Physiology of alpha-fetoprotein as a biomarker for perinatal distress: relevance to adverse pregnancy outcome.

The many physiologic roles of human alpha-fetoprotein (HAFP) and its correlation with perinatal distress/pregnancy outcome are rarely addressed together in the biomedical literature, even though HAFP has long been used as a biomarker for fetal birth defects. Although the well being of the fetus can be monitored by the measurement of gestational age-dependent HAFP in biologic fluid levels (serum, amniotic fluid, urine, and vaginal fluids) throughout pregnancy, the majority of clinical reports reflect largely second trimester and (less likely) first trimester testing due to regulatory clinical restrictions. However, reports of third-trimester and pregnancy term measurement of HAFP levels performed in clinical research and/or investigational settings have gradually increased over the years and have expanded our base knowledge of AFP-associated pregnancy disorders during these stages. The different structural forms of HAFP (isoforms, epitopes, molecular variants, etc.) detected in the various biologic fluid compartments have been limited by antibody recognition of specific epitopic sites developed by the kit manufacturers based on antibody specificity, sensitivity, and precision. Concomitantly, the advances in elucidating the various biologic actions of AFP are opening new vistas toward understanding the physiologic roles of AFP during pregnancy. The present review surveys HAFP as a biomarker for fetal distress during the perinatal period in view of its structural and functional properties. An attempt is then made to relate the AFP fluid levels to adverse pregnancy complications and outcomes. Hence, the present review was divided into two major sections: (I) AFP structure and function considerations and (II) the relationship of AFP levels to the distressed fetus during the third trimester and at term.

Transient decrease in the CD45RA expression on T lymphocytes in neonates with fetal distress.

To determine the expression of CD45 isoforms on T lymphocytes in neonates with fetal distress and to evaluate its diagnostic accuracy, peripheral blood samples were examined in 53 neonates who were classified into one of three groups: group I: 'control' group (n = 23), group II: 'mild distress' group (n = 15), and group III: 'moderate distress' group (n = 15). The expression of CD3 (mean +/- SD 24.2 +/- 10.1%), CD4 (23.0 +/- 5.7%), and CD45RA (27.3 +/- 9.6%) on total lymphocytes and the expression of CD45RA on CD4+ T lymphocytes (13.7 +/- 4.7%) in group III were significantly lower than in the other two groups 0-3 days after birth. Sensitivity and specificity of the CD45RA expression on CD4+ T lymphocytes for discrimination of group III were calculated as 0.79 and 1.0, respectively, when the cutoff value was 22.7%. The low CD3, CD4, and CD45RA expression returned to normal levels 10 days and more after birth. There were no differences in the CD8 and CD45RO expression between the groups. We conclude that CD4+ T lymphocytes from neonates with fetal distress show a transient decrease in the CD45RA expression without an increase in the CD45RO expression, and, therefore, analysis of the CD45 isoform expression is useful for laboratory evaluation of fetal distress.

Relationship between lupus anticoagulant (LAC) and pregnancy-induced hypertension.

Lupus anticoagulant (LAC), a serum antiphospholipid autoantibody, is believed to be one of the causes of infertility or fetal loss. The purpose of the present study was to evaluate the role of LAC in the pathogenesis of hypertension during pregnancy. In this study, 20 pregnant women with hypertension were classified into two groups: 14 patients who did not have hypertension before the pregnancy but developed it during the pregnancy (pregnancy-induced hypertension; Group A) and 6 patients who had hypertensive or renal disease before the pregnancy, and developed further hypertension during the pregnancy (pregnancy-aggravated hypertension; Group B). A LAC coagulation assay was performed, and the presence of LAC in each group was compared. All 14 patients in group A were LAC-negative. In contrast, 3 of the 6 patients in group B were LAC-positive, and had clinical autoimmune diseases. The incidence of pregnancy-induced hypertension was also examined in 15 pregnancies from 9 LAC-positive women who had a history of repeated fetal loss but no systemic autoimmune disease (Group C). None of these 15 pregnancies had hypertensive complications, even when they reached term. In the placentas of LAC-positive women, no characteristic changes other than fibrinoid degeneration and microscopic infarction were observed upon histological examination. These results suggest that LAC does not relate with the onset of hypertension during pregnancy.

Oncofetal antigens. Increasing the specificity of the CEA radioimmunoassay.

The biologic and clinical significance of the oncofetal antigens carcinoembryonic antigen (CEA) and alpha1-fetoprotein (AFP) are discussed. Although the current assays for these molecules are not tumor-specific, measurement of these molecules in the circulation of cancer patients is useful either for tumor diagnosis or for management of the cancer patient in the postoperative or post-chemotherapy state. An approach to increasing the specificity of the CEA radioimmunoassay is described.

Carcinoembryonic antigen in amniotic fluid.

Carcinoembryonic antigen (CEA), a substance which is known to occur in high amounts in the fetal gut and also in certain tumors of the gastrointestinal tract, has been demonstrated in amniotic fluids from different stages of pregnancy. Radioimmunoassays of CEA in amniotic fluids of 91 normal pregnancies showed a decrease from a mean of 53 ng/ml at 19 weeks to 25 ng/ml at the end of gestation. The CEA activity in amniotic fluid was eluted in the same volume as a standard 125I-CEA on a Sephadex G200 column. Amniotic fluid therefore contains CEA similar in molecular weight to the CEA purified from liver metastases of colonic cancer. Among 17 cases of abnormal pregnancies, CEA elevations were observed in five with anomalous fetuses.

The association of maternal lymphocytotoxic antibodies with obstetric complications.

The immunologic relation between mother and fetus has become of interest to those concerned with reproductive physiology. One method to assay this type of relation is to determine the immunologic response to HLA antigens expressed by the fetus which are of paternal origin. Although 20 to 50% of multiparous women develop lymphocytotoxic antibodies during pregnancy, the effect of these antibodies on gestation or the fetus has not been established. In a prospective study, 23 patients at the time of spontaneous abortion had negative cytotoxic antibodies. Of 129 obstetric patients followed with antibody screening over a 6 to 7 month period until delivery, 28 developed positive lymphocytotoxic antibodies (22%). These 28 patients with cytotoxic antibodies delivered male infants by a ratio of 4 to 3, and 11 patients (39.3%) had complications during the gestation. The responsiveness to the paternal histocompatibility antigens is valuable information for furthering the understanding of the fetal-maternal relation.