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PubMed1981

[Changes of dehydroepiandrosterone (DHA), 16 alpha OH-DHA and estriol levels in maternal peripheral blood during late pregnancy and labor--measured by gas chromatography-mass spectrometry with application of deuterated steroids as internal standards (author's transl)].

Serum levels of DHA, 16 alpha OH-DHA and estriol (E3) were determined in maternal peripheral vein by gas chromatography-mass spectrometry (GC-MS) with application of deuterated steroids as internal standards during late pregnancy and labor. Deuterium labeled 3,4,4-d3-DHA, 3,4,4-d3-16 alpha OH-DHA and 2,4-d2-E3 were newly synthesized and highly specific method for determination of serum DHA, 16 alpha OH-DHA and E3 was developed by GC-MS. The mean total steroid concentrations in the third trimester (III), in the stage when patients had irregular contraction (P) and during the first stage of labor (1st) were as follows; DHA, 612.9 +/- 265.3, 877.5 +/- 365.6 and 1522.5 +/- 580.6, 16 alpha OH-DHA, 30.2 +/- 20.2, 49.4 +/- 21.9 and 161.3 +/- 43.6, E3, 50.9 +/0 25.7, 70.4 +/- 19.8 and 108.6 +/- 44.5 ng/ml (mean +/- S.D.). The values of these three steroids increased significantly from the III to the 1st. Correlation between the levels of total DHA and total E2 measured in ten patients individually in the III was 0.8665 (p less than 0.001) which changed to -0.6650 (p less than 0.01) and -0.5362 (p less than 0.05) in the stage of P and 1st. ACTH was given to eight pregnant women in the third trimester, and response of these steroids to ACTH was studied. In addition to these steroids, cortisol (F) levels were also measured by RIA. Following the administration, F increased significantly whereas no changes of DHA, 16 alpha OH-DHA and E3 levels were noticed suggesting that these steroids may not be influenced by maternal adrenal secretion. From the results obtained above, it is suggested that the endocrinological environment in maternal blood as indicated by correlations between DHA and E3 levels, changes prior to the onset of labor.

Dehydroepiandrosterone↗
PubMed1984

Automated continuous-flow radioimmunoassay for salivary estriol.

We have automated a radioimmunoassay for salivary estriol by using the "Southmead" continuous-flow system. The assay, based on a well-validated manual assay, involves a Sepharose-coupled antiserum and an 125I-radioligand. The antibody-bound and free radioligand fractions are separated by on-line filtration. Performance of the automated assay has been reliable during six months of regular use, and compares favorably with that of the manual assay. Drift (0.5 nmol/L per 100 samples) and sample carryover (3%) are acceptable, and the throughput rate is 55 samples per hour. The system is suitable for the assay of the large numbers of samples generated by daily saliva specimen collection in the third trimester of pregnancy.

Autoanalysis↗
PubMed1984

[Rapid measurement of estriol & estradiol by high performance liquid chromatography (HPLC)].

Measurement of Estriol (E3) and Estradiol (E2) within 25 minutes by high performance liquid chromatography (HPLC) was achieved in this study and the values were compared with those of radioimmunoassay (RIA). A totally computerized HPLC method was developed for measuring unconjugated E3 and E2 in the sera of pregnant women. The sera samples were injected directly into the apparatus and transferred to a pretreatment column where estrogens were absorbed while hydrophilic components such as proteins and carbohydrates were excluded. The estrogens then passed through another separation column containing a new type of polymer gel. The mobile phase consisted of an acetonitrile/water mixture, and separation was achieved by means of a reversed phase mechanism. The eluent was monitored for fluorescence. All these procedures were monitored and controlled with a built-in microcomputer. The sera samples from 61 normal pregnant women at 20 to 41 weeks of pregnancy were simultaneously assayed by HPLC and RIA. The correlation of values obtained from HPLC and RIA was; E3: Y = 0.875X-0.172, the coefficient of correlation was 0.899, E2: Y = 0.972X + 6.791, the coefficient of correlation was 0.841 (Y = RIA values, X = HPLC values). The quick measurements of E3 and E2 by HPLC can be a useful method in evaluating the feto-placental function.

Chromatography, High Pressure Liquid↗
PubMed1983

[Statistical analysis of urinary estriol (U-E3), serum leucine aminopeptidase (LAP) and heat stable alkaline phosphatase (HSAP) in toxemia].

The levels of urinary estriol (U-E3), serum leucine aminopeptidase (LSP) and heat stable alkaline phosphatase (HSAP) were determined in toxemic and normal pregnancies. The significance of differences was established by weekly estimation of the parameters for both groups after the 28th week of gestation. Assayed values were classified into 4 types (type I-IV) by the mean values for 3 serial 24h assays and 3 patterns (pattern a-c) observed with these three determinations. The distribution rate for each type and pattern was examined according to the following: Severe toxemia, low birth weight, meconium staining at parturition and low apgar score groups. For U-E3, the incidence of the low value type (type IV) and the descending pattern (pattern c) both increased linearly in all the above groups. These findings suggest the clinical applicability of U-E3 as a reasonable indicator for evaluating intrauterine fetal well being because of the close correlation to the listed conditions. Thus these biochemical parameters should be considered in the antepartum fetal management of third trimester toxemic pregnancies.

Alkaline Phosphatase↗
PubMed1983

Action of estriol on the uropygial gland activity in pigeon.

Administration of estriol (Sigma Chemical Co., U.S.A.) in the female young-adult pigeons at a dose of 50 micrograms/bird/day for 7 consecutive days caused atrophy of the uropygial gland, associated with increased cytopycnosis and drastic cell loss within the holocrine alveoli and reduction in the content of the glandular lipids. Probable mode of action of this steroid upon the uropygial gland has been suggested in the light of the recent data on its anti-estradiol property manifested in rat uterus.

Animals↗
PubMed1981

[Concentration of serum unconjugated estriol and estetrol in pregnant women with intrauterine growth retardation, and significance of these hormones in pregnancy (author's transl)].

Recently, estetrol (15 alpha-hydroxyestriol, E4) has been suggested to be a better indicator of fetal well-being than estriol (E3). In normal pregnancy, the concentration of unconjugated E3 and E4 in serum gradually increased as pregnancy progressed, and especially, rapidly increased in the third trimester. The patients with IUGR were classified in three groups. In the first group with mild pregnancy complications or none, serum E3, E4 and urine E3 almost changed in normal range. In the second group with severe pregnancy complications, only serum E3 changed almost in normal range, but urine E3 shows in low levels and serum E4 in high levels. In the third group with perinatal death of neonate, these three hormone levels was remarkedly low, especially in serum and urine E3. The highest E3 value in 51 pregnant women, significantly correlated with placental weight, birth weight and body length of neonate, and highest E4 significantly correlated with birth weight and chest circumference of neonate. The results signified that E3 predominantly indicated placental function, E4 also fetal function.

Estetrol↗
PubMed1978

Sequential determination of serum human placental lactogen, estriol, and estetrol for assessment of fetal morbidity.

Serial measurements were made of the concentrations of maternal serum human placental lactogen (hPL) (300 determinations), estriol (E3) (460 determinations), and estetrol (E4) (275 determinations) in normal human pregnancy during the third trimester period. Simultaneous determinations of serum hPL, E3, and E4 were also made sequentially on blood samples from 6 diabetic and 5 toxemic pregnant women to ascertain the relative usefulness of these parameters as indicators of fetal welfare. In uncomplicated diabetic patients controlled with insulin, all parameters increased with gestational age. In three pregnancies complicated by severe toxemia in which fetal distress progressed to intrauterine fetal death, both serum E3 and E4 levels decreased progressively, but E4 concentration started to decrease at least 1 day earlier than E3 prior to fetal death. In other women, the E4 levels appeared to drop or decrease significantly whereas the E3 levels remained almost unchanged. Daily hPL levels remained low in chronic fetal distress and, therefore, appeared to be of minimal value for predicting either intrauterine death or acute fetal distress. Therefore, serum E4 measurement seems to provide a more sensitive and reliable indicator of fetal morbidity than the measurement of serum E3 during toxemic pregnancies.

Estetrol↗
PubMed1981

hPL deficiency with normal estriol levels in a normal pregnancy.

The third published case of human placental lactogen (hPL) deficiency in a normal pregnancy is reported. The results of the 3 cases are discussed. In all cases, estriol levels were normal and hPL levels were either unmeasurable or below 1 microgram/ml. The placenta showed no obvious abnormalities. Growth hormone and prolactin determinations did not contribute to the understanding of the deficiency; neither did the glucose levels in the maternal blood. All 3 infants were male.

Adult↗
PubMed1981

Early prediction of individual serum total estriol curves in pregnancy.

Investigating 60 individual serum total estriol (S-E3) courses from normal pregnancies, we found individual S-E3 courses parallel with the general mean, but with half the standard deviation. Thus one can predict the individual S-E3 course, which may function as a reference for every S-E3 estimation later on. A S-E3 decrease of more than 33 per cent from the individual mean is statistically significant at the 2.5 per cent level.

Adolescent↗
PubMed1981

[A liquid chromatography technique for routine determination of urinary estriol in human pregnancy (author's transl)].

A liquid chromatography procedure for routine determination of urinary estriol concentrations is described. After enzymic hydrolysis of a 1 ml sample, automatic extraction with chloroform/ethyl acetate, purification by chromatography on a disposable "minicolumn" of AG 1-X2, urinary estrogens are separated with normal phase column and isocratic elution with isooctane/ethyl acetate/methanol/water and the optical density at 280 nm is measured. The specificity is assessed by comparison of liquid chromatography with fluorometry and gas liquid chromatography. The technique is simple, rapid and quite suitable for routine determination.

Chromatography, High Pressure Liquid↗
PubMed1981

Comparison of serum unconjugated estriol and estetrol in normal and complicated pregnancies.

It has been reported that determinations of maternal serum unconjugated estriol (E3) and estetrol (E4) concentrations provide clinicians with more or less identical information on fetal status. If this is true, then theoretically the levels of E3 should be equally correlated with those of E4 in all conditions of pregnancy. To resolve this question, a study of the relationship between E3 and E4 was performed before labor in normal and complicated pregnancies. In normal pregnancy, they were highly correlated (r = .683, P less than .0001); in complicated cases, they were still correlated, but at a lower level (r = .522, P less than .003). To determine the effect of labor on this correlation, E3 and E4 levels were measured in normal subjects during labor as well as in the corresponding fetuses. The correlations between material E3 and E4, maternal and fetal E4, maternal and fetal E3, and fetal E3 and E4 were highly significant. A similar study with complicated pregnancies, however, indicated no such correlation except between fetal E3 and E4. In addition, day-to-day variability of serial measurements of E3 and E4 on an individual basis was determined in normal and diabetic subjects. The variability was qualitatively determined graphically and quantitatively determined algorithmically. The results of calculated individual variabilities indicated that the variability of E4 was less than that of E3 in most cases. It is therefore concluded that complications in pregnancy and the onset of labor have some effect on E3-E4 correlations, and that measurement of E4 has an additional advantage due to less variability.

Estetrol↗
PubMed1981

[Amniotic fluid cortisol, tetrahydrocortisone, estriol and estetrol in normal and high risk pregnancy (author's transl)].

In order to determine the possibility of assessing intrauterine fetal well being by measuring amniotic fluid steroid levels, a number of selected glucocorticoids and estrogens were assayed. Estriol (E3) and estetrol (E4) levels at 36-40 weeks of pregnancy, especially that of total E3 (T-E3 and unconjugated E4 (U-E4) rose significantly (p less than 0.01), and were at a ratio of T-E3/U-E3 8; T-E4/U-E4 2, respectively. A definite correlation was found between T-E3 and U-E3 (r = 0.97) which was not detected in the case of E4, and there was a high correlation with umbilical arterial levels of both unconjugated and total E3 and E4. Amniotic fluid cortisol (F) levels in both unconjugated (U-F) and sulfate conjugated (S-F) rose preferentially at 36-40 weeks and exceeded the levels of both umbilical arterial and maternal peripheral plasma (p less than 0.01). Both tetrahydro-cortisone (THE) and -cortisol (THF) levels increased at 29-35 weeks which in the select cases were comparable with the increases seen at 36-40 weeks. The THE level showed a definite correlation with that of umbilical artery (r = 0.73) whereas this was not the case for S-F. In pregnancies complicated with toxemia and/or diabetes mellitus, T-E3 and S-F levels are less than the lower limits for normal pregnancies. This tendency was not observed with T-E4 and THE. In pregnancies with severe RH isoimmunization, the levels of T-E3, T-E4 and S-F are markedly lower than those seen in normal pregnancies, and do not display the increase with gestational advances. On the other hand, THE and THF levels were shown to be at levels higher than in normal pregnancies. Thus, in the latter half of pregnancy, amniotic fluid steroid assays, especially T-E3, S-F and THE may be of use in the assessment of fetal well being.

Amniotic Fluid↗
PubMed1980

An algorithm for determining gestational age from unconjugated estriol levels.

Between the 30th and 40th weeks of gestational age (GA), plasma unconjugated estriol (E3) concentrations plotted as a logarithmic function of GA describe a complex bimodal curve. The maximum concentrations for the first peak (GAmax1) occur at approximately 34 weeks' GA, those for the second peak (GAmax2) occur at approximately 38 weeks' GA, and a between-mode nadir occurs at 35 weeks' GA. Using the close relationship between the features of this curve and GA, a computerized algorithmic curve analysis is devised for the estimation of GA during the third trimester of pregnancy. This report describes the algorithm, its clinical application, and its preliminary performance.

Computers↗
PubMed1980

Time trend analysis of unconjugated estriol concentrations in third-trimester pregnancy.

Utilizing a plasma pooling procedure to control short-term pulsatile variability of unconjugated estriol (E3) concentrations, the authors evaluated time trend curves in 42 subjects after normalizing time trend curves in 42 subjects after normalizing gestational age (GA) by a computerized algorithm. Semilogarithmic plots from individual subjects and a median plot derived from pooling the 42 subjects describe complex bimodal curves beginning with an initial steep rise at 30 to 32 weeks' GA, a peak between 32 and 34 weeks' Ga, a transient nadir at 35 weeks' GA, a second steep rise between 35 and 37 weeks' Ga, a second peak between 37 and 39 weeks' Ga, and a downward segment just prior to parturition. Predicted GAs at delivery obtained from individual curve analyses concurred with pediatric GAs within 2 weeks or less in 41 or 42 pregnancies.

Estriol↗
PubMed1994

Second-trimester maternal serum alpha-fetoprotein, unconjugated estriol, and hCG levels in pregnancies with ventral wall defects.

OBJECTIVE: To determine if second-trimester maternal serum concentrations of unconjugated estriol (E3) and hCG are altered in pregnancies associated with fetal gastroschisis or omphalocele. METHODS: Concentrations of alpha-fetoprotein (AFP), unconjugated E3, and hCG were measured in a case-control study involving 23 cases of gastroschisis, 17 cases of omphalocele, and 200 matched unaffected pregnancies. RESULTS: As reported previously, median AFP levels were significantly higher in pregnancies with gastroschisis and omphalocele compared to unaffected pregnancies (9.42 and 4.18 multiples of the unaffected population median [MoM], respectively). The median hCG values were not significantly different for the two defects (1.10 and 1.13 MoM, respectively). Six of the cases of omphalocele were associated with other anomalies, but exclusion of these cases from the analysis did not alter the conclusions. CONCLUSIONS: Unconjugated E3 and hCG measurements are not useful in screening for, or distinguishing between, open ventral wall defects. Alpha-fetoprotein measurements alone will detect nearly all cases of gastroschisis and most cases of omphalocele.

Abdominal Muscles↗
PubMed1993

A prospective evaluation of a second-trimester screening test for fetal Down syndrome using maternal serum alpha-fetoprotein, hCG, and unconjugated estriol.

OBJECTIVE: To test the efficacy of a screening protocol using a combination of maternal age plus three biochemical markers--maternal serum alpha-fetoprotein (MSAFP), hCG, and unconjugated estriol (E3)--for the antenatal detection of fetal Down syndrome. METHODS: We conducted a prospective cohort study of 7718 women who underwent the triple-marker analysis between weeks 15-18 of pregnancy. A second-trimester risk for Down syndrome of 1:195 or greater was considered positive. Sensitivity, specificity, positive predictive value, and their 95% confidence intervals (CIs) were calculated. We evaluated test performance for various maternal age groups and screen-positive cutoffs, as well as the relative screening efficacies of maternal age and MSAFP, MSAFP plus hCG, and MSAFP, hCG, and unconjugated E3. RESULTS: Four hundred sixty-one of the 7718 women screened (6%) were identified as positive; 319 women chose amniocentesis, for an overall amniocentesis rate of 4.1%. Twenty of 22 pregnancies affected with Down syndrome were correctly identified, as were 7255 of 7696 unaffected pregnancies, yielding a sensitivity and specificity of 91% (95% CI 79-100%) and 94% (95% CI 93.8-94.8%), respectively. The use of maternal age plus all three analytes improved test performance compared with maternal age plus MSAFP and hCG, but either had a significantly improved detection rate compared with that for maternal age and MSAFP alone. CONCLUSION: The triple-marker screen appears to be an effective method of detecting Down syndrome pregnancies while maintaining an acceptable amniocentesis rate.

Adult↗
PubMed1993

Cigarette smoking and levels of maternal serum alpha-fetoprotein, unconjugated estriol, and hCG: impact on Down syndrome screening.

OBJECTIVE: To investigate the association between maternal cigarette smoking and serum levels of alpha-fetoprotein (AFP), unconjugated estriol (uE3), and hCG and to determine whether it is appropriate to take smoking status into account when screening for fetal Down syndrome. METHODS: Smoking information was obtained from 23,668 pregnant women at the time of routine screening for fetal Down syndrome. Serum levels of AFP, uE3, and hCG were stratified by smoking status and compared. Individual risks for fetal Down syndrome were analyzed both before and after adjusting the hCG levels for the effect of smoking. The prevalence of Down syndrome in the study population was calculated for both smokers and non-smokers. RESULTS: The average AFP, uE3, and hCG levels in women who smoked cigarettes were 3% greater (95% confidence interval [CI] 2-4%), 3% less (95% CI 2-4%), and 23% less (95% CI 22-24%), respectively, compared with levels in non-smokers. At comparable maternal ages, women who smoked cigarettes were identified as being at high risk for fetal Down syndrome 40% less often than non-smokers (4.0 versus 7.1% at a risk level of 1:250). Adjusting hCG levels for smoking status reduced the overall false-positive rate from 6.4 to 6.1% (using a term risk cutoff level of 1:250). The predicted effect on detection was small (a 0.7% increase). The prevalence of Down syndrome was lower among smokers, but the difference was not statistically significant (odds ratio 0.51, 95% CI 0.15-1.5). CONCLUSIONS: Adjusting the serum markers used for Down syndrome screening for the effect of maternal smoking has a small effect on overall screening performance. Given the uncertainty over whether there is a lower birth prevalence among women who smoke cigarettes, such adjustment is not currently justified.

Adult↗