PurposeWe investigated the diagnostic and clinical performance of exome sequencing (ES) in fetuses with sonographic abnormalities with normal karyotype, microarray and, in some cases, normal gene specific sequencing.MethodsES was performed from DNA of 15 anomalous fetuses and from peripheral blood from their parents. Parents provided consent for the return of diagnostic results in the fetus, medically actionable findings in the parents, and identification as carrier couple for significant autosomal recessive conditions. We assessed perceptions and understanding of ES with mixed-methods in 15 mother-father dyads.ResultsIn 7 (47%) of 15 fetuses, ES 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 ES would explain the results (5.2/10) was higher than the approximately 30% diagnostic yield discussed in pre-test counseling.ConclusionsES has 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 post-test genetic counseling.

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.

Though much progress has been made on inclusion of non-pregnant women in research, thoughtful discussion about including pregnant women has lagged behind. We outline resulting knowledge gaps and their costs and then highlight four reasons why ethically we are obliged to confront the challenges of including pregnant women in clinical research. These are: the need for effective treatment for women during pregnancy, fetal safety, harm from the reticence to prescribe potentially beneficial medication, and the broader issues of justice and access to benefits of research participation. Going forward requires shifting the burden of justification from inclusion to exclusion and developing an adequate ethical framework that specifies suitable justifications for excluding pregnant women from research.

Though much progress has been made on inclusion of non-pregnant women in research, thoughtful discussion about including pregnant women has lagged behind. We outline resulting knowledge gaps and their costs and then highlight four reasons why ethically we are obliged to confront the challenges of including pregnant women in clinical research. These are: the need for effective treatment for women during pregnancy, fetal safety, harm from the reticence to prescribe potentially beneficial medication, and the broader issues of justice and access to benefits of research participation. Going forward requires shifting the burden of justification from inclusion to exclusion and developing an adequate ethical framework that specifies suitable justifications for excluding pregnant women from research.

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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.

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.

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.