Policy Forum Serious and Life-Threatening Pregnancy-Related Infections: Opportunities to Reduce the Global Burden Courtney A. Gravett 1 , Michael G. Gravett 1,2 *, Emily T. Martin 3 , Jeffrey D. Bernson 4 , Sadaf Khan 4 , David S. Boyle 4 , Sophia M. R. Lannon 2 , Janna Patterson 5 , Craig E. Rubens 1,5 , Matthew S. Steele 4 1 Global Alliance to Prevent Prematurity and Stillbirth, Seattle Children’s Hospital, Seattle, Washington, United States of America, 2 Department of Obstetrics and Gynecology, University of Washington School of Medicine, Seattle, Washington, United States of America, 3 School of Pharmacy, Wayne State University, Detroit, Michigan, United States of America, 4 Program for Appropriate Technology in Health, Seattle, Washington, United States of America, 5 Department of Pediatrics, University of Washington School of Medicine, Seattle, Washington, United States of America Introduction Infection is an important, potentially preventable, and yet often overlooked cause of maternal mortality and morbidity as well fetal and neonatal well-being. Puerperal sepsis, narrowly defined by the World Health Organization (WHO) as infection of the genital tract occurring any time between the rupture of membranes or labor and the 42nd day postpartum, is the third leading cause of maternal mortality, responsible for 10%–12% of maternal deaths [1]. Deaths due to puerperal sepsis disproportionately occur in low- and middle-income countries (LMICs). The risk of death from puerperal sepsis is 2.7-fold higher in Africa, 1.9-fold higher in Asia, and 2.1-fold higher in Latin America than in developed countries [2]. However, the impact of infection during pregnancy upon maternal, fetal, and neonatal mortality and morbidity is much greater than that attributed to puerperal sepsis alone—the impact includes deaths and disability from other infections such as urinary tract, soft tissue, and abortion- related infections. Septic abortion, for example, is a significant contributor to maternal infectious mortality, responsible for about 50,000 maternal deaths annually [3]. Intrauterine infection is a risk factor for postpartum endometritis (PPE) as well as a significant contributor to preterm birth, which is now recognized as the second biggest cause of newborn deaths [4]. The burden of pregnancy-related infections goes far beyond puerperal sepsis alone. A useful term that incorporates all of these different infections is ‘‘life-threat- ening pregnancy-related infections,’’ and we use this term in our article. This Policy Forum article aims to highlight opportunities for screening and appropriate treatment of life-threatening pregnancy-related interventions. Our pol- icy recommendations are based on a review of the published literature on the disease burden associated with life- threat- ening pregnancy-related infections and the most common causal pathogens in LMICs. In reviewing maternal infections, when they occur in pregnancy, and their associated pathogens, we sought to identify appropriate strategies for detecting infec- tions and providing effective interventions to help reduce the burden of these mostly preventable maternal, fetal, and neonatal deaths and disabilities. We pay particular attention to Africa and Asia, two regions that together account for 80% of global maternal mortality and where puerperal sepsis accounts for 10%–12% of all maternal deaths [5]. Infections not related specifically to pregnancy (e.g., HIV, curable sexually transmitted infections, tuberculosis, and malaria) are also important contributors to maternal mortality and morbidity. These important non-pregnancy-related infec- tions are beyond the scope of ‘‘life- threatening pregnancy-related infections’’ included in our analysis here, but they indirectly contribute to puerperal sepsis. For example, the risk of puerperal sepsis is increased among women with HIV [6], while chlamydial and gonoccocal infec- tions are important causes of septic abortion [7]. Maternal infections, both pregnancy-related and non-pregnancy-re- lated, remain an important and potentially preventable cause of maternal mortality, especially in LMICs. The review methods are summarized in Figure 1. Distinct Maternal Infectious Syndromes Our review identified four clinical syndromes, and microbes associated with them, that appear to be responsible for most cases of life-threatening pregnancy- related infections in LMICs: (1) puerperal sepsis (chorioamnionitis and PPE), (2) pyelonephritis/urosepsis, (3) septic abor- tion, and (4) skin and soft tissue infections (SSTIs) (Table 1). Each of these occurs at a distinct time during pregnancy, providing opportunities for screening and preven- tion, which we discuss further below (Figure 2; Table 2). Although we found only 55 studies that included microbial culture results, many of which had design weaknesses (e.g., inadequate culture tech- The Policy Forum allows health policy makers around the world to discuss challenges and opportunities for improving health care in their societies. Citation: Gravett CA, Gravett MG, Martin ET, Bernson JD, Khan S, et al. (2012) Serious and Life-Threatening Pregnancy-Related Infections: Opportunities to Reduce the Global Burden. PLoS Med 9(10): e1001324. doi:10.1371/journal.pmed.1001324 Published October 9, 2012 Copyright: ß 2012 Gravett et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Funding: Preparation of this manuscript was made possible with the support of the Bill & Melinda Gates Foundation, http://www.gatesfoundation.org (grant #OPPGH5304). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Abbreviations: ASB, asymptomatic bacteriuria; LMICs, low- and middle-income countries; PPE, postpartum endometritis; SSTIs, skin and soft tissue infections; WHO, World Health Organization. * E-mail: gravettm@u.washington.edu Provenance: Not commissioned; externally peer reviewed PLOS Medicine | www.plosmedicine.org 1 October 2012 | Volume 9 | Issue 10 | e1001324