Implications for Prenatal Genetic Testing in the United States After the Reversal of Roe v Wade

Abstract

Prenatal genetic screening and diagnostic testing should be offered to every pregnant individual, with methods varying based on gestational age. Since Roe v Wade was overturned in June 2022, many states have implemented gestational age–based abortion restrictions. It is critical that reproductive health care professionals be aware of the interaction between the timing of genetic screening and diagnostic testing and the availability of legal abortion services in their state. We examined individual state abortion restrictions per publicly available data from The New York Times and the Guttmacher Institute and reviewed which genetic screening and diagnostic tests could be performed to provide results in time for individuals to decide whether to terminate their pregnancies legally in each state. As of December 11, 2022, 14 states have restrictions in which no diagnostic testing could be completed before gestational age–based cutoffs. Gestational age–based abortion restrictions may also influence a patient to favor chorionic villous sampling (CVS) over amniocentesis. There are two states, Florida and Arizona, where CVS would be feasible before the state's gestational age limit on abortion but amniocentesis would not. Both CVS and amniocentesis are feasible in 35 states, with legal challenges pending in 8 of the 35. Seven states specifically prohibit abortion for fetuses with genetic abnormalities. Clinicians may be placed in the suboptimal position of counseling patients with screening results alone before the gestational age–based ban in their state. There are several potential downstream consequences of gestational age–based termination restrictions for current genetic screening and testing paradigms, from adjustments to counseling options to potentially higher CVS procedure rates. Clinicians should be prepared for practice patterns to change to best serve patients in this evolving legal context.

In Brief

Prenatal genetic screening and diagnostic testing options vary greatly by gestational age, and practice patterns will be affected by gestational age–based abortion restrictions post-Roe.

Prenatal genetic screening and diagnostic testing results are used to optimize prenatal care and often influence delivery planning, allow coordination with neonatology, and provide patients with information that may influence whether they wish to terminate a pregnancy. The American College of Obstetricians and Gynecologists (ACOG) and the Society for Maternal-Fetal Medicine (SMFM) recommend that reproductive health care professionals offer these services to every pregnant individual.¹ Although many factors influence a patient’s decision to have an abortion, fetal genetic abnormalities are a common reason, particularly for terminations after the first trimester. Approximately 1 in every 150 live births has a chromosomal abnormality with an abnormal fetal phenotype.¹ A 2012 systematic review found that, when faced with a trisomy 21 diagnosis, up to 67% of patients in the United States chose to terminate their pregnancies.² These data have remained consistent since the introduction of noninvasive prenatal screening.^3–7 However, data on the incidence of abortions performed for fetal indication in the United States are limited, because this information is not collected at the state or national level.

In June 2022, the U.S. Supreme Court decision in Dobbs v Jackson Women’s Health Organization removed the constitutional right to an abortion, overturning Roe v Wade and marking a monumental decline in access to an already heavily restricted service. The result is that each state has the ability to legislate its own abortion policies, ranging from outright bans to no limitations, with many states implementing gestational age–based restrictions.^8,9

In this context, it is critical that reproductive health care professionals be aware of the interaction between the timing of genetic screening and diagnostic testing and the availability of legal abortion services in their state (Table 1). In this commentary, we briefly review prenatal genetic screening and diagnostic testing, systematically examine state-level abortion restrictions, and, as of December 11, 2022, provide a framework for how to approach genetic screening and testing within this evolving legislative landscape.

Table 1.: Status of Abortion Restrictions by State as of December 11, 2022, and Genetic Screening and Diagnostic Testing Available^*

GENETIC SCREENING AND DIAGNOSTIC TESTING

Prenatal genetic screening assesses a patient’s risk of carrying a fetus with a chromosomal abnormality. Multiple prenatal genetic screening tests are available. Depending on the clinical scenario and patient risk factors, ACOG and SMFM support multiple screening methods, including cell-free DNA (cfDNA), integrated screening, sequential stepwise screening, contingent screening, first-trimester screening, quad screening, and nuchal translucency screening alone.¹ A clinician's choice of a genetic screening modality can be influenced by many factors, including maternal age, gestational age at presentation, the number of fetuses, availability of a reliable nuchal translucency measurement, the screening test's sensitivity and limitations, the cost of screening, and obstetric and family history. The sequential and contingent screening models provide a risk classification to patients based on first-trimester screening test results, and patients at high risk can be offered additional diagnostic testing.¹

Noninvasive prenatal screening with cfDNA has risen in popularity and feasibility over the past decade, because trisomy 21 chromosomal aneuploidy can be identified with an up to 99% detection rate starting at 10 weeks of gestation.^1,6,10,11 The availability of noninvasive prenatal screening has been associated with a decrease in gestational age at the time of termination, with the median age decreasing from 19.0 weeks to 14.0 weeks (P<.001), although the median age at time of termination for patients with structural fetal abnormalities has remained unchanged.¹²

Diagnostic testing involves obtaining placental or fetal cells through chorionic villous sampling (CVS) or amniocentesis for direct genetic testing. The benefits of diagnostic genetic testing methods are multifold, ranging from reassuring patients who had an abnormal screening test with normal diagnostic results, to identifying disorders for which prenatal management and delivery planning may allow optimization of neonatal outcomes, to providing patients with more knowledge to make an informed decision regarding potential pregnancy termination. The confirmation of an abnormal genetic screening result is an important value of diagnostic testing, and diagnostic testing should be performed before pregnancy termination.¹

There are several laboratory techniques to analyze fetal samples, including karyotype, chromosomal microarray (CMA), and fluorescence in situ hybridization. Karyotype and CMA are both considered to be diagnostic tests to identify chromosomal aneuploidy. Chromosomal microarray also can identify copy number variants (CNVs) and is recommended when fetal structural anomalies are identified. Result turnaround times for both karyotype and CMA vary but take approximately 2 weeks. Fluorescence in situ hybridization can identify limited aneuploidies (trisomies 21, 18, and 13 and sex chromosomes) and can provide more rapid results—within 24–48 hours. However, it is still considered a screening test rather than a diagnostic test.³

Noninvasive prenatal screening and other screening methods are not a substitute for diagnostic testing. The American College of Obstetricians and Gynecologists and SMFM do not recommend screening for microdeletions with noninvasive prenatal screening.¹ There are limited data regarding how many patients choose to terminate a pregnancy after a positive cfDNA result alone. Both ACOG and SMFM recommend confirmatory diagnostic testing before termination of pregnancy, because the positive predictive value of genetic screening tests for an individual patient will vary significantly based on their pretest probability.^1,13 A retrospective cohort study by Dobson et al⁴ found that 62% of patients with abnormal cfDNA results opted for diagnostic testing, with a 67% termination rate overall. In their cohort, 19.6% of patients opted for termination without karyotype confirmation, although most of those pregnancies had an anomaly identified on ultrasonography.

A discussion regarding expanded carrier screening is outside the scope of this opinion, but it is available in both prepregnancy and prenatal care. Technological advances in DNA sequencing and analysis have allowed for the development of large screening panels for a large number of conditions at once.¹⁴ Other genetic testing options available in prepregnancy care include preimplantation genetic testing of embryos for aneuploidy and single gene mutations.¹⁵

PROPOSED FRAMEWORK FOR ADDRESSING PRENATAL GENETIC TESTING IN STATES WITH ABORTION RESTRICTIONS

Pregnancy termination is offered to patients as a standard component of posttest counseling for an abnormal genetic test result.^5,13,16 Individualized counseling is vital, because phenotypes and long-term neonatal outcomes vary greatly among genetic conditions, and the patients' values and beliefs inform this decision making. Limitations on abortion impede clinicians' abilities to provide this component of care. These restrictions vary widely across the country. As of December 11, 2022, 13 states ban all abortion, one state bans abortion after 6 weeks of gestation, two states ban abortion after 15 weeks, one state bans abortion after 18 weeks, one state bans abortion after 20 weeks, seven states ban abortion after 22 weeks, four states ban abortion after 24 weeks, and 22 states have abortion protections through viability (Table 1).⁸

The availability of genetic screening and diagnostic testing may not align with legal cutoffs for abortion care in states with gestational age–based restrictions. State-specific timing of bans and laws enforced were gathered from aggregate data from The New York Times' abortion-tracking tool as well as from the Guttmacher Institute (Table 1).^8,9 The compiled data were analyzed and interpreted to create categories by which to sort the states based on gestational age limits, active state laws limiting abortion access, and the likelihood of legislative changes that would further limit access, such as bans being temporarily blocked by courts. In the case of complete bans, states do not legally permit any pregnancies to be terminated outside of state-specific exceptions such as cases of rape, incest, or serious threat to maternal life. States with partial restrictions have bans in place ranging from 6 to 24 weeks of gestation and have laws that further restrict access to pregnancy termination, such as mandatory waiting periods between 24 and 72 hours before a patient can terminate a pregnancy after initially seeking care. States with threatened protection, such as Ohio, have pending legal challenges or judge-ordered holds on bans.⁸Protected states have existing language in their constitutions that protects abortion access or considers abortion to be a right granted to state constituents.

In Figure 1, we present a visual framework for how clinicians can quickly reference the relationship between genetic screening and diagnostic testing based on gestational age and current state-level abortion legislation. We also created a map with the online tool MapChart (mapchart.net) using aggregate data to demonstrate the regional variation in gestational age bans, as well as to highlight where CVS testing, but not amniocentesis, would be feasible before that state's gestational age ban (Fig. 2). Several screening options, such as the sequential screen, as well as the diagnostic testing option of amniocentesis would not result in time for a patient to seek an in-state abortion in the context of a 15-week gestational age ban, as is the case for Arizona and Florida (Fig. 2). Mandatory waiting periods (Table 1) and logistical challenges such as travel may further limit the window for receiving abortion care after an abnormal diagnostic test result.

Fig. 1.: Timeline with genetic screening, diagnostic testing, and termination options by gestational age. This timeline visually demonstrates which health care interventions are available by gestational age as well as how many states, including the District of Columbia, consider termination legal after a certain weeks of gestation based on active bans.⁸ The graphic is meant to provide a framework for clinicians to inform their approach to patient counseling based on gestational age and desired pregnancy outcomes. The timeframes for each intervention are based on American College of Obstetricians and Gynecologists' guidelines as outlined in ACOG Practice Bulletins No. 226 and No. 162.^1,3 *Fetal anatomy ultrasound screening is recommended between 18 and 22 weeks of gestation. Although it can be performed later in gestation for patients late to prenatal care, the images obtained may be suboptimal and limited. CVS, chorionic villus sampling.

Fig. 2.: Feasible confirmatory testing by state. We created a map adapted from The New York Times using our aggregate data to visually demonstrate the regional variation of gestational age bans, as well as to highlight where chorionic villous sampling (CVS) testing would be feasible before that state's gestational age ban, and amniocentesis would not be feasible, particularly in Florida or Arizona. We also indicated states that have pending legal challenges or judge-ordered holds on bans that could further affect available options for genetic screening within the constraints of a gestational age limit.^8,9 Mapchart.net is a tool that was used to digitally create this image. No information from this source was used in this figure or elsewhere.

Chorionic villous sampling can be offered at 10 weeks of gestation, and amniocentesis can be safely performed as early as 15 weeks. The rates of spontaneous miscarriage (3.6% vs 2.5%; average relative risk [RR] 1.41, 95% CI 1.00–1.98) and fetal limb anomalies (4.7% vs 2.7%; average RR 1.73, 95% CI 1.26–2.38) are higher when amniocentesis is performed before 15 weeks of gestation.^3,17–19 Several recent systematic reviews and meta-analyses reiterate the safety of both procedures regarding spontaneous pregnancy loss postprocedure and found no statistically significant difference when comparing transabdominal CVS with second-trimester amniocentesis (3.0% vs 3.9%; average RR 0.77, 95% CI 0.49–1.21).^18–20

Of the 13 states with total bans on abortion, five have specific legislation prohibiting abortion when the fetus is found to have an abnormality. Two additional states (North Dakota and Ohio) also prohibit abortion for a fetus with an abnormality (Table 2).²¹ Five additional states have proposed legislation to this end. Four states require patients with fetuses with abnormalities to receive perinatal hospice counseling. Conversely, several states with total bans have exceptions that allow for providing pregnancy termination for “lethal fetal abnormalities.” Such policies are challenging to interpret clinically. The legislative definitions of fetal abnormality and lethal fetal anomaly vary greatly by state, as summarized in Table 3, ranging from the more vague, “Fetus has been diagnosed with a lethal fetal anomaly” (Indiana), to the highly specific, “'Fatal fetal abnormality' meaning a terminal condition that, in reasonable medical judgment, regardless of the provision of life-saving medical treatment, is incompatible with life outside the womb and will result in death upon birth or imminently thereafter” (Florida).^22–27 Although many genetic diagnoses have profound effects on the quality of life and life expectancy of the fetus or neonate, they may not be immediately lethal at birth. These data are presented as collected by the Guttmacher Institute as well as individual state legislative websites and documents (Table 3).^21–27 For example, trisomy 13 is associated with profound anomalies that lead the condition to be considered to have a universally poor prognosis, with 90% of patients not surviving past 1 year.²⁸ However, under some of the definitions put forward by several states, it could be a condition considered to be compatible with life at birth.

Table 2.: States With Bans or Proposed Bans on Abortion for Fetal Indications*

Table 3.: Examples of Legal Definitions of Fetal Abnormality by State

POTENTIAL TRENDS IN CHORIONIC VILLOUS SAMPLING AND AMNIOCENTESIS RATES POST-ROE

Gestational age limitations on restrictions for abortion may influence a patient's choice of diagnostic testing. As of December 11, 2022, 14 states have restrictions under which no diagnostic testing could be completed in time for a patient to terminate the pregnancy legally. Thirty-four states and Washington, DC, permit abortion up to or exceeding gestational ages that would allow for both CVS and amniocentesis before obtaining a legal in-state abortion.⁹ One of these states, Utah, has an 18-week gestational age ban under which obtaining amniocentesis results before the gestational age limit may be challenging from a logistical perspective. Eight of these 35 states currently have pending legal challenges to statutes protecting abortion access. There are two states, Florida and Arizona, in which CVS alone would be feasible as a diagnostic test before that state's gestational age limit (Table 1, Fig. 2). This could become an issue of national importance if proposed legislation for a national 15-week ban is enacted.²⁹ Chorionic villous sampling may also be desirable over amniocentesis for patients who want more time for decision making or for patients who would have logistical challenges to obtaining an abortion, such as those who would need to travel for the procedure or those in states with long wait times.

Provision of CVS requires physicians who are adept at the procedure. In recent years, there has been a trend of obstetricians and maternal–fetal medicine physicians expressing a greater procedural comfort level with amniocentesis over CVS. In a national survey of maternal–fetal medicine fellows, only 38% reported feeling comfortable performing CVS procedures.³⁰ Trainees in the Northeast were more likely to report comfort with CVS procedures than their counterparts in the South and Midwest, two regions where abortion legislation is generally more restrictive and diagnostic testing at an earlier gestational age becomes of increased importance. This trend may potentially further exacerbate the regional inequities introduced by the Dobbs ruling.

PATIENT COUNSELING IN A POST-ROE LANDSCAPE

Regardless of abortion restrictions, all patients should be offered genetic screening and diagnostic testing. However, many reproductive health care professionals will now need to adapt their counseling to include information on what genetic tests are available before gestational age cutoffs for abortion. Clinicians may also have to adapt to using screening and diagnostic testing in nontraditional ways. For example, patients younger than age 35 years may opt for noninvasive prenatal screening to receive results at an earlier gestational age, even though they are at higher risk for a clinically significant CNV that would not be identified with noninvasive prenatal screening. This would have several consequences, including a higher false-positive rate for aneuploidy because of the patients’ young age, as well as potentially missing the opportunity to screen for other genetic abnormalities and clinically significant CNVs that may be identified with another screening paradigm, such as sequential screen.³¹ Other patients may elect to skip screening altogether and go straight to diagnostic testing. Diagnostic testing by CMA is required for diagnosis of CNVs, with procedures such as CVS or amniocentesis. Patients may choose to terminate a pregnancy based on screening results, such as the first part of a sequential screen alone, for fear that they may no longer be eligible for an abortion if they wait for diagnostic testing results. These circumstances can potentially create significant variance in practice across the country as clinicians navigate their states’ unique legal landscape.

Although our focus in this commentary was on prenatal genetic screening, many structural anomalies are also not identified until the detailed 20-week anatomy ultrasonogram. Several studies have found that, in the case of abortions performed for fetal indications, those for genetic indications were performed at earlier gestational ages than those for structural anomalies.^5,16 Early fetal anatomic assessment has been found to be beneficial for the diagnosis of structural abnormalities at less than 16 weeks of gestation.³² With the increasing evidence for the utility and performance of first-trimester anatomy ultrasonography over the past decade, clinicians and medical institutions may consider adopting first-trimester and early second-trimester anatomy ultrasonography protocols^33,34 to provide patients with more information before a gestational age ban in their state.

Abortion restrictions have further potential implications for the genetic testing available in prepregnancy care. The use of expanded carrier screening is complicated in states with early gestational age bans, because patients who screen positive as carriers may not receive CVS or amniocentesis diagnostic results in time to make a decision regarding pregnancy termination. Patients who screen positive in prepregnancy care may choose to pursue in vitro fertilization and preimplantation genetic testing for a single gene mutation to have a definitive fetal diagnosis before pregnancy. The use of personhood language in abortion bans also has a potential unintended consequence of restricting the provision and legality of fertility services such as in vitro fertilization, further compounding the limited options available to patients in states with more restrictive legislation.³⁵

CONCLUSIONS

After the reversal of Roe v Wade, the variation in abortion access among states has heightened. Gestational age–based abortion limitations could influence decisions about prenatal genetic screening and diagnostic testing for patients who would consider pregnancy termination.

Although our commentary highlights potential issues and provides an overall framework for how to approach genetic screening in this new context (Fig. 1), it is limited by the dynamic nature of state legislation and cannot be considered legal advice. Of note, our definitions of feasibility apply under optimal circumstances and do not consider the logistic limitations of wait times for abortion appointment scheduling nor the distances that patients may need to travel for care. There can also be unexpected and variable delays in laboratory processing and the return of genetic test results. Laboratory screening techniques with quicker turnaround times, such as fluorescence in situ hybridization, may also be increasingly used in addition to the standard karyotype or CMA in this current climate.

Clinicians should be aware of the relationships between gestational age–based termination restrictions and available genetic testing presented in this article when counseling patients on their reproductive options while being mindful of scheduling time for diagnostic procedures as well as processing time for return of genetic test results. Interventions that can be completed at earlier gestational ages, such as CVS and early fetal anatomy assessment, may be increasingly used in states with earlier gestational age bans. In addition, patients without the means to travel out of state for an abortion procedure may disproportionately receive substandard care, such as being forced to continue pregnancies they would otherwise choose to terminate. Clinicians may also be placed in the suboptimal position of counseling patients on the option of pregnancy termination based on screening tests alone.

Providing timely genetic testing results is essential to improve the equity of reproductive options for pregnant individuals throughout the United States. Choosing whether to terminate a pregnancy after receiving an abnormal genetic test result is a nuanced and personal decision. There are a high number of potential downstream consequences of gestational age–based termination restrictions for current genetic screening and testing paradigms, from adjustments to counseling options to potentially higher CVS procedure rates. Clinicians should be prepared for practice patterns to change to best serve patients in this evolving legal context.