Estriol In Pregnancy Research Articles

In utero and postnatal programing of dehydroepiandrosterone sulfate (DHEAS) in young adult women

Fetal adrenal-derived OH-DHEAS is the primary precursor for maternal estriol, an abundant, human, placental estrogen. We measured maternal pregnancy estriol as a marker of fetal adrenal function + placenta capacity to synthesize estriol. We hypothesized that maternal estriol is directly correlated with the adrenal hormone, DHEAS, in young adult women. We tested this hypothesis in a subset of women in the Child Health and Development Studies (351 of 470 eligible). 176 of these had serum samples collected at ages 27–30 for DHEAS assays, archived maternal pregnancy serum for estriol assays, and childhood growth data. In regression analyses, both maternal estriol and accelerated growth in middle childhood were independently, directly associated with DHEAS (+19% for quartile 4 versus quartile 1 of estriol, 95%CI=+ 2%, +36% and +12% for quartile 4 versus quartile 1 for middle childhood growth, 95%CI= +3%, +21%). Adrenal function may be programmed in utero and middle childhood with long-term consequences.

Maternal height, pregnancy estriol and birth weight in reference to breast cancer risk in Boston and Shanghai

Birth weight has been positively associated with breast cancer risk in adult life and is positively associated with the principal pregnancy estrogen estriol. Birth weight is lower among Chinese women than among Caucasian women, but paradoxically, pregnancy estriol levels are higher among the former than the latter. We studied a cohort of 317 Caucasian pregnant women in Boston, MA, and 339 Chinese pregnant women in Shanghai, China. We investigated whether maternal height, which is inversely associated with pregnancy estriol levels, interacts with this hormone in relation to birth weight, thus accommodating the apparently contradictory ecologic and analytic evidence concerning the role of pregnancy estrogens on breast cancer risk in the offspring. In both Boston and Shanghai, there was a positive association of pregnancy estriol with birth weight among taller women, whereas among shorter women the association was essentially null. The relevant interaction terms were highly significant in Boston (p approximately 0.006), whereas in Shanghai, where pregnant women were generally shorter, the interaction term was suggestive (p approximately 0.14). We conclude that maternal height should be considered an important risk factor for breast cancer in the offspring since it is a crucial determinant of birth weight, both directly and through positive interaction with the principal pregnancy estrogen estriol.

Pregnancy estriol, estradiol, progesterone and prolactin in relation to birth weight and other birth size variables (United States).

Because birth weight has been positively associated with adult life breast cancer risk and pregnancy estrogens have been hypothesized to affect breast cancer risk in the offspring, we have evaluated the association of pregnancy estriol (E3), estradiol (E2), progesterone and prolactin in maternal serum samples collected during the 16th and 27th gestational week with birth size parameters. Prospective study of 230 Caucasian women who delivered a live singleton after 37-42 weeks of gestation. E3 at the 27th gestational week was significantly positively associated with birth weight, birth length and placental weight. Progesterone at the 27th gestational week was also significantly positively associated with birth weight and placental weight but, after mutual adjustment among the studied pregnancy hormones, these associations weakened considerably. There was also inconsistent evidence that SHBG and prolactin at the 27th gestational week may be respectively positively and inversely related with birth size parameters. Measurements during the 16th gestational week were generally unrelated to birth size parameters. Because E3 is a dominant estrogen during pregnancy, the positive association of it with birth weight allows the use of the latter as a proxy of in utero exposure to estrogens in breast cancer investigations.

Low or absent unconjugated estriol in pregnancy: an indicator for steroid sulfatase deficiency detectable by fluorescence in situ hybridization and biochemical analysis.

It has been previously reported that a low or absent maternal serum unconjugated estriol (uE3) level is associated with placental steroid sulfatase (STS) deficiency. Here we report a correlation between patients who present with a very low or absent maternal serum uE3 and a deletion of the STS gene as assessed by fluorescence in situ hybridization (FISH). We studied nine prenatal cases that presented to the clinical laboratory with an abnormal triple screen, specifically low or absent maternal serum uE3 and a 46,XY karyotype. FISH analysis showed complete deletion of a probe containing the STS gene in six cases and one case had a partial deletion (reduced but not absent signal). The remaining two cases were not deleted for the STS probe. All mothers tested whose fetus showed a deletion were shown to be STS deletion carriers using FISH. Biochemical analysis was performed on 7/9 prenatal specimens. All fetuses deleted for the STS probe were also found to be deficient for STS by biochemical analysis of cultured amniotic fluid (5/5). Of the two fetuses not deleted for the STS probe, one was deficient for STS activity, while the other had a normal result. The abnormal result of enzyme deficiency by biochemical analysis in a non-deletion case likely represents a mutation in the STS gene, not detectable by this FISH assay. Postnatal FISH confirmation of the STS deletion was performed in 1/7 cases. Clinical follow-up was available for 4/9 cases following birth.

Maternal pregnancy estriol levels in relation to anamnestic and fetal anthropometric data.

In epidemiologic studies of perinatal exposures, birth weight has been proposed as a proxy variable for intrauterine estrogen exposure. To assess the validity of this assumption, we performed analyses of the association between estriol levels in 188 women in the 17th, 25th, 33rd, and 37th weeks of pregnancy and the birth weights of their infants. We found a general increase in mean cumulative estriol dose with increasing birth weight category throughout pregnancy. In late pregnancy, mean pregnancy estriol level of mothers of infants in the highest birth weight category (>4,500 gm) was twice as high as that of mothers of infants in the lowest category (<2,500 gm), 775 nmol/liter and 392 nmol/liter, respectively. Smoking lowered the maternal estriol levels by 20% or more throughout pregnancy. With smoking and birth weight included in a regression analysis, maternal age, placental weight, and infant ponderal index did not add any explanatory power to the model. Our data suggest that, on an aggregate level, birth weight can be used as a proxy variable of intrauterine estriol exposure.

Diurnal variation of salivary estriol in pregnancy

Diurnal variation of salivary estriol in pregnancy

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.

A rapid, non-radioactive method for plasma unconjugated estriol in pregnancy using high-performance liquid chromatography (HPLC)

A rapid, non-radioactive method for plasma unconjugated estriol in pregnancy using high-performance liquid chromatography (HPLC)

Rapid and cost-effective measurement of total urinary estriol in pregnancy using an automatic liquid-chromatographic analyser

Rapid and cost-effective measurement of total urinary estriol in pregnancy using an automatic liquid-chromatographic analyser

Direct, sensitive and specific elisa of plasma estriol in pregnancy

Direct, sensitive and specific elisa of plasma estriol in pregnancy

Elisa for salivary and plasma estriol in pregnancy

A competitive, sensitive, and rapid enzyme-linked immunoadsorbent assay (ELISA) was developed for the determination of estriol in saliva and in plasma. Horseradish peroxidase (HRP) was used as the label enzyme; separation between free and bound steroid was carried out by insolubilized antibody prepared by adsorbing purified IgG of rabbit anti-6-oxoestriol-6-(0-carboxymethyl)oxime-BSA on polystyrene balls. The enzyme activity was measured by a colorimetric reaction using o-phenylenediamine dihydrochloride and hydrogen peroxide as substrate. The sensitivity of the assay was 12 pg/tube. In order to compare ELISA to RIA estriol estimations in different biological fluids, we selected six women during normal pregnancy, from the 30th to the 40th week of gestation. Salivary estriol was assayed by direct and extraction methods, while the corresponding plasma samples of the same subjects were analyzed only for unconjugated estriol by an extraction method. A good agreement was found between the results obtained by RIA and ELISA: r=0.897, p <0.001 between direct RIA and direct ELISA in saliva; r=0.909, p < 0.001 between extraction RIA and direct ELISA in saliva; and r=0.916, p < 0.001 between extraction RIA and extraction ELISA in plasma. A good correlation (r=0.793, p<0.001) was present between plasma samples by RIA and saliva samples by ELISA (direct method). These results indicate that: 1. ELISA is a reliable method for the determination of estriol in plasma and saliva. 2. Saliva samples can be used for the assay of estriol and therefore for the assessment of fetal conditions during pregnancy.

Intermediary metabolism of estriol in pregnancy

Estriol (E 3), the most abundant estrogen in pregnancy is produced predominantly in the placenta from androgen precursors of fetal origin. The estriol so formed is secreted efficiently into the maternal circulation where it is converted to 4 conjugates—estriol-3-sulfate (E 3-3S), estriol-16-glucosiduronate (E 3-16G), estriol-3-glucosiduronate (E 3-3G) and estriol-3-sulfate-16-glucosiduronate (E 3-SG). The order of renal clearances is E 3-16G > E 3-3G > E 3-3S ~ E 3-SG. Unconjugated E 3 and E 3-3G differ from the other forms of estriol in that their removal from the blood compartment is essentially irreversible. E 3-3S, E 3-16G and E 3-SG undergo interconversions during enterohepatic circulation and eventual partial conversion to E 3-3G. Following delivery of the fetus and placenta, unconjugated E 3 is no longer detectable in the maternal serum within l–2h, whereas the concentrations of the conjugates decline more slowly, the rates being determined by the rates of renal clearance and enterohepatic interconversions. E 3-3G levels were dramatically elevated in a case of Group C polycystic kidney disease, providing evidence that this conjugate is indeed an end-product of estriol metabolism.

Plasma oestriol in pregnancies complicated by diabetes mellitus.

We studied the plasma oestriol concentration during increasing gestation in 192 normal pregnancies and 96 pregnancies complicated by diabetes mellitus. Among the 96 patients there were 16 established, 32 gestational, 29 'persistent' gestational and 19 either gestational or 'persistent' gestational diabetic pregnancies. Serial blood samples were collected and their concentrations of oestriol (total oestriol) determined by radioimmunoassay. The distribution of birthweights and placental weights around each gestational period was skewed to the right. Therefore, the 5th and 95th percentiles were obtained after computing a logarithmic transformation of the data. The incidence of big and small babies in all diabetic groups, except that in the gestational diabetic group, was significantly higher than that in the group of normal pregnant women. The distribution of oestriol concentrations was also skewed to the right and had to be normalized by logarithmic transformation. The oestriol profile in normal pregnancies had a wide scatter, especially after the 37th week. Serial measurements with reference to the normal oestriol profile showed a detection rate of approximately 85% for both normal and abnormal foetal outcome. There were 15% of false negative and 16% of false positive results. Results in this study indicate that serial blood oestriol measurement may be a useful additional index for foetal monitoring in pregnancies in diabetic women. Furthermore, if large scale screenings using a single estimation are performed, it is best carried out between the 33rd and 34th week of gestation.

Magnetisable solid-phase separation fluoroimmunoassay for total oestriol in pregnancy serum

A rapid separation fluoroimmunoassay for serum or plasma levels of total oestriol in pregnancy was established, based on the use of fluorescein-labelled oestriol and sheep anti-oestriol serum covalently linked to magnetisable particles. Equilibrium was attained within 10 min, and the fluorescence of the bound fraction of labelled ligand was quantitated fluorimetrically after elution from the magnetisable particles. Results for pregnancy serum samples correlated well with an established radioimmunoassay technique and the sensitivity, precision and accuracy were appropriate for clinical use. Advantages of this system as compared with radioimmunoassay include the speed and-simplicity of end-point detection, prolonged shelf-life of the labelled reactant and absence of any health hazard. The separation step enabled the removal of any endogenous fluorophores or other interfering factors present in biological samples.

Estriol in pregnancy: VI. Experience with unconjugated plasma estriol assays and antepartum fetal heart rate testing in diabetic pregnancies

The reliability of daily unconjugated plasma estriol (E3) as a first-line test for fetal surveillance in the management of diabetic pregnancies was assessed. Seventy consecutive insulin-dependent diabetic women admitted in late pregnancy were followed up with daily 8 am unconjugated plasma E3 assays and weekly antepartum fetal heart rate testing (AFHRT). There were no perinatal deaths, and only two neonates developed the respiratory distress syndrome. The mean gestational age at delivery was 38 weeks. Pregnancies continued until elective delivery at 38 weeks and development of a mature amniotic fluid lecithin/sphingomyelin (L/S) ratio (n = 40) unless spontaneous labor began earlier (n = 20) or early delivery was indicated for either maternal reasons (n = 3) or presumed fetal distress (n = 7). Intervention for fetal distress took place when plasma E3 levels had fallen by 40% or more from the highest mean of three consecutive preceding values (significant drop) and both a nonstress test (NST) and a contraction stress test (CST) were abnormal irrespective of the L/S ratio (n = 2) or, in the presence of a mature L/S ratio, when either plasma E3 levels had fallen significantly or AFHRT was abnormal (n = 5). Five patients without a mature L/S ratio and a significant fall in plasma E3 with a reactive NST were not delivered. Only 14 (1.2%) of the 1,180 plasma E3 assays in 12 (17%) of the 70 patients represented a significant drop and fetal distress was documented in two of these 12 pregnancies, the only two in which both NST and CST were abnormal. In 18 of the 70 patients in whom 317 NSTs were performed, 26 NSTs (8.2%) were nonreactive initially, but 18 of these 26 NSTs were either reactive when repeated within hours or followed by negative CSTs. Documented fetal distress was found to occur 1 day after a reactive NST and a normal plasma E3 but was indicated in time for successful intervention by both tests. These data indicate that: (1) daily unconjugated plasma E3 assays constitute a reliable first-line test of fetal status in diabetic pregnancies, (2) a single daily plasma E3 at 8 a.m. suffices, (3) the 40% limit for a significant drop appears to be sensitive enough to detect fetal distress, (4) AFHRT, if done daily, may be used in lieu of daily plasma E3 determinations, and (5) both plasma E3 assays and AFHRT render false abnormal results. By combining both biophysical and biochemical testing, it is possible to virtually eliminate the need for unwarranted intervention and unnecessary prematurity.

Enzyme immunoassay of estrogen-like substances in plasma, with polyethylene glycol as precipitant.

We devised an enzyme immunoassay for plasma estrogen-like substances in pregnancy, using estriol covalently linked to horseradish peroxidase. Free and bound steroid were separated by use of polyethylene glycol reagent. The assay satisfies the normal criteria of specificity and precision. Results obtained by radioimmunoassay and enzyme immunoassay agreed well. Our assay is particularly applicable in smaller clinical laboratories to routine determination of plasma estriol in pregnancy.

Mechanism for interference of hydrochlorothiazide with the Kober reaction for determination of urinary estriol in pregnancy

Investigation of the mechanism of the lowering effect of hydrochlorothiazide, which was administered orally, in the determination of estriol from the pregnancy urine has been carried out. The isolation and determination of the structure of a copolymer formed from estriol and formaldehyde have suggested the mechanism by which, during the acid hydrolysis process of the glucuronide conjugate of estriol, some copolymers of estriol and formaldehyde generated from hydrochlorothiazide, were formed, thus lowering the observed values of the estriol contents in the urine.

Comparison of total urinary oestrogens and total serum oestriol in pregnancy

The total oestrogens detected by fluorescence in 24-h urine and the concentration of total oestriol detected in serum by radioimmunoassay were estimated in 51 women during the second half of pregnancy. The statistical analysis showed a linear regression between urinary excretion and serum concentration according to the equation y = −2.89 + 2.82 x ( y = serum oestriol). The correlation coefficient over all pairs of estimations ( N = 567) was r = 0.69, which is very highly significant ( P < 0.0001). The analysis of the individual pregnancies showed that the linear correlation coefficient was significant ( P < 0.05) in 35 cases, poorly significant (0.05 < P < 0.1) in 3 cases and not significant ( P > 0.1) in 5 cases. The correlation could not be calculated in 8 cases because the number of estimations was too small. These values were compared empirically (normal/pathological). There was agreement in 6 cases and no agreement in 2 cases. The results show on the one hand that the radioimmunological estimation of total oestriol in serum can be used in the same way as urinary excretion of oestrogens for monitoring the feto-placental unit. On the other hand, the study confirms that a “simple” fluorimetric Kober-Ittrich method can give at least the same clinical information as a radioimmunoassay of relatively high cost. It may be concluded indirectly from the results that a considerable diurnal rhythm or substantial day-to-day fluctuation in the production of oestriol are unlikely.

Estriol in pregnancy: V. Unconjugated and total plasma estriol in the management of pregnant diabetic patients

Sixty-two consecutive diabetic women hospitalized from one to eight weeks prior to delivery were included in this study. Some 1,100 simultaneous unconjugated plasma estriol, total plasma estriol, 24 hour urinary estriol, and creatinine assays were performed on an almost daily schedule. Clinical management was based upon a weekly oxytocin challenge test and daily 24 hour urinary estriol and creatinine determinations. Twenty patients had spontaneous onset of labor and 32 were delivered electively at 38 weeks while three were delivered for maternal and seven for fetal indications. Gestational age at delivery averaged 38 weeks and ranged from 35 to 42 weeks. A total of 840 day-to-day variations of unconjugated plasma estriol, total plasma estriol, and the urinary estriol/creatinine ratio were computed as the per cent rise or fall from the highest mean of three consecutive preceding values. Observed were 369, 419, and 428 decreases in unconjugated plasma estriol, total plasma estriol, and urinary estriol/creatinine, respectively, averaging 12.8 ± 9.6 (S.D.), 13.4 ± 10.1, and 14.4 ± 10.6 per cent. One stillbirth occurred, which was preceded by a 42 per cent decrease in unconjugated plasma estriol but unheralded by either a drop in total plasma estriol or the urinary estriol/creatinine ratio. There were fewer falls of more than 40 per cent unassociated with perinatal morbidity and death with unconjugated plasma estriol (No. = 3) than with total plasma estriol (No. = 8) and urinary estriol/creatinine (No. = 8). These data suggest that unconjugated plasma estriol is the most predictive test among presently available estriol assays for managing the pregnant diabetic patient.

A rapid and direct 125 I-based radioimmunoassay for unconjugated estriol in pregnancy serum and its clinical application (author's transl)

A rapid and simple R.I.A. method for serum unconjugated estriol in pregnancy had been studied for its usefulness as a routine obstetrical test to assess fetal well-being. Diluted serum samples or known amounts of standard estriol were applied with 125 I-estriol on pre-packed minicolumns of Sephadex G-25, followed by appropriately diluted antiserum. During incubation, the columns were counted in an Auto Well gamma-System to read the total counts (T). After a 90 minute incubation period, the columns were eluted with a buffer solution to remove the bound fraction, and the free estriol remaining in the columns was counted (F). Two quality control samples and sera from 74 pregnant women were analysed by this new method, and the results were compared to those obtained by the conventional radioimmunoassay method. The new column method is simple, specific and accurate. Results can be calculated within 4 hours after 30 sample sera are brought into the laboratory. Within and between assay coefficients, variations are 12.6 and 13.5%, respectively. This method correlates well with the results of the conventional method (r=0.7088, p less than 0.001), which requires almost 2 full days to process the same numbers of samples. Results of clinical cases as well as advantages of measuring free-circulating estriol in pregnancy are discussed.