In contrast to national recommendations, the majority of physicians in this sample would not offer any genetic testing/screening to a patient thinking of becoming pregnant for the first time and requesting medical advice. With increasing focus on integrating preconception care into clinical practice and public health, as well as recommendations that carrier testing ideally be performed before conception, should genetic testing have been offered more frequently to the described patients? A 2006 survey found that women prefer to receive preconception health information from their primary care providers, as opposed to other sources [14
]. This finding, coupled with growing knowledge of human genetics and rapid development of genetic tests for both single-gene and polygene disorders, suggests that primary care providers will increasingly need to make decisions regarding recommending preconception genetic screening to their patients.
There could be a number of reasons why family physicians in this study did not frequently choose to offer genetic screening. Inconsistency in primary care providers’ application of general preconception interventions has been attributed to inadequate provider education, lack of confidence that preconception education is valuable, a belief that women will ‘know’ to seek the care appropriate to their needs, and concerns over lack of reimbursement coverage for preconception visits [15
], all factors that likely apply to preconception genetic screening. As the proportion of family physicians offering genetic screening/testing to the black patient decreased and as time since residency increased, our results also suggest that recent training in genetics may increase physicians’ awareness and comfort offering these services. There was no significant association between offering genetic screening/testing and time since residency for the white patient scenario.
Though physicians did not frequently offer genetic screening/testing in response to the clinical vignette, we found that physicians were 1.5 times more likely to offer testing if they saw the vignette with the picture of the black patient (p = 0.0034). Additionally, race was the only factor listed by physicians as influencing their decisions to offer testing that was statistically significant between the 2 patients. These findings suggest that patient race is important to physicians when making decisions about preconception genetic testing and that decision making in this domain is influenced by patients’ physical characteristics. The clinicians’ use of physical appearance as a proxy for race is interesting to note, as current guidelines for carrier testing frequently describe populations using ethnicity or geographic ancestry rather than race. There is substantial debate in the field of human genetics about the relationship between race and genetic variation, namely whether self-identified race can serve as a proxy for an individual genetic background [16
]. Additionally, there can be heterogeneity between an individual's self-identified race, the race that healthcare providers may perceive them as identifying with, and their actual genetic background, which further complicates decision making in offering preconception genetic testing. Thus, questions of importance are what types of screening should have been offered to each patient and what factors should be weighed in making these decisions.
There were 4 disorders where significant differences were seen in genetic testing offers between the 2 patients: sickle cell disease, α-thalassemia, β-thalassemia, and cystic fibrosis. For physicians offering testing, screening for sickle cell disease was offered by over three quarters (78.5%) of the physicians who saw the black patient and less than 10% of the physicians who saw the white patient. Screening for α- and β-thalassemia was also offered more frequently by physicians who saw the black patient and offered testing (table ). Current ACOG Clinical Management Guidelines recommend offering carrier screening for the hemoglobinopathies (sickle cell disease and the thalassemias) to individuals of African, Southeast Asian, and Mediterranean descent [7
]. We believe that physicians who saw the black patient were more likely to interpret her physical features as indicating that she belonged to one of these high-risk groups than physicians who saw the white patient. Sickle cell screening was offered by the physicians who saw the black patient at a higher rate than any other type of genetic screening/testing. This suggests that physicians have knowledge of the prevalence of sickle cell disease individuals of African descent in the United States.
Screening for cystic fibrosis was offered by 49% of the physicians who saw the white patient and by 26% of the physicians who saw the black patient (table ). The 2001 ACOG recommendations were explicitly revised in 2005 to state that cystic fibrosis carrier screening should be offered when both partners are of Caucasian, European, or Ashkenazi Jewish ethnicity and that it is reasonable to offer cystic fibrosis carrier screening to all couples regardless of race or ethnicity as an alternative to selective screening [10
]. Similar to physicians who saw the black patient and subsequently offered testing for the hemoglobinopathies, it is likely that physicians who saw the white patient interpreted her physical features as indicating that she belonged to one of the high-risk groups for cystic fibrosis. The ACOG guidelines on cystic fibrosis screening are not static and have evolved since the implementation of ACOG-recommended population-based carrier screening in 2001. As this process is seen as a model for the successful integration of preventative molecular medicine into routine primary care [19
] it is of interest that cystic fibrosis screening was not offered at a higher rate to both patients.
As scientific knowledge about genetic diseases has grown, it has become apparent that there are differences in the incidence and prevalence of disease-causing mutations between population groups. Current carrier testing guidelines have struggled with defining population groups that will benefit from testing for specific mutations [9
], which is reflected in their use of multiple constructs to define high-risk groups, namely race, ethnicity, and ancestry [7
]. How these constructs correlate with genetic variation and their usefulness in clinical practice is a subject of heated debate [25
]. It has been established, though, that physical characteristics may correlate with race and ethnicity, but that they are weakly correlated proxies for these categories and do not reflect individual genetics [28
The ability of many genetic tests to reliably detect carriers can vary depending on the panel's composition and the individual's genetic history, as is the case with the current cystic fibrosis screening panel. This necessitates a reliable way to estimate individual genetic background in order to communicate relative risk information, which presents a significant challenge for physicians implementing existing genetic screening/testing guidelines, both in terms of targeting high-risk populations and providing relative risk information. Though better than estimates based on physical features, the weaknesses of self-identified race and ethnicity (SIRE) as a proxy for individual genetics raises questions of under which conditions, if any, SIRE is good enough for guiding clinical decisions. Recently, ancestry has been suggested as a potentially more accurate indicator of genetic background [29
] than SIRE, but our findings suggest that the concepts of geographic ancestry and descent may not resonate with physicians, who may base decisions on interpretations of physical features and common views of race. Addressing these issues now is essential to the integration of genetic risk assessment into preconception care, as the complexity of defining the correlation between individual genetics, physical features, and racial, ethnic, or ancestral group memberships will only increase as the United States population becomes more heterogeneous and the frequency of admixture continues to increase [11
Several limitations should be considered when interpreting these results. First, physicians offering genetic screening/testing in response to the clinical vignette offered amniocentesis and maternal serum α-fetal protein at the highest rates. Additionally, they listed age most frequently as a factor influencing their decision to offer testing. The physicians may have interpreted the scenario as asking what genetic screening/testing they would offer to the patient during that visit as well as in the future when she becomes pregnant. As maternal age is a risk factor for fetal chromosomal abnormalities assessed by amniocentesis and MSAP during pregnancy, offering these tests to the patient they were provided is consistent with current clinical recommendations and guidelines. It is also possible that physicians who responded to the clinical vignette misunderstood the patient's status, assuming she was pregnant. Such a misinterpretation of a scenario dealing with reproductive genetics is not entirely surprising. Prenatal care has been a mainstream intervention since the 1980s and is familiar to family physicians. Interventions that identify and modify risks for future pregnancies are less common to family physicians, with estimates showing that only 1 in 4 currently provides age-appropriate preconception care [1
Additionally, there were a number of factors relating to physician decision making that were not measured with this survey. While some conclusions can be drawn about physicians’ perceptions of the patient's race, ethnicity, and ancestry based on the types of tests they offered, these perceptions were not measured directly. Also, while factors that influenced physicians’ decisions to offer any genetic testing/screening are known, those that influenced specific testing offers were not measured. Variation may exist between factors that influence decisions to offer specific genetic tests. Exploring these differences will provide a more complete understanding of physician decision making in the context of preconception genetic testing. Finally, we do not know what additional information, if any, physicians would have wanted to collect from the patient before making decisions about offering genetic testing. It is possible that the number of physicians who would offer genetic screening/testing or the patterns of tests offered would change in a scenario where physicians were able to gather information from the patient in addition to that presented in the vignette.
Finally, our response rate of 10% was low. Physicians are known to be a difficult population to survey [31
], and the family physicians who completed the survey were representative when compared to the overall American Association of Family Physicians membership [13
]. Also our sample was not sufficiently diverse with respect to race and ethnicity to use physicians’ self-reported race/ethnicity as an analytic variable. It should be noted that our results only provide information about the preconception genetic screening practices of family physicians and not other primary care specialties. These areas should be explored further; it is possible that physicians’ decision making and preconception genetic screening behaviors may vary with respect to physicians’ self-identified race/ethnicity and specialty.
In conclusion, our results emphasize the need to widely convey the importance of preconception genetic screening as a component of preconception care to primary care providers. This should be recognized as an important public health issue [32
]. Additionally, only 28% of physicians who offered genetic screening/testing indicated that family history was a factor that influenced their decision. Our respondents may have interpreted the vignette to suggest that the patient's family history of genetic disorders was negative, but these findings still highlight that emphasis of family history as a powerful risk assessment tool and indicator for genetic testing is needed [33
]. Finally, our results also speak to the need to clarify existing guidelines for carrier screening, both in terms of how they describe targeted population groups and how they are interpreted and applied by physicians. Primary care providers need to understand the relationships between physical features, self-identified race and ethnicity, ancestry, and human genetic variation. Further research on how these concepts are used in clinical decision making, including the implications for use of preconception genetic screening, is needed and specific guidelines for preconception care should be developed.
The correlation between physical characteristics and individual genetics is weak at best. Successful application of targeted preconception carrier screening will depend on the development of quick and reliable ways to collect information from patients about their geographic ancestry. However, the United States population is becoming more diverse, and the use of ancestry to guide targeted preconception carrier screening is not the only public health strategy to consider. Universal preconception screening for certain conditions may be a better approach and would certainly be less challenging to implement from an educational standpoint than a strategy based on fluid definitions of race, ethnicity, and ancestral background. Additional research is needed to better understand the benefits and costs of offering all patients seeking preconception care a standard array of carrier screening tests.