Pharmacokinetics of Dapivirine Transfer into Blood Plasma, Breast Milk, and Cervicovaginal Fluid of Lactating Women Using the Dapivirine Vaginal Ring.

Breastfeeding (BF) women are an important population for biomedical HIV prevention strategies, but they are rarely included in trials. The 25-mg dapivirine vaginal ring (VR) reduced women's risk of sexually transmitted HIV infection in two phase 3 trials conducted in Africa. We conducted a phase 1, open-label study (MTN-029/IPM 039) of dapivirine VR use among lactating women in Pittsburgh, PA, and Birmingham, AL, USA. MTN-029/IPM 039 enrolled 16 healthy adult women who had already weaned their infants but were still able to express breast milk. Women were instructed to use the VR continuously for 14 days and provided milk, plasma, and cervicovaginal fluid (CVF) samples for pharmacological analysis. No infants were exposed to the drug, but infant dosage was estimated according to FDA guidance. Adverse events (AEs) were collected at all contacts. The study was completed with 100% participant retention. Median dapivirine concentrations were 676 pg/ml in breast milk, 327 pg/ml in plasma (milk/plasma ratio ∼2.0), and 36.25 ng/mg in CVF. Six participants experienced 10 total AEs, none of which required VR discontinuation. The estimated mean daily infant dosage was 74.3 ng/kg/day. In this first study of dapivirine exposure during lactation, dapivirine VR use was associated with lower concentrations of detectable dapivirine in milk and plasma than in CVF samples and a favorable safety profile. Estimated daily levels of infant dapivirine exposure were also low. Additional studies are needed to evaluate longer periods of dapivirine VR use among BF mother-infant pairs living in regions with higher incidence of sexually transmitted HIV infection. (This study has been registered at ClinicalTrials.gov under registration no. NCT02808949.).

Teratogenic effects of the Zika virus and the role of the placenta.

The mechanism by which the Zika virus can cause fetal microcephaly is not known. Reports indicate that Zika is able to evade the normal immunoprotective responses of the placenta. Microcephaly has genetic causes, some associated with maternal exposures including radiation, tobacco smoke, alcohol, and viruses. Two hypotheses regarding the role of the placenta are possible: one is that the placenta directly conveys the Zika virus to the early embryo or fetus. Alternatively, the placenta itself might be mounting a response to the exposure; this response might be contributing to or causing the brain defect. This distinction is crucial to the diagnosis of fetuses at risk and the design of therapeutic strategies to prevent Zika-induced teratogenesis.

Improving Safe and Effective Use of Drugs in Pregnancy and Lactation: Workshop Summary.

In February 2015, given high rates of use of medications by pregnant women and the relative lack of data on safety and efficacy of many drugs utilized in pregnancy, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the Society for Maternal-Fetal Medicine (SMFM), the American College of Obstetricians and Gynecologists (ACOG), and the American Academy of Pediatrics (AAP) convened a group of experts to review the "current" state of the clinical care and science regarding medication use during the perinatal period. The expert panel chose select medications to demonstrate what existing safety and efficacy data may be available for clinicians and patients when making decisions about use in pregnancy or lactation. Furthermore, these example medications also provided opportunities to highlight where data are lacking, thus forming a list of research gaps. Last, after reviewing the existing vaccine safety surveillance system as well as the legislative history surrounding the use of drugs for pediatric diseases, the expert panel made specific recommendations concerning policy efforts to stimulate more research and regulatory attention on drugs for pregnant and lactating women.

Influenza during pregnancy: a cause of serious infection in obstetrics.

Influenza infection during pregnancy imparts disproportionate morbidity and mortality. This has been primarily noted during occasional influenza pandemics but also during seasonal epidemics. The majority of pregnant women who contract influenza appear to have a mild, self-limited course. However, influenza produces a severe life-threatening respiratory illness among a non-negligible and partially unpredictable portion of susceptible pregnant women. Influenza vaccination is the most effective way to prevent this occasionally fatal infection and is recommended for all pregnant women lacking contraindication. Antiviral medications are indicated for both prophylaxis and treatment for suspected and/or confirmed influenza infection during pregnancy.

Ending the evidence gap for pregnancy, HIV and co-infections: ethics guidance from the PHASES project.

INTRODUCTION: While pregnant people have been an important focus for HIV research, critical evidence gaps remain regarding prevention, co-infection, and safety and efficacy of new antiretroviral therapies in pregnancy. Such gaps can result in harm: without safety data, drugs used may carry unacceptable risks to the foetus or pregnant person; without pregnancy-specific dosing data, pregnant people face risks of both toxicity and undertreatment; and delays in gathering evidence can limit access to beneficial next-generation drugs. Despite recognition of the need, numerous barriers and ethical complexities have limited progress. We describe the process, ethical foundations, recommendations and applications of guidance for advancing responsible inclusion of pregnant people in HIV/co-infections research. DISCUSSION: The 26-member international and interdisciplinary Pregnancy and HIV/AIDS: Seeking Equitable Study (PHASES) Working Group was convened to develop ethics-centred guidance for advancing timely, responsible HIV/co-infections research with pregnant people. Deliberations over 3 years drew on extensive qualitative research, stakeholder engagement, expert consultation and a series of workshops. The guidance, initially issued in July 2020, highlights conceptual shifts needed in framing research with pregnant people, and articulates three ethical foundations to ground recommendations: equitable protection from drug-related risks, timely access to biomedical advances and equitable respect for pregnant people's health interests. The guidance advances 12 specific recommendations, actionable within the current regulatory environment, addressing multiple stakeholders across drug development and post-approval research, and organized around four themes: building capacity, supporting inclusion, achieving priority research and ensuring respect. The recommendations describe strategies towards ethically redressing the evidence gap for pregnant people around HIV and co-infections. The guidance has informed key efforts of leading organizations working to advance needed research, and identifies further opportunities for impact by a range of stakeholder groups. CONCLUSIONS: There are clear pathways towards ethical inclusion of pregnant people in the biomedical research agenda, and strong agreement across the HIV research community about the need for - and the promise of - advancing them. Those who fund, conduct, oversee and advocate for research can use the PHASES guidance to facilitate more, better and earlier evidence to optimize the health and wellbeing of pregnant people and their children.

Brief relaxation training program for hospital employees.

Employee stress leads to attrition, burnout, and increased medical costs. We aimed to assess if relaxation training leads to decreased stress levels based on questionnaire and thermal biofeedback. Thirty-minute relaxation training sessions were conducted for hospital employees and for cancer patients. Perceived Stress levels and skin temperature were analyzed before and after relaxation training.

Treatment of Viral Infections During Pregnancy.

Viral infections are common complications of pregnancy. Although some infections have maternal sequelae, many viral infections can be perinatally transmitted to cause congenital or chronic infection in fetuses or infants. Treatments of such infections are geared toward reducing maternal symptoms and complications and toward preventing maternal-to-child transmission of viruses. This article reviews the treatment of herpes simplex virus, cytomegalovirus, hepatitis B and C viruses, and human immunodeficiency virus during pregnancy.

Emerging Infectious Diseases in Pregnancy.

It has been recognized for centuries that pregnant women have unique susceptibilities to many infectious diseases that predispose them to untoward outcomes compared with the general adult population. It is thought a combination of adaptive alterations in immunity to allow for the fetal allograft combined with changes in anatomy and physiology accompanying pregnancy underlie these susceptibilities. Emerging infectious diseases are defined as those whose incidence in humans has increased in the past two decades or threaten to increase in the near future. The past decade alone has witnessed many such outbreaks, each with its own unique implications for pregnant women and their unborn fetuses as well as lessons for the health care community regarding response and mitigation. Examples of such outbreaks include, but are not limited to, severe acute respiratory syndrome, the 2009 H1N1 pandemic influenza, Ebola virus, and, most recently, the Zika virus. Although each emerging pathogen has unique features requiring specific considerations, there are many underlying principles that are shared in the recognition, communication, and mitigation of such infectious outbreaks. Some of these key principles include disease-specific delineation of transmission dynamics, understanding of pathogen-specific effects on both mothers and fetuses, and advance planning and contemporaneous management that prioritize communication among public health experts, clinicians, and patients. The productive and effective working collaboration among the Centers for Disease Control and Prevention, the American College of Obstetricians and Gynecologists, and the Society for Maternal-Fetal Medicine has been a key partnership in the successful communication and management of such outbreaks for women's health care providers and patients alike. Going forward, the knowledge gained over the past decade will undoubtedly continue to inform future responses and will serve to optimize the education and care given to pregnant women in the face of current and future emerging infectious disease outbreaks.

Treatment of infections during pregnancy: Progress and challenges.

BACKGROUND: Emergence of Zika virus as a pathogen with important implications for perinatal outcomes highlights the need to identify safe and effective strategies for prevention and treatment of maternal infections. METHODS: While substantial progress has been made in this area in recent years, significant regulatory and health systems barriers must still be overcome to identify and deliver evidence-based drug therapies for pregnant women. RESULTS: We review progress and outstanding challenges associated with the identification and implementation of new treatment options for maternal infections. CONCLUSION: We describe several strategies in use to optimize the application of existing evidence.Birth Defects Research 109:387-390, 2017.© 2017 Wiley Periodicals, Inc.

Contemporary Obstetric Triage.

IMPORTANCE: The role of obstetric triage in the care of pregnant women has expanded significantly. Factors driving this change include the Emergency Medical Treatment and Active Labor Act, improved methods of testing for fetal well-being, increasing litigation risk, and changes in resident duty hour guidelines. The contemporary obstetric triage facility must have processes in place to provide a medical screening examination that complies with regulatory statues while considering both the facility's maternal level of care and available resources. OBJECTIVE: This review examines the history of the development of obstetric triage, current considerations in a contemporary obstetric triage paradigm, and future areas for consideration. An example of a contemporary obstetric triage program at an academic medical center is presented. RESULT: A successful contemporary obstetric triage paradigm is one that addresses the questions of "sick or not sick" and "labor or no labor," for every obstetric patient that presents for care. Failure to do so risks poor patient outcome, poor patient satisfaction, adverse litigation outcome, regulatory scrutiny, and exclusion from federal payment programs. CONCLUSIONS: Understanding the role of contemporary obstetric triage in the current health care environment is important for both providers and health care leadership. TARGET AUDIENCE: This study is for obstetricians and gynecologists as well as family physicians. LEARNING OBJECTIVES: After completing this activity, the learner should be better able to understand the scope of a medical screening examination within the context of contemporary obstetric triage; understand how a facility's level of maternal care influences clinical decision making in a contemporary obstetric triage setting; and understand the considerations necessary for the systematic evaluation of the 2 basic contemporary obstetric questions, "sick or not sick?" and "labor or no labor?"

Performing Drug Safety Research During Pregnancy and Lactation: Biomedical HIV Prevention Research as a Template.

Evidence-based guidance regarding use of nearly all pharmaceuticals by pregnant and lactating women is limited. Models for performing research may assist in filling these knowledge gaps. Internationally, reproductive age women are at high risk of human immunodeficiency virus (HIV) acquisition. Susceptibility to HIV infection may be increased during pregnancy, and risk of maternal-child transmission is increased with incident HIV infection during pregnancy and lactation. A multidisciplinary meeting of experts was convened at the United States National Institutes of Health to consider paradigms for drug research in pregnancy and lactation applicable to HIV prevention. This report summarizes the meeting proceedings and describes a framework for research on candidate HIV prevention agent use during pregnancy and lactation that may also have broader applications to other pharmaceutical products.

Enoxaparin for postpartum ovarian vein thrombosis. A case report.

BACKGROUND: Intravenous heparin is a recognized treatment for ovarian vein thrombosis. Although an effective, less cumbersome alternative exists with lowmolecular-weight heparins, the literature does not contain reports of their use for this condition. We report a case of postpartum ovarian vein thrombosis managed with enoxaparin. CASE: A 29-year-old woman, gravida 1, para 1001, was readmitted with postpartum endomyometritis. After 5 days of appropriate antibiotics, computed tomography of the abdomen/pelvis demonstrated a right ovarian vein thrombus. Enoxaparin was initiated, resulting in a rapid clinical improvement, and hospital discharge was achieved within 36 hours. CONCLUSION: Enoxaparin treatment for avarian vein thrombosis is an alternative to intravenous heparin that may permit a shorter hospital stay without the need for coagulation profile monitoring.

Prophylaxis and treatment of anthrax in pregnant women.

OBJECTIVE: To review the safety and pharmacokinetics of antimicrobials recommended for anthrax postexposure prophylaxis and treatment in pregnant women. DATA SOURCES: Articles were identified in the PubMed database from inception through December 2012 by searching the keywords (["pregnancy]" and [generic antibiotic drug name]). Additionally, we searched clinicaltrials.gov and conducted hand searches of references from REPROTOX, TERIS, review articles, and Briggs' Drugs in Pregnancy and Lactation. METHODS OF STUDY SELECTION: Articles included in the review contain primary data related to the safety and pharmacokinetics among pregnant women of 14 antimicrobials recommended for anthrax postexposure prophylaxis and treatment (amoxicillin, ampicillin, chloramphenicol, clindamycin, ciprofloxacin, doripenem, doxycycline, levofloxacin, linezolid, meropenem, moxifloxacin, penicillin, rifampin, and vancomycin). TABULATION, INTEGRATION, AND RESULTS: The PubMed search identified 3,850 articles for review. Reference hand searching yielded nine additional articles. In total, 112 articles met the inclusion criteria. CONCLUSIONS: Overall, safety and pharmacokinetic information is limited for these antimicrobials. Although small increases in risks for certain anomalies have been observed with some antimicrobials recommended for prophylaxis and treatment of anthrax, the absolute risk of these antimicrobials appears low. Given the high morbidity and mortality associated with anthrax, antimicrobials should be dosed appropriately to ensure that antibiotic levels can be achieved and sustained. Dosing adjustments may be necessary for the ß-lactam antimicrobials and the fluoroquinolones to achieve therapeutic levels in pregnant women. Data indicate that the ß-lactam antimicrobials, the fluoroquinolones, and, to a lesser extent, clindamycin enter the fetal compartment, an important consideration in the treatment of anthrax, because these antimicrobials may provide additional fetal benefit in the second and third trimesters of pregnancy.