Methods Self‐administered survey using the RedCap online platform; supported by the ISTH Subcommittee on Women's Health Issues in Thrombosis and Hemostasis. Results Seventy‐five respondents fully or partially completed the survey. Of 1546 reported cases, disease severity was specified in 1298. Sixty‐four percent of COVID‐19 infections were mild, whereas 4% were severe. Of all cases, 1% developed CAC, with 65% classified as severe. The most frequent abnormalities included thrombocytopenia, elevated C‐reactive protein, D‐dimer, and lymphopenia. Low molecular weight heparin was the anticoagulant of choice in CAC and was provided by 77% of respondents, with 60% using standard prophylactic dosing. Thrombosis occurred in seven anticoagulated patients who were receiving standard prophylactic (four) or weight‐based (three) dosing. Disease severity and additional thrombosis risk factors dictated anticoagulation duration. Conclusion In the select population reported by our survey, CAC appears to be uncommon in pregnancy. Anticoagulation practices vary and may not reflect current guidelines. Venous thromboembolism was observed in some CAC patients despite prophylactic anticoagulation (including standard and weight‐adjusted dosing). Urgent research is required to determine appropriate anticoagulant dosing and duration in pregnant women with COVID‐19 infection.

Alongside an interplay of a multitude of factors, attainment of a favorable pregnancy outcome is predicated on successful implantation, which in itself is a complex process anchored by balanced interchange with the hemostatic system. Among other etiologies, failure of implantation can result in infertility, and lead affected couples to consider assisted reproductive technology (ART) in an effort to fulfill their desire for procreation. Given the critical role of the hemostatic system in the process of implantation, documentation of a hypercoagulable state during controlled ovarian stimulation in the context of in vitro fertilization, as well as the potential association of its derangement in the setting of thrombophilia, with infertility, ART, ovarian hyperstimulation syndrome, and failure of implantation are explored. Additionally, current evidence addressing the relationship between ART and thromboembolism is examined, as is the role of therapy with heparin and aspirin to decrease thrombotic risk and improve ART-related pregnancy outcomes. Evidence-based recommendations from relevant professional societies are summarized.

SARS-CoV-2 is a new virus, to which herd immunity has not yet developed and both molecular and serological testing are not without flaws. The virus evokes a state of severe and widespread inflammation, and stimulates both innate and adaptive immune response. The angiotensin-converting enzyme 2 (ACE2), which acts as the SARS-CoV-2 receptor, is present in endothelial cells and has been noted within the human placenta. There are questions about whether pregnancy would increase the susceptibility of pregnant women to COVID-19 and disease severity within this population. In this report, we highlight physiological and immune/inflammatory considerations that may explain the susceptibility and disease pathology in response to SARS CoV-2 during pregnancy, explore testing considerations in asymptomatic individuals, discuss the potential role and of placental ACE2 receptor in the pathogenesis of COVID-19 in pregnancy and in pregnancy outcomes, and finally share our perspective with respect to an urgently needed change concerning involvement of pregnant women in research addressing COVID-19.

POINTS CLES Une femme de 40 ans (gravida 2, para 1) a ete admise dans un hopital de soins tertiaires de Toronto, en Ontario. On a note chez elle : neutropenie familiale, diabete de grossesse et probleme d’infections bacteriennes a repetition, dont 3 episodes (sinusite, dermatite et

Background Novel coronavirus (SARS-CoV-2), which causes COVID-19, has thus far affected more than 15 million individuals, resulting in more than 600 000 deaths worldwide, and the number continues to rise. In a large systematic review and meta-analysis of the literature including 2567 pregnant women, 7% required intensive care admission, with a maternal mortality ~1% and perinatal mortality below 1%. There has been a rapid increase in publications on COVID-19-associated coagulopathy, including disseminated intravascular coagulopathy and venous thromboembolism, in the non-pregnant population, but very few reports of COVID-19 coagulopathy during pregnancy; leaving us with no guidance for care of this specific population. Methods This is a collaborative effort conducted by a group of experts that was reviewed, critiqued, and approved by the International Society on Thrombosis and Haemostasis Subcommittee for Women's Health Issues in Thrombosis and Hemostasis. A structured literature search was conducted, and the quality of current and emerging evidence was evaluated. Based on the published studies in the non-pregnant and pregnant population with a moderate to high risk of bias as assessed by Newcastle-Ottawa scale and acknowledging the absence of data from randomized clinical trials for management of pregnant women infected with SARS-CoV-2, a consensus in support of a guidance document for COVID-19 coagulopathy in pregnancy was identified. Results and conclusions Specific hemostatic issues during pregnancy were highlighted, and preliminary recommendations to assist in the care of COVID-19-affected pregnant women with coagulopathy or thrombotic complications were developed. An international registry to gather data to support the management of COVID-19 and associated coagulopathy in pregnancy was established.

Registries provide an important tool for data collection, particularly in context of rare conditions, or questions not amenable to investigation by means of a clinical trial. The Subcommittee on Women's Health in Thrombosis and Hemostasis (WHITH); one of 20 Scientific and Standardization Subcommittees (SSCs) of the International Society on Thrombosis and Hemostasis (ISTH) has supported 12 registries related to WHITH since 2016. Despite many successes, some challenges have been observed. In this report, we attempt to review the basic tenets of value in developing a registry, discuss observed challenges, share lessons learned, and finally present our views on a potential formula for success in developing and maintaining a registry in WHITH.

Primary immune thrombocytopenia (ITP) is an autoimmune condition affecting women of childbearing age that is characterized by diminished platelet quantity with preserved function. Although pregnant women with ITP are often denied obstetric neuraxial anesthesia (OBNA) with low platelet counts for fear of neuraxial hematoma, the true magnitude of neuraxial hematoma for ITP parturients is unknown. The aim of this systematic review and meta-analysis was to examine OBNA outcomes in ITP parturients with platelet counts below 100 x 109·L-1. Articles published in MEDLINE, Embase, Web of Science, Scopus, Cochrane, and PubMed in process until May 14, 2018 were searched. Two reviewers independently screened 954 articles by title and abstract, reviewed 62 full-texts, extracted data, and assessed risk of bias for 26 articles. Of 291 pregnant women with ITP and platelet counts below 100 x 109·L-1, 166 received OBNA and 61 of these had platelet counts below 80 x 109·L-1. No neuraxial hematomas were reported. Meta-analysis of six studies showed higher platelet counts in those with OBNA than without (mean difference [MD], 19 x 109·L-1; 95% confidence interval [CI], 11 to 26; P < 0.001), with no difference between epidural and spinal anesthesia (MD, 0.4 x 109·L-1; 95% CI, -4 to 4; P = 0.86). Our study highlights continued reluctance to offer OBNA below the commonly quoted 80 x 109·L-1 platelet count, based largely on consensus and theoretical presumption of risk. This further negatively influences the accrual of large-scale data. The evidence of no neuraxial hematoma after OBNA provided herein offers support for considering neuraxial anesthesia at lower platelet count thresholds. Each patient should be afforded individualized discussion of risk and benefit relative to other analgesic measures. PROSPERO (CRD42018059220); registered 2 August, 2018.

Background/Aims: Iron deficiency (ID) and iron deficiency anemia (IDA) are global health concerns associated with adverse perinatal effects. Despite efforts taken at the international level, there is no consensus on unified prevention/treatment strategies, largely stemming from inconsistencies of outcome reporting. Our objective was to comprehensively assess outcome reporting perinatal iron intervention trials as Phase 1 of core outcome set (COS) development to inform future research. Methods: Systematic search in MEDLINE, EMBASE, Cochrane Databases, and CINAHL (January 2000 – April 2016), with inclusion of trials involving pregnant or postpartum women with ID/IDA confirmed before recruitment. Articles were independently screened and selected by 2 reviewers; data were extracted in duplicate. Quality was assessed using published scoring systems. Outcome definitions and measurement methods were tabulated. Results: Of 7,046 citations, 33 randomized controlled trials were included. Sixty-nine reported outcomes were categorized into 8 domains. High methodological quality characterized 25 (76%) studies. Reporting quality was low in 16 (49%), moderate in 13 (39%), and high in 4 (12%) studies. Variation was greatest for outcome definition, timing of assessment and measurement methods. Conclusion: This review identifies a comprehensive long-list of outcomes reported of perinatal iron interventions for ID/IDA. Beyond highlighting existing variation in outcome reporting, it provides a foundation for development of a COS for future trials.

Background Venous thromboembolism (VTE) in pregnancy can have numerous adverse impacts on patients and health care systems. Ongoing research aimed at improving maternal and fetal/neonatal outcomes is hampered by the lack of patient perspective in determining which outcomes are considered important to assess the effectiveness of interventions. Objectives The objective of this study was to elicit outcomes from those who experienced or were at risk for pregnancy-associated VTE (health service users, HSUs) and health care providers (HCPs) involved in their care. Methods Canadian HSUs and HCPs were recruited using convenience and purposive sampling, respectively. Individual, semistructured interviews aimed specifically at eliciting pregnancy-related outcomes were conducted until data saturation was attained. Interviews were audio-recorded and transcribed verbatim. Written transcripts were de-identified and interpretatively analyzed in duplicate to obtain outcomes related to participant experiences. Outcomes were grouped based on a taxonomy developed for medical research and compared between and across interviews with patients and HCPs, and with those obtained through a systematic review of the published literature. Results and Conclusion We interviewed 10 HSUs and eight HCPs and elicited 52 outcomes, 21 of which have not been reported in the literature. Although the majority of elicited outcomes were in the clinical/physiological core outcome area, both HSUs and HCPs highlighted the importance of outcomes related to functioning/life impact and general wellbeing of mother and baby. These outcomes representing the perspectives of HSUs and HCPs should be considered while conducting trials on pregnancy-associated VTE.

Background Acute splenic sequestration crisis, characterized by abrupt fall in hemoglobin, splenomegaly, hypovolemia, and often thrombocytopenia, occurs infrequently in adults with sickle cell disease and extremely rarely during pregnancy. Case A 25-year-old woman with HbSC presented at 33 weeks’ gestation with vaso-occlusive pain. Sudden worsening of abdominal pain and non-reassuring fetal surveillance on day 3 of admission led to emergent delivery. Acute splenic sequestration crisis was the diagnosis of exclusion based on clinical presentation and intra-operative hemoglobin of 37 g/L. Five- and 10-minute Apgar scores were 4. Neonatal brain magnetic resonance imaging revealed significant diffuse white matter abnormalities. Conclusion Acute splenic sequestration crisis in pregnancy must be considered in the differential diagnosis for this patient population as it can evolve rapidly and lead to maternal and fetal compromise.

We agree with Cheng and colleagues regarding the need to generate robust evidence through randomized trials.[1][1] However, we note that inclusion of pregnant individuals is conspicuously absent from this call to action. Of investigations related to coronavirus disease 2019 (COVID-19) registered on

We present a putative link between maternal COVID-19 infection in the peripartum period and rapid maternal deterioration with early organ dysfunction and coagulopathy. The current pandemic with SARS-CoV-2 has already resulted in high numbers of critically ill patients and deaths in the non-pregnant population, mainly due to respiratory failure. During viral outbreaks, pregnancy poses a uniquely increased risk to women due to changes to immune function, alongside physiological adaptive alterations, such as increased oxygen consumption and edema of the respiratory tract. The laboratory derangements may be reminiscent of HELLP (hemolysis, elevated liver enzymes, low platelet count) syndrome, and thus knowledge of the COVID-19 relationship is paramount for appropriate diagnosis and management. In addition to routine measurements of D-dimers, prothrombin time, and platelet count in all patients presenting with COVID-19 as per International Society on Thrombosis and Haemostasis (ISTH) guidance, monitoring of activated partial thromboplastin time (APTT) and fibrinogen levels should be considered in pregnancy, as highlighted in this report. These investigations in SARS-CoV-2-positive pregnant women are vital, as their derangement may signal a more severe COVID-19 infection, and may warrant pre-emptive admission and consideration of delivery to achieve maternal stabilization.

Introduction Abnormal placental development is a unifying factor amongst many adverse pregnancy outcomes (APOs) in Sickle Cell Disease (SCD). Our aim was to describe placental histopathologic findings in women with SCD and their relationship with APOs, and to explore the association between antenatal sonographic findings and placental pathology. Methods Retrospective single-centre case series of all pregnant women with SCD (January 2000–December 2017), pregnancy beyond 20 weeks’ gestation, and available placenta histopathology. APOs included intrauterine fetal death, early neonatal death, preterm birth, small for gestational age, and hypertensive disorders of pregnancy. Review of images for mid-pregnancy ultrasound and one proximal to delivery was completed, blinded to clinical outcomes and histopathology results. Gross and histopathologic findings were reviewed and characterized per published classification. Results Of 72 placentas, abnormalities were present in 69%, with Maternal Vascular Malperfusion (MVM) noted in 40%. APOs were encountered in 61% overall and in 79% of those with MVM. Neither SCD genotype nor severe maternal anemia had an influence on histopathologic placental features. Presence of high-resistance uterine artery waveforms at mid-trimester ultrasound was strongly associated with APOs and with abnormal findings on placental histopathology, most notably MVM. MVM was strongly associated with small for gestational age infants, preterm birth, and stillbirth. Discussion MVM is the predominant lesion in placentas of women with SCD and is strongly associated with APOs. Mid-trimester ultrasound can identify a subset of women at risk. Future research into advanced imaging modalities to aid in antenatal diagnosis alongside investigations of potentially beneficial therapies is needed.

Background: Current guidelines for regional anesthesia advise for the discontinuation of prophylactic and therapeutic low molecular weight heparin (LMWH) 12 hours and 24 hours, respectively prior to the use of neuraxial anesthesia (NA) for obstetric patients. Re initiating a prophylactic dose 12 hours following epidural catheter insertion/spinal anesthesia (SA) and at least 4 hours following epidural catheter removal is also recommended. There are limited data on the recurrent risk of venous thromboembolism (VTE) and bleeding using these standards. We conducted a retrospective single center study to assess the risk of VTE and/or bleeding in pregnant women using these criteria. Methods: Consecutive patients from 2013 to 2018 at Mount Sinai Hospital, a university affiliated tertiary care center in Toronto, Canada who were prescribed therapeutic or prophylactic LMWH antenatally and postpartum and who had NA were included. Hospital records were reviewed to determine the indication and dosage of LMWH, presence of thrombophilia, time of first LMWH injection postpartum, the mode of neuraxial anesthesia and delivery, the time of epidural catheter/spinal anesthesia, the time of epidural catheter removal, laboratory parameters and comorbid illnesses. Patients requiring therapeutic or prophylactic LMWH were assessed in the Hematology clinic and were advised to discontinue anticoagulation according to current recommendations. The primary outcomes were frequency of VTE, spinal hematoma and volume of postpartum blood loss. Statistical Analysis: Continuous variables were summarized as medians and interquartile ranges. Categorical variables were summarized as percentages. Characteristics associated with VTE and hemorrhage were analyzed using regression analysis. Results: Of 169 pregnancies, 158 fulfilled criteria, and 110 had complete data for the time of epidural catheter removal and initiation of LMWH. Median age was 34 (IQR 5) years and median weight 90 (IQR 70) kgs. Diagnoses included antiphospholipid syndrome, Budd Chiari, provoked and unprovoked VTE. Median platelet count at delivery was 185 (IQR 76) x 10(9)/L. Thirty-three percent were using concomitant ASA antenatally. Forty-four percent (n=48) had a vaginal delivery (VD). Sixty five (59%) had epidural anesthesia, 43 (39%) had SA and, two had combined spinal/epidural anesthesia. Median time to restarting LMWH was 7.8 (IQR 4.7) hours from epidural catheter removal/spinal insertion and 9 (IQR 3.9) hours from SA. There were no spinal hematomas. Median blood loss was 500 (IQR 400) ml. One patient, who received prophylactic dose LMWH antepartum, had a Caesarean delivery, spinal anesthesia and a prophylactic dose re-started 13.7 hours after SA, developed a delayed postpartum hemorrhage. One patient developed a VTE (1%). She developed a distal and superficial thrombus immediately after delivery. She was using antenatal prophylactic LMWH as she had an unprovoked VTE predating pregnancy, was heterozygous for the prothrombin gene mutation, had epidural anesthesia and VD. She received prophylactic LMWH three hours after catheter removal which was also 10 hours after catheter insertion. Limitations: Time of discontinuation of LMWH prior to induction could not be confirmed definitively as this was a retrospective review. Conclusion: Prospective studies are required to confirm these findings and to determine the safety of current recommendations of interrupting anticoagulation prior to regional anesthesia and delivery and to identify risk factors for hemorrhage and recurrent VTE to optimize anticoagulation regimens for these patients. Disclosures Malinowski: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy.

Introduction: While BCR-ABL1 negative myeloproliferative neoplasms (MPN) are typically diagnosed in the sixth decade of life, approximately 20% of patients are diagnosed before the age of 40 years. Patients with MPN of reproductive age are being increasingly encountered in clinical practice. Concurrently, there has been increased awareness of the risks of pregnancy complications in patients with MPN and the importance of MPN-specific management to help mitigate these risks. MPN are associated with thrombotic and hemorrhagic complications, and pregnancy may amplify the thrombotic risk. Additionally, MPN may be associated with an increased risk of placental dysfunction and associated complications of preeclampsia, fetal growth restriction, preterm delivery and fetal loss. The aim of this observational study was to report on pregnancy outcomes in a modern cohort of patients with MPN managed according to consensus recommendations. Methods: We conducted a retrospective review of patients with MPN and pregnancy evaluated at either the Princess Margaret Cancer Centre or Mount Sinai Hospital in Toronto, Canada between January 1, 2010 and December 31, 2020. Diagnoses were defined according to the WHO 2016 criteria using information available from hospital records. Descriptive statistics were used to describe selected baseline characteristics. Categorical variables were summarized with counts and percentages. Results: A total of 32 patients with MPN and pregnancy were included in the study (Table 1). The median age at the time of the index pregnancy was 33 (range 21 - 45) years. The most common MPN diagnosis was essential thrombocythemia (ET, n=15), followed by polycythemia vera (PV, n=9) and primary myelofibrosis (PMF, n=8). Driver mutation data was available for 30 patients: 17 (57%) had mutated JAK2, 5 (17%) CALR, and 9 (30%) had no driver mutation identified. Five patients had a prior history of venous thrombosis, all of which were portal vein thrombosis, and 2 patients had a history of bleeding events. Information on antenatal treatment was available for 22 patients: 18 (82%) patients received aspirin, 3 (14%) received antenatal low molecular weight heparin (LMWH) and 3 (14%) received interferon (IFN; interferon alpha 2b in 2 cases and pegylated interferon alfa 2a in 1); 16 (73%) received post-partum LMWH. Information on maternal complications was available for 22 patients. There were 2 thrombotic events (1 antepartum and 1 postpartum) and 1 postpartum hemorrhage. There were no cases of preeclampsia. Of 22 pregnancies, there were 19 live births (86%), 2 first trimester losses (9%) and 1 second trimester loss (5%). Gestational age was 37 weeks or more in 16/17 (94%) and was 33 weeks for 1 patient. Vaginal deliveries were performed in 11/20 (55%) cases and 9/20 (45%) were Cesarean deliveries. Discussion: This observational study represents a modern cohort of MPN patients treated according to consensus recommendations. Our findings highlight that MPN patients have better pregnancy outcomes than those previously described in the literature. Limitations of this retrospective study include a small sample, missing data, and potential underreporting of early pregnancy loss. Pregnancy in patients with MPN is associated with unique risks that may be reduced with interventions such as antepartum aspirin, IFN in higher risk patients, and postpartum LMWH. That not all standard risk patients were managed with aspirin and postpartum LMWH suggests educational opportunities exist for hematologists and maternal-fetal medicine physicians involved in the care of these patients. Figure 1 Figure 1. Disclosures Gupta: Novartis: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS-Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Consultancy, Honoraria; Pfizer: Consultancy; Roche: Consultancy; Constellation Pharma: Consultancy, Honoraria; Sierra Oncology: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Incyte: Honoraria, Research Funding. Malinowski: Alexion: Honoraria, Membership on an entity's Board of Directors or advisory committees; Pfizer: Consultancy. Maze: Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene-BMS: Honoraria; Takeda: Research Funding; PharmaEssentia: Research Funding; Kronos Bio: Research Funding.

OBJECTIVES As thromboembolism (TE) continues to be one of the principal causes of death in obstetrical patients and as the postpartum period is associated with the highest risk for TE, we sought to determine the risk factors associated with TE following cesarean section (CS). METHODS A retrospective analysis of patients who had CS at a large tertiary referral center was conducted. Patients were identified through hospital medical records and were contacted approximately 1 year following their CS. Medical records and a questionnaire were used to identify features that were potentially associated with TE. Univariate analysis was used to determine the risk associated with these characteristics. RESULTS A total of 2206 patients had a CS, of which 1377 (62%) participated. Of the respondents, 137 patients received heparin (94% received a prophylactic dose, 6% received a therapeutic dose) and the remainder, 1233 patients, did not receive heparin. Seven patients (0.5%) developed a TE and 86% developed a TE within 7 days of CS. The odds ratio (OR) for TE for women with hypertension prior to pregnancy compared to patients who did not receive anticoagulation was 21.28 [95% confidence interval (CI) 4.64-90.13] and for patients who had varicose veins with superficial thrombophlebitis when compared to patients who had received heparin postpartum was 21.01 (95% CI 1.55-288.24). DISCUSSION Hypertension and the presence of varicose veins were associated with TE following CS. Larger cohort analyses are required to confirm these associations so that risk scores incorporating these characteristics may accurately predict the occurrence of TE.

Anemia is common in pregnancy, ranging from 5.4% in developed countries to more than 80% in developing countries. Anemia in pregnancy has been associated with prematurity, low birth weight, and adverse pregnancy outcomes.This review uses clinical vignettes to illustrate the clinical presentations, approach to diagnosis, maternal and fetal implications, and treatment for the common etiologies of anemia in pregnancy.Literature review.Normal physiological changes in pregnancy result in alterations of hematological parameters particularly in a reduction of hemoglobin (Hb) concentration. Consequently, the Hb used to define anemia in pregnancy is lower than in nonpregnant patients. As there is an increased requirement of iron in pregnancy, it is not unexpected that iron deficiency remains the most common cause of anemia and warrants a preemptive approach to prevent a further reduction in Hb. The syndromes associated with microangiopathic hemolytic anemia may pose a diagnostic challenge, as there are several potential etiologies that may be difficult to differentiate, and microangiopathic hemolytic anemia can be associated with significant maternal and fetal morbidity andmortality. Anemia secondary to sickle cell disease and autoimmune hemolytic anemiamerit special attention because there are risks secondary to red blood cell transfusion and risks to withholding transfusion.Anemia in pregnancy is potentially associated with maternal and fetal adverse outcomes. Providing evidence-based care is essential to achieving the best pregnancy outcomes.

Venous thromboembolism (VTE) remains among the leading causes of maternal mortality in the developed world, presenting variably as deep vein thrombosis (DVT), pulmonary embolism (PE) or cerebral vein thrombosis (CVT), among others. Obesity in particular has been recognized as the principal contributing factor to the risk of VTE in pregnancy and with the global increase in the rates of obesity affecting reproductive age women, heightened awareness of the risk and consequences of VTE in this population are vital. Thus, prophylaxis, diagnosis and treatment of VTE in the obese gravida are discussed.

BACKGROUND Transfusion data for obstetric patients are scarce. Identifying characteristics associated with red blood cell transfusion (RBCT) is of importance to better identify patients who would benefit from blood conservation strategies as the risk of alloimmunization from RBCT has the potential to affect the fetus and newborn. STUDY DESIGN AND METHODS We conducted a retrospective cohort study using hospital administrative data to identify trends and risk factors of RBCT in obstetric patients. Data were analyzed according to the mode of delivery. RESULTS A total of 45,213 deliveries were captured between January 1, 2007, and December 31, 2013. A higher proportion of patients undergoing cesarean sections (C/Ss) received an RBCT (2.3%) compared to other modes of delivery (0.7% for spontaneous vaginal delivery, 1.5% for instrumental delivery; p

Introduction With advancement in medical knowledge and comprehensive care more women with hematological disorders are proceeding with pregnancy. These women have unique needs during the perinatal period, where the intersection of the Hematological disease and pregnancy can mutually impact each other, resulting in significant morbidity and even mortality. Hematologists, Internal Medicine (IM) physicians and Obstetricians are increasingly faced with the complex care of these women. The aim of this study is to assess the learning needs of these stakeholders in the care of pregnant women with hematological conditions to direct the development of educational activities. Methods We conducted a cross-sectional study using a self-administered electronic questionnaire sent to Hematologists, Obstetricians, Maternal-Fetal Medicine (MFM) Specialists and IM Specialists across Canada. The study was approved by the Research Ethics Board of Sinai Health System in Toronto, Ontario. The questionnaire assessed physician characteristics, physicians' previous educational experiences in Maternal Hematology, self-assessment of knowledge and confidence in managing pregnancy in these women, and preferences for further learning activities in Maternal Hematology. The questionnaire was pilot tested by two hematology resident physicians and two MFM fellow physicians at the University of Toronto and modifications were made to the survey based on this feedback. The survey was administered electronically in English in collaboration with the Canadian Hematology Society and Canadian MFM program directors, using an online survey-distributing website, Survey Monkey™. Participation was voluntary and anonymous. Data were exported into Excel (Microsoft, Redmond, Washington, USA) for statistical analysis. Following overall descriptive analyses (frequencies and proportions), responses were further tabulated by participant specialty. Results The survey was administered from December 2019 to March 2020. 97 participants responded to the survey, and 82 (84.5%) completed it. The 15 (15.5%) incomplete surveys (completion of less than 25% of the questionnaire), were excluded from analysis. Respondents included 17 (20.7 %) MFM specialists, 21 (25.6%) Obstetricians, 34 (41.5%) hematologists and five (6.1 %) IM physicians. Half of respondents had < 5 years of practice (52.6%%) and there was a similar distribution of respondents with 5-10 years (12.8%) and 11-15 years (12.8%) in practice. Most respondents were female (69.6%). Overall, 38% of respondents described the quality of their prior educational experiences as 'very useful' or 'extremely useful'. Approximately half of the respondents rated their knowledge of Maternal Hematology as intermediate, 25% as beginner and 25% as advanced. The majority of Hematologists and IM specialists (64%) considered their knowledge in Maternal Hematology as 'intermediate'; specialists in Obstetrics and MFM were divided with 30.8% considering their knowledge at the 'beginner' level and 38.5% at the 'intermediate' level. Only 3.7% of respondents described their knowledge level as 'expert'. Most respondents in Obstetrics and MFM (84.2%) considered knowledge of how to diagnose venous thromboembolism during pregnancy as 'extremely important followed by knowledge of thromboprophylaxis (63.2%) and therapeutic anticoagulation during pregnancy (63.2%) (Figure 1). Amongst Hematology and IM physicians, thrombotic microangiopathy was rated by the greatest proportion of respondents (59%) as being "extremely important". For the format of educational activity, three quarters of the respondents preferred a blended learning program, which would include a combination of face-to-face teaching and technology-enhanced learning activities. Respondents predominantly (76.2%) agreed that learning collaboratively with other specialties in a combined Maternal Hematology program would be helpful. Conclusion These results suggest that an interdisciplinary learning program involving collaboration across relevant subspecialties would be preferred by participants for the teaching and learning of Maternal Hematology. A program involving blended (in-person and technology-enhanced) learning modalities was viewed favorably by participants, and should aim to incorporate various topics, which may be prioritized differently amongst specific subspecialties. Disclosures Malinowski: Alexion: Other: Advisory board; Alexion: Honoraria. Shehata:Ferring: Honoraria.

Objective We sought to describe the maternal, fetal, and neonatal outcomes of primary hyperparathyroidism in a contemporary setting through a retrospective case series conducted in a tertiary referral centre focused on women diagnosed with primary hyperparathyroidism prior to conception, in the antepartum period, or within 6 weeks postpartum. Methods A retrospective chart review was conducted and data were abstracted to case report forms. Summary statistics are reported. Results From 2000 to 2017, 19 women (23 pregnancies) with primary hyperparathyroidism were identified. Most women (79%) were symptomatic at presentation, though often with non-specific manifestations. While 14% of pregnancies involved maternal/obstetric complications, fetal/neonatal complications were observed in 45%. Mild hypercalcemia was identified in 57% of women, with accompanying hypophosphatemia and hypomagnesemia in 46% and 36% of women, respectively. Surgical intervention was performed for 89% women, and no complications were encountered. Normal calcium levels achieved through treatment before conception did not fully eliminate adverse outcomes. Conclusion Rates of perinatal complications in our series are more reassuring than the ubiquitously quoted rates from small and dated studies. The diagnosis of primary hyperparathyroidism may be easily missed during pregnancy, owing to its non-specific presentation. A high index of suspicion and measurement of ionized calcium levels is encouraged, especially for patients with excessive nausea and vomiting, nephrolithiasis, atypical presentations of hypertensive disorders, or isolated polyhydramnios. Mild degrees of calcium derangement do not preclude adverse perinatal outcomes. Surgery appears to be safe, even in the third trimester. The attenuated rate of complications noted in our series may have been the result of the high proportion of surgery, though this will require verification via meta-analysis or future prospective work.

Aims To review maternal and foetal outcomes in women with mechanical heart valves (MHVs) treated with vitamin-K antagonists (VKAs), first-trimester heparin followed by VKAs (sequential treatment), low molecular weight heparin (LMWH) and unfractionated heparin (UFH) during pregnancy, in order to inform practice. Methods and results Medline, Embase and Central were searched from inception until February 2016. Two reviewers independently screened 1786 titles, reviewed 110 full-texts and extracted data and assessed risk-of-bias from 46 articles. Pooled incidence (95% confidence intervals) was calculated for maternal and foetal outcomes. Included studies had a moderate or high risk-of-bias. With VKAs, sequential treatment and LMWH, maternal mortality occurred in 0.9% (0.4–1.4), 2.0% (0.8–3.1) and 2.9% (0.2–5.7), thromboembolic complications in 2.7% (1.4–4.0), 5.8% (3.8–7.7) and 8.7% (3.9–13.4), livebirths in 64.5% (48.8–80.2), 79.9% (74.3–85.6) and 92.0% (86.1–98.0) and anticoagulant-related foetal/neonatal adverse events (embryopathy or foetopathy) in 2.0% (0.3–3.7), 1.4% (0.3–2.5) and 0%, respectively. When UFH is used throughout pregnancy, 11.2% (2.8–19.6) suffered thromboembolic complications. Foetal loss and adverse events occurred with first-trimester warfarin doses ≤ 5 mg/day, although there were more livebirths [83.6% (75.8–91.4) vs. 43.9% (32.8–55.0)] and fewer foetal anomalies [2.3% (0.7–4.0) vs. 12.4% (3.3–21.6)] with lower doses than with warfarin > 5 mg/day. Conclusions VKAs are associated with fewest maternal complications but also with fewest livebirths. Sequential treatment does not eliminate anticoagulant-related foetal/neonatal adverse events. LMWH is associated with the highest number of livebirths. The safety of UFH throughout pregnancy and first-trimester warfarin ≤ 5 mg/day remains unconfirmed.

Aplastic anaemia (AA) is infrequently observed in pregnancy. We describe 19 pregnancies in 9 women at a tertiary care centre over a period of 30 years. Spontaneous resolution of AA did not occur postpartum in the five pregnancies where AA was first diagnosed in pregnancy. In the remaining pregnancies, although haematological indices declined and transfusion support was needed in 35% of pregnancies, relapses were not observed. There were no deaths, but complications occurred in 79% of pregnancies. Preterm delivery and postpartum haemorrhage were observed in 21% and 26% of pregnancies, respectively.

BACKGROUND Pheochromocytoma, a catecholamine-producing tumor seldom encountered in pregnancy, is often heralded by nonspecific symptoms and undue mortality with delayed diagnosis. The presence of an aortic pseudoaneurysm poses a management challenge given the risk of aortic rupture amplified by hypertensive events. CASE A 30-year-old woman, gravida 3 para 1, presented at 23 6/7 weeks of gestation with vomiting, chest pain, and severe hypertension. Investigation revealed adrenal pheochromocytoma and pseudoaneurysm at the site of a previous aortic injury. Prazosin and phenoxybenzamine achieved α-blockade with subsequent addition of labetalol for β-blockade. Concerns for aortic dissection led to endovascular aortic repair at 30 2/7 weeks of gestation. A female neonate was delivered by urgent cesarean delivery for persistent postprocedure fetal bradycardia. An adrenalectomy followed with near-immediate symptom resolution. Mother and neonate remain well. CONCLUSION The case underscores the necessity of a meticulous approach to hypertension management and the pivotal role of diligent multidisciplinary collaboration to achieve a safe outcome.

Hyperreactio luteinalis is a rare condition in which there is massive cystic enlargement of the ovaries, mimicking malignancy, during pregnancy. When confronted with this condition, the fear of missing a cancer diagnosis often leads the physician to react with unnecessary surgical intervention, potentially resulting in impaired future fertility. The literature on the subject contains mainly case reports and one small case series. A recent review attempted to summarize what is currently known, but there has not yet been a pervasive change in the approach to the management of this condition. In order to define the natural history of the condition and its maternal and fetal effects, we examined all case reports available in the English literature from 1993 to 2014, in addition to another as yet unpublished case report. Our analysis suggests that, despite its impressive presentation with ovarian enlargement and hyperandrogenism, hyperreactio luteinalis tends to be self-limiting, with spontaneous postpartum resolution and without untoward maternal or fetal sequelae. In particular, fetal virilization is rare, and dependent on the timing of hyperandrogenism. Adverse pregnancy outcomes are likely a consequence of the abnormally high hCG levels observed in many of these gestations, and the subset of women with these abnormal values should be considered for enhanced surveillance. Vaginal delivery is preferred, and strategies to sustain the potential for breastfeeding must be introduced while maternal androgen levels fall, allowing lactation to be established. Considering its benign nature and postpartum resolution, management of HL must be conservative, and continued education of health care professionals who may encounter this entity is vital.L’hyperreactio luteinalis est un trouble rare qui donne lieu à une hypertrophie kystique des ovaires de grande envergure, laquelle imite la présence d’une tumeur maligne, pendant la grossesse. La présence d’une telle situation mène souvent le médecin à procéder inutilement à une intervention chirurgicale motivée par la crainte de voir un diagnostic de cancer passer inaperçu, ce qui pourrait affecter la fertilité future de la patiente. La littérature sur le sujet consiste principalement en des exposés de cas et en une série de cas de faible envergure. Bien qu’une récente analyse ait tenté de résumer les données connues à ce sujet à l’heure actuelle, aucune modification n’a encore été universellement apportée à la prise en charge de cette pathologie. Afin de définir l’histoire naturelle de cette dernière et d’en déterminer les effets maternels et fœtaux, nous nous sommes penchés sur tous les exposés de cas ayant été publiés en anglais entre 1993 et 2014, ainsi que sur un exposé de cas n’ayant pas encore été publié. Notre analyse laisse entendre que, malgré sa présentation spectaculaire (hypertrophie ovarienne et hyperandrogénie), l’hyperreactio luteinalis a tendance à être spontanément résolutive à la suite de l’accouchement, sans séquelles indésirables pour la mère ou le fœtus. En particulier, la virilisation fœtale est rare et dépend de la chronologie de l’hyperandrogénie. Les issues de grossesse indésirables sont probablement attribuables aux taux anormalement élevés de hCG qui sont constatés dans bon nombre des grossesses affectées; la mise en œuvre d’une surveillance accrue devrait être envisagée pour ce qui est du sous-groupe des femmes qui présentent de telles valeurs anormales. L’accouchement vaginal est à privilégier et des stratégies visant à soutenir le potentiel d’allaitement doivent être mises en œuvre pendant la chute des taux maternels d’androgènes, afin de permettre la lactation. Compte tenu de la nature bénigne de l’hyperreactio luteinalis et de sa résolution postpartum, la prise en charge de ce trouble doit être conservatrice; de plus, la formation continue des professionnels de la santé qui pourraient devoir y faire face est cruciale.

Objective This study sought to determine whether there is practice variation in the treatment and prevention of acute venous thromboembolism (VTE) in pregnant patients, potentially to prioritize future studies. Background The risk of VTE during pregnancy is five-fold that of the non-pregnant state. Guidance is often lacking for the treatment and prophylaxis of VTE because there are few RCTs. Methods The study used a cross-sectional study design using a self-administered electronic questionnaire consisting of 11 case scenarios that were sent to hematologists, maternal-fetal medicine specialists, obstetricians and gynaecologists, and internal medicine specialists across Canada. Results A total of 254 participants responded to the survey and 193 (76%) completed the survey, 158 of whom indicated that they were involved in the decision to anticoagulate these patients. Anticoagulation of patients with superficial venous thrombosis during pregnancy, monitoring of low-molecular-weight heparin antepartum, and discontinuation of this agent at the time of delivery were the scenarios associated with the largest variability of responses. For the management of acute VTE antepartum, most participants favoured a once-daily regimen, although internists more so than obstetrics and gynaecology physicians (94.7% vs. 73.7%). Cesarean section was not perceived to be a procedure with a marked increased risk of thrombosis to warrant thromboprophylaxis because most physicians elected not to offer thromboprophylaxis for this scenario. However, obesity and severe preeclampsia with Cesarean section led to the predominant use of thromboprophylaxis, at 80.0% and 68.4%, respectively. Conclusion Prospective studies addressing peripartum management where significant discrepancies exist are warranted.

Only through concerted and well-executed research endeavors can we gain the requisite knowledge to advance pregnancy care and have a positive impact on maternal and newborn health. Yet the heterogeneity inherent in individual studies limits our ability to compare and synthesize study results, thus impeding the capacity to draw meaningful conclusions that can be trusted to inform clinical care. The PhenX Toolkit (http://www.phenxtoolkit.org), supported since 2007 by the National Institutes of Health, is a web-based catalog of standardized protocols for measuring phenotypes and exposures relevant for clinical research. In 2016, a working group of pregnancy experts recommended 15 measures for the PhenX Toolkit that are highly relevant to pregnancy research. The working group followed the established PhenX consensus process to recommend protocols that are broadly validated, well established, nonproprietary, and have a relatively low burden for investigators and participants. The working group considered input from the pregnancy experts and the broader research community and included measures addressing the mode of conception, gestational age, fetal growth assessment, prenatal care, the mode of delivery, gestational diabetes, behavioral and mental health, and environmental exposure biomarkers. These pregnancy measures complement the existing measures for other established domains in the PhenX Toolkit, including reproductive health, anthropometrics, demographic characteristics, and alcohol, tobacco, and other substances. The preceding domains influence a woman's health during pregnancy. For each measure, the PhenX Toolkit includes data dictionaries and data collection worksheets that facilitate incorporation of the protocol into new or existing studies. The measures within the pregnancy domain offer a valuable resource to investigators and clinicians and are well poised to facilitate collaborative pregnancy research with the goal to improve patient care. To achieve this aim, investigators whose work includes the perinatal population are encouraged to utilize the PhenX Toolkit in the design and implementation of their studies, thus potentially reducing heterogeneity in data measures across studies. Such an effort will enhance the overall impact of individual studies, increasing the ability to draw more meaningful conclusions that can then be translated into clinical practice.

Introduction Chronic histiocytic intervillositis (CHI) of the placenta although rare, has a high recurrence rate, is associated with serious adverse pregnancy outcomes and has no available treatment. This study aims to determine clinical, biochemical and radiological factors associated with CHI, to guide management of subsequent pregnancies. Methods This retrospective observational study included consecutive cases with a histopathologic diagnosis of CHI after 18 weeks of gestation, between 2001 and 2014, and no controls. Clinical (maternal, fetal and delivery outcomes), biochemical (first- and second-trimester biomarkers for fetal aneuploidy and serum alkaline phosphatase) and radiological (second- and third-trimester fetal, placental and Doppler ultrasound) factors associated with a histopathological diagnosis of CHI were identified and results presented as percentages. Outcomes of subsequent pregnancies were described. Results Of 231 identified cases of ‘intervillositis’, 33 were confirmed to have CHI, of which only 4/33 (12.1%) had prior uncomplicated term deliveries. During pregnancy, 10/18 (55.5%) had abnormal first-trimester screening, 4/16 (25%) had abnormal second-trimester screening, 6/19 (31.6%) had at least one elevated alkaline phosphatase level, and 15/20 (75%) had at least one abnormal feature on mid-trimester placental ultrasound. In subsequent pregnancies that were closely followed with a combination of biochemical and radiologic tests, there were no cases of fetal loss, and lower incidence of fetal growth restriction and preterm birth. Discussion No clinical, biochemical or radiological finding is consistently associated with CHI and adverse outcomes thereof. Whether the incorporation of these tests in individualized care-plans could improve outcomes in subsequent pregnancies needs to be studied further.