Maternal serum alpha-fetoprotein and spontaneous abortion.

The relationship between spontaneous abortion and maternal serum alpha-fetoprotein (AFP) levels was investigated between 9 and 25 weeks of pregnancy. Seven out of 126 (5-6 per cent) women who had spontaneous abortions had raised maternal serum AFP levels at their antenatal booking visit compared to 4 out of 247 (1-6 per cent) control patients who were delivered of single liveborn infants, a statistically significant differences. The raised AFP concentrations were, however, associated with spontaneous abortion only if the serum samples had been taken immediately before, or at sometime after the abortion was first clinically suspected. This suggests that high levels do not predict the development of abortion in women who have not already threatened to abort. It is therefore unlikely that women who have not already threatened to abort. Therefore, when maternal serum AFP levels are used to screen for fetal neural tube defects, women referred for a diagnostic amniocentesis on account of a high level are unlikely to have been selected on the basis of a tendency to abort.     

Pregnancies associated with low maternal serum alpha-fetoprotein concentrations.

A program of routine screening for antenatal detection of neural tube defects by alpha fetoprotein (AFP) testing is described. It was decided to determine the outcome of all pregnancies in which the patients exhibited a low AFP level during the screening process. From May 1975 to September 1976, 3% (53 cases) of the 2100 women tested had low AFP levels. Since maternal serum AFP levels rise with increasing gestational age until 32 weeks, a large number of women with low AFP levels actually have gestational ages more advanced than originally thought. That was true in this test. Ultrasonic examination of the cases with low AFP levels halped in revision gestational ages for some of the women. Among the 49 women with low AFP levels at gestational ages from 12-16 weeks, 12% had a spontaneous abortion eventually, 2% (or 1 case) had a macerated stillborn infant, and 1 woman was not pregnant. All 4 of the women with low AFP levels at gestational ages above 16 weeks had their gestational ages revised downward following ultrasonic examination. The study show that most women with low AFP levels eventually deliver a normal infant; a low AFP level does appear to be associated with spontaneous abortion. A larger study might identify association with other abnormalities. The study data was graphed and tabulated.     

Does ultrasound examination render biochemical tests obsolete in the prediction of early pregnancy failure?

Summary. Serum levels of fetal, placental and maternal hormones and proteins [β-fetoprotein (AFP), human chorionic gonadotrophin, human placental lactogen. schwangerschaftsprotein 1, pregnancy associated plasma protein-A (PAPP-A), oestradiol-17β, progesterone, pregnancy zone protein] were measured in 108 women with bleeding during the first half of pregnancy. Ultrasound examination at the time of each blood sampling revealed a fetal heart action on at least one occasion in 77 women. Spontaneous abortion occurred in 42 pregnancies, 31 of these showed no ultrasound sign of fetal life, whilst the fetal heart action was observed repeatedly until abortion in the remaining 11 women. Abnormally low levels of PAPP-A were most likely to indicate pregnancy failure, in particular if the fetal heart action was seen at the time of blood sampling. The predictive value, sensitivity and relative risk of a single depressed PAPP-A level were respectively 49, 89 and 41%, the predictive value of a normal result being 99%. With the exception of AFP, all other biochemical indices examined were consistently in the normal range in this group of women. If ultrasound findings were not considered, the biochemical indices were of comparable value in the prediction of spontaneous abortion. PAPP-A levels were uniformly depressed in all patients who spontaneously aborted, frequently weeks before this event, in the presence of a live fetus.     

Does ultrasound examination render biochemical tests obsolete in the prediction of early pregnancy failure?

Serum levels of fetal, placental and maternal hormones and proteins [alpha-fetoprotein (AFP), human chorionic gonadotrophin, human placental lactogen, schwangerschaftsprotein 1, pregnancy associated plasma protein-A (PAPP-A), oestradiol-17 beta, progesterone, pregnancy zone protein] were measured in 108 women with bleeding during the first half of pregnancy. Ultrasound examination at the time of each blood sampling revealed a fetal heart action on at least one occasion in 77 women. Spontaneous abortion occurred in 42 pregnancies, 31 of these showed no ultrasound sign of fetal life, whilst the fetal heart action was observed repeatedly until abortion in the remaining 11 women. Abnormally low levels of PAPP-A were most likely to indicate pregnancy failure, in particular if the fetal heart action was seen at the time of blood sampling. The predictive value, sensitivity and relative risk of a single depressed PAPP-A level were respectively 49, 89 and 41%, the predictive value of a normal result being 99%. With the exception of AFP, all other biochemical indices examined were consistently in the normal range in this group of women. If ultrasound findings were not considered, the biochemical indices were of comparable value in the prediction of spontaneous abortion. PAPP-A levels were uniformly depressed in all patients who spontaneously aborted, frequently weeks before this event, in the presence of a live fetus.     

Can a single serum CA125 assay predict the outcome of threatened abortion?

Earlier work suggested that high levels of CA125 could be detected in the sera of women with threatened abortion. In this study, we used CA125 as a method of anticipating outcome in cases of threatened abortion and compared the results with ultrasonic findings. Three groups of patients were studied.(1) 57 women who threatened to abort, but whose pregnancy continued.(2) 43 women with a threatened abortion, who subsequently aborted, and (3) 50 normal women who had no bleeding in early pregnancy. There was a highly significant increase in serum CA125 in women who aborted compared with the other two groups (P<0.001). The results compared well with conventional ultrasound and serum CA125 may be developed as a cheap, sensitive and specific predictor of outcome in cases of threatened abortion.     

Serum polyamine oxidase activity in spontaneous abortion

Summary. Serum polyamine oxidase activity was determined in 38 women admitted to the Maternity Department of Szombathely, Hungary, with clinical signs of threatened abortion between 11 and 22 weeks gestation and who aborted spontaneously with 48 h of admission. Serum polyamine oxidase activity was found to be significantly lower in these women compared with that in women having normal pregnancies of the same gestational age. The higher polyamine oxidase levels which were found in five women who aborted during oxytocin infusion probably resulted from increased contractions expelling enzyme-rich blood from the intervillous space into the maternal circulation. Present evidence is insufficient to explain the full clinical significance of these findings.     

Human placental lactogen, pregnancy-specific beta-1-glycoprotein and alpha-fetoprotein in serum in threatened abortion

The predictive value of HPL, SP1 and AFP in serum were determined in 109 women admitted to hospital because of vaginal bleeding in the 6th to 19th gestational week. The prediction of abortion based on the initial analysis from the day of admission was found to be 91.7%, 75.9% and 81.8% for HPL, SP1 and AFP, respectively. The corresponding values for prediction of successful outcome were 68.7%, 73.6% and 65.4%. The HPL and AFP determinations were, however, found to be valid only after the 9th and 12th gestational week, respectively. A highly significant positive correlation (r = 0.84, P less than 0.001) was demonstrated between HPL and SP1 suggesting that SP1 measurements might replace HPL in the evaluation of the prognosis in threatened abortion.     

Maternal plasma, human placental lactogen, alpha-fetoprotein, prolactin and growth hormone in early pregnancy

Human placental lactogen (HPL), alpha-fetoprotein, prolactin and growth hormones were assayed simultaneously twice weekly in 21 women from 4--16 weeks' gestation. Mean levels were established from 15 of the women for comparison with one woman with a twin pregnancy, two who aborted and three who received progestogen supplements. There was wide interpatient variation in all hormone levels excepting HPL. The mean levels of all except growth hormone showed an upward trend. Mean growth hormone levels were higher initially but remained within a 2--4 ng/ml range throughout. In the twin pregnancy, only HPL and alpha-fetoprotein levels were significantly raised. HPL was detected in one of the two women who aborted, whereas growth hormone was initially extremely high, falling precipitously prior to abortion in both women. Treatment with progestogen supplements did not appear to influence any of the hormones measured. This study suggests that serial estimations of HPL appear to be the most cost-effective guide to early fetal well-being of the four hormones measured.     

Plasma HCG levels in patients with bleeding in the first and second trimesters of pregnancy.

The prognostic value of maternal plasma human chorionic gonadotrophin (hCG) determinations, measured by a specific beta-subunit radioimmunoassay, was studied in 188 patients with bleeding between 6 and 20 weeks gestation. The patients were arranged into different subgroups according to ultrasound findings as well as clinical and histopathological evidence. In threatened abortion with successful outcome (50 per cent of all patients studied), the weekly mean hCG values were normal or even slightly elevated. In patients with a blighted ovum, the first hCG level measured was in the normal range in 34 per cent of the patients. In patients who aborted embryo with former life signs hCG values were generally normal before the abortion. The hCG levels were usually low in patients with incomplete abortion and ectopic pregnancy. An initially subnormal level of hCG was associated with a poor outcome of pregnancy in 92 per cent of patients. If the first hCG level was within the normal range the outcome of pregnancy was favourable in 79 per cent of patients.     

Maternal serum levels of tumor necrosis factor-alpha and interleukin-2 receptor in threatened abortion: a comparison with normal and pathologic pregnancies

OBJECTIVE: We evaluated tumor necrosis factor-alpha (TNF-alpha) and interleukin-2 (IL-2) receptor levels in patients with threatened abortion and compared the levels with normal and pathologic pregnancies. DESIGN: A prospective, nonrandomized, case-control study. SETTING: Academic research setting. PATIENT(S): Twenty-two patients with threatened abortion, 18 patients with pathologic pregnancies, 20 healthy pregnant women, and 20 nonpregnant women. INTERVENTION(S): Maternal serum TNF-alpha and IL-2 receptor levels were measured with a solid-phase, two-site chemiluminescent enzyme immunometric assay method. MAIN OUTCOME MEASURE(S): TNF-alpha and IL-2 receptor levels. RESULT(S): The mean +/- SEM maternal serum IL-2 receptor level for patients with threatened abortion was 481.3 +/- 35.7 U/mL, compared with 426.5 +/- 22.4 U/mL in the normal pregnant group. There was no statistically significant difference in the mean +/- SEM serum TNF-alpha level between the patients with threatened abortion and those with normal pregnancies (16.1 +/- 2.7 pg/mL vs. 10.9 +/- 0.8 pg/mL). The mean +/- SEM maternal serum IL-2 receptor level was significantly higher in patients with pathologic pregnancies than in those with normal pregnancies (506.2 +/- 27.6 U/mL vs. 426.5 +/- 22.4 U/mL). The mean +/- SEM maternal serum TNF-alpha level was significantly higher in patients with pathologic pregnancies than in those with threatened abortion (39.2 +/- 9.5 pg/mL vs. 16.1 +/- 2.7 pg/mL) and normal pregnancies (39.2 +/- 9.5 pg/mL vs. 10.9 +/- 0.8 pg/mL). CONCLUSION(S): In comparison with normal pregnancies, maternal serum IL-2 receptor and TNF-alpha levels were not significantly increased in patients with threatened abortion with good outcome.     

Toxemia of pregnancy: assessment of fetal distress by urinary estriol and circulating human placental lactogen and alpha-fetoprotein levels.

The efficacy of three biochemical methods for the detection of fetal distress was assessed in a prospective study of 224 singleton pregnancies complicated by toxemia. Fetal distress was diagnosed in 65 cases (29 per cent). Abnormally low urinary estriol (E3) excretion pointed out 63 per cent, low serum levels of human placental lactogen (HPL) 27 per cent, and elevated maternal serum alpha fetoprotein (AFP) 10 per cent of distressed fetuses. The efficacy of each test increased with the severity of maternal disease. The frequencies of false pathologic levels were: E3 19 per cent, HPL 0 per cent, and AFP 1 per cent of the cases with a normal fetal outcome. Although E3 was by far the most effective marker, abnormal levels of HPL and AFP provided supportive evidence for fetal distress by pointing out those cases in which E3 reading was not a false positive.     

Plasma hormone profile of threatened abortion and its prognosis

Hormone levels in patients with threatened abortion were compared with those of women with normal pregnancies to determine the relationship between these hormone patterns and patient prognoses. Plasma progesterone, plasma unconjugated estradiol-17beta (estradiol), and plasma human chorionic somato-mammotropin (HCS) were measured serially in 27 patients with threatened abortion. Twelve of these patients were able to continue their pregnancies, and 15 patients aborted. Of the 3 indices tested, 2 (plasma estradiol and HCS levels) showed marked differences in women who were able to continue their pregnancies and women whose pregnancies ended in abortions; moreover, these findings indicated that these 2 levels could be used as indices for the evaluation of a pregnant patient's prognosis.     

Prenatal diagnosis of neural tube defects. IV. Maternal serum alpha-fetoprotein screening

The maternal serum alpha-fetoprotein (AFP) in 6161 women in routine pregnancy [2771 in a hospital obstetric clinic (group 1) and 3390 in private practices (group 2)] was studied. Group 1 studies enabled the delineation of the normal range of serum AFP, whereas group 2 represented a true screening experience. In group 2, 39 (2.5%) of 1566 women at 16 to 18 weeks' gestation had raised (2.5 times the median or more) serum AFP. Of these 39 women, 3 (7.8%) had neural tube defects (NTDs), 6 (15.4%) had multiple pregnancies, 1 (2.6%) had congenital nephrosis, 7 (17.9%) had spontaneous abortions, 7 (17.9%) had miscellaneous associated factors, and 15 (38.5%) had raised serum AFP for no obvious reason. Only 16 (1%) women had "unnecessary" amniocenteses. None of these aborted subsequently. Analysis of the combined data showed that NTDs were detectable in 87.5% of patients-all 6 with anencephaly and 1 of 2 with spina bifida (1 spina bifida lesion closed); multiple pregnancy was determined in 45% (18/40 cases), and spontaneous abortion ensued in 14.5%. In group 1 a raised serum AFP was associated with a host of complications in 77.3% of the women. Low AFP values had associated complications in 72.2% of cases. Maternal serum AFP screening represents another potentially important tool for early detection of high-risk pregnancy.     

Predictive value of hormone determinations in the first half of pregnancy

In a prospective randomized study serial hormone determinations (beta-hCG, HPL, P, 17-OHP, E2 and E3) were performed with 1125 pregnant women from the detection of pregnancy until delivery (n = 994) or abortion (n = 131). In 605 women carrying to term blood sampling started before the 16th wk of gestation, while 389 patients were admitted to hospital between the 16th and 20th wk of gestation. The first value of most of the hormone determinations at the time of diagnosis of pregnancy before the 16th wk was normal in more than 90% (beta-hCG 95%, P 94%, E3 94%, E2 92%, HPL 64%). In the case of women with abortion the first hormone determination was low in more than 50% (beta-hCG 51%, P 56%, E3 54%, E2 62%, HPL 62%). The predictive value was highest for beta-hCG (75%) and E2 (70%) and lowest for HPL (18%). In 249 women with threatened abortion blood samples were obtained at the first days of bleeding. At this time the highest sensitivity in detecting early abortions (before the 16th wk of pregnancy) was 82% for E2, followed by beta-hCG 74%, E3 65%, P 63%, 17-OHP 52% and HPL 34% (n = 112). In late abortion (after the 16th wk of pregnancy, n = 19) the sensitivity of all methods tested was below 40%. In the case of women with bleeding and continuation of pregnancy (n = 118) normal values were found in 95% by P, 94% by beta-hCG, 93% by HPL and E3, and 83% by 17-OHP respectively. Serial determinations in women with abortion revealed that in a normal population trophoblastic disorders with reduced beta-hCG concentrations were most common. Of the remaining patients with normal beta-hCG concentrations every third woman had low P or E2 values. The combined determination of all hormones allowed conclusions to be drawn on the cause of pregnancy failure. It could be established that prior to the 6th wk of pregnancy the determination of beta-hCG was most valuable. From the 7th wk onwards the measurement of E2 or E3 showed the highest sensitivity. Between the 11th and 14th wk of pregnancy the discriminating potency of all methods tested was equally high. After the 14th wk of pregnancy hormone determinations were of little diagnostic value.     

Vitamin A concentration in amniotic fluid and maternal serum related to neural-tube defects

The vitamin A concentration of amniotic fluid and maternal serum was measured during the second trimester of pregnancy in 106 women, 12 of whom had a baby with a neural-tube defect. In these 12 pregnancies the amniotic fluid vitamin A concentration was significantly higher than in 94 normal pregnancies. There was a highly significant correlation between amniotic fluid vitamin A and both zinc and alpha-fetoprotein (AFP) levels. The maternal serum vitamin A levels were also significantly related to serum zinc levels. Women with a raised serum AFP level, but a normal baby, had significantly higher amniotic fluid vitamin A levels and significantly lower serum vitamin A levels compared with those in women with normal serum AFP levels.     

Plasma pregnancy-associated alpha 2-glycoprotein concentrations in complications of pregnancy and foetal abnormality.

Maternal plasma concentrations of pregnancy-associated alpha 2-glycoprotein (alpha 2-PAG) were measured in normal pregnancy and in pregnancies complicated by apparent threatened abortion, pre-eclampsia or intrauterine growth retardation (IUGR). alpha 2-PAG levels were significantly decreased in those women who spontaneously aborted and in those with foetal death, but were unaffected in patients who threatened to abort and in whom pregnancy continued successfully. Concentrations of alpha 2-PAG were also unaffected in subjects with mild or severe pre-eclampsia and in those with IUGR. Patients with high alpha-foetoprotein levels associated with foetal abnormality also had normal alpha 2-PAG levels for stage of gestation. The possible immunological implications of these findings are discussed.     

Vitamin A concentration in amniotic fluid and maternal serum related to neural-tube defects

Summary. The vitamin A concentration of amniotic fluid and maternal serum was measured during the second trimester of pregnancy in 106 women, 12 of whom had a baby with a neural-tube defect. In these 12 pregnancies the amniotic fluid vitamin A concentration was significantly higher than in 94 normal pregnancies. There was a highly significant correlation between amniotic fluid vitamin A and both zinc and α-fetoprotein (AFP) levels. The maternal serum vitamin A levels were also significantly related to serum zinc levels. Women with a raised serum AFP level, but a normal baby, had significantly higher amniotic fluid vitamin A levels and significantly lower serum vitamin A levels compared with those in women with normal serum AFP levels.     

Serial human placental lactogen estimations in serum and placental weight-for-dates.

The relation between serial HPL assays in serum and placental weight-for-dates was studied in 70 randomly chosen pregnant women. Out of five different aspects of the HPL curve only a fall below the 2-3d centile without subsequent recovery was related to low placental weight. When a small-for-dates (SFD) placenta was associated with normal HPL levels, maternal body weight tended to be lower than if both placental weight and HPL levels were abnormal. This suggests that physiologically small placentae are discernible from pathologically small placentae by a normal HPL curve.     

Serum CA 125 levels in early pregnancy and subsequent spontaneous abortion

CA 125 has been found in high concentrations in human amniotic fluid throughout gestation, with significant quantities seen in the decidua and chorion. Because disruption of the epithelial basement membrane of the fetal membrane or the decidua could theoretically lead to a rise in maternal CA 125 levels, this increase may be a predictor of subsequent spontaneous abortion of the fetus. A study was initiated to investigate whether a sudden rise in the serum CA 125 level might predict spontaneous first-trimester abortions. CA 125 levels of 101 pregnant women were evaluated 18-22 days from conception and 6 weeks from conception (a frequent time for spontaneous abortion) to determine whether there is a sudden increase (from baseline or early trimester levels) during the middle or late first trimester immediately before or at the time of abortion. The results indicated that although there was a definite correlation found between elevation of CA 125 and spontaneous abortion, the higher levels occurred early in the first trimester whereas the majority of abortions did not occur until much later, after fetal viability was established. Six of ten women with CA 125 levels of 150 U/mL or greater aborted, compared with four of 92 women with CA 125 levels less than 150 U/mL. One of 11 women pregnant after in vitro fertilization had a CA 125 level above 150 U/mL, and she aborted.     

Cervical and serum IgA and serum IgG antibodies to Chlamydia trachomatis and herpes simplex virus in threatened abortion: a prospective study

Summary. The aetiological role of Chlamydia trachomatis (CT) and herpes simplex virus (HSV) was investigated in 189 patients with threatened abortion. Assessment of infection was based on isolation, and on determination of serum immunoglobulin (Ig)G and IgA antibodies as well as cervical IgA antibody levels with new sensitive radioimmunoassay (RIA) techniques. One third of the women were delivered of a healthy infant and two thirds aborted, but the two groups were otherwise clinically similar. By isolation, only 2.7% of the patients were CT-positive, but increased cervical IgA antibody level to CT was detected in 41.3%. The mean level of these local antibodies was similar in both study groups, but the mean levels of serum IgA and IgG antibodies were somewhat higher in the patients who aborted although the difference was not significant. None of the cervical specimens was positive for HSV by isolation but the cervical IgA antibody level to HSV was raised in 47.1% of the patients. Both cervical and serum IgA antibody levels to HSV were significantly raised among the patients who aborted, but there were no differences between the patients with spontaneous abortion and those with a blighted ovum. There was no clear association between CT and abortion, but an association between HSV and abortion is possible. The incidence of raised levels of both CT and HSV IgA antibodies in the cervix was surprisingly high in both groups and the significance of this finding remains to be investigated.