Congenital Syphilis: a Review of Global Epidemiology.

In 2007, the World Health Organization (WHO) launched a global health initiative for the elimination of mother-to-child transmission (MTCT) of syphilis. This condition is highly preventable through antenatal identification of syphilis infection and treatment with penicillin during pregnancy. This review summarizes the global status of MTCT of syphilis and concludes that this condition remains a significant issue worldwide. There are large variations in case rates by region, with the highest numbers of cases in the African and Eastern Mediterranean regions, where there are also the least data available. There are also pockets of high-incidence areas within the other regions. Although the general trend is of decreasing rates over time, there are concerning indications of consistently increasing congenital syphilis cases in some areas, particularly in areas which have previously had very low case numbers. A concerted effort will be required to achieve the 2007 WHO goal of worldwide elimination of MTCT of syphilis in the near future.

Tenofovir Alafenamide versus Tenofovir Disoproxil Fumarate for Preventing Vertical Transmission in Chronic Hepatitis B Mothers: A Systematic Review and Meta-Analysis.

OBJECTIVE: International guidelines recommend maternal tenofovir disoproxil fumarate (TDF) therapy accompanied by infant immunoprophylaxis to prevent HBV mother-to-child transmission (MTCT) in highly viremic mothers. However, pooled analyses for tenofovir alafenamide (TAF) effects and comparisons between the two regimens are lacking. DESIGN: In this meta-analysis, pairs of independent reviewers performed multiple database searches from inception to March 31, 2024, and extracted data from cohort studies and RCTs in highly viremic mothers. The outcomes of interest were the reduction of MTCT and safety in the TDF-treated, TAF-treated, and control groups. RESULTS: We included 31 studies with 2,588 highly viremic mothers receiving TDF, 280 receiving TAF, and 1,600 receiving no treatment. Compared to the control, TDF therapy reduced the MTCT rate in infants aged 6-12 months (risk ratio: 0.10, 95% confidence interval 0.07-0.16). Pairwise meta-analysis between TAF and TDF revealed similar effects on reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.16-7.61). Network meta-analysis showed the equal efficacy of the two regimens in reducing MTCT (risk ratio: 1.09, 95% confidence interval 0.15-7.65). The surface under the cumulative ranking curve revealed TDF as the best regimen compared with TAF (probability ranking: 0.77 vs. 0.72), while receiving a placebo during pregnancy had the lowest efficacy (probability ranking 0.01). There were no safety concerns for mothers and infants in all regimens. CONCLUSION: Compared to placebo or no treatment, maternal TDF and TAF prophylaxis are equally effective and without safety concerns in reducing MTCT in highly viremic mothers.

Optimization of Mother-to-Child Hepatitis B Virus Prevention Program: Integration of Maternal Screening and Infant Post-Vaccination Serologic Testing.

BACKGROUND: Evaluation of the impact of a hepatitis B virus (HBV) prevention program that incorporates maternal antiviral prophylaxis on mother-to-child transmission (MTCT) is limited using real-world data. METHODS: We analyzed data on maternal HBV screening, neonatal immunization, and post-vaccination serologic testing (PVST) for hepatitis B surface antigen (HBsAg) among at-risk infants born to HBV carrier mothers from the National Immunization Information System during 2008-2022. Through linkage with the National Health Insurance Database, information on maternal antiviral therapy was obtained. Multivariate logistic regression was performed to explore MTCT risk in relation to infant-mother characteristics and prevention strategies. RESULTS: In total, 2 460 218 deliveries with maternal HBV status were screened. Between 2008 and 2022, the annual HBsAg and hepatitis B e antigen (HBeAg) seropositivity rates among native pregnant women decreased from 12.2% to 2.6% and from 2.7% to 0.4%, respectively (P for both trends < .0001). Among the 22 859 at-risk infants who underwent PVST, the MTCT rates differed between infants born to HBsAg-positive/HBeAg-negative and HBeAg-positive mothers (0.75% and 6.33%, respectively; P < .001). MTCT risk increased with maternal HBeAg positivity (odds ratio [OR], 9.29; 95% confidence interval [CI], 6.79-12.73) and decreased with maternal antiviral prophylaxis (OR, 0.28; 95% CI, .16-.49). For infants with maternal HBeAg positivity, MTCT risk was associated with mothers born in the immunization era (OR, 1.40; 95% CI, 1.17-1.67). CONCLUSIONS: MTCT was related to maternal HBeAg positivity and effectively prevented by maternal prophylaxis in the immunized population. At-risk infants born to maternal vaccinated cohorts might possibly pose further risk.

Role of HBsAg levels in guiding hepatitis B virus prophylaxis in pregnancy: Insights from a multi-ethnic cohort.

Pregnant mothers with chronic hepatitis B infection (CHB) need peri-partum antiviral prophylaxis (PAP) to reduce the risk of mother-to-child-transmission. Currently, PAP is recommended in those with high viral load (VL) that is, HBV DNA >200,000 IU/mL. Quantitative hepatitis B surface antigen (qHBsAg) >10,000 IU/mL, a cut-off derived primarily from hepatitis B e-antigen (HBeAg) positive antenatal cohorts in Chinese populations, is advocated as a surrogate marker of VL for guiding PAP. We investigated the utility of qHBsAg to predict high-VL in a multi-ethnic urban cohort with CHB. A consecutive cohort of women with CHB was identified from Barts Health NHS Trust databases in the United Kingdom. We included women with paired HBV DNA and qHBsAg during pregnancy. Women already on antiviral at conception were excluded. A total of 769 pregnancies in 678 CHB pregnant mothers (median age 31 years-old, 8.6% HBeAg+) were included. At median gestational age of 15.3 weeks, HBV DNA was 336 (IQR 44-2998) IU/mL, with 65 (8.5%) being high-VL. Serum qHBsAg was most useful in Black/Black-British/Caribbean/African (AUROC 0.946) with 100% sensitivity and 80.6% specificity to predict high-VL; but it performed less well for other ethnicities: Asian (AUROC 0.877), White (AUROC 0.797) and mixed ethnicities (AUROC 0.742). In conclusion, for settings where healthcare resources are not limited, HBV DNA remains the optimal marker to identify highly viraemic pregnancies for guiding PAP. For resource-limited settings where the prevailing cost is treatment, serum qHBsAg can be used in Black/Black British/Caribbean/African sub-cohorts, but not for other ethnicities.

Risk of mother-to-child transmission after amniocentesis in pregnant women with hepatitis B virus: a retrospective cohort study.

BACKGROUND: Amniocentesis is the most widely used invasive prenatal diagnostic sampling technique. However, whether this increases the risk of mother-to-child transmission of infectious diseases remains controversial. OBJECTIVE: This study aimed to determine whether amniocentesis increases the risk of hepatitis B virus infection in infants who received standard prophylaxis, and to assess the related risk factors for mother-to-child transmission in women who underwent amniocentesis during pregnancy. STUDY DESIGN: This retrospective analysis used the clinical data of pregnant women with hepatitis B virus infection at West China Second University Hospital, Sichuan University in 2019. After meeting the inclusion criteria, the participants were divided into 2 groups on the basis of whether they had undergone amniocentesis during pregnancy. The infant hepatitis B virus serologic status was followed 1 to 6 months after completion of immunization. The infant testing positive for hepatitis B surface antigen and negative for Hepatitis B surface antibody indicated mother-to-child transmission of hepatitis B virus. RESULTS: In total, 1764 pregnant women with hepatitis B virus infection were enrolled. Of these, 846 underwent amniocentesis during pregnancy and 918 did not. All offspring received a standardized immunoprophylaxis schedule. The overall mother-to-child transmission rate for hepatitis B virus was 0.6% (5/846) in the amniocentesis group and 0.4% (4/918) in the control group (P=.745). Subgroup analysis showed that the mother-to-child transmission rate in hepatitis B e antigen-positive women was 1.8% (2/111) in the amniocentesis group and 1.0% (2/209) in the control group (P=.612). In women with high viral load, the mother-to-child transmission rate was 1.3% (1/78) vs 0.9% (1/107) (amniocentesis group vs control group; P=1.000). In the amniocentesis group, 31 amniotic fluid specimens had an abnormal appearance (bloody or brown). Univariate analysis showed that the mother-to-child transmission rates of these mothers were statistically higher than those of mothers with pale yellow or transparent amniotic fluid (2/31 vs 3/815; relative risk, 17.527 [3.037-101.151]; P=.012). CONCLUSION: Amniocentesis did not increase the risk of mother-to-child transmission of hepatitis B virus in infants who received a standardized immunoprophylaxis schedule, including those with mothers who were hepatitis B e antigen-positive or had a high viral load. However, the abnormal appearance (bloody or brown) of the amniotic fluid obtained during amniocentesis may indicate increased risk of mother-to-child transmission for hepatitis B virus.

Differences between Chronically Hepatitis B Virus-Infected Pregnant Women with and without Intrafamilial Infection: From Viral Gene Sequences to Clinical Manifestations.

INTRODUCTION: This study aimed to investigate the differences between pregnant women with chronic hepatitis B virus (HBV) infection and intrafamilial infection and those without intrafamilial infection. METHODS: HBV-DNA was extracted from the sera of 16 pregnant women with chronic hepatitis B (CHB) and their family members for gene sequencing and phylogenetic analyses. A total of 74 pregnant women with CHB were followed up from the second trimester to 3 months postpartum. Viral markers and other laboratory indicators were compared between pregnant women with CHB with and without intrafamilial infection. RESULTS: The phylogenetic tree showed that HBV lines in the mother-spread pedigree shared a node, whereas there was an unrelated genetic background for HBV lines in individuals without intrafamilial infection. From delivery to 3 months postpartum, compared with those without intrafamilial infection, pregnant women with intrafamilial infection were related negatively to HBV-DNA (ß = -0.43, 95% confidence interval [CI]: -0.76 to -0.12, p = 0.009), HBeAg (ß = -195.15, 95% CI: -366.35 to -23.96, p = 0.027), and hemoglobin changes (ß = -8.09, 95% CI: -15.54 to -0.64, p = 0.035) and positively to changes in the levels of alanine aminotransferase (ß = 73.9, 95% CI: 38.92-108.95, p < 0.001) and albumin (ß = 2.73, 95% CI: 0.23-5.23, p = 0.033). CONCLUSION: The mother-spread pedigree spread model differs from that of non-intrafamilial infections. Pregnant women with intrafamilial HBV infection have less hepatitis flares and liver damage, but their HBV-DNA and HBeAg levels rebound faster after delivery, than those without intrafamilial infection by the virus.

Facilitators and Barriers to Adherence to Anti-Retroviral Treatment Among Pregnant or Breastfeeding Women Living with HIV and Perinatally Infected Infants: A Scoping Review.

In 2022, 54% of 1.5 million children (age 0-14) living with HIV had access to anti-retroviral medication (ART). Adherence to ART for pregnant or breastfeeding HIV + women is critical for maintaining their personal health and to prevent mother-to-child-transmission (MTCT). For HIV + infants, adherence is essential to establish early viremic control and is contingent on caregiver administration. We conducted a scoping review to systematically identify and categorize the influences on ART adherence for pregnant or breastfeeding HIV + women and their HIV + infants. We searched databases in June 2023 and employed the Social-Ecological Model (SEM) to organize facilitators and barriers to adherence referenced in published articles. All articles published before 2016 were excluded due to updated guidelines from WHO on MTCT and ART. Our analysis included 52 articles. 50/52 took place in Africa and used cross-sectional and mixed-methods design. Barriers to adherence for pregnant or breastfeeding HIV + women included maternal education, self-efficacy, social support, and social/economic context. Barriers to infant adherence included development, nutrition, age of treatment initiation, disclosure, and ART side effects. Additional facilitators and barriers to adherence are presented at family, extra-familial, and socio-cultural SEM levels. Stigma was the most salient barrier referenced across the entire continuum of HIV care and all SEM levels. This review revealed a dearth of literature focusing on HIV + infants who are dependent on their caregivers for ART adherence and lack of a standard adherence measure. We identified multi-leveled influences on adherence impacting both the mother and infant and are amenable to public health intervention.

Over forty percent of women living with HIV report interruption in antiretroviral therapy during intrapartum and early postpartum inpatient stay: findings from five hospitals in Ghana.

Antiretroviral therapy (ART) adherence during and after pregnancy is essential to reduce perinatal transmission of HIV. However, little is known about adherence during the intrapartum and early postpartum inpatient hospital stay. Using secondary data from a hospital-based cohort study focused on the relationship between birthweight and engagement in HIV care, we examined the magnitude of, reasons for, and factors associated with incomplete intrapartum and early postpartum ART adherence among adult women (18 years or older) living with HIV who delivered within the previous two weeks at one of five hospitals in Accra, Ghana. Of the 142 enrolled participants who had complete adherence data and reported being on ART at the time of hospital admission, 43% (61/142) reported missing at least one ART dose during labor, delivery, and postpartum, including almost 20% (28/142) missing 2 or more consecutive doses. Women who reported frequently missing ART doses during pregnancy had higher odds of reporting missed doses during their intrapartum and postpartum hospital stays. Among those with inpatient ART interruption, the most frequently cited reasons were: forgetting medication at home (42%) and challenges of being in or recovering from labor (29%). Maternal perception of infant health at birth, hospital level of care, and frequency of missing HIV medications during pregnancy were associated with incomplete ART adherence during the intrapartum and early postpartum inpatient stay. An enabling clinical environment to facilitate access to ART during inpatient stays may have positive implications for ART adherence.

Understanding Fijian health system challenges in the prevention of mother-to-child transmission of HIV services in the three tertiary hospitals in Fiji.

Mother-to-child transmission is the most common route of human immunodeficiency virus transmission in children, which could be prevented with proper treatment and access to care. Health system challenges can impede the effectiveness of prevention of mother-to-child transmission (PMTCT) programmes. We aim to understand the health system challenges to the provision of PMTCT services for pregnant women in three tertiary hospitals in Fiji. Data were collected using in-depth interviews in the three tertiary hospitals and associated health clinics in Fiji between April-May 2013 and February-March 2014. Ethical approvals were obtained. A total of 58 healthcare providers were interviewed including doctors (n = 12), midwives (n = 19), nurses (n = 14), laboratory technicians (n = 5) and counsellors (n = 8). The data were analysed using thematic analysis. We found that the healthcare workers faced a wide range of health system challenges including institutional and human resource challenges. Staff shortage, limited PMTCT training and shortage of supplies were barriers to the quality of PMTCT services. Our findings would be useful in developing strategies to overcome barriers as it would be imperative in improving the quality of PMTCT service provision in Fiji and other similar settings.

Antiretroviral therapy adherence among peripartum women with HIV in Kenya: an explanatory mixed methods study using dry blood spot measures and narrative interviews.

ABSTRACTAdherence to antiretroviral therapy (ART) remains sub-optimal among pregnant and postpartum women with HIV (PPWH) in high HIV prevalence low resource settings with few effective behavioral interventions. A large body of qualitative literature has established general barriers and facilitators to ART adherence in PPWH at various levels (individual, interpersonal, structural). However, research exploring the underlying behavioral mechanisms of ART adherence in PPWH with objectively verified adherence biomarkers is extremely limited. We conducted 24 in-depth interviews with postpartum women in western Kenya who had linked ART drug concentrations obtained from three dried blood spot samples across the peripartum period. Among PPWH with a low drug concentration (n = 13) compared to those with continuously high drug concentrations (n = 11), distinct themes emerged related to HIV status disclosure, social support, interactions with the health system, and health beliefs. By combining ART biomarkers with patient reported challenges, there is the potential for real-time interventions to support sustained ART adherence among PPWH and improve maternal and infant health outcomes.

Knowledge of HIV transmission during pregnancy among women of reproductive age in Ghana.

INTRODUCTION: Human immunodeficiency virus (HIV) remains a significant health challenge affecting many people including those from sub-Saharan Africa (SSA). Even though HIV can be transmitted through various means, mother-to-child transmission (MTCT) remains the major route of transmission in children under the age of five. This study examined the correlates of knowledge of HIV transmission during pregnancy among reproductive-age women in Ghana. METHODS: Data for this study were obtained from the 2014 Ghana Demographic and Health Survey. The sample consisted of 9,106 women aged 15 to 49 years. We conducted both descriptive and multivariable logistic regression analyses to determine the prevalence and factors associated with knowledge of HIV transmission during pregnancy. The results were presented using frequencies, percentages, and adjusted odds ratios (aOR) with their corresponding 95% confidence intervals (CI). RESULTS: Approximately, 69.41% of women of reproductive age knew of HIV transmission during pregnancy. Women who had two (aOR = 1.32, 95% CI [1.01, 1.72]) or three (aOR = 1.37, 95% CI [1.07, 1.76]) births were more knowledgeable of HIV transmission during pregnancy. Women who read the newspaper (aOR = 1.56, 95% CI [1.31, 1.86]), listened to the radio (aOR = 1.23, 95% CI [1.05, 1.45]), lived in rural areas (aOR = 1.30, 95% CI [1.09, 1.54]) or ever been tested for HIV (aOR = 1.20, 95% CI [1.05, 1.37]) were more likely to be knowledgeable of HIV transmission during pregnancy than their counterparts in the reference categories. Compared to those in the Western Region, women in the Upper East (aOR = 0.45, 95% CI [0.32, 0.63]), Upper West (aOR = 0.54, 95% CI [0.35, 0.85]), Ashanti (aOR = 0.75, 95% CI [0.58, 0.97]) and Greater Accra Regions (aOR = 0.74, 95% CI [0.56, 0.98]) were less knowledgeable of HIV transmission during pregnancy. CONCLUSIONS: The study highlights a gap in the knowledge of HIV transmission during pregnancy among women in Ghana. Continuous public education is required to educate women on HIV transmission from mothers to their children during pregnancy and how this may be interrupted. Such programs should involve the use of the media and take into consideration the demographic and geographic characteristics highlighted as determinants in this study. This will ultimately contribute to the reduction of MTCT of HIV in Ghana.

Maternal-Fetal Exposure to Antibiotics: Levels, Mother-to-Child Transmission, and Potential Health Risks.

Due to its widespread applications in various fields, antibiotics are continuously released into the environment and ultimately enter the human body through diverse routes. Meanwhile, the unreasonable use of antibiotics can also lead to a series of adverse outcomes. Pregnant women and developing fetuses are more susceptible to the influence of external chemicals than adults. The evaluation of antibiotic exposure levels through questionnaire surveys or prescriptions in medical records and biomonitoring-based data shows that antibiotics are frequently prescribed and used by pregnant women around the world. Antibiotics may be transmitted from mothers to their offspring through different pathways, which then adversely affect the health of offspring. However, there has been no comprehensive review on antibiotic exposure and mother-to-child transmission in pregnant women so far. Herein, we summarized the exposure levels of antibiotics in pregnant women and fetuses, the exposure routes of antibiotics to pregnant women, and related influencing factors. In addition, we scrutinized the potential mechanisms and factors influencing the transfer of antibiotics from mother to fetus through placental transmission, and explored the adverse effects of maternal antibiotic exposure on fetal growth and development, neonatal gut microbiota, and subsequent childhood health. Given the widespread use of antibiotics and the health threats posed by their exposure, it is necessary to comprehensively track antibiotics in pregnant women and fetuses in the future, and more in-depth biological studies are needed to reveal and verify the mechanisms of mother-to-child transmission, which is crucial for accurately quantifying and evaluating fetal health status.

A model of prevention of mother-to-child transmission and health management team for improving adverse outcomes of pregnancy syphilis in Ningxia, China.

Regional variations exist in the implementation of Syphilis Mother-to-Child Transmission Prevention (PMTCT). Thus, it is crucial to assess the effectiveness of this model in the Ningxia region and explore the supplementary role of Health Management Teams (HMT). This study established the PMTCT + HMT model and examined its impact on adverse outcomes in pregnant women with syphilis infection. The majority of participants were urban residents, married, had a minimum high school education, and held public positions; 36.7% and 26.7% were from minority ethnic groups. The PMTCT + HMT model enhanced participants' knowledge, rates of voluntary counseling, and testing. The incidence of adverse pregnancy outcomes (miscarriages, preterm births, stillbirths) significantly decreased, and adverse neonatal outcomes (low birth weight, neonatal mortality, congenital syphilis) were notably reduced. Simultaneously, we identified factors associated with adverse outcomes, including non-residency, unmarried status, lower educational attainment, minority ethnicity, primary syphilis, and positive titers. Thus, HMT may be an effective intervention to enhance the effect of PMTCT for syphilis. The unique population structure in Ningxia is closely linked to adverse outcomes, highlighting the significance of providing equitable treatment for vulnerable populations.

Results of mother-to-child transmission in hepatitis B-positive mothers who underwent amniocentesis.

PURPOSE: This study aims to analyze whether undergoing amniocentesis during pregnancy in women diagnosed with hepatitis B virus (HBV) infection leads to HBV transmission to newborns. METHODS: Retrospective data collection was conducted from June 2019 to November 2022 on expectant mothers positive for hepatitis B surface antigen (HBsAg) who underwent amniocentesis at The Third Affiliated Hospital of Sun Yat-sen University, along with data on their newborns. The study summarized the HBV infection status of newborns born to mothers with different expressions of hepatitis B e antigen (HBeAg), antiviral treatment versus no treatment, and different HBV DNA viral loads before delivery. RESULTS: In this study, 346 expectant mothers tested positive for HBsAg, along with 351 newborns (including 5 sets of twins, with 8 infants (2.28%) testing HBsAg-positive at birth. All newborns received dual immunotherapy and were followed up. At 7-12 months, retesting for HBsAg positivity and HBV DNA positivity among infants revealed that out of the infants born with HBsAg positivity, 7 cases had seroconverted to negative, while the remaining infant, who was positive for both HBsAg and HBeAg at birth, tested positive for both HBsAg and HBV DNA at 7-12 months. Thus, one case of vertical transmission of hepatitis B from mother to child occurred in this study. The proportion of infants born with HBsAg + among newborns born to HBeAg-positive mothers (4 cases, 6.06%) was significantly higher than that among newborns born to HBeAg-negative mothers (4 cases, 1.41%) (P < 0.05). The proportion of infants born with HBsAg + showed no significant difference between newborns born to mothers receiving antiviral therapy (2 cases, 2.90%) and those born to mothers not receiving antiviral therapy (6 cases, 2.13%) (P > 0.05). Among expectant mothers with viral load ≥ 6 log 10 IU/mL before delivery, 3 newborns (30.00%) were manifesting HBsAg positivity at birth, significantly higher than the group with viral load < 6 log 10 IU/mL before delivery (5 cases, 1.47%) (P < 0.05). CONCLUSION: Among HBsAg-positive expectant mothers, only a small number of infants are infected with the hepatitis B virus at birth, the proportion of which is relatively low. Infants born to mothers who are HBeAg-positive or have a viral load ≥ 6 log10 IU/mL have a higher risk of being born positive.

Follow-up for 3 years of a pediatric population diagnosed in 2018 with mother-to-child transmission of HIV in 8 Latin American countries in the PLANTAIDS cohort.

INTRODUCTION: The frequency of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) in Latin America has decreased considerably. However, new infections continue to be recorded, and the pediatric population remains one of the most vulnerable groups in this region. The main objective of the study was to describe the clinical, epidemiological and psychosocial characteristics of new diagnoses of HIV MTCT in 2018 in the PLANTAIDS network (Paediatric Network for Prevention, Early Detection and Treatment of HIV in Children) during the 3 years following diagnosis. METHODOLOGY: Retrospective, multicenter, descriptive study based on a 3-year follow-up of patients diagnosed with HIV infection due to MTCT in 2018 in 10 hospitals in 8 Latin American countries (Costa Rica, Ecuador, Mexico, Honduras, El Salvador, Panama, Guatemala and Venezuela). The hospitals belonged to the PLANTAIDS network, which is included in CYTED (Ibero-American Programme of Science and Technology for Development). RESULTS: The study population comprised 72 pediatric patients (38.9% male). The median age at diagnosis was 2.4 years (IQR: 0.8-5.4). There were 35 cases of opportunistic infections corresponding to 25 patients (34.7%), with tuberculosis being the most common. Adequate childhood vaccination coverage was achieved in 80.5%. There were 3 cases of acute SARS-CoV-2 infection, and these were asymptomatic or mildly symptomatic. According to the Centers for Disease Control and Prevention (CDC) classification, the most frequent clinical-immunological stage at all check-ups was C1. Three patients died from opportunistic infections and/or advanced HIV infection. CONCLUSIONS: It is important to diagnose HIV infection early in pediatrics, since early initiation of ART is associated with a decrease in mortality. Despite this, HIV infection has a poor prognosis in children, necessitating adequate follow-up to ensure adherence to health care and ART, although it can sometimes prove difficult in children.

Efficacy of antiviral therapy for the prevention of mother-to-child transmission of hepatitis B virus and the risk of postpartum hepatitis flare after discontinuation of antiviral therapy.

The use of nucleos(t)ide analogs (NAs) is recommended for mothers with a high viral load of hepatitis B virus (HBV) during the second or third trimester of pregnancy. However, postpartum hepatitis flares can occur in some cases. We examined the efficacy of NA administration for the prevention of mother-to-child transmission of hepatitis B virus, and evaluated the risk of postpartum hepatitis flares in mothers after NA discontinuation. Nine pregnant women with a high viral load (HBV DNA ≥5.3 log IU/mL) received tenofovir disoproxil fumarate (TDF) at approximately 28 weeks of gestation, and TDF was discontinued at 4-10 weeks after delivery. We evaluated the virological and biochemical parameters in mothers after TDF discontinuation. Hepatitis flares in mothers were defined as alanine transaminase level ≥60 U/L. None of the infants developed any congenital anomaly or acquired HBV infection during infancy. Hepatitis flares occurred within 6 months after TDF discontinuation in five of seven cases, whereas two cases were lost to follow-up. Furthermore, three cases required the resumption of NA use. NA administration was highly effective against mother-to-child-transmission of HBV in pregnant women with high HBV DNA levels. However, hepatitis flares were commonly observed after NA discontinuation in the postpartum period. Patients should be followed up carefully after NA discontinuation, and NA resumption should be considered based on a comprehensive assessment of virological and biochemical parameters.

Natural history and clinical features of hepatitis C virus infection during childhood: A nationwide, observational survey in Japan.

AIM: Few data on spontaneous clearance rates of cases of mother-to-child transmission of hepatitis C viral (HCV) infection are available in Japan. Furthermore, the treatment courses of interferon-based and direct-acting antiviral agent (DAA) therapies for children are also unclear. Our aim was thus to clarify the long-term natural progression of HCV infection and the treatment outcomes of children in Japan. METHODS: We conducted a combined multicenter, observational survey involving 65 pediatric institutions in Japan. Pediatric HCV infection cases with patients born between 1973 and 2021 were collected over the 11-year period from 2012 to 2022. A total of 563 patients were enrolled, with 190 excluded for having insufficient laboratory data or treatment information, resulting in 373 eligible cases. RESULTS: Of 328 cases of mother-to-child infection, 34 (10.4%) had spontaneous clearance, with a median time to spontaneous clearance of 3.1 years (range 0.9-7.2 years). Of the total 373 eligible cases, 190 received antiviral therapy (interferon-based therapy, 158; DAA therapy, 32). Sustained virologic response rates after first-line treatment were 75.3% (119/158) and 100% (32/32) for interferon-based therapy and DAA therapy, respectively, with the DAA group showing a shorter time from therapy initiation to viral negativity (2.7 vs. 1.0 months; p = 0.0031). CONCLUSIONS: Approximately 10% of Japanese children infected by mother-to-child transmission achieve spontaneous resolution of HCV infection. Our findings indicate that DAA therapy is safe and highly effective in Japanese children, achieving higher sustained virologic response rates and shorter time to clearance of the virus compared with interferon-based therapy.

Beta-blockers and breastfeeding: a real-life prospective study.

PURPOSE: At Lille University Hospital, a pregnancy heart team including cardiologists, obstetricians, pediatricians, anesthetists, geneticists, and pharmacologists discusses about treatment compatibility taken during breastfeeding in pregnant women (or those wishing to be pregnant) with complex cardiovascular pathologies. Beta-blockers are among the drug most often used in these patients, and data are missing or suggest a risk to the breastfed child. The aim of this study was to evaluate the proportion of women treated with beta-blockers, identified during the multidisciplinary meeting, who breastfed and to monitor adverse effects (AEs) in newborns. METHODS: A prospective descriptive study was conducted from 1 December 2017 to 1 December 2021. All pregnant patients followed up by the pregnancy heart team in Lille University Hospital, treated with beta-blockers and who gave birth, were contacted as part of the pharmacovigilance follow-up. RESULTS: The proportion of women treated with beta-blockers intending to breastfeed was 69.8%. Among the 53 women interviewed, 49% did not breastfeed, including 10 because of the theoretical incompatibility of their beta-blocker with breastfeeding. Among the 27 women who breastfed, 30% breastfed while treated with a theoretically incompatible beta-blocker; 56% was changed from their initial beta-blocker to allow safe breastfeeding. No serious AE was observed. CONCLUSION: To our knowledge, our study is the largest series of patients treated with beta-blockers during breastfeeding. Taking a treatment can be an obstacle to breastfeeding, but for the particular case of beta-blockers, even if the available data are few and sometimes worrying, the data from this study are reassuring.

Effectiveness and Safety of Tenofovir Alafenamide Fumarate in the Prevention of Perinatal Hepatitis B Transmission: A Meta-Analysis.

AIM: This study aimed to assess the effectiveness and safety of tenofovir alafenamide fumarate (TAF) in the prevention of mother-to-child transmission (MTCT) of hepatitis B virus (HBV). METHODS: We performed a meta-analysis of studies from the Cochrane Library, PubMed, ClinicalTrials.gov, Web of Science, EMBASE, China National Knowledge Infrastructure (CNKI), China Medical Information Network, and Wanfang databases. The databases were searched from inception to January 7, 2023, for cohort studies and randomized controlled trials (RCTs) comparing the use of TAF antivirals to other antivirals during pregnancy. We combined the data by means of a random-effect DerSimonian-Laird model and risk ratios (RRs) or a random-effect inverse variance model and standardized mean differences (SMDs) to determine the influence on mothers and infants. Our primary outcomes were infant weight, height, head size, birth defects, and Apgar scores. Additionally, we assessed whether newborns tested positive for hepatitis B surface antigen (HBsAg) at birth and at six months of age. The secondary outcomes of our investigation were alterations in levels of HBV deoxyribonucleic acid (DNA), alanine aminotransferase (ALT), total bilirubin (TBIL), blood creatinine, and urine ß2-microglobulin (ß2-M) in mothers. RESULTS: An extensive literature search identified 216 relevant publications; three cohort studies and two RCTs were included in this study. A total of 341 mothers were treated with TAF, and 342 were treated with other antiviral agents. TAF was as effective as other antiviral medications at lowering HBV MTCT rates at birth and at 6 months of age and ALT, TBIL, and HBV DNA levels. Moreover, compared with other antiviral drugs, TAF did not affect infant weight, height, head size, Apgar scores, and birth defects or maternal blood creatinine or ß2-M levels. CONCLUSIONS: TAF antiviral therapy during pregnancy was found to be safe for both mothers and fetuses.

Evaluation of repRNA vaccine for induction and in utero transfer of maternal antibodies in a pregnant rabbit model.

Mother-to-child transmission is a major route for infections in newborns. Vaccination in mothers to leverage the maternal immune system is a promising approach to vertically transfer protective immunity. During infectious disease outbreaks, such as the 2016 Zika virus (ZIKV) outbreak, rapid availability of vaccines can prove critical in reducing widespread disease burden. The recent successes of mRNA vaccines support their evaluation in pregnant animal models to justify their use in neonatal settings. Here we evaluated immunogenicity of self-amplifying replicon (repRNA) vaccines, delivered with our clinical-stage LION nanoparticle formulation, in pregnant rabbits using ZIKV and HIV-1 as model disease targets. We showed that LION/repRNA vaccines induced robust antigen-specific antibody responses in adult pregnant rabbits that passively transferred to newborn kits in utero. Using a matrixed study design, we further elucidate the effect of vaccination in kits on the presence of pre-existing maternal antibodies. Our findings showed that timing of maternal vaccination is critical in maximizing in utero antibody transfer, and subsequent vaccination in newborns maintained elevated antibody levels compared with no vaccination. Overall, our results support further development of the LION/repRNA vaccine platform for maternal and neonatal settings.