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MS WordPerinatologist Corner - C.E.U/C.M.E. Modules
Prenatal Genetic Screening – Serum and Ultrasound
Sponsored by The Indian Health Service Clinical Support Center
10. Implications of the various screening strategies
What are the implications of the various screening strategies?
The combination of multiple-marker screening, high-resolution ultrasound, chorionic villus sampling, early amniocentesis,
and genetic amniocentesis has significantly advanced prenatal diagnosis. Nevertheless the technology has the downside of being capable of generating significant maternal anxiety. One needs to reassure patients that with multiple-marker screening the odds invariably favor a normal outcome. Many providers maintain a negative attitude regarding the utility and purpose of prenatal diagnosis. Prenatal diagnosis is not a “search and destroy mission” designed to eliminate genetic diseases through pregnancy termination, but rather a modality to maximize the options available to patients. For many couples termination of pregnancy involving an anomalous child may not be an alternative because of ethical, religious, or cultural concerns.
Native Americans are certainly not a homogeneous group as regards their outlook on this subject. Individualization and nondirective counseling, attempting to keep the provider’s own biases minimized, is always appropriate for our patients. Likewise, pregnancy termination is not permissible on site in the federal institutions where most of us practice. Many couples for whom abortion is unacceptable may nevertheless change their minds when an abnormal result is confirmed. Others who would not terminate an abnormal pregnancy would however find it acceptable to avoid cesarean delivery for fetal indications. Many just wish to prepare their families and find a support network to help them care for a disabled child. The knowledge of a structural defect may also be of benefit to the child as regards place of birth and postnatal care. It’s all about the patient’s choices.
Q. The ‘quad’ second trimester screening test is expensive. Is it worth it?
A. The ‘quad’ screen is more cost effective and patient friendly. See details.
Abnormal screen: Other implications
Pregnancy complications such as preeclampsia, fetal growth restriction, preterm birth, fetal death, placental abnormalities, and possibly abruptio placenta and oligohydramnios are more common among women with abnormal maternal analyte concentrations.
Preeclampsia
The second trimester serum markers used for Down syndrome screening are altered in pregnancies that subsequently go on to develop preeclampsia. Levels of AFP, hCG, free beta-hCG, and inhibin A are significantly elevated in such pregnancies, while levels of uE3 are unchanged or reduced. The degree of change in the serum analyte levels is more marked as the interval between sample collection and clinical onset of disease shortens.
The risk of preeclampsia is not currently reported with prenatal serum screening results. At 17 weeks of gestation, a multiple marker test including hCG and inhibin A would detect 23 percent of future preeclampsia at a 5 percent false positive rate. The association is not sufficiently strong to warrant a change in routine prenatal care, which is already oriented toward detection of preeclampsia. A triple marker test of uE3, free beta-hCG and inhibin A performed at 24 weeks of gestation would detect 55 percent of pregnancies that will develop preeclampsia at a 5 percent positive rate; however, 24 weeks is too late in pregnancy for Down syndrome and neural tube defect screening.
Adverse pregnancy outcome — Women who are screen positive for Down syndrome (low AFP and uE3, high hCG and inhibin A), neural tube defects (high AFP) , or trisomy 18 (low AFP, uE3, and hCG) are also at risk for other adverse outcomes, such as fetal growth restriction, preterm delivery, and fetal demise. Elevated MSAFP levels as late as 28 weeks are predictive of preterm birth. In addition, one retrospective case-control study observed that nondiabetic women with unexplained very low MSAFP levels were at increased risk of delivering a macrosomic infant compared to normal controls (26 versus 13 percent).
A low uE3 level (less than or equal to 0.2 ng/mL or 0.15 MoMs) has also been associated with fetal steroid sulfatase deficiency and early fetal death. In one series of 103 cases of unexplained low uE3, 41 fetal demises occurred and 39 of these were at or before 20 weeks of gestation. In almost all of these cases, there were additional maternal analyte abnormalities. Elevated hCG levels are associated with multiple adverse pregnancy outcomes.
However, these are weak associations; thus, it is not appropriate to follow women for these complications based upon screening results alone. Heightened pregnancy surveillance of women with an elevated MSAFP level does not achieve earlier or improved detection of complications or improve pregnancy outcome compared to routine management of such pregnancies.
An isolated low hCG concentration (
0.5 MoMs) was not associated with adverse pregnancy outcome in the only study that evaluated this finding.
