Safekeeping of Pregnant People Experiencing Incarceration.

Safekeeping involves transferring individuals from jails to prisons without the presence of a conviction. In North Carolina, safekeeping is used for pregnant people with the aim of providing better prenatal care. We interviewed 14 stakeholders in the safekeeping process including sheriffs, clinicians, advocates, and lawyers. Three key themes emerged: jails' inability to provide care for pregnant individuals; safekeeping as an additional punishment to incarceration; and differing attitudes on the necessity of safekeeping. Participants perceived that while there may be some benefits of safekeeping such as enhanced prenatal care, safekeeping can also lead to worsened conditions for pregnant people experiencing incarceration.

Diagnostic yield and psychological outcomes among women pursuing trio-exome sequencing: Do women with recurrent anomalous fetal phenotypes experience more negative psychological outcomes?

PURPOSE: To describe psychological outcomes among people with recurrent anomalous pregnancies pursuing trio-exome sequencing (exome sequencing (ES)) compared to those with one affected. METHODS: We analyzed data from a prospective ES cohort, enrolling patients with major fetal anomaly and normal microarray. Participants completed validated scales before and after ES. We (1) compared responses of those with multiple anomalous pregnancies to those with one affected and (2) conducted linear regression to examine associations between multiple affected pregnancies and post-ES constructs. RESULTS: Of 166 trios, 61 (37%) received results from ES. Forty (24%) had more than one affected pregnancy and 45% of those received a result explaining the fetal phenotype. All participants had clinically significant presequencing generalized psychological distress. For the 93 who completed the post-ES surveys, those with multiple affected pregnancies had higher psychological adaptation scores but worse test related distress scores (9.3 (6.2) versus 7.1(5.6), p = 0.12) and (14.3 (1.5) versus 15.4 (1.4), p = 0.01). In linear regression models, there were no significant differences in post-ES constructs after adjusting for clinically relevant covariates. CONCLUSIONS: All individuals experienced significant generalized psychological distress in the pre-ES period, extending our knowledge of how pregnancy history contributes to parental sequencing outcomes.

Experiences Navigating the Pregnancy Care Continuum During the COVID-19 Pandemic.

INTRODUCTION: The COVID-19 pandemic led to unprecedented changes in care delivery across the pregnancy care continuum. Our primary objective with this research was to characterize the range of ways that the early months of the COVID-19 pandemic affected pregnancy, childbirth, and postpartum care experiences. METHODS: Pregnant and recently pregnant patients (n = 20) from obstetrics and gynecology clinical sites associated with Massachusetts General Hospital were interviewed about their experiences with prenatal care, childbirth, and postpartum care during the first wave of the COVID-19 pandemic. Interview transcripts were analyzed for emergent themes. RESULTS: This sample included 20 pregnant and postpartum people, including 11 individuals who tested positive for COVID-19 during pregnancy or postpartum and nine with suspected infection. The ways in which COVID-19 or suspected COVID-19 affected experiences of prenatal care, childbirth, and postpartum care were complex and varied. Three themes were identified across narratives of pregnancy, birth, and postpartum care: patient perceptions of diminished access to care, stigma due to COVID-19 infection, and limited capacity of providers to honor patient preferences. CONCLUSIONS: A better understanding of pregnant and recently pregnant people's experiences during the early months of the COVID-19 pandemic can inform infection control policies and clinical care delivery practices that are more congruent with the needs and values of pregnant, birthing, and postpartum people as institutions craft responses to future pandemics. Approaches that maximize meaningful access across the pregnancy care continuum, center patients' priorities within adapted care models, and honor patient preferences as much as possible are important aspects of an appropriate response to future waves of COVID-19 and other pandemics.

Ethical Criteria for Improved Human Subject Protections in Phase I Healthy Volunteer Trials.

Phase I healthy volunteer trials test the safety and tolerability of investigational pharmaceuticals. In them, participants are exposed to study-drug risks without the possibility of direct medical benefit and typically must spend days or weeks in a residential research facility. Monetary payments are used to incentivize enrollment and compensate participants for their time. Together, these features of phase I healthy volunteer trials create a research context that differs markedly from most other clinical research, including by enrolling disproportionate numbers of economically disadvantaged people of color as participants. Due to these unique trial features and participation patterns, traditional biomedical research oversight offers inadequate ethical and policy guidance for phase I healthy volunteer research. This article details five ethical criteria crafted to be responsive to the particularities of this type of research: translational science value, fair opportunity and burden sharing, fair compensation for service, experiential welfare, and enhanced voice and recourse.

Scientific, ethical, and legal considerations for the inclusion of pregnant people in clinical trials.

Clinical trials to address the COVID-19 public health emergency have broadly excluded pregnant people from participation, illustrating a long-standing trend of clinical trial exclusion that has led to a clear knowledge gap and unmet need in the treatment and prevention of medical conditions experienced during pregnancy and of pregnancy-related conditions. Drugs (includes products such as drugs, biologics, biosimilars and vaccines) approved for a certain medical condition in adults are also approved for use in pregnant adults with the same medical condition, unless contraindicated for use in pregnancy. However, there are limited pregnancy-specific data on risks and benefits of drugs in pregnant people, despite their approval for all adults. The United States Food and Drug Administration-approved medical products are used widely by pregnant people, 90% of whom take at least 1 medication during the course of their pregnancy despite there being sparse data from clinical trials on these products in pregnancy. This overall lack of clinical data precludes informed decision-making, causing clinicians and pregnant patients to have to decide whether to pursue treatment without an adequate understanding of potential effects. Although some United States Food and Drug Administration initiatives and other federal efforts have helped to promote the inclusion of pregnant people in clinical research, broader collaboration and reforms are needed to address challenges related to the design and conduct of trials that enroll pregnant people, and to forge a culture of widespread inclusion of pregnant people in clinical research. This article summarizes the scientific, ethical, and legal considerations governing research conducted during pregnancy, as discussed during a recent subject matter expert convening held by the Duke-Margolis Center for Health Policy and the United States Food and Drug Administration on this topic. This article also recommends strategies for overcoming impediments to inclusion and trial conduct.

Emotional Experiences of Pregnant and Postpartum People with Confirmed or Suspected COVID-19 Infection During the Initial Surge of the Pandemic.

Objectives: The COVID-19 pandemic may have a unique emotional impact on pregnant people. This qualitative study aimed to characterize the emotional effects of the COVID-19 pandemic on pregnant and recently pregnant patients who had either suspected or confirmed COVID-19 infection during the initial 6 months of the pandemic. Methods: Pregnant and recently pregnant participants (n = 20) from Massachusetts General Hospital Obstetrics and Gynecology clinical sites with suspected or confirmed COVID-19 infection were interviewed about their experiences during the COVID-19 pandemic. Interviews were transcribed and coded using NVivo 12 software. Using data display matrices, thematic analysis was performed to identify emergent, crosscutting themes. Results: Twenty pregnant and postpartum patients participated of whom 12 had confirmed COVID-19 infection and 8 had suspected infection. The most frequently described emotions were anxiety (90%), uncertainty (80%), fear (70%), relief (65%), and sadness (60%). The following three crosscutting themes were identified: risk, protection, and change. The ways in which participants articulated their emotional reactions to the themes of risk, protection, and change were complex and varied. Conclusions: There was a broad range of negative and positive emotional experiences of pregnancy, birth, and the postpartum period during the first 4 months of the COVID-19 pandemic. A better understanding of pregnant people's emotional experiences may lead to changes in clinical practice and institutional policies that are more supportive of their needs and congruent with their values.

Parental motivations for and adaptation to trio-exome sequencing in a prospective prenatal testing cohort: Beyond the diagnosis.

PURPOSE: To understand motivations for and parental interpretation of results from trio-exome sequencing (ES) for fetal anomalies with a negative standard genetic diagnosis. METHODS: Analysis of an ongoing, prospective prenatal trio-ES study of pregnancies with ultrasound-identified congenital anomalies and lack of a standard genetic diagnosis. After determination of pregnancy disposition, participants completed questionnaires and a semi-structured interview pre- and post-sequencing. Interviews were analyzed using a constructivist grounded theory methodology to identify themes. Associations between themes and ES result were also examined. RESULTS: One hundred twenty-six trios have been sequenced. Of those, 45 (36%) resulted in fetal diagnosis. One hundred twenty-five women completed pre-sequencing surveys, and 91 women completed post-sequencing surveys. The main themes identified include (1) variable reasons to pursue ES, (2) limited expectations but high hopes from ES, (3) parental adaptation to uncertain results, (4) impact on personal health and reproduction, and (5) gratitude for the process. CONCLUSION: Participants pursued ES for various reasons, most often to identify a diagnosis and guide reproduction. Post-sequencing, most participants described the process, their interpretation of results, and the impact of receiving the results. Less frequently, but of most concern, participants expressed anxiety about testing and implications for themselves, relationships, and other family members, thus identifying an area of high need for additional support among patients undergoing prenatal ES.

Pregnant Individuals' Views on Fetal Tissue Research in the United States.

OBJECTIVE: Fetal tissue research has driven significant medical advances but remains publicly contentious in the United States. The views of pregnant individuals in the United States regarding the donation of fetal tissue offer an important and previously unexplored perspective on this issue. METHODS: We conducted a secondary analysis of data from two separate, broader qualitative studies. Pregnant and recently pregnant individuals (N=79) from clinical sites at the University of North Carolina at Chapel Hill, Johns Hopkins University, and Massachusetts General Hospital were interviewed individually using a semi-structured guide addressing a range of issues related to infectious disease research and pregnancy, including the acceptability of fetal tissue research. Interviews were transcribed, coded, and analyzed for emergent themes. RESULTS: Among this sample of predominantly Black (61%), reproductive-aged pregnant and recently pregnant participants, the majority (72%) generally supported fetal tissue research. The following three themes were identified: choice, respect, and meaning. Respondents discussed the deeply personal nature of decisions surrounding fetal tissue research, emphasizing the importance of informed consent and respect for the person's emotional state when approaching for consent. The ways in which participants regarded how to respectfully handle fetal tissue also shaped views about the acceptability of donation, both for and against. For many participants, fetal tissue donation to research represented one way of ascribing meaning to pregnancy termination or loss. CONCLUSION: Among this diverse sample of pregnant and recently pregnant individuals, most were supportive of fetal tissue donation for research. A better understanding of pregnant individuals' views on this topic may lead to policies and practices that are congruent with the needs and values of people facing decisions regarding the disposition of fetal remains.

Pregnant women & vaccines against emerging epidemic threats: Ethics guidance for preparedness, research, and response.

Zika virus, influenza, and Ebola have called attention to the ways in which infectious disease outbreaks can severely - and at times uniquely - affect the health interests of pregnant women and their offspring. These examples also highlight the critical need to proactively consider pregnant women and their offspring in vaccine research and response efforts to combat emerging and re-emerging infectious diseases. Historically, pregnant women and their offspring have been largely excluded from research agendas and investment strategies for vaccines against epidemic threats, which in turn can lead to exclusion from future vaccine campaigns amidst outbreaks. This state of affairs is profoundly unjust to pregnant women and their offspring, and deeply problematic from the standpoint of public health. To ensure that the needs of pregnant women and their offspring are fairly addressed, new approaches to public health preparedness, vaccine research and development, and vaccine delivery are required. This Guidance offers 22 concrete recommendations that provide a roadmap for the ethically responsible, socially just, and respectful inclusion of the interests of pregnant women in the development and deployment of vaccines against emerging pathogens. The Guidance was developed by the Pregnancy Research Ethics for Vaccines, Epidemics, and New Technologies (PREVENT) Working Group - a multidisciplinary, international team of 17 experts specializing in bioethics, maternal immunization, maternal-fetal medicine, obstetrics, pediatrics, philosophy, public health, and vaccine research and policy - in consultation with a variety of external experts and stakeholders.

Impact of prenatal exome sequencing for fetal genetic diagnosis on maternal psychological outcomes and decisional conflict in a prospective cohort.

PURPOSE: To evaluate associations between prenatal trio exome sequencing (trio-ES) and psychological outcomes among women with an anomalous pregnancy. METHODS: Trio-ES study enrolling patients with major fetal anomaly and normal microarray. Women completed self-reported measures and free response interviews at two timepoints: pre- (1) and post- (2) sequencing. Pre-sequencing responses were compared with post-sequencing responses; post-sequencing responses were stratified by women who received trio-ES results that may explain fetal findings, secondary findings (medically actionable or couples with heterozygous variants for the same recessive disorder), or negative results. RESULTS: One hundred fifteen trios were enrolled. Of those, 41/115 (35.7%) received results from trio-ES, including 36 (31.3%) who received results that may explain the fetal phenotype. These women had greater post-sequencing distress compared with women who received negative results, including generalized distress (p = 0.03) and test-related distress (p = 0.2); they also had worse psychological adaptation to results (p = 0.001). Genomic knowledge did not change from pre- to post-sequencing (p = 0.51). CONCLUSION: Women show more distress after receiving trio-ES results compared with those who do not, suggesting that women receiving results may need additional support or counseling to inform current and future reproductive decisions.

Beyond "Vessels and Vectors": A Global Review of Registered HIV-Related Clinical Trials with Pregnant Women.

BACKGROUND: Since the early 1990s, the HIV research agenda has prioritized to some degree the inclusion of pregnant women. However, concerns remain regarding the extent to which pregnant women's own health needs are addressed, representation in trials of HIV preventives or treatments for comorbidities, and equitable study of newer medications during pregnancy. METHODS: We employed a keyword search of the International Clinical Trials Registry Platform to identify interventional HIV-related trials conducted with pregnant women between January 2001 and December 2015. Retained trials were coded according to several key variables (e.g., study endpoints, trial phase, study compound) and analyzed using information provided in the database. RESULTS: In total, 63 trials studying use of a pharmacological compound during pregnancy were conducted across 35 countries and sponsored by 74 unique organizations, including pharmaceutical companies. Of trials analyzed, 86% (n = 54) listed maternal outcomes as a primary endpoint. More than 35% (n = 23) of trials assessed pharmacokinetic parameters of a study compound during pregnancy. Of 45 trials specifically studying HIV-related medication(s), just 4% (n = 2) focused on HIV preventives. One trial studied tuberculosis in HIV-infected pregnant women; 11 studied malaria. On average, medications were studied during pregnancy 4.4 years after licensure. CONCLUSIONS: Our findings demonstrate that trials with pregnant women are conducted across a range of countries and sponsors, and much progress has been made to better address pregnant women's own health needs in HIV research. However, our findings confirm other concerns, for example, lack of HIV preventives studied and the lag between medication licensure and study during pregnancy.

Prenatal exome sequencing in anomalous fetuses: new opportunities and challenges.

PurposeWe investigated the diagnostic and clinical performance of exome sequencing in fetuses with sonographic abnormalities with normal karyotype and microarray and, in some cases, normal gene-specific sequencing.MethodsExome sequencing was performed on DNA from 15 anomalous fetuses and from the peripheral blood of their parents. Parents provided consent to be informed of diagnostic results in the fetus, medically actionable findings in the parents, and their identification as carrier couples for significant autosomal recessive conditions. We assessed the perceptions and understanding of exome sequencing using mixed methods in 15 mother-father dyads.ResultsIn seven (47%) of 15 fetuses, exome sequencing provided a diagnosis or possible diagnosis with identification of variants in the following genes: COL1A1, MUSK, KCTD1, RTTN, TMEM67, PIEZO1 and DYNC2H1. One additional case revealed a de novo nonsense mutation in a novel candidate gene (MAP4K4). The perceived likelihood that exome sequencing would explain the results (5.2 on a 10-point scale) was higher than the approximately 30% diagnostic yield discussed in pretest counseling.ConclusionExome sequencing had diagnostic utility in a highly select population of fetuses where a genetic diagnosis was highly suspected. Challenges related to genetics literacy and variant interpretation must be addressed by highly tailored pre- and posttest genetic counseling.

Ethical considerations in developing an evidence base for pre-exposure prophylaxis in pregnant women.

Though many women in need of access to HIV preventive regimes are pregnant, there is a dearth of data to guide these care decisions. While oral pre-exposure prophylaxis (PrEP) has been shown to prevent HIV infection in numerous high-risk populations, pregnant women have been excluded from all major prospective trials. We propose for ethical examination a theoretical trial-a prospective, observational study of PrEP for pregnant women at risk for HIV in sub-Saharan Africa-highlighting an ethical tradeoff that characterizes issues faced for advancing research in pregnancy. On the one hand, an "opportunistic" study design has certain ethical advantages: as formally construed, the research activity usually begins after decisions to use PrEP during pregnancy are made in the clinical setting. This minimizes research risks and avoids ethical problems that a randomized controlled trial (RCT) comparing PrEP to placebo would entail, particularly withholding care proven beneficial in other populations. On the other hand, observational studies yield less precise information than RCTs. This raises a broader question about the pace of research with pregnant women, as it typically takes many years after a drug's approval for use in the general population to determine safety of the medication in pregnancy. Such delays can have the effect of making it impossible to ethically conduct an RCT with pregnant women, reducing the likelihood that the research community is able to obtain robust, pregnancy-specific evidence. While an observational cohort is potentially the most ethically and scientifically justified research design to study PrEP in pregnancy, earlier involvement of pregnant women in studies of newer preventives may lead to evidence that is more timely and robust.

Advancing HIV research with pregnant women: navigating challenges and opportunities.

OBJECTIVE: Concerns about including pregnant women in research have led to a dearth of evidence to guide safe and effective treatment and prevention of HIV in pregnancy. To better understand why these evidence gaps persist and inform guidance for responsible inclusion of pregnant women in the HIV research agenda, we aimed to learn what HIV experts perceive as barriers and constraints to conducting this research. METHODS: We conducted a series of group and one-on-one consultations with 62 HIV investigators and clinicians to elicit their views and experiences conducting HIV research involving pregnant women. Thematic analysis was used to identify priorities and perceived barriers to HIV research with pregnant women. RESULTS: Experts discussed a breadth of needed research, including safety, efficacy, and appropriate dosing of: newer antiretrovirals for pregnant women, emerging preventive strategies, and treatment for coinfections. Challenges to conducting research on pregnancy and HIV included ethical concerns, such as how to weigh risks and benefits in pregnancy; legal concerns, such as restrictive interpretations of current regulations and liability issues; financial and professional disincentives, including misaligned funder priorities and fear of reputational damage; and analytical and logistical complexities, such as challenges recruiting and retaining pregnant women to sufficiently power analyses. CONCLUSION: Investigators face numerous challenges to conducting needed HIV research with pregnant women. Advancing such research will require clearer guidance regarding ethical and legal uncertainties; incentives that encourage rather than discourage investigators to undertake such research; and a commitment to earlier development of safety and efficacy data through creative trial designs.

Toward Earlier Inclusion of Pregnant and Postpartum Women in Tuberculosis Drug Trials: Consensus Statements From an International Expert Panel.

Tuberculosis is a major cause of morbidity and mortality in women of childbearing age (15-44 years). Despite increased tuberculosis risk during pregnancy, optimal clinical treatment remains unclear: safety, tolerability, and pharmacokinetic data for many tuberculosis drugs are lacking, and trials of promising new tuberculosis drugs exclude pregnant women. To advance inclusion of pregnant and postpartum women in tuberculosis drug trials, the US National Institutes of Health convened an international expert panel. Discussions generated consensus statements (>75% agreement among panelists) identifying high-priority research areas during pregnancy, including: (1) preventing progression of latent tuberculosis infection, especially in women coinfected with human immunodeficiency virus; (2) evaluating new agents/regimens for treatment of multidrug-resistant tuberculosis; and (3) evaluating safety, tolerability and pharmacokinetics of tuberculosis drugs already in use during pregnancy and postpartum. Incorporating pregnant women into clinical trials would extend evidence-based tuberculosis prevention and treatment standards to this special population.

Ethical dilemmas in women's health in under-resourced settings.

Ethical decision making in women's health presents a series of unique challenges that are exacerbated considerably in under-resourced settings. Severe constraints on both autonomy and resources highlight limitations of principle-based ethics for addressing ethical dilemmas. Other useful ethical "tools" are considered in the context of 2 cases that emphasize the challenges to ethical decision making in under-resourced settings. The cases confront traditional notions of patient autonomy, highlight pervasive issues with regard to allocation of resources, and demonstrate the difficulties encountered in the careful application of medical ethics.