Amniotic fluid pregnancy-specific beta 1-glycoprotein (SP1) in fetal developmental disorders

Concentration of pregnancy-specific beta 1-glycoprotein (SP1) was studied in second and third trimester amniotic fluid from pregnancies with various fetal developmental disorders. The material consisted of 26 cases with chromosomal disorders and 19 cases with non-chromosomal fetal malformations. The SP1 concentration was elevated in two cases of Meckel's syndrome (mean +2.7-4.0 S.D.) as well as in one case of fetal triploidy (mean +22 S.D.), while it was normal in all other 14 different fetal disorders.     

Investigations into the molecular heterogeneity of pregnancy-specific beta 1-glycoprotein (SP1)

The molecular heterogeneity of pregnancy-specific beta 1-glycoprotein (SP1) was examined by analytical immunoelectrophoresis and a radioimmunostaining technique of immunoelectrophoretic plates. Analytical crossed immunoelectrophoretic analysis and radioimmunostaining of these plates demonstrated the presence of normal human serum components in the alpha-mobile precipitate previously considered to be exclusively the high molecular pregnancy-specific protein, SP1 alpha. This observation suggested that two molecular populations were contributing to the alpha-mobile precipitate. Following fractionation of late-pregnancy serum by size chromatography, the radioimmunostaining technique further demonstrated the presence of normal serum components in the intermediate fraction but not in authentic SP1 (i.e., SP1 beta) or the high molecular weight form (SP1 alpha). We suggest that SP1 antigenic determinants are distributed in three different fractions of pregnancy serum, one of which (intermediate fraction) is a complex of authentic SP1 (SP1 beta) and a normal serum protein, whereas non-pregnancy serum components were not demonstrable in the remaining two (i.e., SP1 beta or SP1 alpha).     

The predictive value of pregnancy-specific β1-glycoprotein (SP1) in threatened abortion

Pregnancy-specific β₁-glycoprotein (SP₁) was determined in the serum of 59 patients admitted to hospital with threatened abortion in the 7th–19th wk of pregnancy. A 95% reference area was calculated on the basis of values from patients with threatened abortion who continued pregnancy until delivery. 26 patients aborted; among these 24 showed values below the reference area. 33 continued pregnancy until confinement. 3 of these initially had values just under the lower limit of the reference area; later values from these patients as well as all the values from the remaining 30 patients were all above this limit. The value of a single low SP₁ for prediction of abortion was found to be 89% (95% conf. lim.: 70.8–97.7). Based on serial determinations the predictive value was 100% (95% conf. lim.: 85.8–100.0).     

Serum levels of pregnancy-specific beta 1-glycoprotein (SP1) in women with pregnancies at risk

Pregnancy-specific beta 1-glycoprotein (SP1) concentrations were measured by nephelometry in 133 serum samples from 74 women in their last trimester of pregnancy. All women carried one child but their pregnancies were complicated by pre-eclampsia, essential hypertension, diabetes mellitus or rhesus isoimmunization. Most of the women with pre-eclampsia or essential hypertension who gave birth to infants of normal weight had SP1 values evenly distributed within the reference range. Women with insulin-dependent diabetes mellitus who gave birth to infants to normal birth weight or large-for-date infants had SP1 levels well within the reference range and even showed a tendency to overrepresentation above the geometric mean. Women with rhesus isoimmunization all delivered infants of normal birth weight. Their SP1 values were near or above the geometric mean of the reference range. No special pattern of SP1 levels was observed in relation to the severity of the immunization.     

Comparison of pregnancy-specific beta 1-glycoprotein (SP1) and ultrasound in predicting the date of delivery

The accuracy of ultrasound measurements (crown-rump length and gestational sac diameter) and the serum concentration of pregnancy-specific beta 1-glycoprotein (SP1) in the prediction of the date of birth was analysed in a study population of 94 patients. When measured before 8 weeks after the last menstrual period (LMP) the serum concentration of SP1 was found to be a good predictor of the expected date of delivery and a good alternative to ultrasound, but it was of limited use when determined at a later gestation.     

Reference ranges of alpha fetoprotein (AFP) and pregnancy-specific beta 1-glycoprotein in early pregnancy

alpha-fetoprotein (AFP) and pregnancy-specific-beta 1-glycoprotein (SP1) have been measured in sera from women between the 10th and 16th gestational ranges week. Reference have been calculated for these different of gestation. 10. and 90. percentile were determined as reference levels. All confidence ranges were calculated for a probability level of 10 per cent.     

Two pregnancy-associated serum proteins with pregnancy-specific beta1-glycoprotein determinants.

A protein showing strong antigenic cross-reactivity with the "pregnancy-specific" beta1-glycoprotein (PSbetaG) was demonstrated in serum of pregnant women during the second and third trimesters, but not in sera from normal men and nonpregnant women. The described protein had alpha2-electrophoretic mobility and its molecular weight was estimated to be around 200,000 as compared to 80,000 for PSbetaG. Crossed immunoelectrophoretic analysis, using antiserum to PSbetaG, indicated the presence of additional antigenic determinants in PSbetaG not demonstrable in the cross-reacting alpha2-protein. The PSbetaG/alpha2-protein ratio was rather constant in consecutive serum samples from one woman during pregnancy, but showed a marked variation when sera from different women were compared. Results of rocket immunoelectrophoresis gave a rough estimate of the ratio between these two proteins in a sample of pregnancy serum. The reported findings point to the need for development of specific methods for quantitation of the two proteins and the necessity to re-evaluate earlier quantitative PSbetaG data.     

Detection of pregnancy-specific beta 1-glycoprotein (SP1), of proteins of the "pregnancy zone" (PZ), of pregnancy-associated plasma protein A (PAPP-A) with 24-hour radial immunodiffusion. Detection of pregnancy-specific beta 1-glycoprotein (SP1) with turbidimetry. Current significance of the proteins

The estimations of pregnancy specific beta 1-glycoprotein (SP1), pregnancy associated alpha 2-glycoprotein (PZ) and pregnancy associated plasma protein A (PAPP-A) in serum samples are useful for supervision of pregnancy and diagnosis of gestational diseases. In clinical practice simple inexpensive and short time methods are preferred. Two simple short time methods were described. The 24 hour radial immuno-diffusion (RID) was compared with the usual 48 hour RID in 30 serum samples of normal pregnant women. The SP1-values ascertained with the 24 hour RID and the 48 hour RID correlated with a high coefficient (r = 0.99). In ranges of high SP1-concentrations the correlation was decreased. The correlation coefficients for PZ and PAPP-A amounted to 0.89 and 0.925. The estimation of proteins with turbidimetry is a real short time method. This method was performed in 19 serum samples of pregnant women and the results were compared with the 24 hour RID. The correlation coefficient amounted to 0.81. Between the results of 24 hour RID for SP1 and PAPP-A there was no correlation.     

Complex formation of pregnancy-specific alpha 2-glycoprotein (SP1 alpha) and heparin

The Schwangerschaftsprotein 1 (SP1)alpha values in blood measured by rocket immunoelectrophoresis are affected by the addition of anticoagulants. When compared with values in serum, those in heparin plasma were much higher, while those in sequestrene ethylenediamine-tetra-acetic acid), sodium citrate and fluoride oxalate were lower. On the other hand, SP1 and SP1 beta concentrations were not significantly affected in heparin or sequestrene and were only slightly depressed in sodium citrate and fluoride oxalate. The effect of heparin on SP1 alpha in serum was dose-dependent. We surmise that SP1 alpha forms a complex with heparin and that it may be involved in the coagulation system in pregnancy.     

Maternal serum pregnancy-associated plasma protein A (PAPP-A) but not pregnancy-specific beta1-glycoprotein (SP1) is a useful second-trimester marker for fetal trisomy 18.

The usefulness of early second-trimester serum determinations of pregnancy-associated plasma protein A (PAPP-A) and pregnancy-specific beta1-glycoprotein (SP1) in suspected cases of fetal trisomy 18 was examined in a retrospective, cross-sectional study. Maternal serum PAPP-A and SP1 in 20 cases of fetal trisomy 18 between 15 and 20 weeks of pregnancy, and in 40 controls matched for gestational age and storage time were determined and compared with hCG and free oestriol (uE3). In trisomy 18, the reduction in serum concentration was found to be more pronounced for PAPP-A than for hCG and free oestriol. While none of the 40 control sera had a MoM below 0.2 for either PAPP-A, hCG or uE3, in the trisomy 18 group (20 cases) 17 (85 per cent) of the PAPP-A but only 5 (25 per cent) of the hCG and 4 (20 per cent) of the uE3 results were below the 0.2 MoM threshold. SP1 did not distinguish between controls and trisomy 18. This chromosomal abnormality is too rare a condition to justify maternal serum PAPP-A determination in the second trimester as a routine procedure, but such a test can play a useful role whenever the risk of trisomy 18 is found to be only marginally increased after hCG and uE3 measurements.     

Pregnancy-specific beta 1-glycoprotein (SP1) and its relation to fetal birth weight at term pregnancy.

The relation between serum levels of pregnancy-specific beta 1-glycoprotein (SP1) and actual fetal and placental weights was studied in 100 full-term pregnant women. This was compared with fetal weight determination by ultrasound. SP1 levels significantly correlated with fetal and placental weights. Its determination was found to be comparable to ultrasonography in placental fetal weight assessment, especially at the extremes of fetal weight (macrosomia and small for gestational age) where special obstetric management is warranted.     

Pregnancy-specific beta 1-glycoprotein (SP1) levels measured by nephelometry in serum from women with vaginal bleeding in the first half of pregnancy

Pregnancy-specific beta 1-glycoprotein (SP1) levels were measured by nephelometry in sera from 107 women admitted to hospital because of vaginal bleeding in weeks 8 to 20 of pregnancy. The SP1 results were compared with those in single samples from 655 women and serial samples from 9 women with uncomplicated single pregnancies in the same period. The possibility of predicting the outcome of a pregnancy complicated by vaginal bleeding was calculated on the basis of the SP1 level on admission to hospital. In 65% a normal SP1 value predicted continuation of pregnancy, whereas a low SP1 value invariably predicted spontaneous abortion.     

Pregnancy-specific beta 1-glycoprotein (SP1) after in vitro fertilization and embryo transfer

Recent reports indicate that SP1, a "pregnancy-specific beta 1-glycoprotein", can be used as a biological marker for very early pregnancy and occult abortion. In this investigation, SP1 serum concentrations were measured in the luteal phase of 48 menstrual cycles stimulated for in-vitro fertilization (IVF) and embryo transfer (ET). All patients received hMG for ovarian stimulation. Ovulation was induced by beta-hCG and also administered to support the luteal phase. In the 8 pregnancies arising after ET, SP1 (less than 0.5 ng/ml) was not detected before 13 to 19 days after laparoscopy. In contrast, the pregnancy-dependent beta-hCG increase was detectable earlier than SP1 despite the administration of hCG given for luteal support. However, low SP1 readings (0.5-1.1 microgram/ml) as early as 3 days after laparoscopy were observed in 11 cycles without a positive sign of beta-hCG production. Our results suggest that SP1 determinations cannot be used as a marker for occult abortion; also, positive SP1 readings without increase beta-hCG, especially during the early luteal phase after ET, have to be interpreted with caution.     

Trophoblastic disease monitoring: Evaluation of pregnancy-specific beta 1-glycoprotein

Pregnancy-specific beta 1-glycoprotein (SP1) was evaluated as a potential marker protein for monitoring trophoblastic disease. Four patients with post-molar pregnancy accompanied by spontaneous titer remission and three patients with nonmetastatic trophoblastic disease were found to have regression curves for both human chorionic gonadotropin (hCG) and SP, which closely followed each other. Of three patients with metastatic choriocarcinoma, two were shown to have discordant hCG and SP1 patterns, SP1 in both cases was plateauing or rising while hCG continued to fall. Two other patients are described, one with a spontaneous remission, and one who previously had had choriocarcinoma and was found to have low levels of hCG with higher levels of SP1.