Prenatal Screening Overview and Tests for Ongoing Fetal Surveillance*
*Fetal Assessment and Surveillance Protocols contributed by Sue-Ellen Abney-Roberts.
One of the greatest responsibilities and most important of challenges in obstetrics is properly advising would-be parents on their options for evaluating the potential health of their prospective offspring. There is a veritable maze of choices to navigate, and those involved in providing perinatal care need to be well-versed in all the possible selections. Although there are no absolute guarantees in terms of desired pregnancy outcomes, there are well-established professional standards for guiding obstetric care providers. This chapter combines early prenatal screening and diagnostic tests with later tests of fetal surveillance to provide a perspective of the ongoing duty to deliver the highest quality of care possible throughout pregnancy in any given practice or clinic. Failure to educate patients on their options, failure to refer for proper testing at the appropriate stage in pregnancy, and failure to provide appropriate interpretation and intervention create medical-legal minefields and serious ethical dilemmas.
» PRENATAL SCREENING OVERVIEW
Many women contemplating pregnancy may want to consider their chances for a normal pregnancy and risk for potential problems. For some women, it may come as a surprise that they are at greater risk for developing problems than anticipated. Some women do not know their family background or the background of their baby’s father until questions are prompted by their obstetric care providers. Regardless, all women should be offered prenatal screening and have the opportunity to make informed decisions. In fact, in some states, it is mandatory for obstetric care providers to offer certain tests to pregnant women and document their response. It is imperative that providers know their responsibilities based on their state(s) of employment.
The decision to undergo any type of prenatal screening requires that the prospective parents ask themselves, “What will this information mean to us during the course of our pregnancy?” There are personal, moral, religious, and ethical considerations inherent in these decisions. In short, there is no one right answer for every prospective parent. It can be an emotional experience to face the reality of a possible poor pregnancy outcome just at the time one is excited about being pregnant.
For many prospective parents with known risks, the potential for a poor outcome and definitive tests to ascertain the degree of risk have prompted them to undergo this step as part of their preconceptual planning. This is the ideal situation for every
prospective pregnancy. Individuals with known risks who want a thorough genetic assessment should be referred to a qualified genetic counselor to obtain the full benefits of such planning. However, providers of early prenatal care need to know the limitations and risks of recommended testing. Ideally, if not done preconceptually, such testing should be discussed prior to 10 weeks of a documented pregnancy for patients and their partners to have adequate time to make decisions on a course of action. Many of these testing options are time-specific and must be performed in prescribed gestational ranges to allow for other actions or testing to be performed.
prospective pregnancy. Individuals with known risks who want a thorough genetic assessment should be referred to a qualified genetic counselor to obtain the full benefits of such planning. However, providers of early prenatal care need to know the limitations and risks of recommended testing. Ideally, if not done preconceptually, such testing should be discussed prior to 10 weeks of a documented pregnancy for patients and their partners to have adequate time to make decisions on a course of action. Many of these testing options are time-specific and must be performed in prescribed gestational ranges to allow for other actions or testing to be performed.
The American Congress of Obstetricians and Gynecologists (ACOG) takes a primary role in establishing the standards for prenatal care in the United States. It is important that patients understand that although routine prenatal screening endorsed by all major perinatal organizations in the United States (such as evaluating blood type and Rh, blood cell counts, etc.) may offer clues to some potential fetal problems, family history may reveal the need for more detailed testing that is not within the scope of this chapter. Prenatal screening is a vast subject, and caution is warranted to make certain all of those providing prenatal care stay current in this area.
ACOG’s position on offering screening options to all women is very clear, and all facilities offering obstetric care in this country should have a clear understanding of acceptable standards. An important point in ACOG’s recommendations is that all patients need to understand the difference between a screening and a diagnostic test, and all obstetric care providers should have a standardized method of educating women on their options. ACOG recommends that all pregnant women should be offered screening for chromosomal abnormalities before 20 weeks of gestation. Additionally, ACOG suggests all pregnant women, regardless of their age, should be offered diagnostic invasive procedures. These invasive genetic studies involve retrieval of material via chorionic villi sampling or amniocentesis for direct study (ACOG Committee on Practice Bulletins, 2007). Obviously, financial considerations associated with these tests should be made known to patients because costs may be significant if they are not covered by insurance.
There are also less invasive tests that fall into two major categories. They are as follows:
The evaluation of definitive biochemical markers found in maternal serum that are linked to trisomy 18 (Edwards syndrome) and trisomy 21 (Down syndrome). These biochemical markers can be assessed with or without an ultrasound.
The evaluation of DNA in maternal circulation linked to trisomy 18, 21, and 13 (Patau syndrome) and sex chromosome abnormalities.
It is worth reviewing ACOG’s statement on what should be offered to all pregnant women regarding carrier screening:
Ethnic-specific, pan ethnic, and expanded carrier screening are acceptable strategies for prepregnancy and prenatal carrier screening. Each obstetrician-gynecologist or other
health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening. … All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. (Committee on Genetics, 2017)
health care provider or practice should establish a standard approach that is consistently offered to and discussed with each patient, ideally before pregnancy. After counseling, a patient may decline any or all carrier screening. … All patients who are considering pregnancy or are already pregnant, regardless of screening strategy and ethnicity, should be offered carrier screening for cystic fibrosis and spinal muscular atrophy, as well as a complete blood count and screening for thalassemias and hemoglobinopathies. (Committee on Genetics, 2017)
This section contains brief descriptions of the major tests available to all patients seeking prenatal screening. A full-range discussion of genetic screening is beyond the scope of this book. Couples with known, specific genetic histories should be referred to, and evaluated by, a qualified genetic counselor. Every facility providing care to women seeking pregnancy should have available resources and referral services to help them obtain the appropriate evaluation to aid patients in making informed decisions.
» TESTS FOR ONGOING FETAL SURVEILLANCE
The objective of fetal surveillance testing is twofold. First, the goal is to identify fetuses at risk for intrauterine demise or potential complications from lack of oxygen in utero. As well, the concomitant goal is to prevent an adverse outcome by early recognition and intervention of a developing hostile intrauterine environment. The following protocols cover the most common surveillance tests; a full discussion of all tests available in maternal-fetal medicine practice is beyond the scope of this book.
It is important to recognize the limitations of these tests. Although these well-known tests have been employed for over 40 years, no large, controlled randomized trials have been conducted to determine best timing or frequency to perform them nor has evaluation of their ability to improve pregnancy outcomes been robustly evaluated (Devoe, 2008). The tests’ acceptance is based on observational studies where high-risk pregnancies that underwent such testing had lower rates of fetal death. The current conventional wisdom on decisions on test choice, timing, and frequency “are based on expert opinion, clinical experiences with similar high risk pregnancies and community standards” (Signore & Spong, 2017, para. 30) and take into consideration gestational age, need for fetal biometry or heart rate monitoring, test availability, and cost, among other factors.
REFERENCES
American Congress of Obstetricians and Gynecologists Committee on Practice Bulletins. (2007). ACOG Practice Bulletin No. 77: Screening for fetal chromosomal abnormalities. Obstetrics & Gynecology, 109, 217-227.
Committee on Genetics. (2017). Committee Opinion No. 690: Carrier screening in the age of genomic medicine. Obstetrics & Gynecology, 129, e35-e40.
Devoe, L. D. (2008). Antenatal fetal assessment: Contraction stress test, nonstress test, vibroacoustic stimulation, amniotic fluid volume, biophysical profile, and modified biophysical profile—an overview. Seminars in Perinatology, 32(4), 242-252. doi:10.10531/jsemiperi.2008.o4.005
Signore, C., & Spong, C. (2017). Overview of antepartum fetal surveillance. Retrieved from http://www.uptodate.com/contents/overview-of-antepartum-fetal-surveillance
Early Prenatal Genetic Screening for Aneuploidy (Abnormal Chromosomes)
» Key Questions
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» Actions
STEP A: Chorionic Villus Sampling and Amniocentesis
Chorionic villus sampling (CVS) is a genetic test that detects chromosomal abnormalities such as Down syndrome as well as other genetic disorders such as trisomy 13, trisomy 18, cystic fibrosis, sickle cell disease, Tay-Sachs disease, and sex chromosome abnormalities including Turner syndrome and Klinefelter syndrome.
For the procedure, an ultrasound is performed to determine the position of the placenta. A small sample of cells is taken from projections on the placenta, called the chorionic villi, for genetic analysis. This is usually done between 11 and 12 weeks of pregnancy. Depending on where the placenta is lying down, the tissue sample is taken through either the cervix by a thin catheter or through the abdominal wall by a long needle. This test is more than 99% accurate in diagnosing these conditions. There is a slight risk of a miscarriage associated with a CVS, estimated to be between 1 in 100 and 1 in 200.
Because the test is done early in pregnancy, CVS cannot detect neural tube defects, such as spina bifida. If a patient elects to undergo CVS, she will usually be offered a
blood screening test, called an alpha-fetoprotein (AFP) test, in the second trimester to determine whether the fetus is at increased risk for neural tube defects.
blood screening test, called an alpha-fetoprotein (AFP) test, in the second trimester to determine whether the fetus is at increased risk for neural tube defects.
Amniocentesis, which is typically performed between 15 and 20 weeks of pregnancy, is another genetic test that detects chromosomal abnormalities. For this test, a small amount of amniotic fluid is taken from the amniotic sac surrounding the fetus for genetic analysis. This fluid is extracted by a long needle inserted through the uterus into the amniotic sac under ultrasound guidance. This test is used to detect the same disorders as CVS, as well as neural tube defects such as spina bifida, and is more than 99% accurate in diagnosing these conditions.
Neither CVS nor amniocentesis can detect certain birth defects such as heart malformations or a cleft lip or palate.
STEP B: First Trimester Combined Screening, Serum Integrated Screening, and the Quadruple Second Trimester Screen
First trimester screening is used to assess the developing fetus’s risk for certain chromosomal abnormalities, notably Down syndrome. This screening is done between weeks 11 and 13 6/7 of pregnancy. Combined screening is composed of three markers. It involves a blood test (for two of the markers) and a targeted ultrasound (the third marker) which measures the size of nuchal translucency, a luminous area in the posterior portion of the developing fetus’s neck.
This screen involves two steps. First, a sonogram is used to confirm the gestational age and to evaluate the skin thickness of the fetus’s neck (known as the nuchal translucency or NT). Other so-called “soft markers” (other ultrasound findings associated with Down syndrome) are sometimes evaluated. Second, a maternal blood test measures substances in the blood known as human chorionic gonadotropin (B-hCG) and pregnancy-associated plasma protein-A (PAPP-A). With first trimester screening, the detection rate is 90% for Down syndrome and 97% for trisomy 18 and 13, with a false-positive rate of 5%. This first trimester combined screening is a practical approach for pregnant women seeking the earliest, least invasive approach to screening.
Keep in mind that the results of these tests do not predict with absolute certainty whether or not the developing infant has a chromosomal problem. The results of the NT screening are then combined with those of the blood tests and the mother’s age to assess the risk for the fetus. The results are reported in the form of a ratio that expresses the chance of the fetus having a chromosomal abnormality. The detection rate for the first trimester combined screening is approximately 90%. There is a 5% false-positive rate. Other tests are needed to confirm or rule out a diagnosis.
It is important to remember that this early screening does not evaluate for spinal cord defects. A plain AFP test may be offered in the second trimester for this. A level II ultrasound at 18 to 20 weeks is also often offered with this testing and is considered the acceptable standard of care by most obstetric providers.
If nuchal translucency screening is not available in the first trimester but laboratory services are available, the serum integrated test may be offered. This combines the four blood tests described later in the second trimester quadruple test with the first trimester PAPP-A test. This is not the ideal choice.
The quadruple screening test in the best choice for a woman who has delayed prenatal screening until the second trimester. Quad screening is a blood test that is done between 15 and 22 weeks of pregnancy to screen for Down syndrome, trisomy 18, and neural tube defects. This test measures AFP, which is a substance found in amniotic fluid, fetal blood, and the mother’s blood; estriol, which is a hormone made by the placenta and the liver of the fetus; hCG, which is hormone made by the placenta; and inhibin A, a hormone that is also produced by the placenta. An elevated screening score may indicate neural tube defects (opening in the spine), and a lower screening score may indicate Down syndrome. This screening test is not as accurate as the first trimester screening. The quad screen detects Down syndrome in 81% of cases. The AFP test detects neural tube defects in 80% of cases. Because levels of the substances measured change during pregnancy, it is important to ensure that the gestational age is accurate.
» Patient Education
There is a window of opportunity for many of these tests. Evaluating gestational age is important for accurate screening and testing.
Important Reminder: In cases where patients decline carrier screening testing, it is especially important to make certain they have received the usual information regarding these disorders in alignment with your facility’s standard of care and based on ACOG recommendations. Before starting any conversation about genetic screening or testing, it may be important to ask the woman and her partner how important it is to know this information and whether the information will change the course of their course of action. Pregnant women and their partners fall along a continuum from not needing to know the information because it would not change the course of a pregnancy to needing to know with absolute certainty the information because they might terminate the pregnancy and knowing that these tests have small risks associated with them. There is no one right decision. People have different feelings about what risks are acceptable.
Early Prenatal Screening for Carrier Status
ACOG’s recommendations for carrier screening have been described in the overview for this chapter. Generally, carrier screening is usually carried out for the following categories of disorders:
Cystic fibrosis
History of fragile X syndrome (or undiagnosed intellectual disability, developmental delay in either gender, other familial reports of intellectual or developmental delay and sometimes even undocumented family reports of suspected autism)
Spinal muscular atrophy disorders (such as Duchenne and Becker muscular dystrophy, Prader-Willi syndrome, Zellweger syndrome, and many others)
Ashkenazi Jewish population (Tay-Sachs is the usual associated disorder with this ethnic group, but other disorders are not uncommon, such as Canavan disease, cystic fibrosis, and familial dysautonomia. Extended panels for diagnosis of other disorders are available. It is important to remember that there are other ethnic groups with clusters of carrier disorders.)
Hemoglobinopathies (There are essentially two classifications of these disorders: [1] the thalassemias [which are disorders of decreased globin chain production] and [2] hemoglobin structural variants [specifically, hemoglobin S, hemoglobin C]; remember that a combination of the two is also possible. Previously, the offer of screening for these disorders was based on established ethnicity. However, due to the wide diversity of multiethnic persons in today’s population in the United States, thorough family history of both parents is needed to make the most accurate assessment of need for testing.)
» Key Questions
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STEP A: Desires Carrier Screening
If the patient has knowledge of a specific known carrier disorder for either her or her baby’s father, the following information should be gathered:
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