Pertussis Non-Vaccination During Pregnancy Despite Advice From Prenatal Care Providers.

OBJECTIVE: The purpose of this study was to measure the proportion of non-vaccination for pertussis in mothers in Canada who had been advised by their prenatal care provider to get vaccinated, and to identify sociodemographic factors and beliefs associated with non-vaccination. METHODS: The Survey on Vaccination during Pregnancy (part of childhood National Immunization Coverage Survey) included biological mothers of children born from September 2018 to March 2019. This analysis was restricted to 2657 mothers who had been advised by their prenatal care provider to get vaccinated against pertussis during pregnancy and knew whether or not they had been vaccinated. RESULTS: Of those who had been advised to get vaccinated against pertussis, 21% were not. This rate varied across provinces and territories, ranging from 9% in Prince Edward Island to 32% in Newfoundland and Labrador. Factors independently associated with pertussis non-vaccination included lower household income, having had past live births, and having received prenatal care from an obstetrician-gynecologist or a midwife compared to a family doctor. The risk of pertussis non-vaccination despite prenatal care advice was higher for those who disagreed that the baby would be at greater risk of pertussis if the mother did not get vaccinated. It was also higher for those who disagreed with statements regarding perceived benefits of vaccination. Conversely, disagreement with statements on perceived barriers was negatively associated with pertussis non-vaccination. CONCLUSION: These findings highlight the underlying factors associated with non-vaccination against pertussis despite prenatal care provider recommendation. Some inaccurate beliefs about pertussis and vaccination during pregnancy persist, leading to non-vaccination.

Resources available for parent-provider vaccine communication in pregnancy in Canada: a scoping review.

OBJECTIVE: Vaccination in pregnancy (VIP) is a protective measure for pregnant individuals and their babies. Healthcare provider's (HCP) recommendations are important in promoting VIP. However, a lack of strong recommendations and accessible resources to facilitate communication impact uptake. This study sought to determine the extent of and characterise the resources available for parent-provider vaccine communication in pregnancy in Canada using a behavioural theory-informed approach. DESIGN: Scoping review. METHODS: In accordance with the JBI methodology, nine disciplinary and interdisciplinary databases were searched, and a systematic grey literature search was conducted in March and January 2022, respectively. Eligible studies included resources available to HCPs practising in Canada when discussing VIP, and resources tailored to pregnant individuals. Two reviewers piloted a representative sample of published and grey literature using inclusion-exclusion criteria and the Authority, Accuracy, Coverage, Objectivity, Date, Significance guidelines (for grey literature only). Sixty-five published articles and 1079 grey reports were screened for eligibility, of which 19 articles and 166 reports were included, respectively. RESULTS: From the 19 published literature articles and 166 grey literature reports, 95% were driven by the 'Knowledge' domain of the Theoretical Domains Framework, while n=34 (18%) addressed the 'Skills' domain. Other gaps included a lack of VIP-specific tools to address hesitancy and a lack of information on culturally safe counselling practices. CONCLUSION: The study suggests a need for resources in Canada to improve VIP communication skills and improve access to vaccination information for HCPs and pregnant individuals. The absence of such resources may hinder VIP uptake.

Understanding COVID-19 vaccination decisions during pregnancy and while breastfeeding in a Canadian province.

BACKGROUND: Vaccination in pregnancy is important for preventing illness for mothers and babies; however, vaccine uptake in pregnant individuals is lower than non-pregnant females of fertile age. Given the devastating effects of COVID-19 and the increased morbidity and mortality risk for pregnant individuals, it is important to understand the determinants of vaccine hesitancy in pregnancy. The focus of our study was to explore COVID-19 vaccination among pregnant and breastfeeding individuals and its association with their reasons (psychological factors) for vaccination using the 5C scale and other factors. METHODS: An online survey investigating prior vaccinations, level of trust in healthcare providers, demographic information, and the 5C scale was used for, pregnant and breastfeeding individuals in a Canadian province. RESULTS: Prior vaccinations, higher levels of trust in medical professionals, education, confidence, and collective responsibility predicted increased vaccine uptake pregnant and breastfeeding individuals. CONCLUSIONS: There are specific psychological and socio-demographic determinants that affect COVID-19 vaccine uptake in pregnant populations. Implications of these findings include targeting these determinants when informing and developing intervention and educational programs for both pregnant and breastfeeding individuals, as well as healthcare professionals who are making vaccine recommendations to patients. Study limitations include a small sample and lack of ethnic and socioeconomic diversity.

Comparing adverse neonatal and maternal outcomes of chlamydia, gonorrhoea, and syphilis infections and co-infections in pregnancy.

BACKGROUND: While maternal sexually transmitted infections (STIs) during pregnancy have been extensively studied, fewer studies have directly compared the associations of different infections and co-infections or investigated the association between STIs in pregnancy and maternal outcomes. OBJECTIVES: We examine associations between STIs and co-infections in pregnancy on risks of adverse neonatal and maternal outcomes. METHODS: Data from the 2019 US natality files (n = 3,747,882) were used to assess the associations between STIs in pregnancy on adverse pregnancy outcomes. Five mutually exclusive STI groups were examined: a single chlamydia, syphilis, or gonorrhoeal infection, chlamydia and gonorrhoea co-infection, and syphilis co-infection (with chlamydia, gonorrhoea, or both). Demographic and obstetric characteristics among each STI group were compared to those of an uninfected comparison group. Prevalence ratios (PR) of adverse neonatal outcomes (preterm birth, small for gestational age [SGA] births, and 5-min APGAR (Appearance, Pulse, Grimace, Activity, and Respiration) score < 7) and maternal outcomes (gestational hypertension) by STI status were examined using log-binomial regression. RESULTS: Increased prevalence of preterm birth was apparent, especially among those with a syphilis infection (PR 1.19, 95% confidence intreval [CI] 1.10, 1.30 for single infections and PR 1.31, 95% CI 1.10, 1.57 for co-infections). All STI groups, except gonorrhoea and chlamydia co-infections, were associated with an increased prevalence of gestational hypertension, with the strongest association among those with syphilis co-infections (PR 1.41, 95% CI 1.13, 1.76). CONCLUSIONS: An increased prevalence was of preterm birth and low APGAR scores were associated with syphilis infection. Increased prevalence of GH among those with STIs warrants further investigation into the relationships and corresponding mechanisms of STIs in pregnancy on adverse maternal outcomes.

Association of SARS-CoV-2 Infection During Pregnancy With Maternal and Perinatal Outcomes.

Importance: There are limited high-quality, population-level data about the effect of SARS-CoV-2 infection on pregnancy using contemporaneous comparator cohorts. Objectives: To describe maternal and perinatal outcomes associated with SARS-CoV-2 infection in pregnancy and to assess variables associated with severe disease in the pregnant population. Design, Setting, and Participants: CANCOVID-Preg is an observational surveillance program for SARS-CoV-2-affected pregnancies in Canada. This analysis presents exploratory, population-level data from 6 Canadian provinces for the period of March 1, 2020, to October 31, 2021. A total of 6012 pregnant persons with a positive SARS-CoV-2 polymerase chain reaction test result at any time in pregnancy (primarily due to symptomatic presentation) were included and compared with 2 contemporaneous groups including age-matched female individuals with SARS-CoV-2 and unaffected pregnant persons from the pandemic time period. Exposure: SARS-CoV-2 infection during pregnancy. Incident infections in pregnancy were reported to CANCOVID-Preg by participating provinces/territories. Main Outcomes and Measures: Maternal and perinatal outcomes associated with SARS-CoV-2 infection as well as risk factors for severe disease (ie, disease requiring hospitalization, admission to an intensive care unit/critical care unit, and/or oxygen therapy). Results: Among 6012 pregnant individuals with SARS-CoV-2 in Canada (median age, 31 [IQR, 28-35] years), the greatest proportion of cases were diagnosed at 28 to 37 weeks' gestation (35.7%). Non-White individuals were disproportionately represented. Being pregnant was associated with a significantly increased risk of SARS-CoV-2-related hospitalization compared with SARS-CoV-2 cases among all women aged 20 to 49 years in the general population of Canada (7.75% vs 2.93%; relative risk, 2.65 [95% CI, 2.41-2.88]) as well as an increased risk of intensive care unit/critical care unit admission (2.01% vs 0.37%; relative risk, 5.46 [95% CI, 4.50-6.53]). Increasing age, preexisting hypertension, and greater gestational age at diagnosis were significantly associated with worse maternal outcomes. The risk of preterm birth was significantly elevated among SARS-CoV-2-affected pregnancies (11.05% vs 6.76%; relative risk, 1.63 [95% CI, 1.52-1.76]), even in cases of milder disease not requiring hospitalization, compared with unaffected pregnancies during the same time period. Conclusions and Relevance: In this exploratory surveillance study conducted in Canada from March 2020 to October 2021, SARS-CoV-2 infection during pregnancy was significantly associated with increased risk of adverse maternal outcomes and preterm birth.

Pertussis Vaccination in Canadian Pregnant Women, 2018-2019.

OBJECTIVE: This study was undertaken to measure the uptake of pertussis vaccination during pregnancy in Canada and to identify sociodemographic factors associated with non-vaccination. METHODS: A total of 5091 biological mothers of children born between September 2, 2018, and March 1, 2019, were interviewed about pertussis vaccination during their pregnancy. RESULTS: Among 4607 mothers who recalled whether they had been vaccinated for pertussis, 43% had been vaccinated and 57% had not. The main reason given by mothers for not having been vaccinated was not being aware that pertussis vaccination was recommended. Factors independently associated with non-vaccination were being born outside Canada, lower household income, living in a province or territory where pertussis vaccination was not provided free of charge, having had previous live births, and having received maternity care from a midwife. CONCLUSION: Advice from the maternity care provider is an important driver of pertussis vaccination during pregnancy.

Knowledge of Congenital CMV, Risk Behaviours for CMV Acquisition, and Acceptance of an Educational Infographic Among Postpartum Women: A Pilot Study.

Congenital cytomegalovirus (cCMV) infection in the newborn can present with sensorineural hearing loss and microcephaly. The objectives of this study were to determine baseline knowledge of cCMV and the acceptability of an infographic about cCMV among a group of postpartum women. Participants completed a questionnaire assessing their perceptions of an infographic as well as their knowledge and risk behaviours for acquisition of CMV. Of all 140 respondents, 119 (85%) had no prior knowledge of cCMV, and all 12 women (8.6%) who viewed the infographic indicated that it was helpful. Our study also demonstrated that passive dissemination of an infographic in clinics results in limited viewership.

Guideline No. 420: Cytomegalovirus Infection in Pregnancy.

OBJECTIVE: To provide an update on current recommendations for cytomegalovirus (CMV) infection during pregnancy. The objectives of this guideline are: TARGET POPULATION: Patients of child-bearing age, pregnant patients, and patients planning a pregnancy. BENEFITS, HARMS, AND COSTS: The patient partners urged us to make awareness of preventive strategies a high priority, despite concern that discussing CMV with patients could cause unnecessary anxiety. CMV educational interventions have shown benefits from increased awareness of cCMV prevalence and preventive strategies among providers, patients, and families. EVIDENCE: We searched MEDLINE, EMBASE, and CENTRAL databases for CMV in pregnancy. The search terms were developed using MeSH terms and keywords (Appendix). The results were filtered for articles published between January 2010 and October 2020 and systematic reviews, meta-analyses, clinical trials, and observational studies. The main inclusion criteria were pregnant patients and infants, as the target population, and CMV infection, as the diagnosis of interest. Recommendations are graded according to the U.S. Preventive Services Task Force grade of recommendations and level of certainty. VALIDATION METHODS: We collaborated with patient partners, including members of CMV Canada (cmvcanada.com). In formulating our recommendations, we included patients' voices to add a unique and valuable perspective, thus ensuring that our recommendations are relevant to the patient-provider partnership. INTENDED AUDIENCE: All perinatal health care providers. RECOMMENDATIONS (GRADE AND LEVEL OF CERTAINTY IN PARENTHESES).

Vaccination in pregnancy: Challenges and evidence-based solutions.

Vaccination in pregnancy (VIP) is dually beneficial - it protects the mother and the baby from tetanus, influenza, and pertussis. VIP uptake is low in many countries. Vaccine hesitancy, defined by the World Health Organization (WHO) as a "delay in acceptance or refusal of vaccination despite the availability of vaccination services" is one of WHO's ten threats to global health per 2019. According to extensive research, mostly from high-income countries (HIC) and limited to tetanus, influenza and pertussis vaccines, lack of provider recommendations, safety concerns, and limitations in access are the main barriers to VIP. Health care provider recommendation is the leading facilitator for VIP across various socioeconomic status groups. Data on strategies to overcome patient, provider, and system barriers to VIP are inconsistent, contradictory, or lacking. Patient-focused research on evidence-based strategies to overcome provider and system barriers is needed. Furthermore, VIP programs require embedded continuous quality improvement to ensure sustainability.

Real-world clinical and virological outcomes in a retrospective multiethnic cohort study of 341 untreated and tenofovir disoproxil fumarate-treated chronic hepatitis B pregnant patients in North America.

BACKGROUND: There are limited long-term data on outcomes of chronic hepatitis B (CHB) in untreated and tenofovir disoproxil fumarate (TDF)-treated women during pregnancy. AIMS: To assess clinical outcomes in a multiethnic cohort of patients during pregnancy and post-partum in a low HBV endemic region. METHODS: Retrospective real-world study of women with CHB (treated or untreated with TDF) from 2011 to 2019; data including ALT, HBV DNA, HBeAg and liver stiffness measurement were collected during pregnancy and post-partum. RESULTS: In 341 women (446 pregnancies) followed for a median of 33 months (IQR: 26.7-39.5) post-partum, 19% (65/341) received TDF (11 initiated pre-pregnancy, 53 for mother-to-child transmission (MTCT) prevention). During follow-up, 72/341 had subsequent pregnancy, including 18/53 on TDF for MTCT risk, of whom 7/18 were re-treated. In all TDF-treated women, HBV DNA declined but rebounded after TDF withdrawal (median baseline, near birth and early follow-up levels were 7.2, 3.0 and 5.5 log IU/mL respectively [P < 0.01]). In HBeAg+ patients (65/341) ALT flares were more common (P = 0.03), especially for those who stopped TDF post-partum, requiring re-treatment in 21% (11/53). In comparison, 54% (116/215) of untreated women had a post-partum ALT flare; one with fulminant hepatitis underwent transplant 13 months post-partum. HBsAg clearance occurred in 2.6% (9/341, 3/9 HBeAg+, 2/9 TDF treated) at median 30 months (IQR: 23-40) and 37% (24/65) of HBeAg+ patients had HBeAg loss at median 17 months (IQR: 12-26) post-partum. CONCLUSIONS: Post-partum ALT flares were common, especially after TDF withdrawal. Overall, 37% achieved HBeAg clearance and 2.9% had HBsAg loss during long-term follow-up.

Vaccination during pregnancy: Canadian maternity care providers' opinions and practices.

A number of countries have implemented vaccination in pregnancy as a strategy to reduce the burden of influenza and pertussis. The aim of this study was to assess the involvement of Canadian maternity care providers in administration of vaccines to their pregnant patients. A cross-sectional web-based survey was sent to family physicians, obstetricians-gynecologists, midwives, pharmacists, and nurses. A multivariable logistic regression model was used to determine variables independently associated with offering vaccination services in pregnancy in providers' practice. A total of 1,135 participants participated. Overall, 64% (n = 724) of the participants reported offering vaccines in their practice and 56% (n = 632) reported offering vaccines to pregnant patients. The main reasons reported for not offering vaccination services in pregnancy were the belief that vaccination was outside of the scope of practice; logistical issues around access to vaccines; or lack of staff to administer vaccines. In multivariable analysis, the main factors associated with vaccination of pregnant patients in practices where vaccination services were offered were: providers' confidence in counseling pregnant patients about vaccines, seeing fewer than 11 pregnant patients on average each week, and being a nurse or a family physician. Although the majority of participants expressed strong support for vaccination during pregnancy, half were not offering vaccination services in their practice. Many were not equipped to offer vaccines in their practice or felt that it was not their role to do so. To enhance vaccine acceptance and uptake in pregnancy, it will be important to address the logistical barriers identified in this study.

CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis.

BACKGROUND: The intracellular concentration of heavy-metal cations, such as copper, nickel, and zinc is pivotal for the mycobacterial response to the hostile environment inside macrophages. To date, copper transport mediated by P-type ATPases across the mycobacterial plasma membrane has not been sufficiently explored. RESULTS: In this work, the ATPase activity of the putative Mycobacterium tuberculosis P1B-type ATPase CtpB was associated with copper (I) transport from mycobacterial cells. Although CtpB heterologously expressed in M. smegmatis induced tolerance to toxic concentrations of Cu2+ and a metal preference for Cu+, the disruption of ctpB in M. tuberculosis cells did not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper. In addition, the Cu+ ATPase activity of CtpB embedded in the plasma membrane showed features of high affinity/slow turnover ATPases, with enzymatic parameters KM 0.19 ± 0.04 µM and Vmax 2.29 ± 0.10 nmol/mg min. In contrast, the ctpB gene transcription was activated in cells under culture conditions that mimicked the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper. CONCLUSIONS: The overall results suggest that M. tuberculosis CtpB is associated with Cu+ transport from mycobacterial cells possibly playing a role different from copper detoxification.

Presence of Precore (C)/C Promoter Mutants in Peripheral Blood Mononuclear Cells of Chronic Hepatitis B (CHB) Carriers During Pregnancy Does Not Correlate with Increased Risk of Liver Disease in 4 Years of Follow-Up.

PURPOSE: HBV precore (PC) and basal core promoter (BCP) mutants are associated with liver disease severity, yet have been suggested to protect against HBV vertical transmission. HBV within peripheral blood mononuclear cells (PBMC) has been reported in association with intrauterine HBV infection. We analyzed HBV replication status in PBMC and PC/BCP mutants in PBMC from pregnant chronic hepatitis B (CHB) patients. METHODS: Pregnant CHB carriers were assessed for HBeAg, HBV-DNA, ALT in second-third trimester and liver stiffness measurement (LSM) postpartum. HBV-DNA, HBV-cccDNA, and HBV-mRNA were tested in PBMC by in-house PCR. BCP/PC variants were determined by Sanger sequencing and analyzed using MEGA7. RESULTS: In 37 CHB pregnant carriers, median age 32 years, 53% Asian, median ALT 19 versus 26 U/L, median HBV-DNA 2.6 versus 8.1 logIU/mL (untreated vs. treated), eight HBeAg+, with genotype 10%A, 29%B, 21%C, 10%D, 19%E, eight received tenofovir in pregnancy to reduce vertical transmission risk. HBV-DNA was detected in ~ 55% (25/45) PBMC, and PC/BCP mutations were found in 36% (9/25) and 4% (1/25), respectively. All infants received HBV immunoprophylaxis and tested HBV surface antigen negative at 9-12 months of age. During a median 4 years (IQR 3-5), follow-up all mothers showed normal LSM, with no significant change in ALT, HBeAg status, or HBV-DNA levels compared to baseline in untreated CHB carriers. CONCLUSION: In this multiethnic cohort of pregnant CHB carriers, HBV replicative intermediates and PC/BCP mutants were found in significant proportion of PBMC, but were not associated with increased risk of HBV immunoprophylaxis failure or liver disease severity over long-term follow-up.

CtpB is a plasma membrane copper (I) transporting P-type ATPase of Mycobacterium tuberculosis

BACKGROUND: The intracellular concentration of heavy-metal cations, such as copper, nickel, and zinc is pivotal for the mycobacterial response to the hostile environment inside macrophages. To date, copper transport mediated by P-type ATPases across the mycobacterial plasma membrane has not been sufficiently explored. RESULTS: In this work, the ATPase activity of the putative Mycobacterium tuberculosis P1B-type ATPase CtpB was associated with copper (I) transport from mycobacterial cells. Although CtpB heterologously expressed in M. smegmatis induced tolerance to toxic concentrations of Cu2+ and a metal preference for Cu+, the disruption of ctpB in M. tuberculosis cells did not promote impaired cell growth or heavy-metal accumulation in whole mutant cells in cultures under high doses of copper. In addition, the Cu+ ATPase activity of CtpB embedded in the plasma mem-brane showed features of high affinity/slow turnover ATPases, with enzymatic parametersKM 0.19 ± 0.04 µM and Vmax 2.29 ± 0.10 nmol/mg min. In contrast, the ctpB gene transcription was activated in cells under culture conditions that mimicked the hostile intraphagosomal environment, such as hypoxia, nitrosative and oxidative stress, but not under high doses of copper. CONCLUSIONS: The overall results suggest that M. tuberculosis CtpB is associated with Cu+ transport from mycobacterial cells possibly playing a role different from copper detoxification.

Developing product label information to support evidence-informed use of vaccines in pregnancy.

BACKGROUND: Product labelling information describing the use of vaccines in pregnancy continues to contain cautionary language even after clinical and epidemiological evidence of safety becomes available. This language raises safety concerns among healthcare providers who may hesitate to recommend vaccines during pregnancy. PURPOSE: To develop clear evidence-based language about vaccine safety and effectiveness in pregnancy for inclusion in vaccine product labels. METHODS: We conducted a three-stage consensus-methods project with stakeholders, including: healthcare providers, vaccine regulators, industry representatives, and experts in public health, communication, law, ethics, and social sciences. Using qualitative and quantitative methods, we held a nominal group technique (NGT) meeting, followed by a Delphi survey, and then a consensus workshop with a subset of Delphi participants. We developed a methodological tool to analyse data for consensus. PRINCIPAL RESULTS: Stakeholders (N = 14) at the NGT meeting drafted product label statements for evaluation in the Delphi survey. Survey participants (N = 41) provided feedback on statements for five hypothetical vaccines. Workshop participants (N = 27) initiated discussions that demonstrated a lack of awareness that the regulatory purpose of product labels is to provide a scientific summary of product-specific pre-clinical and clinical trial data. Each stage of this project built on earlier stages until we achieved strong consensus on the language, structure, and types of data that stakeholders wanted to include in inactivated influenza vaccine (IIV) and tetanus-diphtheria-acellular pertussis (Tdap) vaccine product labels in Canada. CONCLUSIONS: The revised statements for IIV and Tdap aligned with workshop participants' goals that the product label be evidence-based, with a consistent structure and language that is easily understood by healthcare providers. Emergent methods uncovered stakeholder concerns about the regulatory purpose, content, and evidence used in product labels. Involving healthcare providers in the development and regular updating of product information could prevent interpretations of that information that contribute to vaccine hesitancy.

Analysis of serum hepatitis B virus RNA levels in a multiethnic cohort of pregnant chronic hepatitis B carriers.

BACKGROUND: Hepatitis B virus (HBV) flares have been reported due to alterations in the immune system during pregnancy. Recent studies in non-pregnant chronic hepatitis B (CHB) carriers have indicated that serum HBV RNA is a novel viral marker to assess treatment response and risk of disease flares. OBJECTIVES: To analyze serum HBV RNA levels in association with established HBV markers in pregnant and/or post-partum CHB carriers. STUDY DESIGN: In this prospective cohort study, serum and plasma were collected from 46 pregnant and/or post-partum CHB patients. Clinical data included demographics, hepatitis B e antigen (HBeAg) status (Abbott), quantitative hepatitis B s antigen (qHBsAg) levels (Abbott), HBV DNA (Abbott, sensitivity 10 IU/mL), alanine aminotransferase (ALT), liver stiffness measurement (LSM, post-partum), and treatment regime. Serum HBV total RNA and pre-genomic (pg)RNA were quantified using in-house assays, and HBV genotype was determined by direct population sequencing of HBV surface gene. Parametric and non-parametric statistical methods were used for analysis. RESULTS: In this study, we found that serum HBV total RNA levels correlated with the HBeAg status, HBV DNA, qHBsAg, ALT, and LSM while serum HBV pgRNA levels did not (p < 0.05, N = 46). Additionally, HBV total RNA & pgRNA levels increased, HBV DNA levels decreased, and qHBsAg levels remained unchanged throughout tenofovir disoproxil fumarate (TDF) treatment (N = 2). CONCLUSIONS: The associations between serum HBV total RNA with other validated markers indicates it may be a complementary HBV marker to monitor liver disease and HBV replication during pregnancy.