Global Stillbirth Policy Review - Outcomes And Implications Ahead of the 2030 Sustainable Development Goal Agenda.

BACKGROUND: Globally, data on stillbirth is limited. A call to action has been issued to governments to address the data gap by strengthening national policies and strategies to drive urgent action on stillbirth reduction. This study aims to understand the policy environment for stillbirths to advance stillbirth recording and reporting in data systems. METHODS: A systematic three-step process (survey tool examination, identifying relevant study questions, and reviewing country responses to the survey and national documents) was taken to review country responses to the global 2018-2019 World Health Organization (WHO) Reproductive, Maternal, Neonatal, Child and Adolescent Health (RMNCAH) Policy Survey. Policy Survey responses were reviewed to identify if and how stillbirths were included in national documents. This paper uses descriptive analyses to identify and describe the relationship between multiple variables. RESULTS: Responses from 155 countries to the survey were analysed, and over 800 national policy documents submitted by countries in English reviewed. Fewer than one-fifth of countries have an established stillbirth rate (SBR) target, with higher percentages reported for under-5 (71.0%) and neonatal mortality (68.5%). Two-thirds (65.8%) of countries reported a national maternal death review panel. Less than half (43.9%) of countries have a national policy that requires stillbirths to be reviewed. Two-thirds of countries have a national policy requiring review of neonatal deaths. WHO websites and national health statistics reports are the common data sources for stillbirth estimates. Countries that are signatories to global initiatives on stillbirth reduction have established national targets. Globally, nearly all countries (94.8%) have a national policy that requires every death to be registered. However, 45.5% of reviewed national policy documents made mention of registering stillbirths. Only 5 countries had national policy documents recommending training of health workers in filling out death certificates using the International Classification of Diseases (ICD)-10 for stillbirths. CONCLUSION: The current policy environment in countries is not supportive for identifying stillbirths and recording causes of death. This is likely to contribute to slow progress in stillbirth reduction. The paper proposes policy recommendations to make every baby count.

HIV, Placental Lesions, and Adverse Perinatal Outcomes.

Africa has the highest number of pregnant women with human immunodeficiency virus (HIV). In some studies, HIV has been associated with adverse perinatal outcomes. However, the pathophysiological mechanism leading to adverse fetal outcomes is not known. Maternal vascular malformation, chorioamnionitis, and decreased placental weight have been described as placental features associated with HIV in some studies. The use of antiretroviral therapy has reduced perinatal transmission of HIV and adverse fetal outcomes. However, placental mechanisms associated with HIV and the fetal immune response to maternal HIV infection are poorly understood. Additional research is required to understand whether altered maternal immunity in women living with HIV can trigger fetal responses leading to stillbirth or preterm birth.

Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy.

The emergence of drug resistance continues to plague TB control, with a global increase in the prevalence of MDR-TB. This acts as a gateway to XDR-TB and thus emphasizes the urgency for drug development and optimal treatment options. Bedaquiline is the first new anti-TB drug approved by the FDA in 40 years and has been shown to be an effective treatment option for MDR Mycobacterium tuberculosis infection. Bedaquiline has also recently been included in clinical trials for new regimens with the aim of improving and shortening treatment periods. Alarmingly, efflux-mediated bedaquiline resistance, as well as efflux-mediated cross-resistance to clofazimine, has been identified in treatment failures. This mechanism of resistance results in efflux of a variety of anti-TB drugs from the bacterial cell, thereby decreasing the intracellular drug concentration. In doing so, the bacillus is able to render the antibiotic treatment ineffective. Recent studies have explored strategies to reverse the resistance phenotype conferred by efflux pump activation. It was observed that the addition of efflux pump inhibitors partially restored drug susceptibility in vitro and in vivo. This has significant clinical implications, especially in MDR-TB management where treatment options are extremely limited. This review aims to highlight the current efflux pump inhibitors effective against M. tuberculosis, the effect of efflux pump inhibitors on mycobacterial growth and the clinical promise of treatment with efflux pump inhibitors and standard anti-TB therapy.