The effects of ursodeoxycholic acid treatment for intrahepatic cholestasis of pregnancy on maternal and fetal outcomes: a meta-analysis including non-randomized studies.

OBJECTIVE: The benefits of ursodeoxycholic acid (UDCA) use for treating intra-hepatic cholestasis of pregnancy (ICP) remain uncertain. A 2010 Cochrane Review of randomized control trials was unable to recommend either for or against the use of UDCA in treating ICP. We conducted a meta-analysis of the literature, including both non-randomized studies (NRSs) and RCTs. The objective of the study was to determine if patients included in NRSs were comparable to those in RCTs, and to determine whether the inclusion of NRSs could strengthen the available evidence and guide clinical practice on UDCA use in women with ICP. DATA SOURCES: We searched Medline (Ovid), Embase (Ovid), EMB Reviews, Cinahl (Ebsco), and Web of Knowledge (Thomson Reuters) for articles published from 1966 to June 2012. STUDY SELECTION: We included all eligible RCTs of UDCA versus placebo or other treatments, and all NRSs comparing UDCA with any other treatment in women with ICP. DATA SYNTHESIS: We included 11 RCTs (n = 625 pregnancies) and six NRSs (n = 211 pregnancies). The women included in RCTs and NRSs were comparable, but study quality was poorer for NRSs. Overall, women treated with UDCA had decreased pruritus in 73% of RCTs and in 100% of NRSs with available data. Liver function tests were improved in 82% of RCTs and in 100% of NRSs with available data. UDCA use did not affect the Caesarean section rate, but was associated with less prematurity, less use of neonatal intensive care units (data available in only 3/17 studies), and trends towards increased birth weight and decreased meconium staining. There were 0/356 stillbirths with UDCA and 3/399 stillbirths with comparator. CONCLUSION: UDCA treatment should be recommended for women with ICP to reduce adverse maternal and fetal outcomes.

Objectif : Les avantages de l'utilisation d'acide ursodésoxycholique (AUDC) pour la prise en charge de la cholestase intrahépatique de la grossesse (CIG) demeurent incertains. Une analyse Cochrane de 2010 ayant porté sur des essais comparatifs randomisés n'a pas été en mesure de se prononcer pour ou contre l'utilisation d'AUDC pour la prise en charge de la CIG. Nous avons mené une méta-analyse de la littérature, en englobant tant les études non randomisées (ENR) que les ECR. Nous avions pour objectif de déterminer si les patientes ayant participé aux ENR étaient comparables à celles qui avaient participé aux ECR; nous avions également pour objectif de déterminer si l'inclusion des ENR pouvait renforcer les données probantes disponibles et orienter la pratique clinique quant à l'utilisation d'AUDC chez les femmes qui présentent une CIG. Sources de données : Nous avons mené des recherches dans Medline (Ovid), Embase (Ovid), EMB Reviews, Cinahl (Ebsco) et Web of Knowledge (Thomson Reuters) en vue d'en tirer les articles publiés entre 1966 et juin 2012. Sélection des études : Nous avons inclus tous les ECR admissibles ayant comparé l'AUDC à un placebo ou à d'autres traitements et toutes les ENR ayant comparé l'AUDC à tout autre traitement chez des femmes présentant une CIG. Synthèse des données : Nous avons inclus 11 ECR (n = 625 grossesses) et six ENR (n = 211 grossesses). Bien que les femmes ayant participé aux ECR et aux ENR aient été comparables, la qualité des études était plus faible dans le cas des ENR. De façon générale, les femmes traitées à l'AUDC ont connu une atténuation du prurit dans 73 % des ECR et dans 100 % des ENR disposant de données disponibles. Les épreuves de fonction hépatique ont présenté une amélioration dans 82 % des ECR et dans 100 % des ENR disposant de données disponibles. Bien que l'utilisation d'AUDC n'ait pas affecté le taux de césarienne, elle a été associée à une prématurité moindre, à une utilisation moindre des unités néonatales de soins intensifs (données disponibles pour seulement trois des 17 études) et à des tendances à l'augmentation du poids de naissance et à l'atténuation de la teinte méconiale du liquide amniotique. Aucune mortinaissance n'a été constatée dans le cadre de 356 grossesses ayant fait l'objet d'un traitement à l'AUDC et trois mortinaissances ont été constatées dans le cadre de 399 grossesses ayant fait l'objet d'un traitement au moyen d'un agent de comparaison. Conclusion : Le traitement à l'AUDC devrait être recommandé aux femmes qui présentent une CIG en vue d'atténuer les issues indésirables maternelles et fœtales.

Prospective Evaluation of Fetal Hemoglobin Expression in Maternal Erythrocytes: An Analysis of a Cohort of 345 Parturients.

It is believed that fetal hemoglobin (HbF) expression in adults is largely genetically regulated. The increased expression of HbF in pregnancy has been reported in a small number of articles. Different mechanisms have been proposed, but the description of HbF expression during pregnancy remains unclear. The objectives of this study were to document HbF expression during peri and postpartum periods, confirm its maternal origin, and assess clinical and biochemical parameters potentially associated with HbF modulation. In this observational prospective study, 345 pregnant women were followed. At baseline, 169 had HbF expression (≥1% of total hemoglobin) and 176 did not have HbF expression. Women were followed at the obstetric clinic during their pregnancy. Clinical and biochemical parameters were measured at each visit. Analyses were made to determine which parameters had a significant correlation to HbF expression. Results show that HbF expression of ≥1% during peri and postpartum periods in pregnant women without influencing comorbidities is at its highest peak during the first trimester. In all women, it was proven that HbF was of maternal origin. A significant positive correlation between HbF expression, ßeta-human chorionic gonadotropin (ß-HCG), and glycosylated hemoglobin (HbA1c) was present. A significant negative association between HbF expression and total hemoglobin was found. HbF expression induction during pregnancy is probably associated with an increase in ß-HCG and HbA1C, and a decrease in total hemoglobin, which could temporarily reactivate the fetal erythropoietic system.

Pregnancy-associated pelvic vein thrombosis: Insights from a multicenter case series.

BACKGROUND: Pelvic vein thrombosis (PVT) is a rare complication of pregnancy that can lead to life-threatening complications, such as pulmonary embolism (PE). OBJECTIVE: To describe characteristics of PVT and its treatment in pregnancy in the province of Quebec, Canada. PATIENTS/METHODS: We developed a province-wide case series of PVT in pregnancy including four tertiary care centers and the Registry of Rare Diseases of the Groupe d'Étude en Médecine Obstétricale du Québec. Using diagnostic codes, we included cases with confirmed PVT on imaging during pregnancy or within 6 weeks postpartum from July 2003 to June 2018. RESULTS: A total of 47 cases were identified. PVT diagnosis was generally made in the early postpartum period (median of 9 [interquartile range (IQR) 4.5-12] days postpartum). Most PVT (94%) included in this series were symptomatic. Women presented primarily with abdominal pain (77%) and fever (55%), often prolonged despite antibiotics (mean 4.45 ± 2.39 days, with 39% having fever for more than 5 days). The most common risk factor was surgery (57%) and peripartum infections (54%). Thirty-eight (83%) women received antibiotics and 41 (89%) were anticoagulated. Three cases of PE (7%) occurred concomitantly, 11% of women required intensive care, and 19% had inferior vena cava (IVC) clot extension. The episode resulted in prolonged hospitalization (median 6 [IQR 3-10.75] days), with 48% being hospitalized more than 7 days. CONCLUSION: Symptomatic PVT has significant clinical implications with prolonged fever and risks of extension in the IVC and PE, leading to prolonged hospitalization including in the intensive care unit. Therapeutic anticoagulation and antibiotics, when infection is documented, should be considered for management.

Gestational diabetes insipidus: a review of an underdiagnosed condition.

OBJECTIVE: To review the etiology, diagnosis, and management of diabetes insipidus during pregnancy. DATA SOURCES: A search of the literature was performed in PubMed using key word searching and citation snowballing to identify articles published in English between January 1, 1980, and December 31, 2008, on the subject of diabetes insipidus during pregnancy. Once the articles were identified, a thorough review of all results was conducted. Results and conclusions were compiled and summarized. STUDY SELECTION: We reviewed 50 studies selected using the following key words: diabetes insipidus, pregnancy, arginine vasopressin, vasopressinase. CONCLUSION: Gestational diabetes insipidus is underdiagnosed because polyuria is often considered normal during pregnancy. Clinicians caring for pregnant women should consider screening for gestational diabetes insipidus, because it could be associated with serious underlying pathology.

Evaluation of Complications in Postpartum Women Receiving Therapeutic Anticoagulation.

OBJECTIVE: To evaluate complications associated with early postpartum therapeutic anticoagulation. METHODS: A multicenter retrospective cohort study was done to evaluate the association between therapeutic anticoagulation postpartum and major complications (hemorrhagic and wound complications). Secondary outcomes included minor complications, risk factors associated with total complications (including the time to therapeutic anticoagulation resumption after delivery) and recurrent thrombotic events within 6 weeks postpartum. RESULTS: From 2003 to 2015, 232 consecutive women were treated with therapeutic anticoagulation within 96 hours postpartum; among those treated, 91 received unfractionated heparin, 138 received low-molecular-weight heparin, and three received other anticoagulants. The primary outcome, a composite of major hemorrhagic complications (requiring transfusion, hospitalization, volume resuscitation, transfer to intensive care unit, or surgery) and major wound complications, occurred in 7 of 83 (8.4%) for cesarean deliveries and 9 of 149 (6.0%) for vaginal deliveries (P=.490). Total complications (including major and minor hemorrhagic and wound complications) occurred in 13 of 83 (15.7%) for cesarean deliveries compared with 9 of 149 (6.0%) for vaginal deliveries (P=.016). When comparing cases associated with and without complications, the median delay before resuming anticoagulation was significantly shorter for both cesarean (12 vs 33 hours, P=.033) and vaginal deliveries (6 vs 19 hours, P=.006). For vaginal deliveries, 8 of 51 (15.7%) women had complications when anticoagulation was started before 9.25 hours postpartum, compared with 1 of 98 (1.0%) when started after 9.25 hours. For cesarean deliveries, 7 of 21 (33.3%) of women experienced complications compared with 6 of 62 (9.7%) if anticoagulation was started before or after 15.1 hours, respectively. Two (0.9%) episodes of venous thromboembolism occurred within 6 weeks postpartum. CONCLUSION: Among postpartum women who received early therapeutic anticoagulation, major complications occurred in 8.4% for cesarean deliveries and 6.0% for vaginal deliveries. Complications were associated with earlier resumption of therapeutic anticoagulation, particularly before 9.25 hours for vaginal deliveries and before 15.1 hours for cesarean deliveries.

Mixed connective tissue disease in pregnancy: A case series and systematic literature review.

OBJECTIVE: To investigate the impact of medical and obstetric complications associated with mixed connective tissue disease (MCTD) in pregnancy. METHOD: We analyzed 68 pregnancies from a systematic literature review and 12 pregnancies affected by MCTD at our centre between 1986 and 2015 for medical and obstetric complications. RESULTS: During pregnancy 37.1% had active MCTD and 26.7% had relapsed. Maternal complications included caesarean section (31.1%, n = 19), preeclampsia (17.6%, n = 13), thromboembolism events, and death (2.5%, n = 2 for each). Fetal complications included prematurity (48.1%, n = 25), intrauterine growth restriction (38.3%, n = 19), and neonatal lupus (28.6%, n = 18, including chondrodysplasia punctata). More than half (n = 10) of the neonatal lupus cases were explained by anti-U1RNP only. The perinatal mortality rate was 17.7% (n = 14). Pregnant women with active disease had higher rates of prematurity (OR = 7.60; 95%CI [1.93; 29.95]) and perinatal death (OR = 16.83; 95%CI [1.90; 147.70]). CONCLUSION: MCTD in pregnancy puts women at risk of medical and obstetric complications, and disease activity probably increases this risk.

Henoch-Schonlein purpura in pregnancy: A case report.

Henoch-Schonlein purpura is a relatively common pediatric vasculitis. Very few cases of Henoch-Schonlein purpura during pregnancy have been described. Henoch-Schonlein purpura is variable in its presentation, from completely benign to possibly catastrophic complications. This rarely encountered condition in adults can also be a recurrence of a previous childhood disease. We present a case of a pregnant 40-year-old woman with Henoch-Schonlein purpura, resulting in a viable birth with no fetal complications. Her presentation is discussed in detail and a general presentation of Henoch-Schonlein purpura is explored, with particular attention to its rare onset during pregnancy.

Pregnancy-Related Venous Thromboembolism Risk in Asymptomatic Women With Antithrombin Deficiency: A Systematic Review.

OBJECTIVE: To evaluate the risk of pregnancy-associated venous thromboembolism in women with asymptomatic antithrombin deficiency. DATA SOURCES: The search was performed on MEDLINE (Ovid and PubMed databases) for the period 1966 to June 2012 and ClinicalTrials.gov as of December 15, 2015. METHODS OF STUDY SELECTION: A systematic review including randomized controlled trials, cohort studies, and case-control studies was conducted. Selection criteria included objectively diagnosed venous thromboembolism or venous thromboembolism treated with 3 months of anticoagulation before the availability of objective testing. The study population consisted of pregnant women with asymptomatic antithrombin deficiency. TABULATION, INTEGRATION, AND RESULTS: Seven publications were included in the review. No randomized controlled trials were identified. The best available data consist of three retrospective cohort studies and four case-control studies. Pooled results from case-control studies yielded an estimated odds ratio for venous thromboembolism of 6.09 (95% confidence interval 1.58-23.43). No pooled estimates could be obtained for cohort studies. Data on use of thromboprophylaxis were scarce. CONCLUSION: Despite the small number of patients included, and the variation in study designs, pooled results from case-control studies show a significant association between asymptomatic antithrombin deficiency and pregnancy-associated venous thromboembolism. Thromboprophylaxis during pregnancy and postpartum should be considered in these women.

Are There Benefits for Gestational Diabetes Mellitus in Treating Lower Levels of Hyperglycemia Than Standard Recommendations?

OBJECTIVES: The new International Association of Diabetes and Pregnancy Study Groups (IADPSG) recommendations for diagnosis of gestational diabetes mellitus (GDM) are generating discussion regarding their universal adoption. Our centre is currently using stricter GDM diagnostic criteria than those proposed by the IADPSG. Evaluation of complication rates and their predictors in our cohort may provide insight for the care of this high-risk population. Therefore, we determined complication rates and identified antepartum maternal predictors of adverse outcomes in our cohort with mild GDM. METHODS: A retrospective cohort study was performed between 2005 and 2011. It included women with and without GDM, which was diagnosed if fasting plasma glucose levels were 5.0 or above or 2-hour post 75 gram oral glucose tolerance test (OGTT) were 7.8 mmol/L or higher. RESULTS: A total of 3712 women, with and without diabetes, were included. Rates of macrosomia and pre-eclampsia were significantly higher in the group with GDM but were lower than the rates usually reported. Macrosomia, the need for insulin therapy or caesarean section and postpartum glucose intolerance predictors included prepregnancy body mass index, excessive gestational weight gain and OGTT screening results, although no specific threshold was found. CONCLUSIONS: This study provides insight into GDM-related complications rates and the benefits of intervention in a large cohort of women with levels of hyperglycemia lower than those currently recommended for diagnosis of GDM. These findings suggest a continuous association between adverse outcomes and maternal hyperglycemia and highlight the important role of maternal risk factors other than glycemic results in the development of pregnancy-related complications. Milder forms of hyperglycemia that would not be identified by IADPSG guidelines may benefit from treatment.

Pituitary apoplexy in pregnancy: A case series and literature review.

BACKGROUND: Severe headache during pregnancy is a challenging condition that may rarely imply endocrine disturbances. Rapid recognition of pituitary apoplexy is needed to improve pregnancy outcome. OBJECTIVE: To review and compare maternal and fetal outcomes after pituitary apoplexy. METHODS: Four cases of pituitary apoplexy during pregnancy in our centre are reported and literature review covering the past 54 years was performed. RESULTS: In the four cases presented and the 33 reported in the literature, most women presented with severe headaches and systemic symptoms. Overall, 42% were treated surgically, 31% received bromocriptine or cabergoline and 61% were given hormone replacement. No major obstetrical complication was reported and all babies were healthy. CONCLUSION: Pituitary apoplexy is a rare cause of sudden and severe headache during pregnancy. Rapid identification of this condition with potentially associated endocrine disturbances is important to ensure maternal and fetal well-being. A multidisciplinary team approach seems to reduce morbidity and mortality.

A 30-year-old pregnant patient with massive haemoptysis and influenza A: Atypical presentation of a common pathogen.

A 30-year-old woman presented at 19 weeks of gestation with symptoms of sore throat, rhinorrhea and haemoptysis that progressed to massive haemoptysis. Her medical history included asthma and a history of smoking prior to pregnancy. Investigations revealed no obvious cause of bleeding. Right lower lobe lobectomy was performed, given the suspicion of a lesion within the intermediate bronchus. The patient developed adult respiratory distress syndrome around 36 h postoperatively. Polymerase chain reaction testing on bronchoalveolar lavage samples was positive for influenza A. Therapy with oseltamivir was initiated. She was discharged two weeks later. This is a rare case of a severe complication from seasonal interpandemic influenza during pregnancy, which underscores the importance of immunization for pregnant women.

Hepatic rupture in hemolysis, elevated liver enzymes, low platelets syndrome.

OBJECTIVE: Rupture of hepatic hematoma associated with hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome is a catastrophic complication of pregnancy. Maternal and fetal mortality rates are still high despite advances in diagnosis and treatment. We aimed to present our experience at two referral centers for hepatic disease and to compare it with cases from the literature. METHODS: We reviewed nine cases that occurred over the past 6 years in our centers and made an extensive literature review covering the past 10 years. We reviewed and compared multiple outcomes for all these cases. RESULTS: The median maternal age of our patients was 29 years (interquartile range 27-32). Embolization treatment was used with seven of nine (78%) of our patients compared with 5 of 88 (6%) in the literature (P<.001). Our maternal and fetal mortality rates were 0% (95% confidence interval [CI] 0-34%) and 30% (95% CI 7-65%), respectively, compared with 17% (95% CI 10-26%) and 38% (95% CI 31-52%]) from our review of the literature from 2000 to 2010. CONCLUSION: The use of hepatic artery embolization to address hepatic rupture associated with HELLP syndrome may help minimize morbidity and maternal mortality.