The therapeutic effect of DHEA-S has been studied in 15 cases of intra-uterine growth retardation. This double-blind study has not been able to demonstrate any difference between the effect DHEA-S and of NaCl on oestriol excretion, HPL values, and biparietal diameter. Only the uterine growth seems to be affected by DHEA-S. Thus it can be concluded that DHEA-S has no therapeutic effect on placental insufficiency.

The present prospective study is aimed to estimate the effect of a low-dose combined oestrogen drug Cyclo-Menorette on climacteric syndrome in women with early menopause.

METHODS

The criteria for inclusion in the study were ac follows: 9-12 months of menopause, increased FSH levels, moderately expressed climacteric syndrome confirmed by the menopausal index of Kupperman and Hamilton-Anxiety-Scale /HAMA/. According to acceptance of hormone replacement therapy /HRT/ the women were divided into 2 groups--control T /n = 31/ and Cunder treatment T /n = 35/. The degree of climacteric syndrome expression after Kupperman and HAMA was estimated in all patients at the beginning as well as on the 3-d, 6-th 12-d months. The presence and dynamics of side effects were followed in the patients treated with HRT.

RESULTS

Spontaneous improvement of complaints was found out in the control group with an increase of intragroup differences during the follow-up period. Most expressed improvement in the group under treatment was established during the first 3-6 months, the beneficial effect being preserved until the end of the study.

CONCLUSIONS

The use of 1 mg oestradiol valerat in combination with 2 mg oestriol results in a significant decrease of climacteric syndrome manifestation with slightly expressed and transient side effects.

Blood was collected from 53 normal women in the 38th week of pregnancy. The plasma concentration of unconjugated oestriol, total oestriol and oestriol sulphate was measured and also human placental lactogen and pregnancy specific beta1 glycoprotein. The normal spread of the two proteins was found to be slightly smaller than that of the oestrogens. The concentrations of unconjugated and of total oestriol were related; otherwise these substances varied independently of one another. The concentration of these substances was not related to other obstetric parameters.

Previous studies, as early as 1984, have demonstrated the efficiency of maternal serum markers to screen for Down syndrome. These markers were AFP, hCG, oestriol and beta-1-glycoprotein. A pilot study was initiated in France in 1990 to evaluate these markers. It lasted from May 1990 until April 1991. 22,410 pregnancies were monitored in total, and 19,407 for women between 30 and 37 years of age. The pregnancy outcome was known for 20,151 cases (86.6%). Sensitivity and predictive value of the test was calculated on 17,362 dosages which outcome was known. The sensitivity based on hCG only was 59.4% (38/64) for trisomy 21 and positive predictive value 1.65% (38/2,307). This test is a better marker than maternal age. In the pilot study it induced a 13.2% rate of amniocentesis. If the risk was calculated using both hCG and AFP results, the performances of the test were better. At equal rate of amniocentesis, the double test increases the sensitivity (+9.5% at risk 1/200, +7% at risk 1/250, +14.4% at risk (1/350). The strategy of double dosages decreases the number of amniocentesis for a given sensitivity rate. This decrease is more spectacular for high levels of sensitivity. This pilot study confirms already published results. Maternal serum markers are the best tools, combined with maternal age to evaluate the risk of trisomy 21.

Sixty pregnant women whose fetuses were considered to be at high risk were intensively studied with fetal and placental function tests. Fetal breathing movements were studied with real-time ultrasound and the amount of time spent breathing and the variability of the breath-to-breath interval were measured. A reduction in the amount of time the fetus spent making breathing movements and decreased variability were indicative of fetal compromise. When these results were compared with those of other tests of fetal wellbeing measurement of fetal breathing movements and ultrasound assessment of growth were more sensitive tests of fetal wellbeing than the biochemical measures (urinary oestrogen, human placental lactogen, pregnancy-specific beta-1-glycoprotein, and unconjugated oestriol concentrations) or fetal heart rate. The predictive value was highest with serum unconjugated oestriol but the results of other tests were similar. Study of fetal breathing movements or an ultrasonic assessment of growth may provide a better screening test for fetal compromise than biochemical estimations.

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.

BACKGROUND

Three serum tests, alpha-fetoprotein (AFP), human chorionic gonadotrophin and unconjugated oestriol, are now widely used for screening for Down's syndrome. Lens culinaris agglutinin-reactive alpha-fetoprotein (AFP-L3) is a variant of alpha-fetoprotein with alpha1-->6 fucose appended to the reducing terminal N-acetylglucosamine. It is the most prominent AFP detected in the serum of patients with hepatocellular carcinoma.

METHODS

We investigated microheterogeneities of the carbohydrate chain on AFP in fetal liver tissues, amniotic fluids and maternal sera obtained from pregnancies with Down's syndrome using lectin affinity electrophoresis with four lectins. The percentages of AFP-L3 in maternal sera from 22 Down's syndrome and 227 unaffected pregnancies were determined.

RESULTS

Unlike the case with AFP concentration, the percentage of AFP-L3 in maternal serum and amniotic fluid was similar, and apparently not influenced by membrane permeability. Knowing the percentage of AFP-L3 in maternal serum was effective for discriminating between Down's syndrome-affected pregnancies and unaffected pregnancies. The percentage of AFP-L3 in maternal serum identified 55% of Down's syndrome cases with a 5% false-positive rate.

CONCLUSIONS

AFP-L3 should be an effective replacement for AFP in prenatal Down's syndrome screening.

150 women with serious climacteric complaints were continuously treated from January, 1970, up to April, 1972, with Ovestin¿, an orally effective preparation containing 1 mg of oestriol per tablet. After one month of treatment subjective complaints were already considerably improved. Oestrogenic activity was markedly increased, according to vaginal smears and total gonadotrophin excretion in the urine. Its high tolerance and beneficial therapeutic effect make Ovestin the preparation of choice in the treatment of the climacteric syndrome.

During the 6-year period 1971 to 1976, 10,545 patients had urinary oestriol determinations during pregnancy and 333 (3.2%) had persistently low values. Of the 335 resultant infants 206 were from patients treated with intravenous dextrose and/or amino-acids (treated group) and 129 from nontreated patients (nontreated group). The stillbirth rate was 2.4% in the treated group and 11.6% in the untreated group (p greater than 0.001), and the neonatal death rates were 2.9% and 4.7% respectively (p = NS). Assessment of the surviving infants to 7 years of age revealed no significant differences in growth between treated and nontreated groups. There was no increase in the incidence of major neurological abnormalities in the treated infants (2.9%) when compared to those from nontreated pregnancies (1.3%) (p = NS), nor was there a significant difference in the incidence of minor neurological abnormality or findings on psychological assessments. We conclude that dextrose and/or amino-acid infusions given to pregnant women with low oestriol excretion reduced the perinatal mortality rate without significant compromise to subsequent development of surviving infants.

In a previous report we showed that oestriol succinate administered to postmenopausal women caused fewer changes in haemostatic function over a four-month period than ethinyloestradiol. Potential longer-term effects were studied in postmenopausal women treated for osteoporosis with oestriol succinate for up to 12 months. Over this period there was no significant change in concentration of plasma coagulation factors, an increase in plasminogen concentration and euglobulin lysis activity, and an inconsistent increase in platelet sensitivity to aggregation induced by ADP and collagen. The relative lack of effect of oestriol succinate on coagulation function is encouraging with regard to the future incidence of thromboembolic complications of therapy.

BACKGROUND

The introduction of a second trimester quadruple test for fetal Down's syndrome adds the measurement of serum inhibin A (InhA) and unconjugated oestriol (UE3) to the existing repertoire of alphafetoprotein and intact human chorionic gonadotrophin. The aim of this study was to assess the stability of InhA and UE3 in whole blood and serum.

METHODS

To determine whole blood stability, five extra blood specimens were obtained from each of 10 women attending an antenatal clinic. Samples were stored at room temperature for either two hours, one, three, five or seven days and centrifuged prior to analysis. Serum stability was studied by the analysis of surplus serum from 14 routine second trimester screening samples: seven stored at room temperature and seven stored at 4°C. An aliquot from each specimen was analysed two hours, one, three, five or seven days post centrifugation. Specimens were analysed for InhA and UE3 using the Beckman Access 2(®) Immunoassay analyser.

RESULTS

No significant difference (P>> 0.05) was shown in InhA or UE3 concentrations between the initial time point on the day of venepuncture and each of the subsequent analyses at one, three, five and seven days following collection for either whole blood or serum.

CONCLUSIONS

InhA and UE3 are stable in whole blood and serum for seven days.

The effects of abdominal decompression applied over a period of several weeks (mean 4 weeks) in late pregnancy on biochemical and haemodynamic parameters as well as fetal growth and cardiotocogram patterns were studied in a group of 64 pregnant women with identified placental insufficiency. A statistically significant improvement was demonstrated in the following findings after treatment: placental perfusion measurements 113mIn and unconjugated oestriol and human placental lactogen, both in serum. A positive influence on antepartum cardiotocogram was observed only immediately after therapy. An acceleration of fetal growth (biparietal diameter) could not be demonstrated. Frequency and severity of EPH gestosis did not change after abdominal decompression. Abdominal decompression seems to be a valuable aid in the still unsatisfactory treatment of placental insufficiency.

The concentration of unconjugated oestriol in serum was measured in venous and capillary blood from 41 pregnant women. 22 women had uncomplicated pregnancies. The others had different kinds of complications including severe oedema and pre-eclampsia. The correlation between values of unconjugated oestriol in venous and capillary blood was high. In 77 out of 78 samples the conclusions drawn about the feto-placental function from venous and capillary blood were similar. The day-to-day variability was of the same order for capillary as for venous samples. A few samples were analysed for total oestriol and also in this case a high correlation was found between capillary and venous blood. It is concluded that capillary blood samples may well be used for estimation of total and unconjugated oestriol. Capillary blood could replace venous blood for estimation of unconjugated oestriol in the management of high risk pregnancies.

Serum levels of placental alkaline phosphatase (PLAP), human placental lactogen (HPL) and oestriol (E3) were investigated in 33 women with high-risk pregnancies. In pregnancies complicated by intrauterine growth retardation (IUGR) low PLAP values were constantly recorded. HPL values showed a similar pattern while E3 levels were between normal mean and the lower limit of -2 SD. A clear differentiation between IUGR and pre-eclampsia was achieved by the simultaneous determination of PLAP and HPL. It is suggested that PLAP determinations may be more informative than E3 to detect placental insufficiency.

The conversion of oestrogens into mixed derivatives comprising a phenolic silyl ether and one or more alcoholic perfluoroactyl ester(s) is described. They are easily formed in quantitative yield and have excellent gas chromatographic and mass spectrometric properties, making them suitable for analysis by selected ion monitoring. Reaction mechanisms are examined which propose explanations for the experimentally observed optimal reaction conditions. The 3-t-butyldimethylsilyl ether-16 alpha 17 beta-bis(pentafluoropropionate) has been used for the quantitative determination of oestriol in plasma by gas chromatography/mass spectrometry using a stable isotope internal standard. Comparison with the pertrimethylsilyl ether of oestriol indicates higher specificity and better precision for low-level (less than 0.5 ng ml-1) estimations.

In a series of 794 patients who had glucose tolerance tests done before the onset of pre-eclampsia, both hypoglycaemia (less than 5th percentile) and hyperglycaemia (P less than 95th percentile) had a significant association with early-onset severe pre-eclampsia ( less than 0.05). In the total series of 794 patients, hypoglycaemia had a significant association with low oestriol excretion (p less than 0.01), fetal growth retardation (p less than 0-05), low Apgar score (p less than 0.05), and perinatal mortality (p less than 0.05). These data indicate that, in patients with pre-eclampsia, hypoglycaemia is directly related to the cause of perinatal death.

This study reports the associations between antenatal complications, subnormal urinary oestriol excretion and perinatal death in 500 pregnancies when the baby weighed less than the 10th centile for gestational age at birth, compared with those in a series of 500 pregnancies when the baby was of a normal weight for gestation. The overall incidence of antenatal complications was not higher in those pregnancies in which the fetus was growth retarded, although early onset pre-eclampsia, threatened abortion, diabetes mellitus and accidental haemorrhage were commoner (P less than 0.05). The incidence of subnormal urinary oestriol excretion was significantly higher in pregnancies in which the fetus was growth retarded, both when other antenatal complications were present (54.7% in the study group, 18.4% in the control group P less than 0.001) and in uncomplicated pregnancies (37.7% and 13.3%, respectively, P less than 0.001). Subnormal oestriol excretion identified 20 of the 26 perinatal deaths in the growth retardation group and 4 of the 6 perinatal deaths in the control group. Perinatal mortality was 10 times higher in growth retarded infants than in infants of appropriate size for gestation when pregnancy was not complicated antenatally. This study confirms the need to identify the presence of fetal growth retardation antenatally to enable appropriate treatment and improvement in perinatal mortality. The presence of antenatal complications is not appropriate for identification, whilst subnormal urinary oestriol excretion was seen to have highly significant predictive value.