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In 311 high-risk pregnancies between 28 and 42 weeks of gestation a fetal weight estimation by ultrasound, a Doppler sonography of the umbilical artery, an analysis of estriol and HPL-levels in maternal serum and a CTG nonstress-test were performed approximately at the same time. The aim of the study was to compare the value of these methods in the diagnosis of fetal growth retardation. By variation of cut-off levels between normal and pathological range, ROC curves were created which allowed an objective comparison of methods at any cut-off level from ranges of high sensitivity to ranges of high specificity. The course of these ROC curves determine the following rank of test validity: 1. ultrasound measurement, 2. Doppler sonography, 3. HPL assay, 4. CTG nonstress-test, 5. estriol assay.

In a prospective study estriol, estradiol, progesterone, human placental lactogen (HPL) prolactin and SP1 (a placental glycoprotein specific for pregnancy), were performed in the second half of uncomplicated pregnancies in order to answer the question if there exist a circadian rhythm of these hormones in serum. All serum concentrations were measured by radioimmunoassay at 8.00, 10.00, 16.00, 20.00, 24.00 and 4.00 o'clock. 58 pregnant women with uncomplicated pregnancies show no circadian rhythm of serum levels from estriol, progesterone, HPL and SP1, while serum levels of estradiol and prolactin have a significant circadian rhythm. The estradiol serum levels are significant higher at 8.00 and 12.00 o'clock, significant less at 24.00 and 4.00 o'clock. The prolactin serum levels are significant less at 16.00 and 20.00, at 4.00 and 8.00 significant higher. In 20 pregnancies complicated by preeclampsia and 12 pregnancies complicated by intrauterine growth retardation serum levels of all hormones were measured at 8.00, 10.00, 16.00, 20.00, 24.00 and 4.00 o'clock. The serum concentrations in complicated pregnancies show no difference to the serum levels in uncomplicated pregnancies.

The following parameters of glucose biokinetics in pregnancy, in which the behavior of the glucose in the steady state is described, were investigated mathematically following short-term disturbance of the steady state of the maternal metabolism by intravenous administration of glucose. The glucose assimilation coefficient (KG) is unchanged in pregnancy. However, both during pregnancy and post partum (2.30; 2.20; 2.36; 1.79 [%/min]), the values are higher than in the non-pregnant control group (1.2%/min). Analogously to these findings, the glucose distribution space increases during pregnancy from 13 liters to 16.3 liters, decreasing post partum to 13.4 liters. The easily exchangeable glucose pool, i.e., the quantity available for assimilation in the distribution space, is unchanged during pregnancy; nor is there any change as compared to the non-pregnant and postpartal control groups. Glucose transfer, i.e., the glucose quantity which enters or leaves the pool per unit of time, is increased during pregnancy (0.45; 0.444; 0.47 [g/kg/h]) as compared to the non-pregnant and postpartal controls (0.25; 0.35 [g/kg/h]). The findings above indicate that the maternal glucose metabolism is increased during pregnancy. Owing to the lipolytic effect of HPL, the mother is obliged to meet a portion of her energy requirements from the lipid metabolism, so that there is enough glucose available for the fetus. HPL appears to develop this glucose-saving effect doubly.(ABSTRACT TRUNCATED AT 250 WORDS)

The mean values of the maternal HPL are significantly decreased in cases of threatened abortion from the 10th to the 16th week post menstruation. But the HPL concentration is only of prognostic value after the 13th week because only after that time the HPL concentration is significantly decreased in cases with following abortion. The common therapy with gestagens or with a combination of estrogens and gestagens has no influence of the mean HPL concentrations. For the first time it could be shown an influence of an exogen estrogen-gestagen combination on the individual values of HPL serum-concentrations.

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.

of urinary total oestrogen and pregnanediol were undertaken in 65 high risk pregnancies which resulted in the delivery of 65 hypotrophic infants. The relative clinical relevance of the three examined parameters was investigated by graphical comparison of the pathological ranges with the normal ranges (degree of overlapping). In respect of hypotrophy the ratio of pregnanediol : total oestrogen : HPL is equal to 7 : 5 : 1. This shows a sevenfold improved correlation between pregnanediol and fetal weight than between HPL and fetal weight.

Radioimmunoassay of human placental lactogen (HPL) is a valuable diagnostic tool for the early recognition of placental dysfunction. But, the rather wide normal range hampers HPL estimations to be used as a good prognostic tool. However, the simultaneous determination of HPL in maternal serum and in amniotic fluid allows a better diagnosis of the fetal well-being. Results of amniotic fluid HPL levels are expressed as percent of maternal serum levels. In this pilot study it was shown that this ratio of maternal serum HPL level to amniotic fluid level is below 10% in normal pregnancies. The ratio is between 10 to 20% in subjects where fetal distress was recorded, and dystrophic babies were observed. The value is above 20% in cases where intrauterine fetal deaths were found. This good correlation of the HPL ratio in maternal serum and amniotic fluid with the outcome of pregnancy offers a new means of using HPL estimation as prognostic tool.

The experience published in medical literature on the pregnancy hormones HPL and estrogens, is subjected to a critical review. The reported studies are examined in detail, first of all, with regard to the performance of the pregnancy hormones in fetal risk situations, taking certain pregnancy complications into account. The ranking of these paremeters in arriving at obstetric decisions in fetal emergency situations, is then described. This is followed by an assessment of the importance of the pregnancy hormones as prognostic parameters for forecasting fetal hazard in cases where pregnancy appears to have taken an uneventful courese, basing on few results available to date. All findings indicate that biochemical monitoring during pregnancy contributes toward individualization of the obstetric decisions.

The influence of transcutaneous nerve stimulation (TNS) on the hormonal parameters of placental function (HPL and Estriol) in the serum of 39 patients between the 28th and 39th week of pregnancy was investigated. In this patients placental insufficiency was suspected because of low hormonal parameters or a diminished radioisotope placental perfusion test. During a hospitalization of 2 weeks these patients underwent a daily TNS-therapy for 2-3 hours. 2 or 3 hormonal values before these two-weeks therapy and 2 or 3 values after the therapy were compared. A significant difference (p less than 0.05; t-test) was found. HPL and Estriol mean values raised absolutely, but also in comparison to a group of patients of our clinic without placental insufficiency. A correlation between the onset of therapy at a certain week of gestation and it's effect could not be proved. The use of this riskless method as a therapy of placental insufficiency is recommended.

Repeated intramuscular application of HPL to pregnant women did not significantly influence serum concentrations of HPL, SP-1 and estriol. Thus, this mode of application seems to be not adequately for substitutional therapy during pregnancy.

The efficacy of five different methods for detection of fetoplacental distress has been compared in 265 risk pregnancies. The tests were urinary oestriol, urinary pregnanediol, human placental lactogen and heat-stable alkaline phosphotase in the serum and phonocardiotokographie. 13 fetuses died antepartum, 47 of surviving infants were growth-retarded. The gestational age was calculated from clinical dates, serial ultrasonic measurements and immediate postnatal studies. In the I part the methods and the analysis of the results are described.

Serum, cord blood and amniotic fluid beta2-microglobulin contents were measured from normal pregnancies complicated by EPH gestosis, Rh immunisation and pathological serum levels of HPL and alpha1-fetoprotein. We found no changes in high risk pregnancies from normal serum levels. beta2-microglobulin seems to be no parameter in managing complicated pregnancies and fetal growth retardation.

The efficacy of four different methods for detection of placental dysfunction has been compared in 265 risk pregnancies. The test were urinary oestriol, urinary pregnanediol, activity of human placental lactogen and heat-stable alkaline phosphatase in the serum. It was concluded that best results were obtained by simultaneous use of urinary oestriol und human-placental-lactogen activity. Early detection of placental dysfunction by urinary pregnanediol and heat-stable alkaline phophatase in the serum were rather exceptional.

In a prospective study covering 175 gravidae it was investigated whether the risk of a "small" placenta could be detected by determining HPL or serum estriol once during the first 18 weeks of pregnancy. The results show that neither the HPL value nor the serum estriol value correlate with the weight of the placenta or the child. Therefore, the problem of early detection of a "small" placenta cannot be resolved with these hormone parameters.

The placentas of ninety-six pregnancies supervised by measurements of human placental lactogen (HPL) were examined. The histometrically determined placental villous surface and the degree of maturation of the villous tissue were compared to HPL-values in late pregnancy and to the weight of the newborn. The production of HPL is dependent on the extent of the syncytiotrophoblast surface area and, in addition, is modulated by the grade of differentiation of the chorionic epithelium. Placental villi with abnormalities of maturation apparently synthesize more HPL than villi of normal maturation.

32 patients with high-risk pregnancies were treated with 3 X 5 mg of 17alpha-ally1-17beta-hydroxy-estr-4-ene (allylestrenol, Gestanon) daily. Only those patients entered this study, who had pathological HPL serum levels during two successive control investigations. In addition, cytological analyses of vaginal smears were performed before treatment was started. The patients were treated with allylestrenol until normal HPL levels were recorded, but at least during 14 days. HPL serum levels were estimated every second day through 14 days. Thereafter HPL assays were performed in weekly intervals. Determinations of HPL were done by radioimmunoassay. Analyses of vaginal smears were done weekly. Statistical analysis of HPL serum levels were performed by Student's-t-test. A statistical significant increase of HPL serum levels were registered during allylestrenol therapy. These results suggest that the pregnancy maintaining effect of allylestrenol is at least partly due to a stimulation of placental function. Analyses of vaginal smears indicate a progestational effect of the norsteroid.

The digital estimation of utero-placental circulation by means of nuclear-medical examinations with help of 113 m In-Cl and regarding to the "region of interest" gives no depositions in cases with an intrauterine retardation. This concerns the activity as well in the placenta as in the uterus too. Exceptions represents intrauterine retardations on the base of heaviness EPH-gestosis and placenta previa. Herewith the rise of activity corresponds with the thickness in the III. trimester of pregnancy. A treatment about several weeks with Hepain under bed conditions leads to no proofed influence of the uteroplacental circulation, on the contrary to a rise of estriol and HPL-values, meaning a improvement of placental performance. The estimation of the utero-placental circulation by means of nuclear-medical examinations is situated to the problem of fetal condition by EPH-gestosis, placenta previa and other.

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.

Serum concentrations of SP1, HPL and estriol were investigated for circadian variations: levels of SP1 were significantly decreased at the 24th and 4th hour. An investigation of serum concentrations of SP1, HPL and estriol during labours revealed a tendency of decreasing levels of estriol.

Apart from rest in bed, various pharmacotherapeutic approaches are recommended in the treatment of chronically deficient foetal supply. Xantinol nicotinate (Complamin retard) was examined with regard to its influence on the human placental lactogen (HPL) values in a preliminary study followed by a double-blind study. In the first experimental series, 53 pregnant women were treated on an in-patient basis because of suspected placental insufficiency. In 22 women treatment was effected by ordering complete rest in bed, whereas 31 women received for at least three weeks Complamin retard in addition to the "rest in bed" treatment. Rise in HPL levels was significantly more frequent with the Complamin group than with the group of women who had rested in bed only without receiving any pharmacotherapy. A double-blind study was conducted also in patients suspected of placental insufficiency. 25 pregnant women received Complamin retard for three weeks in succession, whereas 25 other pregnant women were given placebo tablets only. Here, too, it was statistically evident that the HPL values increased more often with the Complamin than with the placebo group of patients.