A 24-year-old white woman has a maternal serum α-fetoprotein (MSAFP) level at 17 weeks’ gestation of 6.0 multiples of the median (MOM). She had an ultrasound the same day that appeared normal.
Which of the following is the most appropriate next step in management?
The MSAFP may be performed between 15 and 21 weeks’ gestation to screen for NTDs. The screen positive cut-off is usually set at 2.5 MoM, which results in a screen positive rate of 5% or less, and identifies 85% of NTDs. In the past, if the patient had only a moderately elevated value, a second MSAFP value could be drawn, as a small number of these patients will have a normal test and therefore drop back into the “low risk” category. Ultrasound evaluation may have high sensitivity and specificity in detecting fetal NTDs in specialized centers; however, in less experienced hands, there is a higher false negative rate. Therefore, you cannot reassure the patient that the fetus does not have a NTD. Ultrasound will help identify other reasons for elevated MSAFP, such as anencephaly, twins, wrong gestational age of the fetus, or fetal demise. The traditional diagnostic test to offer women with positive MSAFP results is genetic amniocentesis. Testing may be done to evaluate for elevated AFP in the amniotic fluid, as well as elevated acetylcholinesterase. In the setting where both of these amniotic fluid levels are elevated, this test has been shown to identify 100% of cases of anencephaly and open NTDs, as well as 20% of ventral wall defects. The other benefit of amniocentesis is that amniotic fluid may be used for karyotype assessment, as several studies have shown that elevated MSAFP independently increases the risk of fetal aneuploidy. Amniography is an outdated procedure in which radiopaque dye is injected into the amniotic cavity for the purpose of taking x-rays. Termination of pregnancy should not be recommended on the basis of MSAFP testing alone. MSAFP is a screening test used to define who is at risk, and requires further diagnostic testing in order to confirm or rule out a diagnosis.
The fetus is confirmed to have an open NTD with a diagnosis of spina bifida.
What is the most appropriate counseling for this woman regarding future pregnancies?
The incidence of NTDs in the general population is approximately 1.4 to 2.0/1000. It is a multifactorial defect and is not influenced by maternal age. Women who have a previously affected child have a NTD recurrence risk of about 3% to 4%. This patient is at increased risk of having another child with a NTD and, therefore, should be offered prenatal diagnosis with an amniocentesis and targeted ultrasound. A CVS will determine a fetus’ chromosomal makeup but will give no information regarding AFP levels or risk for a NTD. Woman with a previously affected fetus should take 4 mg of folic acid daily before conception and through the first trimester, as this has been shown to result in a 72% reduction in the recurrence risk. The neural tube is almost formed by the time of a missed period, and therefore, beginning supplementation with folic acid when a woman finds out she is pregnant is not sufficient to decrease the risk of NTDs. Women with no prior history of NTD who are of childbearing age should be encouraged to take 400μg of folic acid daily.
The patient asks how the diagnosis of spina bifida will impact her obstetric management and delivery. You should counsel her that:
There is good data that outcomes are better when these neonates are delivered in settings that offer specialized personnel and neonatal intensive care facilities. Delivery at term is preferred, and preterm delivery is not known to improve neurologic outcomes. Breech presentation is common in pregnancies complicated by fetal spina bifida, resulting from either hydrocephalus with an enlarged head, or from fetal neurologic compromise. These infants should be delivered by cesarean. The best delivery route for a cephalic fetus is controversial, but several studies suggest that vaginal delivery does not adversely impact fetal outcome. The role of fetal surgery for repair of spina bifida is considered investigational. The studies in this field were not randomized and were largely limited to fetuses with lesions at or below the thoracic spine. Data suggested no improvement in bowel or bladder function or ambulatory ability. There may be a modest improvement in the degree of hindbrain herniation.
A 41-year-old woman had a baby with Down syndrome 10 years ago. She is anxious to know the chromosome status of fetus in her current pregnancy. She is currently at 8 weeks of gestation.
Which of the following tests will provide the most rapid and reliable diagnosis of Down syndrome?
Amniocentesis and CVS are techniques of obtaining fetal cells for cytogenetic analysis. Amniotic fluid cells (obtained by amniocentesis at 15-20 weeks) require tissue culture to obtain adequate cell numbers for analysis. CVS at 10 to 13 weeks, either by transcervical or transabdominal access to the placenta, will provide the earliest results in order to diagnose Down syndrome. Multiple maternal serum marker analysis (Quad screen) may be done between 15 and 21 weeks, but it is primarily used for screening otherwise low-risk women for Down syndrome. Similarly, first trimester screening with NT measurements and maternal serum markers is not a diagnostic test. Neither of these tests are the most correct choice in this patient of advanced maternal age with a prior affected child. Cell free fetal DNA testing may be ordered as early as 10 weeks’ gestation, and has a sensitivity of 98% with low false positive rates (< 0.5%), but is still a screening test. A normal screen would be reassuring, but an abnormal screen would still require diagnostic testing. Therefore, CVS is the best choice in this setting.
A 44-year-old pregnant woman is trying to choose CVS versus amniocentesis for prenatal diagnosis due to her increased risk of having a child with a chromosomal anomaly.
Which of the following is an advantage of amniocentesis over CVS?
CVS has many advantages over amniocentesis, including its earlier performance and quicker results. Normal results provide early reassurance, while abnormal results may allow for earlier and safer options for pregnancy termination. However, CVS does have a higher complication rate. Mid-trimester amniocentesis carries a procedure-related fetal loss rate of 1 in 300 to 500. This may be even lower in experienced hands. The procedure-related loss rate for CVS is probably similar to that of amniocentesis; however, the overall pregnancy loss rate for CVS is higher than for amniocentesis due to the increased baseline loss rate between 9 and 16 weeks’ gestation. First-trimester amniocentesis has a complication rate higher than that for CVS, and has been shown to have an increased risk of amniotic fluid culture failures and membrane rupture. For these reasons, early amniocentesis should not be offered.
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