James N. Macri

An association between low maternal serum α-fetoprotein and fetal chromosomal abnormalities

Abstract An index case of “undetectable” maternal serum α-fetoprotein at 16 weeks in the first pregnancy of a 28-year-old woman was associated with birth of an infant with trisomy 18. This fortuitous finding stimulated a retrospective study of prenatally diagnosed chromosomal abnormalities. From among a series of 3,862 genetic amniocenteses, 32 cases of fetal autosomal trisomy were diagnosed for which corresponding maternal serum and amniotic fluid α-fetoprotein data could be retrieved. From a second laboratory, nine additional cases were added. The maternal serum α-fetoprotein levels expressed as multiples of the median were significantly lower in distribution for these 41 women than those from a group of normal matched control subjects (p

Second-trimester placental changes associated with elevated maternal serum α-fetoprotein

Measuring maternal serum alpha-fetoprotein (AFP) levels in the second trimester is an effective screening test for identifying pregnancies at increased risk for neural tube defects. In the absence of a neural tube defect there are many nonpathologic and pathologic causes for elevated AFP including underestimated gestational age, twin gestation, impending fetal death, and rare fetal malformations. In this series, intraplacental sonolucent spaces were detected in a significant percentage of second trimester pregnancies with elevated serum AFP in the absence of any other cause for the elevation. It is postulated that these cystic spaces are a conduit for the transfer of fetal blood into the maternal circulation, thus accounting for the nonpathologic AFP elevation in the maternal serum.

Prenatal detection of neural tube defects: Comparison between alpha-fetoprotein and beta-trace protein assays

The prenatal diagnosis of neural tube defects is now possible in about 90 per cent of cases by assaying the amniotic fluid for alpha fetoprotein. The accuracy of beta-trace protein assays on amniotic fluid samples from defective fetuses was compared to alpha-fetoprotein studies. At present, alpha-fetoprotein studies provide more reliable results.

The clinical significance of low maternal serum α-fetoprotein

Abstract Lowered maternal serum α-fetoprotein was retrospectively investigated in 20,000 patients who underwent prenatal maternal serum α-fetoprotein screening. Two hundred thirty-two patients were initially evaluated as having maternal serum α-fetoprotein levels less than 0.25 multiple of the normal median. Correction factors, such as incorrect estimation of gestational age, reduced to 180 the number of patients with low α-fetoprotein. In this target group, patients with known pregnancy outcomes sustained a fetal loss in 38% of the cases. It appears that significantly low maternal serum α-fetoprotein is associated with a dramatic increase in second-trimester fetal wastage.

Critical issues in prenatal maternal serum α-fetoprotein screening for genetic anomalies

Abstract Prenatal screening, in this Clinical Opinion article, is defined as a population-based search for subgroups of pregnancy that by virtue of their maternal serum α-fetoprotein levels may be at increased risk for genetic anomalies. The identification of subgroups at risk for (1) neural tube defects, (2) ventral wall defects, and (3) chromosomal trisomies presents clinicians with unprecedented information and issues, including the biomedical basis for prenatal screening, the distinction between screening and diagnosis, and the decision-making function of the patient. The interest and, perhaps, ambivalence of the clinical community to prenatal screening are understandable. Obstetricians ordering prenatal screens are challenged by medical data associated with epidemiology, pathology, and genetics, including: (1) prevalence of disease, (2) interpretive biochemical reporting, and (3) the assessment and communication of patient-specific risks. Obstetricians ordering screens will be called on to provide information generally used by other specialists at other stages of care. What information, how it is biomedically determined, its form for communication to patients, and pitfalls in the process are discussed.

Maternal serum α-fetoprotein screening

Maternal serum α-fetoprotein levels are higher in black women. Misinterpretation of maternal serum α-fetoprotein screening results can subject black gravid women to unnecessary invasive diagnostic procedures and their calculable risks. Screening errors for black women can result from the use of normative data bases established with maternal serum samples drawn from other racial groups or the use of such data bases in conjunction with a published correction factor. Because the incidence of open neural tube defects is lower for blacks than for others, excessive false positive results for blacks (estimated to be 8817 to 28,215 cases annually) would be a pernicious misapplication of maternal serum α-fetoprotein screening. We address the problem outlined above and recommend independently developed, valid, normative data bases.

γ-Glutamyl transpeptidase of human amniotic fluid

Abstract γ-Glutamyl transpeptidase (GGTP) activity in normal amniotic fluids and corresponding maternal sera obtained at various gestational periods was measured. The ontogenic pattern of enzyme activity in amniotic fluid is very similar to alpha fetoprotein (AFP). However, the levels of these two proteins behaved differently in corresponding maternal sera. Also, in amniotic fluids obtained from pregnancies with neural tube defects (NTD), only AFP concentration was abnormally high whereas GGTP activity was normal.

Maternal serum α-fetoprotein screening, maternal weight, and detection efficiency

Various methods of adjusting maternal serum α-fetoprotein levels based on maternal weight have been recommended in order to more appropriately assign risk in maternal serum α-fetoprotein screening. These adjustments may, however, result in a larger proportion of pregnancies designated as having increased risk and reduction in detection accuracy.

Amniography in the Prenatal Diagnosis of Neural Tube Defects

Amniography for the visualization and confirmation of suspected neural tube defect was performed in 9 midtrimester gravidas. In all cases, amniotic fluid alpha-feto protein (AFP) was abnormally elevated. Four cases of anencephaly and one of spina bifida were demonstrated by amniography. These pregnancies were terminated and the defects were confirmed by gross pathologic examination. In 4 remaining cases, amniography was normal. Three of these pregnancies proceeded to term, culminating in the birth of a normal child. The fourth patient had spontaneous abortion of a normal fetus at 23 weeks of gestation. The experience reported here suggests that amniography is an important adjunctive diagnostic technique in the prenatal diagnosis of neural tube defect, and if used correctly, may significantly reduce the chance of false-positive diagnosis.

Prolactin and human placental lactogen changes in maternal serum and amniotic fluid in midtrimester induced abortions

Abstract Prolactin (hPRL) and human placental lactogen (hPL) concentrations in maternal serum and amniotic fluid were serially determined in 19 patients undergoing midtrimester elective abortion. Two subgroups were studied: Group 1 (10 patients) received 40 mg. of intra-amniotic prostaglandin F2α (PGF2α); in Group 2 (nine patients), 200 ml. of 20 per cent sodium chloride was instilled in the amniotic cavity. Maternal serum samples were serially obtained for 24 hours after induction of abortion by either abortifacient. Serial anmiotic fluid samples were obtained in Group 1 for the first seven hours after induction of abortion. The time from induction of abortion to fetal death (IDT) as well as the induction-abortion time (IAT) were recorded in all cases. Maternal serum hPL values declined significantly within one and one half hour from the induction of abortion. At six hours, a decline of more than 50 per cent of the original hPL value occurred in both groups. Prolactin in maternal serum did not show significant changes until six hours after induction. In Group 1, a significant drop of 40.5 per cent occurred at this time. In Group 2, a similiar declining trend was apparent, but this did not reach statistical significance until 12 hours after induction. In the amniotic fluid, no significant change in the hPRL values was noticed throughout the observation time. Amniotic fluid hPL did show a rising trend, ranging to between 41.1 and 79.4 per cent above the base-line value. However, this change was not statistically significant. The decrease in maternal serum hPRL following the more rapid fall in hPL in both study groups indicates a close dependency of hPRL levels on the intact functions of the fetoplacental unit. Changes in the amniotic content of these lactogenic hormones appear to be independent of the respective changes of these hormones in maternal serum.