Gender and Sex Inclusive Approaches for Discussing Predicted Fetal Sex: A Call for Reflection and Research

Technology has rapidly transformed the centuries-old practice of fetal sex prediction, and significant social and medical progress is changing the way prenatal health care providers (HCPs) address the often-asked question, "Am I having a boy or a girl?" Access to prenatal cell-free fetal DNA (cfDNA) screening is expanding broadly, and medical societies recommend cfDNA screening for all pregnancies.1, 2 Prenatal cfDNA screening offers sex chromosome assessment for sex chromosome aneuploidy (sex chromosome complements other than XX or XY), along with other aneuploidy screening (for trisomies 13, 18, and 21), as early as 10 weeks' gestation. Patients may have a limited understanding of the prevalence of aneuploidy in the general population, the implications of these differences, and the purpose of screening for them. This gap in understanding could lead patients to believe the test is solely about gender determination. There is increased awareness that gender and sex diversity are essential components of health, health care, and social reality.3 In this commentary, we posit that many prenatal HCPs are currently underprepared to talk to parents about fetal sex prediction and sex chromosome variation during the course of prenatal care in a manner that is accurate and inclusive of gender and sex diversity, which would promote family function and individual well-being for gender- and sex-diverse children and adults. This skill is relevant to midwives, nurses, genetic counselors, physicians, physician associates, radiologists, and radiology technicians. Of note, in this commentary, we have largely chosen to use the term parents to align with the focus on childhood gender socialization, presupposing a context of desired pregnancies leading to birth and parenting. Radiology and prenatal HCPs have examined the morphology of the fetal genitals by ultrasound and then predicted whether parents should expect a girl or a boy for the past 50 years. More recently, fetal diagnostic testing through amniocentesis or chorionic villus sampling enabled specialized HCPs, including perinatologists and genetic counselors, to report fetal sex chromosomes to parents before 20 weeks' gestation. Currently, increasing access to clinical grade cfDNA screening in the first trimester means that the primary prenatal provider is often responsible for communicating results from sex chromosome screening to patients with limited knowledge or familiarity with sex chromosome variations. Prenatal HCPs are a trusted source of some of the earliest information parents receive. They interpret information obtained by advanced technologies that provide images of fetal genital morphology and detect fetal sex chromosomes. However, the practice of fetal sex prediction has the potential to erase gender and sex diversity if not handled with care. Continuing education (CE) is available for this article. To obtain CE online, please visit http://www.jmwhce.org. A CE form that includes the test questions is available in the print edition of this issue. When prenatal HCPs tell patients, "It's a girl!" or "It's a boy!" they reinforce an erroneous bioessentialist framework: people with XX chromosomes or an apparent vulva are assigned female and socialized as girls, and people with XY chromosomes or an apparent penis are assigned male and socialized as boys. (See Table 1 for relevant terms and definitions.) However, a person's own construct of gender identity is the result of interactions between biological and social factors and relies on cognitive development across the life span. Misconceptions about both sex and gender that are often enacted during the prenatal period among HCPs and pregnant people include: (1) sex and gender are determined by sex chromosomes alone, (2) a person's sex chromosomes can only be XX or XY, and that sex is strictly binary, and (3) there are only 2 gender categories: boy or girl.4, 5 These incorrect assumptions jeopardize the child's autonomy6 and contribute to the inflexible binary social model and dimorphic biological model that underlie bigotry, erasure, phobias, and discrimination against gender-diverse and sex-diverse people.7 Structural medical and social discrimination against transgender individuals is reflected in persistent health disparities.8 Furthermore, individuals with variations of sex characteristics and chromosomes are subject to the pathologization of benign variations, resulting in unnecessary nonconsensual medical procedures and trauma.9 In the following sections, we outline key questions that need further exploration and research. There are cases in which knowing the sex chromosomes or genitalia of the fetus is clinically relevant, and the cfDNA screening test was primarily designed to identify these variations early in pregnancy for planning for neonatal and childhood interventions and for parental decision-making on pregnancy management. For some X-linked genetic conditions, risk assessment may differ based on the sex chromosomes of the fetus. Some variations in sex characteristics may be identified if the fetal sex chromosomes and genitals appear to be incongruent. However, parents and HCPs regularly discuss the binary category in which the fetus is predicted to belong. Some parents express strong feelings of gender disappointment upon learning their child's presumed gender identity based on sex chromosome testing and struggle with these feelings throughout pregnancy and after their children are born. Parents' preference for fetal sex prediction includes a range of personal and social interests, including sex preference, room-sharing arrangements with siblings, future childbearing decisions, plans to host a gender reveal party, and desire to obtain infant clothing and supplies before birth that align with a socially-constructed gender paradigm.11 Parents' preferences regarding a child's gender-related social performance may evolve when provided with shared decision-making resources, such as education on the distinctions between sex and gender as well as implications of sex chromosome variations. Limited research suggests that parent-based interventions may increase familial support for queer youth.12 Communication from HCPs extends beyond live consultations or phone calls. Disclosing cfDNA results can occur asynchronously through secure messaging or electronic health record systems. There may be an important opportunity to enhance templated messages for cfDNA disclosures, ensuring the language is inclusive and informative for patients about the purpose and limitations of results when considering sex and gender. In part due to the 21st Century Cures Act, clinical laboratories are increasingly delivering results directly to patients, and clinicians are mandated to share all data regarding clinical laboratory results with patients. This is an opportunity to bring reporting practices into alignment with best practices for sex and gender inclusivity. For example, clinical laboratories can avoid using gendered colors (eg, pink for cfDNA results that suggest XX chromosomes) and use language that differentiates sex chromosomes, sex, and gender.13 Differences of sex development, variations in sex characteristics, and intersex traits are terms applied by pediatric or adult HCPs to individuals whose chromosomal, gonadal, or phenotypic sex characteristics do not align with the socially-constructed sex binary. The combined prevalence of this sex diversity may be around 1.7%.9 Preferences in terminology differ among individuals with variations of sex characteristics. Prenatal HCPs may receive little training regarding the purpose of cfDNA, cultural humility, counseling on the implications of diagnoses, and the health care needs of gender-diverse and sex-diverse people. Genetic conditions associated with sex chromosome aneuploidy are characterized by a wide phenotypic spectrum, much of which cannot be predicted by genetic testing results. Although phenotypes associated with sex chromosome aneuploidies vary, the presentation is generally milder than common autosomal trisomies, and many individuals with sex chromosome aneuploidies go undiagnosed.14 This leads to a historic lack of visibility of sex chromosome variations that further limits general understanding of these conditions. When counseling provided by a genetic specialist accompanies positive prenatal genetic testing, patients may make different decisions regarding pregnancy termination and continuation than without skilled counseling.15 Gender-diverse individuals experience their gender identity or expression beyond the binary gender framework of their sex assigned by their HCPs at birth (see Table 1). In 2022, about 0.5% of the adult population and 1.4% of the youth population in the United States identified as transgender.16 A rising proportion of young adults are nonbinary. Parents cannot know the gender of their child until the child is ready and able to disclose it, and this complicates impulses from parents and society to gender the child in the prenatal and early childhood periods. Children may express their gender identity in various ways—through style of dress, choice of toys, or pronouns—and gender identity and expression can be fluid and change over time. However, the openness of caregivers and other societal constraints can severely limit gender expression. Transgender youth disproportionately experience higher rates of mental health challenges and suicidality compared with cisgender youth due to societal discrimination. Parental acceptance and support are significantly associated with improved health outcomes among transgender youth.17, 18 Prenatal HCPs in the United States are guided by various professional societies, and these societies assert that parents have the fundamental right to self-determination and active participation in health care decisions. This model of autonomy includes the right of parents to access fetal sex prediction by cfDNA testing and obstetric ultrasound. Prenatal HCPs may feel they have no role in parents' decision-making process concerning fetal sex prediction. However, there are potential harms when parents hold a rigid view of the child's sex or gender or when the purpose of testing is poorly explained to the patients. In one study, transgender and gender-diverse participants recommended that HCPs acknowledge the possibility that a child could be gender diverse and use gender-inclusive language when talking about sex chromosomes with expectant parents.19 Informed consent is critical to ensure that parents have all the information they need to make the right decision for their family. Without research or guidance from professional societies to orient prenatal HCPs at this time, we suggest that this informed consent discussion should include: (1) an explanation of the purpose of the screening, namely the identification of chromosomal variation; (2) a review of the limits of the results, including the long term implications of the conflation of sex and gender on the future of childhood; and (3) alternatives to the screening. To our knowledge, a shared decision-making process related to fetal sex prediction, by cfDNA or ultrasound imaging, has not been discussed by professional societies that guide prenatal HCPs. Prenatal HCPs may feel overwhelmed by the number and complexity of the tasks they wish to provide during their limited time with parents and families. We acknowledge how difficult it is to provide patient-centered counseling and simultaneously assert that prenatal patient education about sex and gender is a critical component of cfDNA testing. Patients may vary in their awareness of gender and sex diversity and preparedness to engage in nuanced discussions of sex and gender. Given the politicization of transgender and gender-diverse identities, erasure of intersex variations, and the surge of transphobia in recent years, some patients may actively resist discussions of gender and sex diversity. In this scenario, it may be judicious to rely on written patient education materials. As HCPs, it is imperative to approach discussions with cultural humility and to be open to alternative concepts of sex and gender as mitigated by culture and language. Furthermore, the medical terminology used to describe the differences between sex chromosomes and sex characteristics may not be accessible to some patients based on medical literacy or may not be easily translatable to languages other than English. This requires careful navigation for providers and all discussions should balance the potentially competing principles of efficiency, informed consent, and justice. More research is needed on the most effective ways to scale such education. Sex chromosomes are one of several factors that influence a person's sex. HCPs can educate parents about the differences between sex chromosomes, primary and secondary sex characteristics, and gender. There are many people who exist outside of binary frameworks of sex and gender, such as transgender, gender-diverse, and intersex people. HCPs can normalize sex and gender diversity by acknowledging this in discussions of fetal sex information. Understand that a child's gender cannot be known until the child chooses to disclose it. HCPs can reinforce that gender development occurs over time and can be fluid over the course of a person's life. This commentary raises important questions and presents suggestions for promoting gender-expansive and intersex-inclusive perspectives when discussing fetal sex prediction during pregnancy. Prenatal HCPs and their care teams can play an important role in normalizing positive attitudes toward sex-diverse and gender-diverse children. We call for additional implementation research, clinical quality improvement, and health care systems change that (1) create inclusive and affirming prenatal care environments, (2) enhance support for gender-diverse and sex-diverse people, and (3) prioritize initiatives led by members of gender-diverse and sex-diverse communities. This work was fulfilled during Kimberly Zayhowski's time in the Genetic Counseling Fellowship in ReSearch Training (GC-FIRST) program through the University of Minnesota. Therefore, this publication was supported by the National Human Genome Research Institute of the National Institutes of Health under Award Number R25HG012322. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would like to thank Andrew Givens, MA, for his expertise and guidance in this project. H.L and T.L. served as co-first authors and contributed equally to the work. S.C. and K.Z. served as co-last authors and contributed equally to the work. Hannah Llorin is a recent employee and equity holder of 23andMe. The remaining authors have no conflicts of interest to disclose.