History:

A 38-year-old gravida 5 para 4 mother has a normal prenatal course to 16 weeks gestation. Her doctor has the following tests run: a "triple screen" with maternal serum alpha fetoprotein (MSAFP), beta-HCG, and unconjugated estriol (uE3). The beta-HCG and estriol were normal for gestational age, but the MSAFP was 8 MoM (multiples of the median). A fetal ultrasound was performed and there appeared to be a defect of the back of the torso in the mid-thoracic region. The pregnancy was terminted with a D&E (dilation and extraction) procedure.

There is a large neural tube defect in this cases. This is a meningomyelocele. Other types of neural tube defects include: spina bifida, meningocele, encephalocele, and anencephaly (as seen in images 7.2 and 7.3).

Answers:

1. Why did the physician get a "triple screen" (MSAFP, beta-HCG and unconjugated estriol [uE3])?

The advanced maternal age of the mother puts her at greater risk for having a fetus with Down syndrome. The MSAFP is also useful for screening for neural tube defects. Ultrasonography in the second trimester is useful to determine whether fetal abnormalities or placental abnormalities are present. In selected cases where a chromosomal abnormality may be suspected, then amniocentesis with karyotyping of fetal cells can be performed (in the first trimester, chorionic villus sampling for karyotyping can be done).

Additional markers may include inhibin-A and pregnancy-associated plasma protein-A (PAPP-A). Inhibin is secreted by the placenta and the corpus luteum. Inhibin-A can be measured in maternal serum. An increased level of inhibin-A is associated with an increased risk for trisomy 21. A high inhibin-A may be associated with a risk for preterm delivery. Low levels of PAPP-A as measured in maternal serum during the first trimester may be associated with fetal chromosomal anomalies including trisomies 13, 18, and 21. In addition, low PAPP-A levels in the first trimester may predict an adverse pregnancy outcome, including a small for gestational age (SGA) baby or stillbirth. A high PAPP-A level may predict a large for gestational age (LGA) baby.

2. What is the significance of the laboratory findings?

The markedly elevated MSAFP suggests a neural tube defect is present. Down syndrome would be suggested by an elevated beta-HCG along with a decreased MSAFP. Findings suggested by the triple screen are shown in the following table:

Condition	MSAFP	uE3	HCG
Neural tube defect	Increased	Normal	Normal
Trisomy 21	Low	Low	Increased
Trisomy 18	Low	Low	Low
Molar pregnancy	Low	Low	Very High
Multiple gestation	Increased	Normal	Increased
Fetal death (stillbirth)	Increased	Low	Low

Note: the levels of these analytes change markedly during pregnancy, so interpretation of the measurements depends greatly upon knowing the proper gestational age. Otherwise, results can be misinterpreted.

3. What is the frequency of these kinds of defects?

Anencephaly is the most common congenital malformation--about 0.5 to 2/1000 live births. The frequency of neural tube defects has been shown to be reduced below that incidence if women supplement their diet with folic acid (before and during pregnancy).

4. What would happen if the physician did not tell the mother about prenatal diagnostic tests?

Even if you do not believe any pregnancy should be terminated, it is still the standard of practice to inform patients of the options available. Furthermore, even if no abortion is planned, the prenatal testing will still be useful for optimal management of the pregnancy and planning for possible outcomes.

5. Is ultrasonography sufficient to detect congenital anomalies?

NO! Ultrasound can detect many abnormalities, but not all. Therefore, NEVER tell the mother that the baby is fine just because the ultrasound revealed no abnormalities. For example, most initial screening ultrasounds of fetuses with Down syndrome will appear normal.



6. What can you tell parents about potential disabilities for a child with a neural tube defect?

There is a wide range of potential outcomes, depending upon the severity of the defect. The size and location of the neural tube defect may be known from ultrasound, and this can provide a guide to potential outcomes. Some affected babies can lead a normal life after corrective surgery, but most will have some lifelong disability, including either incontinence or need for crutches or a wheelchair. Any mental disability is unlikely, but curiously, that is also why the life of the child may be worse. Here the issue of shame and how to deal with the pity of others is something the child has to deal with, as well as the parents and the siblings. This may be the biggest hurdle for parents and siblings to overcome. Usually the child himself does not have this problem as much as the rest of the family.

When asked, most people with this type of disability say they are glad to be alive, and are happy, so the most common error we able bodied people make in these cases is to falsely exaggerate how awful life with disability would be. Life itself is enough of a good to outweigh many problems. (That should not be considered the final word, just an important factor for doctors to share with potential parents. Not all persons with these defects are happy; some will confide that they love their parents for all they have done for them, but wonder if it was all worth it, and some will even assert that it is not worth it, especially those with the worst defects and resultant disabilities.)