https://orcid.org/0000-0003-3574-2306
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Abstract
New fetal therapies offer important prospects for improving health. However, having to consider both the fetus and the pregnant woman makes the risk–benefit analysis of fetal therapy trials challenging. Regulatory guidance is limited, and proposed ethical frameworks are overly restrictive or permissive. We propose a new ethical framework for fetal therapy research. First, we argue that considering only biomedical benefits fails to capture all relevant interests. Thus, we endorse expanding the considered benefits to include evidence-based psychosocial effects of fetal therapies. Second, we reject the commonly proposed categorical risk and/or benefit thresholds for assessing fetal therapy research (e.g., only for life-threatening conditions). Instead, we propose that the individual risks for the pregnant woman and the fetus should be justified by the benefits for them and the study’s social value. Studies that meet this overall proportionality criterion but have mildly unfavorable risk–benefit ratios for pregnant women and/or fetuses may be acceptable.
DISCLOSURE STATEMENT
The views expressed are the authors’ own and do not necessarily reflect those of the National Institutes of Health, the Department of Health and Human Services, or the United States government.
Notes
1 Although 45 CFR46.207 provides a mechanism for research not otherwise approvable.
2 In some cases, experimental (fetal) therapies can be provided as innovative therapy (i.e. with the primary purpose of benefitting the individual patient, as opposed to research that primarily aims to create generalizable knowledge) and therefore not be subject to the research regulations. Innovative therapy may be patient-driven: pregnant women asking their provider for a prescription after, for example, reading about experimental therapies online (apparently, some healthy women carrying a fetus with Down syndrome are requesting fluoxetine prescriptions outside the trial assessing its effectiveness in reducing cognitive impairment in Down syndrome (Bacharach Citation2016; Rochman Citation2016; Tamminga et al. Citation2017)). Whether, and under which conditions (e.g., for how long), innovative therapy is appropriate, is an ongoing debate. However, even innovative therapy advocates argue that research should almost always precede adoption of new therapies into regular clinical practice (Antiel and Flake Citation2017; Chervenak and McCullough Citation2007, Citation2018; Flake Citation2001; American College of Obstetricians and Gynecologists, Committee on Ethics Citation2011). This paper focuses on using experimental therapies in research.
3 Since the fetus is inside of the pregnant woman, she has to physically undergo the fetal therapy and the risks and benefits of this intervention to her need to be considered. This is not the case for pediatric therapies. Therefore, the proposed consideration of the risks and benefits for the pregnant woman does not imply that parental interests need to be considered in a similar way in pediatric research.
4 To be socially valuable, studies should evaluate a treatment that has the potential to improve health and well-being or increase knowledge that is relevant to that goal (Emanuel et al. 2000; NCPHS 1979). Social value is discussed in further detail on page 10.
5 Myelomeningocele is the most severe form of spina bifida, characterized by protrusion of the spinal cord and meninges. Fetal surgery appears to have more favorable long-term outcomes for affected children than postnatal repair, however it is associated with increased risks of significant obstetrical complications such as placental abruption (Cohen et al. Citation2014). To our knowledge, fetal surgery for myelomeningocele has no benefits for pregnant women beyond psychosocial benefits of improved outcomes for the future child (Antiel et al. 2016; Houtrow et al. 2020).
6 Whether acceptable unfavorable risk–benefit ratios for pregnant women should be higher, lower, or the same as for other competent adults is an open question.
7 Two articles referred to social interests or value (Pendl 1988; Rodrigues and van der Berg 2014). Some additional authors have referred to the need for therapies to have a good possibility of being effective (Harrison et al. 1982; Sgreccia 1989) and to have been proven feasible in animal models (Deprest et al. 2011; Papadopulos et al. 2005), which may be understood as a recommendation relating to social value, risk–benefit analysis for individuals, or scientific validity.