Serum Unconjugated Estriol Research Articles

Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in pregnancies with insulin-dependent diabetes: implications for screening for Down's syndrome.

To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in pregnant women with insulin-dependent diabetes mellitus and to consider the implications of the results for antenatal screening for Down's syndrome. Descriptive study using stored antenatal serum samples. Stored serum samples collected from women receiving routine antenatal care in Oxford. 126 singleton pregnancies in 92 women with insulin-dependent diabetes mellitus and for each pregnancy, two pregnancies without diabetes matched for gestational age and duration of storage of the serum sample. None of the pregnancies was associated with fetal neural tube defect or Down's syndrome. Maternal serum uE3 and hCG levels at 15-22 weeks gestation. Alpha-fetoprotein (AFP) levels were also measured for comparison. The median uE3 level in the diabetic pregnancies was 0.92 multiples of the median (MoM) for pregnancies without diabetes at the same gestational age (P less than 0.05); and the hCG level was 0.95 MoM (P = 0.48). The median AFP level was also reduced to 0.77 MoM (P less than 0.001). The reduction in uE3 and AFP levels in insulin-dependent diabetic pregnancies is sufficiently great to be taken into account in maternal serum screening programmes for Down's syndrome. Dividing the uE3 and AFP levels in such pregnancies by the corresponding median for insulin-dependent diabetic pregnancies will yield a similar false-positive rate in pregnancies with and without insulin-dependent diabetes mellitus.

Maternal serum unconjugated oestriol and human chorionic gonadotrophin levels in twin pregnancies: implications for screening for Down's syndrome

To investigate maternal serum unconjugated oestriol (uE3) and human chorionic gonadotrophin (hCG) levels in twin pregnancies and to consider the implications of the results for antenatal screening for Down's syndrome. Measurement of maternal serum uE3 and hCG levels from 15-22 weeks of gestation in twin and singleton pregnancies. Previously available maternal serum alpha-fetoprotein (AFP) levels were also presented. Stored serum samples collected from women receiving routine antenatal care in Oxford were used. 200 women with a twin pregnancy and, for each, three singleton control pregnancies matched for gestational age (same completed week of pregnancy) and duration of storage of the serum sample (same calendar quarter). The median uE3, hCG and AFP levels in the twin pregnancies were respectively, 1.67 (95% CI 1.56-1.79), 1.84 (95% CI 1.64-2.07) and 2.13 (95% CI 1.97-2.31) multiples of the median (MoM) for singleton pregnancies at the same gestational age. The variance of values for the three serum markers (expressed in logarithms), and the correlation coefficients between any two, were similar in the twin and singleton pregnancies. In maternal serum screening programmes for Down's syndrome dividing uE3, hCG and AFP MoM values in twin pregnancies by the corresponding medians for twin pregnancies will, in expectation, yield a similar false-positive rate in twin pregnancies as in singleton pregnancies.

First‐trimester maternal serum unconjugated oestriol and alpha‐fetoprotein in fetal Down's syndrome

Maternal sera (MS) taken from 1396 women prior to chorionic villus sampling at 9-12 menstrual weeks were assayed for unconjugated oestriol (uE3) and alpha-fetoprotein (AFP). Median levels increased by 41 and 26 per cent per week respectively in normal pregnancies. There were 32 pregnancies with a chromosome abnormality. The median MS uE3 and AFP were 0.73 and 0.75 multiples of the median (MoM) respectively in the ten cases of Down's syndrome (DS) but not decreased in the other abnormalities. These results suggest that both uE3 and AFP may be useful in identifying DS in the first trimester. Additional prospective studies are needed to confirm these findings.

Screening for fetal Down's syndrome with maternal serum markers—an experience in italy

The effectiveness of maternal serum alpha-fetoprotein, unconjugated oestriol, and human chorionic gonadotrophin in screening for Down's syndrome (DS) was evaluated on 840 women who underwent amniocentesis for fetal karyotype on account of their age. The risk of a DS pregnancy was established using the method of Wald et al. (1988b), which combines the age-specific risk with that indicated by the levels of the three serum markers. In women over 35, at cut-off risk levels of 1:250 and 1:380, the false-positive rate was 24 and 34 per cent, respectively. In all nine cases of DS, the estimated risk was higher than 1:250. The best screening strategy with the lowest false-positive rate was obtained by combining the three serum markers. The results suggest that this kind of screening can be proposed during genetic counselling for women under 35 and older women wishing to avoid the risk of miscarriage induced by amniocentesis.

Second‐trimester levels of maternal serum unconjugated oestriol and human chorionic gonadotropin in pregnancies affected by fetal anencephaly and open spina bifida

Unconjugated oestriol (uE3) and human chorionic gonadotropin (hCG) levels were determined in second-trimester maternal serum (MS) samples from 21 pregnancies associated with fetal anencephaly and 15 pregnancies associated with fetal open spina bifida. Each measurement was expressed as a multiple of the median (MoM) for unaffected pregnancies for each completed week of gestation. In pregnancies associated with anencephaly, the median value for MSuE3 was very low (0.17 MoM, range less than 0.12-0.33 MoM), suggesting a functional defect in the fetal adrenal prior to 20 weeks' gestation; the median value for MShCG was also low (0.73 MoM), although not to the same extent as for MSuE3. A biological explanation for the hCG result is not apparent. In pregnancies associated with open spina bifida, the MSuE3 and MShCG values were unremarkable, consistent with a lack of involvement of these open fetal defects in the synthesis and secretion of uE3 and hCG.

Measurement of serum unconjugated estriol and estradiol by high‐performance liquid chromatography

Measurement of Estriol (E3) and estradiol (E2) within 22 min by high-performance liquid chromatography (HPLC) was achieved in this study, and the values were compared with those of a radioimmunoassay (RIA). A totally computerized HPLC method was developed for measuring unconjugated E3 (u-E3) and E2 (u-E2) in the sera of pregnant women. The serum samples were injected directly into the apparatus and transferred to a pretreatment column where the estrogens were absorbed while hydrophilic components such as proteins and carbohydrates were excluded. The estrogens were 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 procedure. The eluate was monitored for fluorescence. All procedures were monitored and controlled with a built-in microcomputer. Serum samples from 97 normal pregnant women at 20-41 wk gestation were simultaneously assayed by HPLC and RIA. The correlations obtained by HPLC and RIA were as follows: u-E3, y = 0.905x - 0.385, with a coefficient of correlation of r = 0.912; for u-E2, y = 0.964x + 5.024, with a coefficient of correlation of r = 0.841 (y, RIA value; x, HPLC value). The quick measurement of u-E3 and u-E2 by HPLC can be a useful method for evaluating fetoplacental function.

Low second trimester maternal serum unconjugated oestriol in pregnancies with Down's syndrome.

Second trimester maternal serum unconjugated oestriol levels were measured in the stored serum samples from 22 pregnancies associated with Down's syndrome and 110 unaffected control pregnancies, matched for maternal age, gestational age, duration of storage of the serum sample, smoking habits and maternal weight. The serum unconjugated oestriol level of each affected pregnancy was expressed as a multiple of the median (MoM) of its five matched controls. The unconjugated oestriol levels were significantly lower in the affected pregnancies than in the unaffected pregnancies; the median MoM was 0.79 (P less than 0.05). This association between low serum unconjugated oestriol and fetal Down's syndrome early in pregnancy raises the possibility that serum unconjugated oestriol measurement may be added to maternal age and alpha-fetoprotein measurement in the antenatal screening for Down's syndrome.

Maternal serum unconjugated oestriol as an antenatal screening test for Down's syndrome

The median maternal serum unconjugated oestriol level between 13 and 27 weeks gestation in 77 pregnancies associated with Down's syndrome was lower than the median level in 385 unaffected control pregnancies matched for maternal age, gestational age, and duration of serum sample storage (P less than 0.001). The median level for the affected pregnancies was 73% of that in the controls. Low unconjugated oestriol levels can be used to detect fetal Down's syndrome; at cut-off levels selected to detect at least 35% of affected pregnancies, unconjugated serum oestriol was a better screening test than either maternal age or serum alpha-fetoprotein (AFP). The use of all three variables in combination to select women with a 1:250 or greater risk of a Down's syndrome term pregnancy would yield a 45% detection rate with a false-positive rate of 5.2%. The same detection rate using maternal age alone or using age and serum AFP in combination would yield higher false-positive rates, 15% and 9.8% respectively. The addition of unconjugated oestriol to a Down's syndrome screening programme would therefore be more efficient than the use of age and AFP alone; for a given detection rate fewer women would need an amniocentesis or, for a given percentage of women having an amniocentesis, more pregnancies with Down's syndrome would be detected.

Serum unconjugated estriol levels during spontaneous labor.

We measured maternal serum unconjugated estriol (SUE3) levels in 244 cases (218 cases with labor and 26 without labor) and investigated the relationships among several obstetrical factors and SUE3 levels. There was no significant difference in the SUE3 level between the group with labor and the group without labor. However, the SUE3 level decreased gradually with prolonged duration of labor in multipara. There were significant positive correlations between the SUE3 levels and birth weights (n = 82, r = 0.375, p less than 0.01) or placental weights (n = 82, r = 0.381, p less than 0.01) in the multipara with labor. The SUE3 levels of fetal distress cases (n = 30, 20.0 +/- 8.6 ng/ml) were significantly (p less than 0.05) lower than those without fetal distress (n = 188, 24.5 +/- 9.7 ng/ml). These data suggest that maternal SUE3 might have been affected with feto-placental function, even after the onset of labor SUE3 levels decrease with prolonged duration of labor.

Effect of the oxytocin challenge test on levels of maternal serum unconjugated serum estriol and estetrol pre- and post-test in high-risk pregnancies.

Effect of the oxytocin challenge test on levels of maternal serum unconjugated serum estriol and estetrol pre- and post-test in high-risk pregnancies.

Serum unconjugated estriol level as a predictor of pulmonary maturity

Lack of respiratory distress syndrome in infants delivered after the maternal serum estriol value attained ≥15 ng/ml was investigated. In 91 cases after 34 weeks' gestation no lecithin-sphingomyelin ratio <2.0 was found where the serum estriol level was ≥15 ng/ml and no respiratory distress syndrome in the patients delivered ≤3 days from amniocentesis.

Daily variation of serum unconjugated estriol and estetrol in normal pregnancy.

Serum unconjugated estriol and estetrol were assayed daily in seven nondiabetic, uncomplicated third-trimester pregnancies to define the daily variation of these compounds. When compared to the mean of the three preceding days' values, or to the highest mean of three consecutive daily values previously obtained in a pregnancy, daily estriol and estetrol values fell greater than or equal to 40% on 1.2 and 0% of occasions, respectively. Isolated estriol values represented falls of greater than or equal to 40% from previously obtained single estriol values on 2% of occasions, and no isolated estetrol values fell greater than or equal to 40% from any other isolated values obtained in a given pregnancy. These results define the stability of daily serum estriol and estetrol in late-gestation normal pregnancy, although they emphasize the large variability encountered when comparing isolated estriol values.

Changes in placental lactogen, beta 1-chorionic gonadotropin, and unconjugated and total estriol levels in the late course of normal human pregnancy.

The levels of human placental lactogen (hPL), beta-human chorionic gonadotropin (beta-hCG), unconjugated estriol (UE3) and total estriol (TE3) were measured radioimmunologically in women along their course of pregnancy. The serum hPL and beta-hCG levels were relatively constant in uncomplicated pregnancy, while UE3 and TE3 significantly rose towards 41 weeks of gestation. There were positive correlations between hPL and beta-hCG (n = 49, r = 0.737, p less than 0.001), and between UE3 and TE3 (n = 49, r = 0.904, p less than 0.0001). The ratios of placental hormones to estriol showed moderate declines towards 41 weeks of gestation. These data suggest that the fetal adrenal function increased toward the term, while the placental peptide hormones decrease or remain unchanged. Determination of serum unconjugated estriol was found to be convenient and useful for monitoring the fetoplacental function.

Serum unconjugated estriol concentrations before and after the oxytocin challenge test: An index of fetal well-being

Serum unconjugated estriol concentrations before and after the oxytocin challenge test (stress test) were measured in 54 high-risk, obstetric patients. Six of the stress test results were positive, and eight were equivocal. Eleven patients demonstrated decrements in estriol of ≥25% after stress tests, and the infants of six of these patients demonstrated perinatal morbidity. Three patients exhibited positive stress test results but had estriol concentrations which were unaltered by the stress test; all were delivered vaginally of healthy infants shortly after the stress test. The coefficient of correlation between the stress test and perinatal outcome was 0.58 (P < 0.001). When the estriol and stress test results were combined to predict outcome, a multiple correlation coefficient of 0.71 was obtained (P < 0.001). This increment represents a significant (P < 0.001) and substantial (18%) improvement in the prediction of perinatal outcome. These findings indicate that the measurement of changes in estriol with the stress test significantly improves one's ability to define the fetus at risk.

Correlation of serum unconjugated oestriol to red cell 2,3-diphosphoglycerate levels in diabetic pregnancy.

In order to evaluate the possible underlying factors for the increase in red cell 2,3-diphosphoglycerate content observed in late diabetic pregnancy, its relationship with serum unconjugated oestriol, human placental lactogen, haemoglobin and hydrogen ion concentrations was investigated in 42 pregnant diabetic women. A significant correlation was found between red cell 2,3-diphosphoglycerate and serum unconjugated oestriol (r = 0.54, p less than 0.001), whereas no correlation was present between 2,3-diphosphoglycerate and the following variables: arterial pH, haemoglobin concentration and human placental lactogen. The content of 2,3-diphosphoglycerate correlated significantly with haemoglobin-oxygen affinity expressed as P50 at pH 7.4 (r = 0.34, p less than 0.05). The results of this study indicate that serum unconjugated oestriol may participate in the regulation of red cell 2,3-diphosphoglycerate content and thereby of the maternal blood oxygen release to the fetus.

Effect of dextran-coated charcoal on radioimmunoassays of unconjugated estriol in serum

Lipid interference in the radioimmunoassay of steroids can cause an apparent variation in post-prandial serum concentrations of unconjugated estriol. The effects of increased concentrations of dextran-coated charcoal (15–60 g/l) in the radioimmunoassay of estriol standards with and without triglycerides were studied. All concentrations of dextran-coated charcoal used in this study eliminated the previously observed effects of estriol-lipid partitioning. When we used similar concentrations of dextran-coated charcoal, we found that serum cortisol levels in pregnant women declined significantly during the day ( P < 0.001), but no significant variation in estriol concentrations was observed. These results indicate that the previously reported diurnal variation in serum unconjugated estriol concentrations attributed to steroid-lipid partitioning can be eliminated by increasing the concentration of dextran-coated charcoal in assays using this method of separation.

Late third trimester unconjugated serum oestriol levels in normal and hypertensive pregnancy: relation to birth weight.

In 100 normal singleton pregnancies and in 44 patients with pregnancy hypertension (pre-eclampsia) linear regression analyses demonstrated highly significant positive correlations between birth weights and late third trimester maternal serum unconjugated oestriol (O3) levels. Correlation coefficients increased, though not significantly, after standardising birth weights according to maternal size, parity and sex of infant. Pregnancy hypertension was classified according to the duration of clinical signs. In 23 patients with short duration pregnancy hypertension (onset 14 days or less before delivery) neither maternal age nor birth weight differed from normal controls. Mid-pregnancy weights were greater and unconjugated O3 levels lower and only one infant was growth retarded. Twenty one patients with long duration pregnancy hypertension (onset more than 14 days before delivery) were found on average to be heavier at mid-pregnancy and older than those in whom the condition was short-lived. Unconjugated O3 levels in patients with long duration hypertension were significantly below those in the short duration group. One third of infants born following long duration hypertension were growth retarded.

Effect of phenobarbitone on serum unconjugated oestriol levels in pregnancy: A case report

Effect of phenobarbitone on serum unconjugated oestriol levels in pregnancy: A case report

Estimation of gestational age and maternal serum steroid concentrations. Unconjugated estriol

Inflection points superimposed on the usual increase of maternal serum unconjugated estriol during the 35–37 week interval have been reported as indicators of gestational age. A commercially available radioimmunoassay was used to evaluate patients concentrating on this period of pregnancy in an attempt to confirm a surge phenomenon. No statistically significant variations from the predicted regression lines were reproducibly demonstrated.

Estimation of gestational age and maternal serum steroid concentrations: Total estriol

Acute increases in maternal serum unconjugated estriol between 35 and 37 weeks of pregnancy have been reported to correlate predictably with gestational age. In this study estriol was measured by radioimmunoassay in an effort to define maturational surges. Statistically significant variations from predicted regression lines were not demonstrated in any individual patient or in grouped data.