Statistical methods for fetal monitoring with alpha-fetoprotein in maternal serum.

Methods are presented for dealing with screening or diagnostic variables which exhibit trends over time. The number and spacing of observations is assumed to vary among patients. Criteria for establishing 'normal' trends, and for detecting extremes and pattern deviations, are developed. The methods are applied to a pregnancy study in which longitudinal data on alpha-fetoprotein in material were obtained in 1501 patients.

Point estimates of concentrations by simple immunoassays.

Point estimates can be generated by simple immunoassays when combined with a sequential statistical procedure. The method is called an extended simple immunoassay. A simple immunoassay for alpha-fetoprotein (counterimmunoelectrophoresis) was used to test the hypothesis that simple immunoassays are not restricted to qualitative "yet" or "no" results, but can provide quantitative results similar to radioimmunoassay. Potential benefits of this finding are discussed.

Early detection of human chorionic gonadotropin in urine by simple immunoassays.

Data are presented to show that human chorionic gonadotropin (hCG) in urine can be detected early in pregnancy by simple immunoassays performed prior to or around the time of the expected but missed menstrual period. Differences between the use of simple immunoassays with urine and radioimmunoassays and radioreceptor assays with serum are discussed.

Pitfalls and problems in the interpretation of AFP data--myths and misuse of the "normal range".

Drawing a line more intelligently for AFP data means using as a denominator two fairly well-defined populations (abnormal and normal), instead of one ill-defined normal population. The line is drawn at the intersect between two curves to minimize the error of misclassification; this replaces an arbitrarily defined cutoff level (multiples of the standard deviation unit). Moving the line to the right reduces the false positive error when screening for NTD, whereas moving the line to the left provides a sensitive alert signal for routine screening of maternal sera by AFP determinations for fetal distress. Adjustment of the line for cost and benefit factors and the use of probability statements that include the prevalence of specific conditions all help sharpen medical classification and decisions. Cross-sectional analysis is separated from longitudinal analysis. A benefit from this discussion may be the replacement of the normal range with a simple plot of AFP results or a percentile distribution, which would be more meaningful and more easily understood by all.

Changes in alpha-fetoprotein levels in a case with multiple congenital anomalies.

PIP: A chromosomally normal women, who previously lost an infant with meningomyelocele and hydrocephalus, with a chromosomally normal husband, had normal alpha fetoprotein (AFP) levels in both amniotic fluid and maternal serum at about 19 weeks gestation. At 34 weeks, suspected hydramnios was confirmed clinically and radiographically; the latter showed no evidence of hydrocephalus. AFP levels at 36 weeks showed 224 ng/ml in maternal serum and 1249 ng/ml in amniotic fluid. Maternal serum rose from the 25th-19th percentile, and amniotic level was 5-fold greater than normal (200 ng/ml). At 39 weeks, abnormal AFP values of 258 and 1500 ng/ml for maternal serum and amniotic fluid, respectively, were measured. Though AFP patterns did not suggest an open neural tube defect (higher 19-week values were expected), spontaneous labor at 39 weeks resulted in a 1930-gm female with multiple congenital abnormalities. These AFP assays suggest: 1) that signaling of abnormalites other than neural tube defects is a valid use of AFP assays; 2) that the slope rather than single point values should be used in interpreting AFP results; 3) that assays in both amniotic fluid and maternal serum should be obtained and interpreted simultaneously in screening for birth defects; and 4) that sequential assays should be performed even in the presence of initially normal findings.^ieng

A capillary tube pregnancy test.

The experience with a new, simple, and sensitive capillary tube pregnancy test requiring no refrigeration is described. The results of this test and other tests are compared against histologic results. The 1/2 unit capillary test, defined as having a sensitivity of 0.5 I.U. of HCG per milliliter, had a higher percentage of agreement with histopathologic results (99.65 per cent) than all other tests studied. The false-positive rate was 0.07 per cent and the false-negative rate was 0.28 per cent. In this series of 1,486 tests, 21 cases of pregnancy, identified by a 1/2 unit test, were missed by one or two unit tests. The earliest detection of pregnancy by the 1/2 unit capillary test confirmed by histology was 3 weeks from the last menstrual period (four cases).

Alpha-fetoprotein.

Despite all the information about AFP presented, a great deal still needs to be discovered especially in pregnancy. Geographical and racial differences remain to be elucidated. Similarly, differences in obstetric population in Helsinki and Baltimore, for example, are only now being studied. Sex differences may exist; Lardinois and associates195 cited a higher level of AFP in male than female fetuses. The important questions that need to be answered are whether AFP assays can help improve the other half of prenatal care- that directed to the fetus- and whether the AFP model can help enhance our understanding of the similarities and differences of fetal and cancer cells.