Biomedical subjects
Publications and source records attributed to E Dvorin.
The past year has seen major challenges to existing maternal serum alpha-fetoprotein testing protocols for both neural tube defects and chromosomal anomalies. These challenges are reviewed along with the physiology of alpha-fetoprotein; the use of amniocentesis, ultrasonography, and additional serum markers in women with elevated alpha-fetoprotein levels; and epidemiologic implications of maternal serum alpha-fetoprotein screening.
Some recent reports have suggested that invasive testing is unnecessary when ultrasound either confirms or refutes a neural tube defect (NTD). However, counseling for recurrence risks and the possibilities for in utero therapy would be significantly altered by an aneuploid karyotype. We report our experience with 53 pregnancies affected by NTD in which we found 13.2% of these fetuses with abnormal chromosomes. In view of the higher than previously published incidence of aneuploidy, we believe that fetal karyotypes are essential in the evaluation of all fetuses with NTDs.
In common usage, a low maternal serum alpha-fetoprotein (MSAFP) value is associated with an increased risk of Down syndrome. We have performed amniocenteses for the indication of age-adjusted low MSAFP in 1154 patients and found 13 chromosomally abnormal conceptions. Autosomal trisomies were detected in half the cases. Additional abnormalities included sex-chromosome aberrations, deletions, or triploidy in proportions consistent with those seen in an advanced-maternal-age population. Patients with low serum AFP should be counseled that not only Down syndrome, but other aneuploidies as well, may be diagnosed. The risk quoted should be that of all chromosomal abnormalities, which is about twice the risk calculated for Down syndrome.
The application of correction factors for maternal serum alpha-fetoprotein (MSAFP) is expected to increase the accuracy of this screening tool. Correction for maternal weight compensates for the dilution effect of a larger plasma volume in women of greater weight. We analyzed the effect of a previously published linear correction formula for weight on the frequency of abnormal MSAFP results. Serum samples from 8276 patients were studied for AFP and were grouped according to maternal weight in 50-lb increments. Abnormal results were defined as 0.4 or less or 2.5 or more multiples of the median for gestational age. Without correction, the highest rate (15%) of low MSAFP results was obtained in the obese population. Conversely, the rate of elevated MSAFP was highest (3.8%) in the lowest maternal weight group. Correction for weight up to 250 lb significantly increased the rate of abnormally high results in the obese group, indicating an overcorrection effect. The number of amniocenteses indicated for abnormal MSAFP was reduced by about 9% with weight correction. We suggest that linear correction of serum AFP results is adequate for maternal weights up to 200 lb. Results in women weighing more than this upper limit should be corrected as if the weight were 200 lb only. This balances the frequency of abnormal results in all weight groups and maintains the reduction in number of procedures performed.
The variation in reported laboratory values, medians, and confounding variables used in the interpretation of alpha-fetoprotein (AFP) values from 14 laboratories servicing the Detroit-Metropolitan area was assessed by reviewing the laboratory report forms. The wide variation found in reported values, medians, and use of correction factors makes interpretation of results difficult and inaccurate. The need for large data bases for continuous correction of medians, uniform use of correction factors, and clinical decision making is emphasized.