Availability of genetic testing and screening options has advanced significantly, and increasingly becoming included in obstetric (OB) and gynecologic practices. Advanced technologies have caused genetic screening to become more complex. Genetic screening is recommended for all pregnant patients and is routinely offered in OBs and gynecology. Genetic screening may increase emotional distress, including anxiety and depression. Patients with a negative result have a reduction in anxiety. Patients with a positive screen require additional support. Incorporating a standard practice of clear, objective, non-directive counseling pre- and post-test, with appropriate time to allow for patient decision-making reduces emotional distress.
Key points
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Genetic testing causes psychosocial risk of anxiety and emotional distress.
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Informing a patient about options for testing, indications, limitations, and costs reduces anxiety.
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Social, cultural beliefs, and practices influence patients’ decision-making.
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Positive carriers of BRCA 1/2 balance personal values with a complex set of medical recommendations and prevention strategies. Support for decision-making reduces the emotional and cancer-related distress.
Introduction
Availability of genetic testing and screening options has advanced significantly and increasingly becoming a part of obstetric (OB) and gynecologic practices. Screening for genetic conditions in reproductive age women, may include screening for hereditary genetic conditions that may inform risk for future or present pregnancies; screening for aneuploidy or other chromosomal abnormalities, structural fetal abnormalities in a current pregnancy; or screening for risk of hereditary cancer syndrome due to a new cancer diagnosis or family history. With advanced technologies, genetic screening has become more complex.
Genetic screening requires counseling prior to the test to address the test, benefits and limitations, reliability of results, and an opportunity for the patient to pose questions pertaining to meaning of positive results. Anxiety and worry commonly occur in women addressing screening options.
Although screening allows for detailed preparation for a pregnancy or about the fetus early in pregnancy, or about hereditary risk, it can also elicit emotional distress, anxiety, worry, feelings of guilt, or anger. Women with a high-risk assessment for hereditary cancer, experience increased stress, with questions about undergoing testing to reduce feelings of uncertainty, fears about developing cancer and how severe, questions regarding future reproductive planning, and prevention strategies. Counseling about risks and testing options should be in stages and include support for decision-making.
Given genetic counseling has become a significant practice in OB and gynecology, understanding the psychosocial aspects of screening may help reduce the stresses of decision-making and follow-up.
Prenatal genetic screening has become more complex
Pregnancy is a life changing event in a couple’s life. Early in the prenatal period, it is natural to have questions about expectations. Some are balancing the emotional toll of a new pregnancy along with other life stressors, with unanswered questions. Additionally, there are unanswered questions regarding prenatal genetic screening options. Especially for first-time pregnant patients undergoing a family and genetic history, learning about inherited genetic risks, maternal age-related risks and the prevalence of common genetic conditions, or undergoing an OB ultrasound, and anxiety can commonly occur.
Chromosomal abnormalities occur in approximately 1 in 150 live births. They occur at any age but increase in incidence as maternal age increases. The most common chromosomal aneuploidy in liveborn infants is Trisomy 21 (Down Syndrome) with a prevalence of approximately 1/700 live births. Trisomy 18 (Edward syndrome) is the second most common live birth autosomal trisomy. Trisomy 13 (Patau syndrome) is approximately 1/6000 at birth. Sex chromosome abnormalities can also be present at birth. Now with chromosomal microarray analysis, an array based cytogenetic technique can be used with chorionic villus sampling (CVS) or amniocentesis, microdeletions and duplications, known as copy number variants, can be identified. These occur in approximately 0.4% of pregnancies.
Significant advances in prenatal genetic screening and diagnosis have increased the possible options for screening, which has become more complex. Fetal structural anomaly and chromosomal prenatal genetic screening is increasingly available and considered as a standard option.
Screening options in the first trimester include
Non-invasive prenatal testing (NIPT) for common chromosomal abnormalities, including sex aneuploidy, is offered after 9 w gestation. This is called cell-free DNA screening. The fetal component of cell-free DNA (fetal fraction) is derived from placental trophoblasts released into maternal circulation from cells undergoing programmed cell death. The amount of fetal fraction is affected by factors including but not limited to gestational age, maternal body mass index, maternal medications, maternal race, aneuploidy status, fetal or maternal mosaicism, and singleton or multiple gestation. Even though cell-free DNA screening is the most sensitive and specific screening test for common fetal aneuploidies, false positive and false negative or a no-call test result may occur. The no-call test results increase the risk for chromosomal abnormalities.
Screening by incorporating serum analytes are utilized in lower resourced communities. Combined first- and second-trimester screening tests using serum analytes, nuchal translucency or both, integrated serum screening, and sequential and contingent screening have limitations in the timing of the results until the second trimester, or potential for no results if the second blood draw is not completed in the time designated. Each test offers varying levels of performance characteristics, and each has relative advantages, risks, and limitations.
Ultrasound screening in the first trimester (including nuchal translucency screening), second trimester ultrasound for fetal structural defects, and diagnostic testing (CVS, amniocentesis) options should be offered to all pregnant patients with pre and post counseling.
The American College of Obstetricians and Gynecologists recommends all women be offered prenatal screening for aneuploidy early in pregnancy. Counseling should be non-directive, objective, allowing sufficient time to understand, and make informed decisions regarding testing. Once counseled and offered options, every patient has the right to accept or decline prenatal genetic screening or diagnostic screening.
Screening and testing provide women and their families more understanding of their health or the health of the fetus. Prenatal screening allows for early intervention, opportunity for education. Informed consent is critical to informing women about the benefits and risks to screening and testing. Women can decide what they will do with the results. Most counseling for pre- and post-tests is offered through the patient’s OB provider. Patients with elevated risks can be referred to genetic counselors or maternal fetal medicine specialists.
Prenatal screening options are complex, with benefits and limitations. Patients may understandably have increased anxiety or worry during the decision-making process and waiting for results. Clinicians play a significant role in reducing anxiety and stress during pre-test counseling and post follow-up. As prenatal genetic screening becomes standard-of-care, the risk of limiting pre- and post-test counseling, allowing adequate time for answering questions, may increase emotional distress.
Prenatal genetic screening: psychosocial impact
Studies demonstrate elevated risks of anxiety at testing. Anxiety peaks after a positive result, and normalizes after a negative result, with no evidence of residual anxiety.
Lewis and colleagues found a third of women had elevated states of anxiety at testing. Women at high risk for Down syndrome were found to have significantly higher levels than those with medium risk. In the high-risk category, women who opted for invasive testing and NIPT were significantly more anxious than women who opted for NIPT only. In a small minority (including both medium- and high-risk for down syndrome screening [DSS]), anxiety scores remained high even after negative NIPT results.
Of women offered NIPT in the nationwide Dutch TRIDENT study, the majority were glad to have been offered NIPT as an alternative to invasive testing. High-risk pregnant women were satisfied and reassured. Most perceived the waiting time for NIPT results (mean: 15 d, range 5 – 32) as too long. Most women with normal NIPT results felt reassured and anxiety levels were significantly lower after receiving a normal result versus at initial intake. Women with inadequate health literacy or a medical history (eg, previous child with trisomy) experienced significantly higher post-test-result anxiety, indicating they might benefit from extra information, and/or guidance when receiving NIPT results.
An abnormal screening result is an unwelcomed disruption in any pregnancy. Studies have found increased anxiety following a positive result and the resultant burdensome decision-making. , Women worry about the health of the fetus, benefits and risks of diagnostic procedures, including risk of loss, and what to do if an abnormal result. A high-risk screening result made some women ‘withhold the pregnancy’ as if they were not pregnant. Others suggested that high-risk women created a distance to the pregnancy as a defense mechanism.
In a systematic review of women’s experiences with NIPT, most received their pre-test counseling from clinicians. Factors such as accuracy, risks, and timing of results were critical in decision-making. Perceived lack of clinician knowledge, appointment time constraints contributed to dissatisfaction with counseling. Women sought information from additional sources, such as online discussion groups and blogs, friends, and family with experience of NIPT, to learn about the test. Some women felt that too much information was received at once. Patients with information overload described it as hindering their ability to contextualize and prioritize information for decision-making. ,
Women who were provided pre-test counseling regarding benefits, risks, and alternate testing options, felt they made informed decisions and had positive attitudes. Facilitating informed decision making with non-directive counseling and access to information regarding various options for prenatal screening and access to additional specialists, such as genetic counselors, maternal fetal medicine specialists, and reduces anxiety.
Positive screen: psychosocial aspects
Increased anxiety and unanswered questions are common with positive screen results. Vuorenlehto and colleagues found that the majority of patients with positive results experienced the upcoming examinations with remarkable distress. Almost half of the women felt increased anxiety about their pregnancy, even if nothing abnormal was found, especially for those who had not considered the possibility of a positive screen. Many desired more information about the risk factors for the chromosomal abnormality and wanted more details regarding further diagnostic options. Searching the internet for information was common, even if they did not mention this to their clinicians.
Mirtabar and colleagues identified 3 reactions in women in whom fetal anomalies were diagnosed: concealment, extreme fear and anxiety, and denial. The primary causes for worries included challenges with spouse and relatives, medical diagnosis processes, previous unpleasant experiences, physical and mental problems, financial worries, and misinformation. Insufficient and wrong information from cyberspace, the internet, and uninformed people increased worries and “physician’s uncertainty”. Emotion-oriented coping style was the most common release mechanism. This included sharing the problem with relatives, trust in the doctor’s diagnosis, and trust in God.
A qualitative study of the experiences of pregnant couples following high-risk prenatal screen results identified a range of practical and emotional management strategies couples employed to cope with worry and uncertainty while awaiting results.
Coping strategies included withdrawing from activities to address the situation, gathering information and seeking support; infusing the uncertain situation with positive, reassuring interpretations. Although the couples were initially shocked or sad with the results, they were not unprepared to deal with worry and uncertainty.
Preparing patients for the possibility of receiving positive results with the possibility of further testing and discussions about options, including personal values about pregnancy termination as part of the pre-test counseling, reduces anxiety. Danish and British studies reported that women had less decisional conflict the better they were informed. ,
Many factors influence women’s decision-making regarding positive results. Ethnographic studies on women’s concerns and experiences in prenatal screening highlight decision-making are influenced by religious, economic, social, and cultural factors. , Patients described the information provided was not sufficient and sought additional counseling from family or religious counselors prior to making decisions. Cost of prenatal diagnosis testing is a significant factor in anxiety and stress in the decision-making.
Latina immigrant populations describe social and cultural networks as powerful influences when making decisions regarding prenatal testing. Participants described their faith was an important part of decision-making. Also, fear that amniocentesis might lead to miscarriage was highly weighted.
The diagnosis of structural or chromosomal abnormalities increases the risk for perinatal mental health difficulties, including anxiety, depression, and traumatic stress in expectant parents. Couples may experience emotional challenges including uncertainty about the diagnosis/prognosis, anticipated neonatal course, fears of fetal or neonatal demise, loss of an uncomplicated pregnancy and postpartum course, and disruption of family roles due to medical care-related activities and restrictions. This may be added to other life stressors.
Additional expertise is recommended to help patients address the psychosocial health risks whether patients are considering terminating or continuing the pregnancy. Psychotherapy can aid in screening and assessment, incorporating coping strategies, relaxation techniques, traumatic stress, and depression reduction following an abnormal fetal diagnosis. Multi-disciplinary fetal care centers incorporate additional expertise to assist preparing for birth and a complicated neonatal course, encouragement to discuss thoughts, and feelings as a family and to address psychologic support for palliative care.
An additional stressor in decision-making regarding abnormal prenatal genetic screening is the limitations for pregnancy termination in some states. The reversal of Roe versus Wade has caused some states becoming more restrictive in providing termination. Gestational age-based abortion limitations could influence decisions about prenatal screening and diagnostic testing, especially for patients who would consider pregnancy termination. Future studies on psychosocial effects of this limitation are needed to understand the mental health impact on patients.
Genetic carrier screening
Traditionally, carrier screening was recommended for ethnic populations considered at-risk for specific disorders. Today, genetic carrier screening is recommended for all pregnant patients to determine their risk for having a child with a recessive genetic condition. Screening tools include targeted screening or expanded carrier screening. Various panels test between 5 to several hundred conditions.
Ideally, carrier screening is performed pre-pregnancy, to provide time for understanding reproductive risks, and allow consideration of reproductive options, including whether to conceive, or use advanced reproductive technologies, such as preimplantation genetic diagnosis or donor gametes.
A full, comprehensive family and genetic history of the patient and partner helps assess inherited risks, including ethnic background, consanguinity, and family history of genetic conditions. Before any carrier testing, pre-test counseling and informed consent are necessary. If both partners are carriers of a genetic condition, genetic counseling, and prenatal diagnosis should be offered to provide information that can help guide their pregnancy planning.
Many studies have investigated the short- and long-term psychosocial effects of carrier screening. In general, carrier screening with negative results has little psychosocial impact.
Individuals with increased risk experienced a higher range of emotions.
A Dutch study described high-risk individuals (with a priori increased risk of being a carrier or carrier couple) and pregnant women as having significantly higher anxiety before receiving screening results versus the general risk and non-pregnant individuals
A systematic review regarding patient perspectives on carrier screening identified ‘sorrow’ and ‘great sadness’, in individuals identified as increased risk, when undergoing further testing and making decisions about a current pregnancy, and long-term when working toward a healthy pregnancy. Grief was evident across increased risk couples due to tangible losses like termination of affected pregnancies and fetal losses, and the expected pregnancy journey. Grief was experienced with prenatal diagnosis leading to termination of an affected pregnancy, undertaking in vitro fertilization/pre-implantation genetic diagnosis with unsuccessful cycles, loss of planned future children.
Rothwell and colleagues interviewed women with a positive expanded carrier screen during pregnancy. Most confused the results with other prenatal screening tests. The way the results were discussed varied greatly, and influenced participants’ thoughts about reproductive decisions causing a range of emotional uncertainty. They suggested that educational interventions are needed to improve maternal understanding of positive carrier screening results.
Cultural beliefs and practices influence uptake of information and understanding of genetic disease. A systematic review of ethical, social, and cultural issues related to clinical genetic testing and counseling in low- and middle-income countries with limited resources and training, recognized psychosocial effects of genetic screening due to patients denying risk, contributing to an unwillingness to undergo screening. Fear and anxiety were associated with genetic screening, particularly with implications of a positive result, and the psychologic distress affecting extended family members. Social stigma and religious principles posed barriers to acceptability and utilization of genetic services. Patients were encouraged to inform relatives of the risk of inherited diseases. The social stigma posed barriers to informing relatives. Clinicians can directly speak about the misconceptions to assuage guilt. These findings apply to high income countries with high immigration influx. It is valuable to incorporate a careful approach, grounded in ethical and cultural understanding, to address the unique needs of these patient populations.
McAllister and colleagues used focus group interviews to identify emotional effects of genetic disease. Eight emotional effects were identified: anxiety, worry about risks to children, guilt, anger, uncertainty, sadness and grief, depression, and redemptive adjustment. Factors that could modify the emotional effects were variability of genetic diseases, and lack of diagnosis/inappropriate care. Despite many negative effects of genetic disease being identified, redemptive adjustment is possible where a genetic condition is present in a family. Interventions designed to adjust the modifying conditions and manage the emotional effects may facilitate adjustment and improve patient outcomes.
Most studies focused on psychosocial effects of genetic carrier screening, found anxiety, emotional distress, and depression. Genetic testing in impact of other diseases depends on perceived risk, severity, and controllability related to specific categories of disease, on the genetic test predictability or nature of the disease, and on the presence or absence of treatments.
Hereditary cancer syndrome screening
Hereditary cancer syndrome is a genetic predisposition to certain cancers, with onset at early age, caused by inherited pathogenic variants in 1 or more genes. The most common female hereditary cancer syndromes include breast and ovarian cancer syndrome, Lynch syndrome, Li-Fraumeni syndrome, Cowden syndrome, Peutz-Jeghers syndrome, and hereditary diffuse gastric cancer.
Inheritance of BRCA1/2 mutations or pathogenic variants increases risks of several cancers, especially breast and ovary. Gene mutations are also associated with hereditary breast and ovarian cancer syndromes. Over 60% of women with BRCA1/2 mutations will develop breast cancer during their lifetime versus 13% in the general population. A multimodal approach to breast and ovarian cancer risk reduction and early detection should begin in young age, utilizing surveillance, chemoprevention, surgery, and lifestyle changes.
A meta-analysis of 20 studies analyzed emotional distress and cancer-specific distress for patients at risk for hereditary cancer syndromes. Among mutation carriers, general and carrier specific distress levels increased slightly, but returned to pre-test levels over time. Changes in distress observed shortly after disclosure of test results frequently differed from the distress seen subsequently. For most, BRCA1/2 testing did not dramatically increase distress.
People pursuing predictive genetic testing believe their risk for developing or passing on the disorder is high, and undergo testing to reduce feelings of uncertainty, aid decisions about reproduction, and understand risks to family members. Women at high-risk for hereditary cancer syndrome often experience anxiety, anger, depression, or guilt. , They may face uncertainty and stress about testing, timing of developing breast, or ovarian cancer, severity of their disease, and effectiveness of prevention strategies. Genetic testing results have implications for the health of family members, personal relationships, future plans including reproductive decisions, and insurance availability and discrimination.
Noncarriers are found to experience decreased distress from before testing through receiving the results. , Distress increased for those receiving the positive mutation result. Schlich and colleagues assessed psychologic distress during the first year after diagnosis in breast cancer patients when offered genetic counseling at the start of adjuvant radiotherapy. Patients actively approached for genetic counseling showed same long-term distress than patients not eligible for such counseling. Predictors for long-term high distress or increase in distress over time were pre-existing high distress and low quality-of-life, having children, and having no family members with breast cancer. Thus, breast cancer patients can be systematically screened and offered genetic counseling during adjuvant radiotherapy, without imposing extra psychologic burden. Patients vulnerable to long-term high distress already displayed high distress shortly after diagnosis, with no influence of the medical treatment on their level of distress at long-term.
The United States Preventive Services Task Force reviewed 28 studies indicating genetic counseling is associated with reduced breast cancer worry, anxiety, and depression; increased understanding of risk; and decreased intention for testing. Twenty studies indicated breast cancer worry and anxiety were higher after testing for women with positive results and lower for others, and understanding of risk was higher.
Patients with positive results of genetic testing for BRCA1/2 mutations reported increased worry about cancer risk after learning the results. None regretted the decision to undergo genetic testing. Patients expressed an interest in attending support groups in addition to regular follow-up with the genetic counseling team to get updates on new research studies or treatments, and to have their psychologic well-being assessed.
Among women undergoing genetic counseling and testing, baseline distress is shown as one of the strongest predictors of distress experienced post-genetic counseling and/or post-genetic testing , Levels of distress are associated with genetic testing decision-making, risk reduction decisions, and screening adherence.
Anxiety after receiving the results was significantly higher than depression. Having a prior diagnosis of cancer and presenting with a baseline risk of anxiety and depression were associated with clinically significant anxiety at 1 y.
Patients without cancer and a deleterious BRCA1/2 mutation seek balance between knowing versus acting on the cancer risk. The cycle of complex decisions increases after a positive result. For some, the balancing act is ongoing, considering future personal and medical values, compounded by the complexity of the medical recommendations. Underhill and colleagues stated it is not only a challenge to understand personal cancer risk, but to be placed in a situation where it is important to truly understand oneself, needs and values, and make decisions that are not currently important but have future impact. These decisions are dynamic and change over time. Decision-making support is important to have available at different levels of care.
Long-Term Psychologic Impact of Carrying a BRCA1/2 Mutation and Prophylactic Surgery
van Ostrom showed a significant increase in anxiety and depression from 1 to 5 y follow-up. Carriers after prophylactic surgery (21/23) had a less favorable body image than noncarriers and 70% reported changes in sexual relationships. A major psychologic benefit of prophylactic surgery was reduction in the fear of developing cancer. Predictors of long-term distress were hereditary cancer-related distress at blood sampling, having young children, and having lost a relative to breast/ovarian cancer. Long-term distress was also associated with less open communication about the test result within the family, changes in relationships with relatives, doubting the validity of the test result, and higher risk perception.
In a prospective cohort study up to 8 mo after the test results, baseline anxiety levels in women opting for risk-reduction mastectomy were high but decreased over time. They increased in women choosing intensified breast surveillance (IBS). Choosing IBS may benefit from additional medical and psychologic counseling.
Overall, BRCA1/2 testing has emotional consequences, but for negative carriers this appears to reduce overtime. For positive carriers, balancing personal values with a complex set of medical recommendations increases stress and anxiety.
For patients with BRCA1/2 mutations, support for decision-making to reduce risks through various modalities (genetic counseling, support groups, and online support) should be provided at various times in their journey. This reduces the emotional and cancer-related distress.
Summary
Genetic testing for women of reproductive age may be for various purposes, including identifying fetal aneuploidy or chromosomal risk, identifying carrier risk of disease, or cancer risk. Offering genetic testing is not without psychosocial risk, leading to anxiety a range of emotional distress.
Obstetrician Gynecologists are recommended to have a standard practice for genetic testing so that similar testing strategies are made available to all patients, allowing time for appropriate counseling to patients. Expectations regarding genetic testing, including significance of the test, limitations, and options for diagnostic testing should be discussed with patients before a test is offered. Pre- and post-test counseling should be performed in a clear, objective, and non-directive fashion, allowing time for patients to understand the information and make informed decisions.
For patients with a positive screen, empathetic communication reduces stress and anxiety.
For patients with a positive fetal anomaly or positive chromosomal abnormality, additional counseling and support regarding diagnosis, prognosis and further evaluation and management should be provided in a clear, objective, and non-directive manner.
For patients with hereditary cancer risk additional decision support is recommended for patients navigating medical recommendations and prevention strategies to reduce risk.
For pregnant women, an additional factor adding to the psychosocial stress to personal decision-making and counseling is the increasing limited options for termination of a pregnancy for patients with abnormal diagnostic results. Since the Supreme Court decision overturned Roe versus Wade, many states have implemented gestational-age based abortion restrictions. Future studies are warranted to understand the impact of the reversal of Roe v. Wade on the psychosocial stresses of genetic testing.
Clinics care points
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Genetic screening increases anxiety and worry. The more informed a patient is about options for testing, benefits, limitations, and costs, reduces anxiety.
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Pre-test and post-test counseling is required for genetic screening for reproductive age women. It should be nondirective, clear, and objective. Allocating adequate time to address patient questions reduces anxiety and stressors.
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Social, cultural beliefs, and practices influence patient’s decision-making.
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Counseling may need to address short- and long-term grief for high-risk patients with prior pregnancy experiences resulting in loss.
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BRCA1/2 testing has emotional consequences, but reduces over time. For positive carriers, balancing personal values with a complex set of medical recommendations increases stress and anxiety. Support for decision-making, through various modalities (genetic counseling, support groups, and online support), available at various times in their journey to reduce risks, decreases the emotional and cancer-related distress.
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