In order to prove the progress in diagnosis and treatment of pregnancies with low birthweight we performed a retrospective computer-analysis of three groups of patients including newborns below 2750 g delivered dumping the last 10 years. The first group contains the years 1967/68; the deliveries of low birthweight infants were monitored without cardiotocogram. The second group of patients from the years 1971/72 was monitored continuously during delivery by cardiotocogram. The endocrinologic diagnostic methods for detection of a possible placental insufficiency in low weight fetus were applied regularly (DHEA-S-loading test, oestriol, HPL). The treatment of premature newborns with respiratory distress syndrome was facilitated by CPAP. A thorough ultrasound diagnosis was available additionally for the third group of patients. Long term treatment with Partusisten was applied in cases of premature labour in this group and betamethasone-therapy was used for accelleration of fetal lung maturation. With a nearly constant number of preterm eutrophic newborns, preterm infants with retarded growth and mature infants with retarded growth over a period of ten years the unpurified mortality rate decreased from 14.3% to 6.7% when the pregnancies and deliveries had intensive (obstetrical medical) care. With the help of Shirodkar procedure and tocolytic treatment the birthweight could be shifted significantly into the favourable group over 2000 g. The prenatal prophylactical treatment of the respiratory distress syndrome with beta-methasone and the postnatal CPAP-therapy decrease the mortality rate caused by respiratory deficiency from 13.7% to 6.4%. The preventive caesarean section in cases of low birthweight infants with abnormal positions in utero helped to reduce the mortality rate from 21% to 10.6% in these cases. The accuracy of prenatal diagnosis of intrauterine retarded fetal growth by hormone analysis and ultrasonic measurement of the fetus was improved from 24% to 66%.

At the university women's clinic Zurich between 1963 and 1974, 29 babies in a total of 32255 babies were born with Down's syndrome. 11 of these had a cardiac vitium and 2 an intestinal malformation. 5 babies died during the first year of life. This high morbidity demands an analysis of the criteria in the obstetrical history and clinical picture in order to reach a diagnosis in those cases which would otherwise not be diagnosed if one used the normal criteric for amniocentesis in early pregnancy. Maternal age was the only relevant factor to emerge. In 6 pregnancies a tentative diagnosis for poor intrauterine growth was made in which only one case showed a retarded growth of the bipariental diameter. In all 7 cases in which cephalometry was performed after the 24 week of pregnancy, the concurrent hormonal parameters showed significantly lowered oestriol levels with normal HPL levels. From this information we draw the conclusion that transabdominal amniocentesis should be performed in in pregnancies with permanently low oestriol levels and normal HPL levels; especially in cases which clinically appear "small for dates" and for which there is no other explanation such as anencephaly for the low maternal oestriol levels.

The results of oestriol excretion, HPL activity and fetal heart rate monitoring are presented during the last three weeks before the birth or the intrauterine fetal death. Abnormal results were found in all cases at least two weeks before the intrauterine death. In the same periode, we observed a raise of abnormal values in cases with intrauterine growth-retardation. In cases with normal birth weight, the majority of values were normal and without a significant decrease.

A total of 440 women who had low oestriol excretion in a previous pregnancy was investigated by urinary oestriol assays in one or more subsequent pregnancies. The incidence of low oestriol excretion in the subsequent pregnancy was 29.1 per cent, or more than double that in the total obstetric population (13.4 per cent; p less than 0.001). Patients with persistently low oestriol excretion had a 40.8 per cent recurrence rate in subsequent pregnancies. When oestriol excretion was low in successive pregnancies it retained a significant association with increased incidences of stillbirths, neonatal deaths and fetal growth retardation. It was concluded that low oestriol excretion in a previous pregnancy is a definite indication to test fetoplacental function in subsequent pregnancies even when the clinical findings are normal.

The value of serial human placental lactogen and plasma total oestriol measurements in assessing fetoplacental function early in the third trimester, is discussed. In particular, the use of the two measurements simultaneously may provide an indication of impending fetal death, of growth retardation, or of gross fetal malformation.

Maternal plasma oestriol and human placental lactogen (HPL) were measured serially in 383 at-risk pregnancies. Eight-five infants were growth retarded and 122 developed fetal distress or neonatal asphyxia. Of the infants whose mothers had either abnormal plasma oestriol or HPL levels, 58 per cent were growth retarded, while 65 and 73 per cent in each group respectively developed fetal distress. The incidence of fetal complications when both plasma oestriol and HPL were abnormal was consistently greater than 66 per cent.

Warburg's manometric method was used to check the action of oestrone, oestradiol, and oestriol on aerobic and anaerobic glycolysis of placental respiration. Oestrogen concentrations of 10(-4) M were found to reduce oxygen consumption and to increase aerobic glycolysis. Such reduction of oxygen consumption was most strongly pronounced in connection with oestradiol, while the strongest rise in aerobic glycolysis took place in the wake of oestradiol and oestrone. Oestrogen action upon anaerobic glycolysis was variable, with the latter remaining unchanged by oestradiol, reduced in response to oestriol, and slightly increased by oestrone.

We studied maternal plasma levels of oestriol (measured by radioimmunoassay) and total cortisol (measured by a protein binding method) in 11 women from 8 to 22 weeks gestation. Blood specimens (5 ml) were drawn over a 24-h period at 60 and 30 min intervals. The diurnal rhythm of cortisol with higher values in the morning than in the afternoon and evening was present at all gestational ages studied. Unconjugated plasma oestriol showed a similar circadian rhythm to maternal cortisol (r = 0.576, P less than 0.01) in the 8th week. From the 9th to the 11th week oestriol values rose and there was no evidence of a circadian rhythm. In the 12th week plasma oestriol again showed a circadian rhythm, with higher values at night (117.3 +/- 9.5 pg/ml) than during day-time (104 +/- 7.5 pg/ml, P less than 0.001). This pattern remained until the 22nd week, when plasma oestriol levels at night (3.78 +/- 0.49 ng/ml) were markedly higher than in the day-time (3.16 +/- 0.3 ng/ml, P less than 0.001). An inverse relation between oestriol and cortisol levels as shown in late human pregnancy could not be demonstrated for the early stages we studied. The interval between rising cortisol and falling oestriol levels decreased from 6 h in the 12th week to 3.5 h in the 22nd week of gestation. This suggests an increasing sensitivity of the fetal hypothalamus to the feedback effect of maternal cortisol.

The present study investigates the suppression of free plasma oestriol by cortisol in mature and immature foetuses. 6 patients in the 32nd week of gestation and 6 patients in the 38th week received an infusion of 100 mg cortisol (Hydrocortison Hoechst) from 10 a.m. to 12 a.m. Blood specimens (5 ml) were drawn from 8 a.m. to 5 p.m. in 60 or 30 minutes intervals, respectively. Free plasma oestriol was measured by radioimmunoassay, total plasma cortisol by the protein binding method. In the 32nd week of gestation plasma oestriol rose from 501 +/- 240 ng/ml to 1035 +/- 301 ng/ml, whereas oestriol decreased from 5.2 +/- 1.0 ng/ml to 3.9 +/- 1.5 ng/ml (p less than 0.001). After an analogous rise of cortisol, oestriol levels in the 38th week were suppressed from 12.5 +/- 3.3 ng/ml to 4.0 +/- 1.6 ng/ml (p less than 0.001). The degree of oestriol suppression of 68 percent in the 38th week markedly exceeded that of the 32nd week (25%). According to these results, the hypothalamic-hypophyseal system of mature foetuses exhibits a higher sensitivity to the feed back action of cortisol than immature foetuses.

The present study investigates the significance of a circadian changing sensitivity on the feed back action of cortisol for the foetal hypothalamic hypophyseal system. 9 patients with uncomplicated courses of pregnancy in the 37th to 40th week volunteered in this study. All of them delivered healthy babies at term. 5 patients received a continuous infusion of 0.25 mg ACTH1-24 (Synacthen) in the morning from 10 a.m. to 4 p.m. (group I). To 4 patients an analogous ACTH infusion was applied in the evening from 8 p.m. to 2 a.m. (group II). Blood specimens (5 ml) were drawn from 8 a.m. to 5 p.m. in group I and from 5 p.m. to 3 a.m. in group II in 60 and 30 minutes intervals, respectively. Free plasma oestriol was measured by radioimmunoassay, total plasma cortisol by the protein binding method. In group I cortisol increased from 294.3 +/- 52.9 ng/ml to 774.5 +/- 170 ng/ml, whereas oestriol decreased from 13.1 +/- 6.1 ng/ml to 6.8 +/- 2.1 ng/ml (p less than 0.001). In group II cortisol rose from 267.5 +/- 76.2 ng/ml to 1010 +/- 284 ng/ml, whereas oestriol levels were suppressed from 21.7 +/- 10.5 ng/ml to 10.8 +/- 3.2 ng/ml (p less than 0.001). Two hours after starting ACTH infusion rising cortisol and falling oestriol concentrations were negatively correlated (r = -0.9657, p less than 0.001 in the morning; r = -0.9119, p less than 0.001 in the evening). Plasma oestriol levels were in the evening suppressed on an average of 10.9 ng/ml and exceeded the oestriol decrease in the morning (6.3 ng/ml).(ABSTRACT TRUNCATED AT 250 WORDS)

Dehydroepiandrosterone sulphate (DHAS) was injected intravenously or intra-amniotically into eight volunteers carrying live anencephalic foetuses (including one microcephalic foetus). Urinary and unconjugated serum oestrone, oestradiol and oestriol were measured before and after DHAS administration. In seven pregnant women with live anencephalic foetuses the urinary excretion of oestriol was very low, and the ratio of oestriol to oestrone + oestradiol was much less than that during normal pregnancy. Increases of urinary oestrone and oestradiol but no significant change in the ratio of oestriol to oestrone + oestradiol were observed 24 h after i.v. administration of DHAS to five patients. In three patients, between 1 and 12 h after i.v. administration of DHAS (100-200 mg), the concentrations of serum oestrone, oestradiol and oestriol increased to 13-5, 6-8 and 3-1 times the control values, respectively. After injection of DHAS (200 mg) intra-amniotically into two patients, the urinary excretion of all three oestrogens increased much more on day 2 than on day 1, and the ratio of urinary oestriol to oestrone + oestradiol rose greatly. On the other hand, the concentrations of unconjugated serum oestrogens in these patients increased progressively between 1 and 12 h or more after DHAS administration, and the maximal level of serum oestriol was 9-8 times the control value while those of oestrone and oestradiol were 4-6 times and 5-0 times the control values, respectively. These results suggest that in late human pregnancy DHAS in the circulation of the mother is converted to oestriol largely via the phenolic pathway (DHAS leads to oestrone leads to oestriol), whereas DHAS circulating within the foeto-placental compartment is converted to oestriol via both the phenolic and the neutral intermediates.

Human placental lactogen (HPL) and urinary and serum oestriol levels were studied in patients in whom the contraction stress test was positive. After birth the infants were assessed for growth retardation. Low HPL, serum oestriol and urinary oestrogen levels were found in 66%, 30% and 15% of patients respectively. Gestational ages were known in 148 patients, of whom 72 (49%) had infants whose weights were below the 10th percentile for gestational age. HPL values were low in 81% of mothers who gave birth to growth-retarded infants, but serum and urinary oestriol levels were low in only 43% and 21% respectively. When both a positive stress test and a low HPL value were present, 69% of infants were growth retarded. The incidence of growth retardation rose to 85% when both HPL and serum oestriol levels were abnormal in patients with positive contraction stress tests. In this study estimation of HPL levels was found to be superior to that of oestrogen levels in detecting growth-retarded infants.

Serial plasma oestriol levels were measured by a radioimmunoassay in 49 normal pregnancies, Plasma oestriol rose from 43 ng/ml (149-1 nmol/l) at 22 weeks to 357 ng/ml (1237-91 nmol/l) at 40 weeks. The rise was gradual between 22 and 32 weeks and steep between 32 and 40 weeks. No significant relationship could be found between plasma oestriol and parity, maternal age, maternal height, maternal weight or fetal sex. However, a significant but low correlation was found between birth weight and plasma oestriol prior to labour and also oestriol increments from 30 weeks to delivery. The average day to day coefficient of variation of plasma oestriol in 11 patients was found to be 16-2 per cent.

A method for the determination of ethynyloestradiol in samples of rabbit plasma containing pentobarbital and heparin, the former used as an anaesthetic and the latter as an anticoagulant, has been developed. Quantification was carried out using a reversed-phase high-performance liquid chromatographic (HPLC) method in isocratic mode at room temperature, with electrochemical detection at an applied potential of +1 V vs. Ag/AgCl. Under these conditions, the retention time for ethynyloestradiol was ca. 2.9 min, the average recovery from plasma was 74.5%, and the limit of detection was 10 pg, corresponding to a plasma concentration of 50 pg/ml using 1 ml of plasma. Natural oestrogens, oestriol, oestradiol and oestrone showed peaks that did not interfere with ethynyloestradiol, and retention times of ca. 0.8, 2.4 and 3.4 min, respectively.