Antepartum Assessment & Laboratory Evaluation:
Ongoing Laboratory Evaluation
Maternal Serum Screening
The goal of maternal serum screening is to identify patients at increased risk of having a baby with a serious birth defect.
The goal of maternal serum screening is to identify patients at increased risk of having a baby with a serious birth defect, including a neural tube defect (NTD), Down syndrome or trisomy 21. Maternal serum alpha-fetoprotein (MSAFP) screening is commonly offered to all pregnant women between 15 and 20 weeks gestation.
The fetal yolk sac, the gastrointestinal tract, and the liver sequentially synthesize alpha-fetoprotein (AFP), a fetal-specific protein. The concentration of AFP is highest in amniotic fluid around the 13th week of gestation and then diminishes. Detection of AFP in maternal serum forms the basis of screening for both NTDs (elevated levels) and Down syndrome (low levels). The concentration of AFP in maternal serum is dependent on gestational age, maternal weight and race, multiple gestation, and maternal diabetes. Accurate information on all these parameters is necessary for valid interpretation of this test.
Typically, test results are reported as multiples of the median (MoM), a statistical test that allows different laboratories to compare results. Most screening programs establish 2.0 to 2.5 times the median values (2.0-2.5 MoM) as the cutoff to designate a positive result for a possible NTD (ACOG, 1996). Regardless of the chosen cutoff, false-positive and false-negative results will always occur.
Any abnormal finding warrants additional testing; however, screening protocols vary. If the initial ultrasound examination does not explain the MSAFP elevation (e.g., inaccurate dating, multiple gestation, or fetal demise), a comprehensive ultrasound examination is performed to evaluate the fetus for malformations. Some centers also offer genetic counseling and amniocentesis as a follow-up to abnormal findings.
Low MSAFP levels are associated with Down syndrome and other chromosomal abnormalities. The median MSAFP level in pregnant women carrying fetuses with Down syndrome is about 0.8 MoM of that for control pregnancies. In contrast to the cutoff used for NTD screening, Down syndrome screening uses a series of age-specific cutoffs for each MSAFP level. Maternal age and a positive result are directly related: The older the pregnant women, the greater the likelihood of a positive result.
Human chorionic gonadotropin (hCG) and unconjugated estriol (uE3) are serum markers used in combination with MSAFP to improve the detection rate of fetuses with Down syndrome and trisomy 18. In fetuses with Down syndrome, hCG is markedly elevated; thus, it is the most sensitive maternal-screening marker for this abnormality (ACOG, 1996). The addition of (uE3) to MSAFP and hCG (triple-marker screening) decreases the false-positive rate by about 25 percent, thereby decreasing the number of amniocenteses needed while achieving the same level of detection.
Although double and triple markers are superior to MSAFP alone when screening for fetal Down syndrome, these methods still fail to detect Down syndrome in the fetuses of pregnant women less than 35 years of age (ACOG, 1996). Additionally, double-marker (AFP and hCG) and triple-marker screening is more costly than MSAFP alone.Quad Screen
Combined testing for alpha-fetoprotein, human chorionic gonadotropin, unconjugated estriol, and inhibin A, known as the quad screen or quadruple test, is the most effective multiple-marker screening test for Down syndrome in the second trimester. This approach yields an 81 percent detection rate and a false-positive rate of 5 percent (Dugoff et al, 2005).
According to findings from the First- and Second-Trimester Evaluation of Risk Trial (FASTER), first-trimester combined screening [measurement of nuchal translucency, pregnancy-associated plasma protein A (PAPP-A)] at 11 weeks gestation is better than second-trimester quadruple screening; however, at 13 weeks, results are similar to second-trimester quadruple screening (Malone et al., 2005). The objective of FASTER was to compare, in a single population, first-trimester screening for Down's syndrome with (1) second-trimester screening (the current standard of care) and (2) screening in both trimesters.
The FASTER researchers have noted that clinicians may have difficulty consistently measuring nuchal translucency by ultrasonography, as evidenced by the 7 percent rate of failed or suboptimal imaging in the study. Therefore, appropriate quality control is essential. Additionally, health care providers should consider patient preferences and the costs associated with different screening strategies as they choose among the various approaches.
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