Prenatal maternal serum screening in midtrimester (AFP, estriol, hCG, and inhibin-A) is without doubt the most misunderstood test routinely offered to women during pregnancy. Misconceptions and uncertainty abound on the parts of both patients and providers related to necessity, interpretation, and potential significance of this test. As a result, this test is vastly underused, even though it is recommended as a standard of care by the American College of Obstetricians and Gynecologists, and liability exists when not offering screening, when the case for screening is offered in a biased fashion, and when inadequately documenting that the test has been offered and declined.
Summarized below are comments, observations, and responses to common questions that have helped me to improve patient (and provider) acceptance of this valuable screening tool during my 20-odd years in the practice of maternal-fetal medicine:
1. What is Prenatal Maternal Serum Screening?
Maternal serum screening is a blood test done on the mother that measures several chemicals that are either unique to, or associated with, pregnancy. It is most accurate when done between 16 and 20 weeks’ of pregnancy.
2. What is the primary purpose of the test?
The test is performed to help identify babies at risk for neural tube defects (openings in the spinal column or head) and other open body wall defects (most commonly abdominal wall) as well as certain chromosomal abnormalities, such as trisomy 21 (Down syndrome) and trisomy 18. These latter abnormalities are usually unexpected, may occur at any age, and typically do not run in families.
3. Are there other benefits of the test?
Additional fetal abnormalities and pregnancies at risk for complications of “placental insufficiency,” such as fetal growth restriction, hypertensive disorders of pregnancy, fetal death in utero, and premature delivery may also be identified by abnormal test results.
4. What benefit is there in knowing the baby may have an abnormality or there may be a placental abnormality that could lead to complications?
In some cases, known abnormalities can benefit from corrective measures taken before delivery that may decrease morbidity. In other circumstances, awareness of certain abnormalities will help us to advise the patient on the best place to deliver the baby. At the very least, awareness allows the physician to provide information and counseling to help the patient and her family prepare for birth as well as events and decisions that might follow delivery. This proven benefit should not be denied to any patient because, in some instances, the time a family may have with the baby following birth may be limited.
5. Does an abnormal test result mean something is wrong with the baby or the pregnancy?
Not necessarily. It is a screening test rather than a diagnostic test. Abnormal results do NOT automatically mean that a baby has a problem or condition, but it does mean the pregnancy has a greater risk and needs further evaluation. Screening tests are designed to identify, and avoid missing, certain abnormalities; to do this most effectively, they may be accompanied by high “false positive” rates, i.e., situations where abnormal test result lead to further tests that reveals no problem Approximately 5% of maternal serum screening tests require further evaluation. Recently, a fourth biochemical marker (dimeric inhibin-A) has been added to the serum screen, which reduces the false positive rates for risk assessment of aneuploidy (chromosomal abnormalities). It is true that the more abnormal the test, the greater the likelihood there will be a problem with the baby or a pregnancy complication.
6. Are there “normal” conditions that can cause an “abnormal” test result?
Yes. Conditions such as twins or a pregnancy that is further along or less along than expected are common causes of abnormal test results. Nevertheless, unless a clear reason exists (e.g., 4 weeks off on dates) for the test abnormality, it is recommended the patient receive counseling and a targeted sonogram. Even if twins are found as the result of follow-up of an abnormal serum screen, a targeted scan is indicated because multiple gestations are at higher risk for birth defects and placental abnormalities.
7. How is a pregnancy with an abnormal test result evaluated further?
Under ideal circumstances, an abnormal test result is best managed by collaborative consultation with a genetic counselor and a specialist in maternal-fetal medicine. A good genetic counselor provides up-to-date, accurate, and unbiased information as a foundation for further evaluation; this professional also serves as a focal point for additional counseling if an abnormal pregnancy is eventually detected. The genetic counselor should see the patient even before a targeted sonogram is performed to educate and prepare the patient for indications and options regarding further testing. Patients who have abnormal screens, but apparently normal babies, are still at risk for placental insufficiency syndromes. Doppler flow studies in mid-trimester, which measure blood flow resistance patterns in the umbilical cord, brain, uterine arteries, and sometimes other blood vessels, may anticipate these because abnormal Doppler flow patterns usually precede significant deviations of fetal growth.
8. Who follows a patient if an abnormality is found?
Usually, the patient can continue to receive routine prenatal care, and perhaps even delivery, with her primary care provider. Even if an abnormality is found that will be best handled at a tertiary care center, the patient often can be followed at home until delivery. Depending on the abnormality, follow-up consultation with the genetic counselor and maternal-fetal medicine specialist and care team will also be recommended.
9. What can be “done” if an abnormal pregnancy is found?
That decision is ultimately up to the patient. It is the responsibility of the healthcare team to provide the patient with sufficient information, depending on the specific diagnosis, to make decisions with which she feels comfortable. In some cases this involves intervention by MFM specialists, or referral to other tertiary sites that may specialize in the management of a particular abnormality. Other circumstances may involve preparation for delivery and consultation with specialists who will coach the patient through decisions that will have to be made at that time. Actions range from finding appropriate support groups for the patient to terminating the pregnancy. The latter is of great concern to patient and providers alike, and it is the option that is chosen least for further management of pregnancies involving non-lethal abnormalities.
10. Is the patient at risk for aborting a “normal” baby because of a suspected abnormality?
No recommendations or decisions regarding pregnancy outcome are EVER made based on the maternal serum screening test alone. While this may seem obvious to providers, it is not so clear to many patients. Many patients choose not to have screening done because they are concerned about the “false positive” rates. They tend to extrapolate this occurrence to mean they might have to make a decision that could lead to termination of a pregnancy that is really normal. With current diagnostic tools, a patient today should never find herself in this situation.
11. If a provider is hesitant to recommend routine maternal serum screening, are there certain indications where this is readily justifiable?
Yes. Examples include patients who have had poor obstetrical outcomes, intrauterine growth restriction, severe preeclampsia, insulin-dependent and pregestational diabetes, autoimmune disorders, known thrombophilia, recurrent pregnancy loss, infertility, placental abruption or accreta, fetal demise of unknown etiology, previous child with chromosomal abnormality or syndromic problem, family history of certain birth defects, and other conditions associated with placental insufficiency syndromes.
Now that we have had the opportunity to address midtrimester maternal serum screening, we will be in a better position to discuss first trimester screening in a subsequent post. It is very likely that this will become the new standard of care within the next 5-10 years…..