Guideline No. 452: Diagnosis and Management of Intrahepatic Cholestasis of Pregnancy.

OBJECTIVE: To summarize the current evidence and to make recommendations for the diagnosis and management of intrahepatic cholestasis of pregnancy. TARGET POPULATION: Pregnant people with intrahepatic cholestasis of pregnancy. OPTIONS: Diagnosing the condition using fasting or non-fasting bile acids, classifying disease severity, determining what treatment to offer, establishing how to monitor for antenatal fetal wellbeing, identifying when to perform elective birth. BENEFITS, HARMS, AND COSTS: Individuals with intrahepatic cholestasis of pregnancy are at increased risk of adverse perinatal outcomes including preterm birth, neonatal respiratory distress and admission to a neonatal intensive care unit, with an increased risk of stillbirth when bile acid levels are ≥100 µmol/L. There is inequity in bile acid testing availability and timely access to results, along with uncertainly of how to treat, monitor. and ultimately deliver these pregnancies. Optimization of diagnostic and management protocols can improve maternal and fetal postnatal outcomes. EVIDENCE: Medline, PubMed, Embase, and the Cochrane Library were searched from inception to March 2023, using medical subject headings (MeSH) and keywords related to pregnancy, intrahepatic cholestasis of pregnancy, bile acids, pruritis, ursodeoxycholic acid, and stillbirth. This document presents an abstraction of the evidence rather than a methodological review. VALIDATION METHODS: The authors rated the quality of evidence and strength of recommendations using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. See Appendix A (Tables A1 for definitions and A2 for interpretations). INTENDED AUDIENCE: Obstetric care providers, including obstetricians, family physicians, nurses, midwives, maternal-fetal medicine specialists, and radiologists. SOCIAL MEDIA ABSTRACT: Intrahepatic cholestasis of pregnancy requires adequate diagnosis with non-fasting bile acid levels which guide optimal management and delivery timing. SUMMARY STATEMENTS: RECOMMENDATIONS.

Usage of DNA Fingerprinting Technology to Check Sample Error and Contamination in Molecular Laboratories.

Sample identification error is a severe medical error in clinical molecular diagnostic laboratories, which can lead to reporting the wrong results for the patient involved. Sample contamination can also lead to incorrect test reports. Avoiding sample identification error and sample contamination could be life-saving. Sample switch and sample contamination could happen on laboratory bench works, especially when pipetting into multi-well plates. It is difficult to realize such errors during laboratory bench work. Laboratory staff may not be aware of such an error when it happens. DNA fingerprinting technology can be used to determine sample identity and subsequently identify sample switch and sample contamination in the laboratory. Our laboratory has explored the usage of this technology in our quality control process and successfully established that DNA fingerprinting can be used to monitor sample switch and sample contamination in next-generation sequencing and BCR/ABL1 real-time PCR bench work.

Pregnancy outcomes following single and repeat liver transplantation: An international 2-center cohort.

Due to advances in obstetric and transplant medicine, women with a history of liver transplantation can have successful pregnancies. However, data on pregnancy outcomes is still limited, especially for women who have had a repeat liver transplant following graft rejection. This retrospective study compares pregnancy outcomes in women with single and repeat liver transplants managed at 2 tertiary hospitals in Toronto, Canada and Leuven, Belgium. We identified 41 pregnancies in 28 transplanted women, 6 of whom conceived following a second liver transplant after the first was rejected. Mean maternal age at delivery was 30 ± 7 years, and transplant-to-pregnancy interval was 8.5 ± 5.1 years. All women had normal liver function upon conception. Immunosuppressants included tacrolimus ± azathioprine (n = 26), cyclosporine (n = 4), and prednisone with immunosuppressants (n = 11). There were no maternal deaths. Maternal complications included hypertensive disorders of pregnancy (n = 10), deterioration in renal function (n = 6), gestational diabetes (n = 4), graft deterioration (n = 2), and anemia requiring blood transfusion (n = 1). Fetal/neonatal adverse outcomes included 2 miscarriages, 3 stillbirths, 1 neonatal death, 5 small-for-gestational-age infants, and 1 minor congenital anomaly. Mean gestational age at delivery was 36.7 ± 4.2 weeks. There were 14 (38.9%) preterm births. Outcomes in women with a second transplant were similar to those with a single transplant, except for a higher incidence of hypertensive disorders. In conclusion, with appropriate multidisciplinary care, stable graft function at pregnancy onset, and adherence to immunosuppressive regimens, women with single and repeat liver transplants have low rates of graft complications but remain at increased risk for pregnancy complications. Immunosuppressants and high-dose glucocorticoids can be safely used for maintenance of graft function and management of graft deterioration in pregnancy. Liver Transplantation 24 769-778 2018 AASLD.

The Approach to Peripartum Management of Anticoagulation: A Multidisciplinary Survey.

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.

The Pulmonary Edema Preeclampsia Evaluation (PEPE) Study.

BACKGROUND: Women with preeclampsia may develop pulmonary edema, but the reasons for this are largely unknown. METHODS: We performed a case-control study of women with preeclampsia at two major obstetrical centres in Toronto, ON, between 2005 and 2012. Cases (n = 28) were women with preeclampsia who had pulmonary edema on a chest CT or plain X-ray during the index delivery hospitalization. Control subjects (n = 64) were those with preeclampsia but no diagnosis of pulmonary edema or heart failure in the index hospitalization for delivery. Study variables were abstracted from each woman's paper chart and electronic medical record. Multivariable logistic regression with backward elimination was used to select a final set of significant predictors. RESULTS: Approximately one half of the cases of pulmonary edema occurred antepartum. Each 10 × 10(9)/L reduction in platelet count (OR 1.32; 95% CI 1.06 to 1.65) or 10 µmol/ L increase in peak serum uric acid concentration (OR 1.19; 95% CI 1.06 to 1.34) was significantly associated with pulmonary edema, as was receiving magnesium sulphate (OR 10.42; 95% CI 1.39 to 78.22). Multiparity (OR 0.03; 95% CI 0.004 to 0.29) and each 500 mL increase in the volume of intravenous crystalloids received (OR 0.60; 95% CI 0.37 to 0.98) were associated with a lower risk of pulmonary edema. CONCLUSION: We identified several preliminary risk factors for pulmonary edema in women with preeclampsia. Additional work is needed to better understand the role of these and other factors predicting the development of pulmonary edema in women with preeclampsia.

Contexte : Les femmes qui présentent une prééclampsie peuvent en venir à connaître un œdème pulmonaire; toutefois, les raisons pouvant expliquer cette situation demeurent largement inconnues. Méthodes : Nous avons mené, entre 2005 et 2012, une étude cas-témoins auprès de femmes présentant une prééclampsie au sein de deux centres majeurs offrant des services d'obstétrique à Toronto (Ont.). Les « cas ¼ (n = 28) étaient représentés par les femmes présentant une prééclampsie chez qui la présence d'un œdème pulmonaire avait été révélée par tomodensitographie thoracique ou par radiographie régulière au cours de l'hospitalisation dans le cadre de la grossesse probante. Les « témoins ¼ (n = 64) étaient représentés par les femmes présentant une prééclampsie qui n'avaient toutefois pas reçu un diagnostic d'œdème pulmonaire ou d'insuffisance cardiaque au cours de l'hospitalisation dans le cadre de la grossesse probante. Les variables à l'étude ont été résumées à partir du dossier papier et du dossier médical électronique de chacune des femmes. Une régression logistique multivariée (s'accompagnant d'une élimination descendante) a été utilisée aux fins de la sélection d'un ensemble final de facteurs prédictifs significatifs. Résultats : Près de la moitié des cas d'œdème pulmonaire se sont manifestés pendant la période antepartum. Tant chacune des baisses de 10 × 109/l de la numération plaquettaire (RC, 1,32; IC à 95 %, 1,06 - 1,65) que chacune des hausses de 10 µmol/l du pic de concentration sérique en acide urique (RC, 1,19; IC à 95 %, 1,06 - 1,34) ont été associées de façon significative à l'œdème pulmonaire, tout comme le fait de recevoir du sulfate de magnésium (RC, 10,42; IC à 95 %, 1,39 - 78,22). La multiparité (RC, 0,03; IC à 95 %, 0,004 - 0,29) et chaque hausse de 500 ml du volume de cristalloïdes administrés par intraveineuse (RC, 0,60; IC à 95 %, 0,37 - 0,98) ont été associées à un risque moindre d'œdème pulmonaire. Conclusion : Nous avons identifié plusieurs facteurs de risque préliminaires en ce qui concerne l'œdème pulmonaire chez les femmes présentant une prééclampsie. D'autres études s'avèrent requises pour nous permettre de mieux comprendre le rôle de ces facteurs et celui d'autres facteurs pour ce qui est de la prévision de l'apparition d'un œdème pulmonaire chez les femmes qui présentent une prééclampsie.

Micronutrient screening, monitoring, and supplementation in pregnancy after bariatric surgery.

We present the case of a woman with a history of biliopancreatic diversion and duodenal switch procedure who developed severe malnourishment requiring total parenteral nutrition during three pregnancies. The widespread use of bariatric surgery, particularly among those of reproductive age, has led to an increase in the number of women who become pregnant following bariatric surgery. There is a paucity of evidence to guide nutritional recommendations for women during pregnancy post bariatric surgery. We review this literature and summarize key published evidence and provide comprehensive recommendations concerning the common challenges in the management of nutrition status during pregnancy. The focus is on the impact of malabsorptive bariatric surgeries on pregnancy outcomes, nutrient deficiencies, recommendations for micro- and macronutrient monitoring and supplementation, and altered glucose metabolism and implications for diabetes screening. Optimizing pregnancy outcomes for individuals following bariatric surgery requires multidisciplinary team management including obstetrical providers, obstetric medicine specialists, and dietitians.

Performance characteristics of the first Food and Drug Administration (FDA)-cleared digital droplet PCR (ddPCR) assay for BCR::ABL1 monitoring in chronic myelogenous leukemia.

Chronic myelogenous leukemia (CML) is a hematopoietic stem cell malignancy that accounts for 15-20% of all cases of leukemia. CML is caused by a translocation between chromosomes 9 and 22 which creates an abnormal fusion gene, BCR::ABL1. The amount of BCR::ABL1 transcript RNA is a marker of disease progression and the effectiveness of tyrosine kinase inhibitor (TKI) treatment. This study determined the analytical and clinical performance of a droplet digital PCR based assay (QXDx BCR-ABL %IS Kit; Bio-Rad) for BCR::ABL1 quantification. The test has a limit of detection of MR4.7 (0.002%) and a linear range of MR0.3-4.7 (50-0.002%IS). Reproducibility of results across multiple sites, days, instruments, and users was evaluated using panels made from BCR::ABL1 positive patient samples. Clinical performance of the assay was evaluated on patient samples and compared to an existing FDA-cleared test. The reproducibility study noted negligible contributions to variance from site, instrument, day, and user for samples spanning from MR 0.7-4.2. The assay demonstrated excellent clinical correlation with the comparator test using a Deming regression with a Pearson R of 0.99, slope of 1.037 and intercept of 0.1084. This data establishes that the QXDx™ BCR-ABL %IS Kit is an accurate, precise, and sensitive system for the diagnosis and monitoring of CML.

Maternal atrial arrhythmia detected by uterine artery Doppler.

BACKGROUND: Uterine artery Doppler ultrasound assessment is used to assess uteroplacental blood flow and the risk of placental ischemic-thrombotic injury in high-risk pregnancies. We report here a case in which this examination identified the presence of a maternal atrial arrhythmia. CASE: A 50-year-old woman with no significant past medical history received antenatal care in our fetal medicine unit clinic because of advanced maternal age, a history of recurrent pregnancy loss, multiple uterine fibroids, and a history of in vitro fertilization using donated oocytes. Uterine artery Doppler ultrasound was normal at 19 weeks, but was repeated at 33 weeks because of abnormal placental texture and maternal risks, revealing an irregular maternal heart rhythm. Paroxysmal atrial fibrillation was confirmed by Holter monitor at 34 weeks. The patient was asymptomatic and declined the cardiologist's recommendation of antepartum and postpartum anticoagulation. She remained asymptomatic and had delivery by Caesarean section at term. CONCLUSION: Uterine artery Doppler flow studies may identify a significant maternal cardiac arrhythmia.

Thromboembolism following cesarean section: a retrospective study.

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.

Canadian Stroke Best Practice Consensus Statement: Acute Stroke Management during pregnancy.

The Canadian Stroke Best Practice Consensus Statement Acute Stroke Management during Pregnancy is the second of a two-part series devoted to stroke in pregnancy. The first part focused on the unique aspects of secondary stroke prevention in a woman with a prior history of stroke who is, or is planning to become, pregnant. This document focuses on the management of a woman who experiences an acute stroke during pregnancy. This consensus statement was developed in recognition of the need for a specifically tailored approach to the management of this group of patients in the absence of any broad-based, stroke-specific guidelines or consensus statements, which do not exist currently. The foundation for the development of this document was the concept that maternal health is vital for fetal well-being; therefore, management decisions should be based first on the confluence of two clinical considerations: (a) decisions that would be made if the patient wasn't pregnant and (b) decisions that would be made if the patient hadn't had a stroke, then nuanced as needed. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include initial emergency management, diagnostic imaging, acute stroke treatment, the management of hemorrhagic stroke, anesthetic management, post stroke management for women with a stroke in pregnancy, intrapartum considerations, and postpartum management. These statements are appropriate for healthcare professionals across all disciplines and system planners to ensure pregnant women who experience a stroke have timely access to both expert neurological and obstetric care.

Canadian stroke best practice consensus statement: Secondary stroke prevention during pregnancy.

The Canadian Stroke Best Practice Consensus Statement: Secondary Stroke Prevention during Pregnancy, is the first of a two-part series devoted to stroke in pregnancy. This document focuses on unique aspects of secondary stroke prevention in a woman with a prior history of stroke or transient ischemic attack who is, or is planning to become, pregnant. Although stroke is relatively rare in this cohort, several aspects of pregnancy can increase stroke risk during or immediately after pregnancy. The rationale for the development of this consensus statement is based on the premise that stroke in this group requires a specifically-tailored management approach. No other broad-based, stroke-specific guidelines or consensus statements exist currently. Underpinning the development of this document was the concept that maternal health is vital for fetal wellbeing; therefore, management decisions should be based on the confluence of two clinical considerations: (a) decisions that would be made if the patient was not pregnant and (b) decisions that would be made if the patient had not had a stroke. While empirical research in this area is limited, this consensus document is based on the best available literature and guided by expert consensus. Issues addressed in this document include general management considerations for secondary stroke prevention, the use of antithrombotics, blood pressure management, lipid management, diabetes care, and management for specific ischemic stroke etiologies in pregnancy. The focus is on maternal and fetal health while minimizing risks of a recurrent stroke, through counseling, monitoring, and the safety of select pharmacotherapy. These statements are appropriate for health care professionals across all disciplines.