Search

Since the U.S. Supreme Court's decision in Dobbs vs. Jackson Women's Health Organization, a growing web of state laws restricts access to abortion. Here we consider how, ethically, doctors should respond when terminating a pregnancy is clinically indicated but state law imposes restrictions on doing so. We offer a typology of cases in which the dilemma emerges and a brief sketch of the current state of legal prohibitions against providing such care. We examine the issue from the standpoints of conscience, professional ethics, and civil disobedience and conclude that it is almost always morally permissible and praiseworthy to break the law and that, in a subset of cases, it is morally obligatory to do so. We further argue that health care institutions that employ or credential physicians to provide reproductive health care have an ethical duty to provide a basic suite of practical supports for them as they work to ethically resolve the dilemmas before them., (© 2024 The Hastings Center.)

Over the past 30 years, progress has been made in increasing women's representation in clinical research. However, women continue to be underrepresented in phase I clinical trials-those trials that test the safety and tolerability of investigational drugs, often on healthy individuals. As sex-based differences in adverse drug reactions are often linked to drug dose, pivotal safety information in phase I trials is often insufficiently-and inequitably-captured for females. Yet there has been little attention to how clinical investigators and those charged with overseeing the ethical conduct of these trials perceive the barriers to women's inclusion in phase I trials. To address this gap, we report on 22 interviews with U.S. phase I investigators and institutional review board (IRB) members. Our findings indicate that although these investigators and IRB members acknowledged the importance of including women in clinical trials, they justified women's exclusion from phase I trials by citing the need to manage their reproductive potential. In particular, we identified four key themes that informants used to warrant women's exclusion from phase I trials: the structure of the drug-development system itself, fears about risks to potential fetuses, distrust of women to prevent pregnancy, and concerns about risks and burdens to institutions from resulting pregnancies. We argue that these rationales reflect structural and cultural barriers to women's inclusion in clinical research that ultimately fail to respect female research participants as persons, highlighting the need for broad-based solutions., (© 2023 by The Hastings Center. All rights reserved.)

Following the 2022 US Supreme Court decision in Dobbs vs. Jackson Women's Health Organization, numerous states have passed laws banning or severely restricting abortion. The consequences of the decision stretch beyond abortion contexts, including progress on developing a more robust evidence base for care in pregnancy. In this Robert L. Brent lecture, I explore the impact of the Dobbs decision on teratology research, arguing that it is of importance even and perhaps especially for those concerned about the moral complexities of ending a pregnancy. For as abortion restrictions threaten teratology research, they also threaten its life-affirming aims. First, I show how teratology research and abortion are intertwined, highlighting the stories of Sherri Finkbine and Frances Kelsey, two courageous women whose lives intersected with both. Second, I describe how restrictions on abortion make teratology research more difficult and ethically complex, highlighting additional risks to research participants and staff, as well as new challenges to scientific validity and feasibility. And third, foregrounding yet another story of courage (and heartbreak), I highlight how abortion restrictions make teratology research more important than ever. Honoring Dr. Brent's legacy requires addressing-rather than avoiding-the ethical challenges of pregnancy-related research, especially now in the post-Dobbs era., (© 2023 Wiley Periodicals LLC.)

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., (© 2023 John Wiley & Sons Ltd.)

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., (Copyright © 2022 Jacobs Institute of Women's Health, George Washington University. Published by Elsevier Inc. All rights reserved.)

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.

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., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022 by The Hastings Center. All rights reserved.)

In this paper, I reflect on an important article by Bob Veatch in the inaugural issue of the Hastings Center Report, entitled "Experimental Pregnancy." It is a report and elegant analysis of the Goldzieher Study, in which nearly 400 women were randomized to receive hormonal contraception or placebo absent consent or disclosure about placebo use, resulting in several pregnancies. Noting the study's limited notoriety, I first consider the narratives that have instead dominated bioethics' approach to pregnancy and research: thalidomide and diethylstibesterol (DES). These narratives have facilitated a narrow focus on avoiding fetal risk, to the exclusion of other ethically relevant considerations. I then revisit "Experimental Pregnancy" and offer two ways in which Bob's analysis serves as an important corrective, first, by foregrounding research subjects (persons who are or may become pregnant), and second, by normalizing pregnancy and thus foregrounding foundational ethical considerations that are sometimes lost amidst pregnancy's presumed exceptionalism., (© 2022. The Author(s), under exclusive licence to Springer Nature B.V.)

Despite great need for improved understanding of the use of drugs and biological products in pregnancy, clinical trials in pregnancy are rare, therapeutics in pregnancy are woefully understudied, and pregnant individuals are routinely excluded as trial participants. Recently, however, the U.S. Food and Drug Administration (FDA) has signaled strong support for advancing scientific research with pregnant populations, marking a significant shift from the past. Over the last sixty years, precaution and fear have largely characterized clinical research in pregnancy, deriving in large part from a protectionist ethic that materialized after the thalidomide drug disaster. FDA reviewer Frances Kelsey courageously prevented thalidomide from being marketed in the United States, and her work guided and solidified the FDA's image as protector of the general population from unsafe and ineffective drugs. Yet, when it comes to protection, pregnant persons have been left behind, and experts refer to the "shadows of thalidomide" that hamper clinical trials in pregnancy. Drawing on analysis of Frances Kelsey's archived papers in addition to focused media coverage of Kelsey and thalidomide, we discuss the durable cultural narrative surrounding Kelsey's important work. We argue that revisiting Kelsey's legacy with attention to themes that have characterized her achievement-staying vigilant, prioritizing safety, and mitigating pharmaceutical-based harm-in fact facilitates progress toward the ethical obligation to protect pregnant people through research, toward the generation of pregnancy-specific data for evidence-based care, and toward realizing Kelsey's legacy of safeguarding pregnant people and their offspring from the harms of untested drugs., (Copyright © 2022 Elsevier Inc. All rights reserved.)

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., (© 2022 John Wiley & Sons Ltd.)

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., Competing Interests: No competing financial interests exist., (© Natalie C. Spach et al., 2022; Published by Mary Ann Liebert, Inc.)

Pregnant and breastfeeding populations are at substantial risk of acquiring HIV in some settings, yet are underrepresented in clinical trials of new pre-exposure prophylaxis (PrEP) agents. Several PrEP formulations are in development (eg, vaginal rings, long-acting injectables, and other modalities). Pregnant and breastfeeding populations are typically excluded from initial clinical trials. We identified 14 PrEP trials of novel agents in non-pregnant or non-breastfeeding populations, and six phase 1-3 trials and open label extensions among pregnant and breastfeeding populations, that are currently ongoing or complete. A framework shift is needed to consider the ethical costs of excluding pregnant and breastfeeding populations at risk for HIV in PrEP clinical trials and promote inclusion to maximise the benefits from PrEP tools in the pipeline. Research on new PrEP agents should include pregnant and breastfeeding populations to avoid delays in reaching those who could benefit from PrEP after efficacy is established., Competing Interests: Declaration of interests DLJD received funding from the US National Institutes of Health (K01TW01187 from the Fogarty International Center and National Institute of Mental Health R01MH116771), an honorarium for a meeting on long-acting PrEP by ViiV, donations of the study drug (Truvada) from Gilead, and donations of the STI test kits from Cepheid. NM has an investigator initiated trial from Merck. ADL declared funding for the PHASES Project (grant number R01 AI108368-05; principal investigator) and The FAIRER Project (grant number R01 HG 011480), and is the chair and on the data safety monitoring board for TNF-alpha Blockade with Certolizumab to Prevent Pregnancy Complications in High-Risk Patients with APS, is a member and on the interim review panel for MTN/042-DELIVER, is a member and on the external advisory board for the Infectious Diseases Clinical Research Consortium, and is a member and on the data safety monitoring board for the MOMPOD Study. CS is on the NIAID drug safety monitoring board for several HIV vaccine trials and has received an honorarium, is on a Clover biopharmaceuticals drug safety monitoring board for a COVID-19 vaccine trial and has received an honorarium, and is a member of the Coalition to Advance and Support Prevention Research funded by USAID. LMN received funding to their institution (the Magee-Womens Research Institute) from the US National Institutes of Health and funding from USAID and PEPFAR through a cooperative agreement (7200AA19CA00003; Jhpiego, Johns Hopkins University, Baltimore, MD, USA). The Microbicide Trials Network is funded by the National Institute of Allergy and Infectious Diseases (UM1AI068633, UM1AI068615, and UM1AI106707), with co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the National Institute of Mental Health, all components of the US National Institutes of Health. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

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., (© 2021 The Authors. Journal of the International AIDS Society published by John Wiley & Sons Ltd on behalf of the International AIDS Society.)

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., Competing Interests: Financial Disclosure Jean Anderson disclosed that they received money from stock in AbbVie, Merck, and Bristol Myers Squibb. They also received honoraria from the International AIDS Society in December 2019. The other authors did not report any potential conflicts of interest., (Copyright © 2021 by the American College of Obstetricians and Gynecologists. Published by Wolters Kluwer Health, Inc. All rights reserved.)

Pregnant individuals are often excluded from research without clear justification, even when the research poses minimal risk of harm to the fetus. Little is known about institutional review board (IRB) decision-making practices when reviewing such research. We conducted a survey of current and former IRB personnel in the United States to elicit their interpretations of "minimal risk"-a formal regulatory category-and to identify factors that may influence IRB decisions to approve or disapprove research involving pregnant participants. Study results revealed some consensus among IRB members about the risk level of individual research procedures and hypothetical study vignettes. However, we uncovered important variations not only in the assessment of risk but also in the willingness of IRB members to approve minimal risk research that includes pregnant women. Based on our findings, guidance is needed to assist IRB members in characterizing risk, applying federal regulations, and appropriately ensuring the inclusion or justified exclusion of pregnant people in research., (© 2021 by The Hastings Center. All rights reserved.)

Pregnant people's exclusion from COVID-19 vaccine research highlights both the harms of excluding pregnant people from clinical trials and the growing public support for their equitable inclusion. Protectionary tendencies must be challenged for the sake of progress. The COVID-19 pandemic presents an opportunity to translate recognition of an unjust paradigm into action., Competing Interests: The authors have no conflicts of interests to declare., (© 2021 Elsevier Inc.)

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.

Background: Since the National Institutes of Health (NIH) Revitalization Act of 1993, focus on the equitable inclusion of women in clinical research has been ongoing. NIH's 2015 sex as a biological variable (SABV) policy aims to transform research design, analysis, and reporting in the preclinical sphere by including male and female organisms in vertebrate animal research as well as human studies. However, questions remain regarding how researchers and members of research oversight committees perceive the value and need of the SABV policy. Materials and Methods: Based on 62 interviews with animal researchers and oversight personnel, we analyze what the animal research community knows about the policy and sees as the benefits and challenges of implementation. Results: We found that the 62 interviewees disagreed about the need for the policy, with some being supportive and others questioning whether the policy is based on science or is politically motivated. There were also tensions in how interviewees conceptualized the challenges to and resources needed for implementing the SABV policy. For instance, while some thought implementation would require a significant increase in numbers of animals used for each study, others explicitly rejected this claim. Conclusions: We conclude by discussing the practical and social implications of our findings about the views of members of the animal research community regarding the SABV policy.

The increased risk of harm from COVID-19 infection in pregnancy highlights the importance of including pregnant people in COVID-19 vaccine development and deployment. Promising vaccines being developed include replication-competent platforms, which are typically contraindicated during pregnancy because of theoretical risk. However, replicating vaccines are administered in and around pregnancy, either inadvertently because of unknown pregnancy status or when recommended.The historical cases of Ebola virus, yellow fever, and rubella demonstrate that contradictory messages around the safety of live vaccines in pregnancy have critical public health costs. First, restricting study or use of replicating vaccines in pregnancy may delay or deny access to the only available protection against deadly diseases. Additionally, not vaccinating pregnant people may slow epidemic control. Finally, uncertainty and worry around the safety of live vaccines may lead to terminations of otherwise desired pregnancies after inadvertent vaccination in pregnancy.If one of the vaccines deployed to combat the current global COVID-19 pandemic is replication competent, historical cases offer important lessons for ethical and effective protection for pregnant populations.

Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

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., Competing Interests: Conflict of interest disclosure RAK has received grants from the Bill and Melinda Gates Foundation and PATH as well as personal fees from MERCK, outside the submitted work. JSA served as the Chair of the Global Alliance for Vaccines and Immunizations (Gavi) Vaccine Investment Strategic (VIS) Steering Committee (June 2017 – present) as well as the Co-chair of the Vaccine Innovation Prioritization Strategy Alliance (Gavi, WHO, UNICEF, Gates and PATH) Steering Committee (July 2018 – present) during the conduct of this work. BGG is President, Global Immunization at the Sabin Vaccine Institute. Sabin receives support from the Bill and Melinda Gates Foundation, Gavi, the National Philanthropic Trust, and private philanthropy. In addition, Sabin receives project-specific support from GlaxoSmithKline, Merck & Co., Pfizer, Sanofi Pasteur, Takeda Vaccines, Inc. None of this support is related to the focus of the PREVENT Working Group or the published Guidance. DCK has grant support from the Bill and Melinda Gates Foundation for work outside the scope of this Guidance. DCK oversees PATH's Center for Vaccine Innovation and Access (CVIA), which has grants from by the Bill and Melinda Gates Foundation for related work, including Advancing Maternal Immunization. The other authors do not have conflicts of interest to declare., (Copyright © 2019 Pan American Health Organization. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Despite historical exclusion, there has been recent recognition of the need to address the health of pregnant women in research on vaccines against emerging pathogens. However, pregnant women's views and decision-making processes about vaccine research participation during infectious disease outbreaks remain underexplored. This study aims to examine women's decision-making processes around vaccine research participation during infectious disease outbreaks., Methods: We conducted qualitative semi-structured in-depth interviews with pregnant and recently pregnant women (n = 13), eliciting their views on four hypothetical Zika Virus vaccine research scenarios and probing their decision-making processes around participation. After recorded interviews were transcribed, thematic analysis was conducted based on a priori and emergent themes., Results: Most women interviewed were accepting of vaccine research scenarios. Three broad themes-evidence, risk, and trust-characterized women's decision-making processes. Women varied in how different types and levels of evidence impacted their considerations, which risks were most salient to their decision-making processes, and from whom they trusted recommendations about vaccine research participation. Exemplary quotes from each theme are presented, and lessons for vaccine development during the current COVID-19 pandemic and future outbreaks are discussed., Conclusion: Some pregnant women are accepting of participation in vaccine research during infectious disease outbreaks. Incorporating their priorities into trial design may facilitate their participation and generation of evidence for this important population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background: The pressing need to expand the biomedical HIV prevention evidence base during pregnancy is now increasingly recognized. Women's views regarding participation in such trials and initiating PrEP while pregnant are critical to inform evolving policy and best practices aimed at responsibly expanding evidence-based access for this population., Methods: We conducted 35 semi-structured interviews with reproductive-aged women in Malawi in the local language, Chichewa. Participants were HIV-negative and purposively sampled to capture a range of experience with research during pregnancy. Women's perspectives on enrolling in three hypothetical HIV prevention trial vignettes while pregnant were explored, testing: (1) oral PrEP (Truvada) (2) a vaginal ring (dapivirine), and (3) a randomized trial comparing the two. The vignettes were read aloud to participants and a simple visual was provided. Interviews were audio-recorded, transcribed, translated, and coded using NVivo 11. Thematic analysis informed the analytic approach., Results: A majority of women accepted participation in all trials. Women's views on research participation varied largely based on their assessment of whether participation or nonparticipation would best protect their own health and that of their offspring. Women interested in participating described power dynamics with their partner as fueling their HIV exposure concerns and highlighted health benefits of participation-principally, HIV protection and access to testing/treatment and ancillary care, and perceived potential risks of the vignettes as low. Women who were uninterested in participating highlighted potential maternal and fetal health risks of the trial, challenges of justifying prevention use to their partner, and raised some modality-specific concerns. Women also described ways their social networks, sense of altruism and adherence requirements would influence participation decisions., Conclusions: The majority of participants conveyed strong interest in participating in biomedical HIV prevention research during pregnancy, largely motivated by a desire to protect themselves and their offspring. Our results are consistent with other studies that found high acceptance of HIV prevention products during pregnancy, and support the current direction of HIV research policies and practices that are increasingly aimed at protecting the health of pregnant women and their offspring through responsible research, rather than defaulting to their exclusion.

The scientific and ethical importance of including women of reproductive age in biomedical research is widely acknowledged. Concerns about preventing fetal exposure to research interventions have motivated requirements for contraception among reproductive aged women in biomedical studies-often irrespective of risks and benefits or a woman's actual potential for pregnancy, raising important questions about when such requirements are appropriate. The perspectives of women themselves on these issues are largely unexplored. We conducted 140 interviews, 70 in the U.S. and 70 in Malawi, with women either living with or at-risk for HIV, exploring their views about the practice of requiring contraception in clinical trials. A majority of women interviewed from both countries indicated overall support for the practice, with seven themes characterizing advantages and disadvantages raised: reproductive control, health effects, prevention of fetal harm, burden on women, deferral to authority, autonomy regarding enrollment and birth control method, and relationship concerns. While women in the US frequently raised prevention of fetal harm as a key advantage, many other positives noted by women in both countries were related to contraception use in general, not specific to a trial context. With regard to disadvantages, U.S. women tended to focus on biomedical risks such as side effects and impact on fertility, whereas Malawian women focused on the social risks of contraception requirements, including violations of trust in marital relations and suspicions of potential infidelity. Given the potential benefits and burdens highlighted, contraception in research should be sensitive to actual fetal risk assessments; directed where justified at optimizing effective pregnancy prevention; responsive to women's reproductive preferences; and made available as an ancillary benefit even where risk thresholds do not justify requirement-in order to facilitate trials that are both ethical and robustly oriented around the interests and lives of women who will participate in them., Competing Interests: The authors have declared that no competing interests exist.

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.

Objective: Ethical and counseling challenges are expected with the introduction of prenatal whole exome sequencing. In this study, we describe specific challenges identified through the UNC-Chapel Hill Prenatal Exome Sequencing Study., Methods: Participants were a subset of women participating in the fetal exome study, which has enrolled 73 mother-father-fetus trios in pregnancies diagnosed with structural anomalies and normal standard genetic testing results. In this descriptive study, cases were reviewed by members of the research team, including a bioethicist, to identify counseling challenges. Illustrative cases were chosen by group consensus., Results: Four illustrative cases were identified for further analysis. Challenges included need for adequate counseling and informed consent, challenges in prenatal variant interpretation, performing prenatal diagnosis in subsequent pregnancies, inability to identify a genetic etiology, and identifying parental secondary findings., Conclusion: Our study illustrates several challenges identified in an ongoing prenatal exome study. While genomic medicine is a powerful tool for prenatal diagnosis, it is important that clinicians understand the ethical implications and parental perceptions of this testing modality., (© 2018 John Wiley & Sons, Ltd.)

Introduction: As Zika virus infection during pregnancy can cause a range of congenital anomalies, pregnant women may be a target population for vaccination in future outbreaks. Their inclusion in vaccine trials is critical to ensure safe and effective vaccines in pregnancy. Though many vaccine candidates are in development, pregnant women's willingness to participate in Zika virus vaccine research is unknown. This study aims to describe pregnant women's attitudes toward Zika virus vaccine research participation, as well as perceived barriers to and facilitators of enrollment., Methods: Pregnant and recently postpartum women (n = 128) attending prenatal care at Massachusetts General Hospital completed surveys querying their willingness to participate in four hypothetical Zika virus vaccine trials and their motivations for participation. Demographics, information on prior Zika virus exposure, and vaccine acceptance were collected., Results: Most women (77%) accepted participation in at least one hypothetical Zika virus vaccine trial, and women were significantly more likely to accept prospective enrollment in an inactivated vaccine trial compared to a live-attenuated vaccine trial (p-value <0.0001) or a nucleic acid-based vaccine trial (p-value <0.0444). Important motivators for participation included evidence from research with pregnant and non-pregnant people, a desire to protect the baby from Zika, perceptions of vaccine safety, and provider recommendation., Conclusions: A majority of women in this cohort were willing to participate in a Zika virus vaccine trial while pregnant, however, differences in acceptance exist between vaccine platforms. The high value placed on evidence by participants highlights the importance of gathering and communicating pregnancy-specific data to potential research participants and their providers. Women's motivations for accepting research participation during pregnancy are important to inform the Zika virus vaccine research agenda, candidate prioritization, and trial design., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Clinical research to inform the evidence base to guide nonobstetrical care during pregnancy is critically important for the well-being of women and their future offspring. Conversations about regulations for such research, including whether paternal consent should ever be required, should be informed by the perspectives of those most affected, namely, pregnant women. We conducted in-depth interviews with 140 pregnant women living with or at risk of HIV-70 in Malawi, 70 in the United States-exploring their views on requiring paternal consent for pregnant women's participation in trials offering the prospect of direct benefit solely to the fetus. The majority of women supported such a requirement; others raised concerns. A trio of themes-the father's or pregnant woman's rights, fetal protection, and gender/relationship dynamics-characterized views both supporting and against a paternal consent requirement, expanding the range of considerations that should inform approaches to paternal involvement in research with 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.

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.