Info

Amniotic Fluid AFP (MoM)

Amniotic Fluid AFP (MoM)

Fig. 2. The relative frequency distributions of AFAFP in unaffected, OSB, and anencephalic pregnancies. The commonly used cutoff value of 2.0 MoM is shown.

OSB, and anencephalic pregnancies. By 1981, a second diagnostic test, acetylcholinesterase (AChE) in amniotic fluid, was also confirmed (24).

Second-trimester AFAFP testing is the first instance of the use of a biochemical test to diagnose a fetal malformation. With the validation of a diagnostic test, a screening program could now be established. Attention then focused on the development of a serum-based screening test. Wald, Brock, and Bonnar reported the first use of maternal serum AFP (MSAFP) as a screening test in 1974 (25). The UK Collaborative Study reported in 1977 that elevated MSAFP, in the early midtrimester of pregnancy could identify 80% of OSB and 90% of anencephaly cases (26) at an FPR of 5%.

The physiological basis for AFAFP as a prenatal diagnostic test for ONTD, and for MSAFP as a prenatal screening marker for increased risk, is very simple: an open defect represents a leak in what is normally the confined circulation of AFP within fetal plasma and CSF. In ONTD, AFP is able to pass from fetal plasma and CSF, where it exists at concentrations of 1-3 g/L, into amniotic fluid, where it normally exists through fetal micturition at concentrations of 10-15 mg/L. AFP from the fetus reaches the maternal compartment (20-50 ^g/L) via the placenta and by diffusion across the amniotic membranes (27). The presence of an ONTD represents a breakdown of this normally well-contained concentration gradient, resulting in concentrations 7- to 20-fold higher in amniotic fluid (Fig. 2) and 4-fold higher in maternal serum (Fig. 3).

By 1981, a number of breakthroughs in prenatal screening for ONTD had been achieved: two diagnostic tests had been validated in amniotic fluid (AFP and AChE), both requiring an invasive amniocentesis procedure; a noninvasive screening test— MSAFP, by itself not diagnostic of any condition—had been confirmed to identify at least 80% of ONTD patients within the 3% of the population with the highest MSAFP concentrations (26); and a new method had been developed (25) for reporting concentra-

98% screen NEGATIVE

2% screen positive, 85% detection

98% screen NEGATIVE

2% screen positive, 85% detection

Retinoids Pregnancy

Maternal Serum AFP Concentration

Fig. 3. MSAFP as a screening marker for OSB.

Maternal Serum AFP Concentration

Fig. 3. MSAFP as a screening marker for OSB.

tions as the multiple of the median (MoM) concentration of unaffected patients (see Using the MoM To Adjust for Gestational Age, below). The MoM designation is useful because AFP concentrations in both maternal serum and amniotic fluid change with gestational age, and this is reflected by changes in the median concentrations seen at each gestational week. The use of the MoM designation not only eliminated the concentration effect of different gestational ages, but it also reduced differences between analytical methodologies, allowing the multisite collaboration that is critical for the effective study of relatively rare conditions.

Several clinical factors, or attributes of the patient, influence the concentration of AFP in maternal serum and amniotic fluid Optimal screening performance for ONTD depends on the collection and uniform application of clinical information about each patient screened.

Gestational Age for Testing

AFP concentrations, particularly in maternal serum, are informative about the risk or presence of ONTD only within a specified period of early midtrimester gestation. With MSAFP, the OSB population has the greatest separation from the unaffected population during the 16th to 18th wk of gestation (26). Screening is less effective in week 15 and beyond week 19; performance in weeks 20 to 24 has been estimated as 70% detection for a somewhat elevated 5% FPR (26,28). AFAFP diagnostic testing is best between weeks 16 and 22; detection rates during weeks 13 to 15 are slightly lower (23,29), and given the constraints of MSAFP timing, would be performed only on patients having an amniocentesis for reasons other than an elevated MSAFP result.

Using the MoM to Adjust for Gestational Age. AFP concentrations change throughout pregnancy in the fetus, amniotic fluid, and maternal serum. During the midtrimester, AFAFP concentrations decrease and MSAFP concentrations increase by approx 12-15%

Was this article helpful?

0 0

Post a comment