Eliana Castillo

Clinical course of 161 untreated and tenofovir-treated chronic hepatitis B pregnant patients in a low hepatitis B virus endemic region.

Hepatitis B immunoprophylaxis failure is linked to high maternal viraemia. There is limited North American data on hepatitis B outcomes in pregnancy. Pregnant hepatitis B carriers were enrolled January 2011–December 2014 and offered tenofovir in the 3rd trimester if hepatitis B virus (HBV)‐DNA was >7‐log IU/mL. Outcomes were determined in treated vs untreated patients. In total, 161 women with 169 pregnancies (one twin, 170 infants; median age 32 years), 18% (29/161) HBeAg+ and median HBV‐DNA 2.51 log IU/mL (IQR 1.66–3.65; range 0.8–8.1) were studied. 14.3% (23/161) received tenofovir due to high viral load (16/23, median 74 days, IQR 59–110) or due to liver disease (7/23). In 10/16 treated due to high viraemia, with confirmed adherence, follow‐up HBV‐DNA showed a 5.49 log decline (P = 0.003). In treatment naïve mothers, median alanine aminotransferase (ALT) increased from 17 IU/L (IQR 12–24) to 29 (IQR 18–36) post‐partum (P = 1.5e‐7). In seven highly viraemic mothers who declined therapy (HBV‐DNA >8‐log IU/mL); median ALT increased ~3X from baseline (P < 0.01). 26% (44/169) had Caesarean section with no difference in treated vs untreated subjects. No tenofovir‐treated mothers had renal dysfunction. Data were available on 167/170 infants; in 50.8% (85/167) who completed immunoprophylaxis, 98.8% (84/85, including 12 exposed to tenofovir in utero) were HBV immune. One infant born to an HBeAg+ mother with HBV‐DNA >8‐log IU/mL failed immunoprophylaxis. In this prospective Canadian cohort study, most untreated mothers experienced mild HBV flares. Tenofovir in pregnancy is well tolerated and reduces viral load prior to parturition.

Hepatitis B Virus (HBV) Variants in Untreated and Tenofovir Treated Chronic Hepatitis B (CHB) Patients during Pregnancy and Post-Partum Follow-Up

Background Chronic hepatitis B (CHB) is a dynamic disease that may be affected by immune changes in pregnancy. Guidelines suggest consideration of nucleos/tide analogs (NA), i.e., tenofovir, (TDF) in highly viremic mothers to reduce vertical transmission risk. HBV variability affects CHB outcome, but little is known about HBV genetic changes in pregnancy due to immune or NA selection. Objectives To evaluate HBV diversity in NA treated or untreated pregnant vs. post-partum CHB carriers. Study Design In plasma collected from 21 mothers (7 matching pre/post-partum), HBV serological tests, genotype and viral load were assayed. The HBV pre-surface (S) /S overlapping polymerase (P) (N = 20), pre-core (C) /C (N = 11) and/or full genome PCR amplicons (N = 3) underwent clonal sequence analysis. Results The median age was 31 y, 71% Asian, 68% genotype B or C, 33% HBV eAg+, 5 received TDF (median HBV DNA 8.5 log IU/ml). In untreated mothers, median antepartum vs. post-partum ALT was 21 vs. 24 U/L and HBV DNA was 2.7 vs. 2.4 log(10) IU/ml. ALT and/or HBV DNA flares occurred during pregnant and/or post-partum period in 47% (10/21). Clonal sequencing antepartum showed the presence of minor “a determinant” and/or vaccine escape mutants (VEM) but drug resistant variants were infrequent. Analysis of pregnant vs. post-partum samples showed different HBV variants and viral diversity. Conclusions Differences in immune and/or by NA selective pressures during pregnancy may affect HBV evolution during pregnancy. The presence of minor VEM warrant infant follow-up.

Cost effectiveness of quantitative hepatitis B virus surface antigen testing in pregnancy in predicting vertical transmission risk.

Vertical transmission of hepatitis B virus (HBV) can occur despite immunoprophylaxis in mothers with high HBV DNA levels (>5–7 log10 IU/ml). Quantitative hepatitis B surface antigen (qHBsAg) testing could be used as a surrogate marker to identify high viral load carriers, but there is limited data in pregnancy. We conducted a prospective observational study to determine the cost‐effectiveness and utility of qHBsAg as a valid surrogate marker of HBV DNA.

Global obstetric medicine: Collaborating towards global progress in maternal health

Globally, the nature of maternal mortality and morbidity is shifting from direct obstetric causes to an increasing proportion of indirect causes due to chronic conditions and ageing of the maternal population. Obstetric medicine can address an important gap in the care of women by broadening its scope to include colleagues, communities and countries that do not yet have established obstetric medicine training, education and resources. We present the concept of global obstetric medicine by highlighting three low- and middle-income country experiences as well as an example of successful collaboration. The article also discusses ideas and initiatives to build future partnerships within the global obstetric medicine community.

Post partum infections: A review for the non-OBGYN

The epidemiology of infections in the puerperium (post partum period) is not well understood and remains underestimated because surveillance systems are often limited to the acute care setting. The most common source of persistent fever after delivery is genital tract infection for which diagnosis remains mostly clinical and antibiotic treatment empiric. This review will emphasize surgical site infections (SSIs) and endometritis. Septic thrombo-phlebitis, mastitis, urinary tract infections and rare infections will be covered in less detail. Puerperal sepsis will not be reviewed.

A Systematic Review of Barriers to Vaccination During Pregnancy in the Canadian Context

OBJECTIVE Although vaccination in pregnancy has the potential to affect maternal and infant morbidity and mortality dramatically, uptake of recommended vaccinations in pregnancy remains low. The objective of this study was to identify barriers and facilitators of vaccination during pregnancy in Canada. METHODS The Medline database and the tables of contents of four relevant Canadian journals were screened to identify all studies that considered barriers and/or facilitators to vaccination during pregnancy, specifically in Canadian settings. Citations were screened, and a narrative synthesis of findings was undertaken given the heterogeneity of study design. RESULTS In total, 17 studies met inclusion criteria, most with a focus on the seasonal and pandemic influenza vaccines. Facilitators and barriers were identified at the level of the patient and the provider. At both levels, knowledge was an important facilitator of vaccine acceptance during pregnancy and was notably improved in studies following the 2009 pandemic H1N1 influenza outbreak compared with earlier studies. Vaccine endorsement by a prenatal care provider and clear messages of safety for the fetus emerged as key motivators. Few studies addressed system-level barriers or interventions for improving vaccine uptake during pregnancy in the Canadian setting. CONCLUSION Common themes have emerged from the Canadian literature addressing barriers and facilitators of vaccination during pregnancy. However, there is a paucity of literature to suggest strategies to improve the uptake of vaccination during pregnancy in Canadian settings. Further research is urgently needed given the expanding role of vaccination during routine prenatal care.

L'immunisation pendant la grossesse : l'avenir de la protection néonatale

Le présent numéro du JOGC contient la version révisée de la directive clinique sur l’immunisation pendant la grossesse. Cette révision formule une nouvelle recommandation sur la vaccination universelle contre la coqueluche, qui abonde dans le même sens que les recommandations récentes du CCNI, afin de protéger les nouveau-nés et les jeunes enfants. Elle précise également des indications pour la vaccination contre d’autres agents pathogènes visant à protéger les femmes atteintes de certaines comorbidités, et réitère sa recommandation sur la vaccination universelle contre l’influenza pour protéger les mères et les bébés.

Atrial mass in a pregnant patient with antiphospholipid antibody syndrome.

Dear Editor, A 26-year-old gravida 7, para 1 woman had been previously diagnosed with antiphospholipid antibody syndrome (APS). She had a history of recurrent venothromboembolic events (VTEs) with her first deep venous thrombosis (DVT) at the age of 17. She later developed a right internal jugular vein thrombosis that was complicated by intracranial hypertension requiring a lumboperitoneal shunt. She also had a history of recurrent pregnancy losses with one spontaneous abortion at 7 weeks gestational age (GA) and four fetal deaths after 10 weeks GA. Lupus anticoagulant testing had been positive. As there were no features suggestive of systemic lupus erythematosus (SLE), she was diagnosed with primary APS. She presented to the clinic at 25 weeks GA with a 2-week history of dyspnea. She had previously decided against medical advice to remain on warfarin, as she had attributed the cause of previous pregnancy losses to heparin. Her only medication was warfarin and recently her international normalized ratio (INR) had been maintained within the goal therapeutic range of 2.0– 3.0. On examination, pulse was 110 bpm, blood pressure was 150/70, and oxygen saturation was 96% on room air. She was admitted to hospital for further investigations and management. Blood work revealed a normal complete blood count, electrolytes and creatinine. Chest X-ray, electrocardiogram and Doppler ultrasound of the legs were normal. A transthoracic echocardiogram (TTE) demonstrated a mobile mass measuring 35 9 12 mm in the right atrium which was suspicious for a thrombus given the patient’s history of APS. The TTE did not show signs of pulmonary hypertension. The patient’s clinical presentation was considered to be secondary to embolic phenomena from the atrial mass. Ventilation/ perfusion scan or computed tomography pulmonary angiogram were not done. She was started on lowdose aspirin and intravenous unfractionated heparin (UFH) infusion with careful monitoring of partial thromboplastin time to a goal range of 80–100 s. Warfarin was discontinued. The patient had cardiac magnetic resonance imaging, which showed a 37 9 28 mm mobile, homogenous, pedunculated mass attached to the right atrial wall. The findings were highly suggestive of atrial myxoma rather than thrombus. Resection of the mass was judged to be necessary due to the risk of possible catastrophic embolic events. A combined surgery was planned with Cesarean section followed by atrial mass resection at 29 weeks GA, which would allow for a reasonable time for fetal development. The patient was monitored closely in hospital until then. She remained clinically stable on UFH, and two repeat TTEs showed that the atrial mass was unchanged. She received steroids for fetal lung maturation. At 29 weeks GA, a healthy live baby boy was delivered by Cesarean section. The patient was subsequently placed on cardiopulmonary bypass and the atrial mass was removed, appearing to be thrombus. She tolerated both procedures very well. A follow-up TTE showed no residual atrial mass/thrombus. She was discharged home on post-operative day 10 in a stable condition after being transitioned to warfarin. The target INR on discharge was 2.5–3.5. The pathology of the mass revealed thrombosis. APS is a condition that predisposes individuals to develop venous and arterial thrombotic events and pregnancy-related complications. APS can exist in a primary form or can be secondary to SLE. Updated APS diagnostic criteria require the presence of a clinical event (thrombosis or recurrent pregnancy morbidity) and laboratory evidence (positive anticardiolipin antibody, lupus anticoagulant, or anti-b2 glycoprotein-1 antibody on repeated testing). The mainstay of treatment of APS is anticoagulation/ antithrombotic therapy. In patients with APS with previous thrombosis, life-long anticoagulation is recommended. In pregnant APS patients without previous thrombosis but with recurrent early miscarriages, a

Peripartum cytokine flares in a multiethnic cohort of chronic hepatitis B carriers does not correlate with hepatitis B virus suppression or increased risk of liver disease

In chronic hepatitis B (CHB) carriers, alanine transaminase (ALT) flares are common in the peripartum period. There are limited data on immunological changes of pregnancy in CHB. We hypothesize that in pregnant CHB carriers, the Th1/Th2 cytokine ratio is altered resulting in changes in biochemical/virological and liver fibrosis markers.