[Experiences with HELLP syndrome]. / Erfahrungen mit dem HELLP-Syndrom.

Between 1988 and 1991 thirty-nine pregnant women suffering from HELLP-Syndrome were treated in our hospital. A retrospective analysis of clinical course and of the changes in the relevant laboratory values was performed. The incidence of the HELLP-Syndrome at Freiburg University Hospital was 0.85% for all pregnancies or 17% of the patients with toxaemia. 90% of the women were primipara, there was no prevalence of a certain group. The clinical course was characterized by the perseverance of symptoms for more than two weeks in 18% of the cases and a perinatal mortality of 25%, the latter mainly due to prematurity of the infants. This suggests that perinatal mortality due to respiratory distress syndrome can be reduced by conservative and expectative management of these patients. However on the other side a high rate of caesarean sections (77%) and sometimes even induced abortions were necessary to avoid maternal mortality and severe pre-or postpartal complications for these women.

[Prolongation of premature multiple pregnancy after abortion of one or more fetuses]. / Prolongation unreifer Mehrlingsschwangerschaften nach Abort eines oder mehrerer Feten.

In four cases of one twin pregnancy and three triplet pregnancies, efforts were made to prolong the pregnancy after the death of one foetus between 15th and 26th weeks of gestation. Two patients had a history of spontaneous abortion, three patients had undergone infertility treatment. In a further three cases the membranes ruptured prematurely in association with severe disturbance of the vaginal flora. Treatment consisted of rest in bed, sedation, and administration of magnesium and antibiotics. Neither cervical cerclage nor general IV tocolysis were performed. Although the pregnancies could be prolonged for 4, 22, 28, and 76 days, they all terminated before the 27th week, mainly due to ascending infection. Of the 11 children, two survived with no morbidity, two children (B and C of the third triplet pregnancy), died 2 and 19 days after delivery, respectively, and seven were stillborn. A comparison with prolongations of twelve twin and four triplet pregnancies reported in the literature, reveals the various concepts for treatment. After infection has been ruled out and the parents have been fully informed, efforts could be made to prolong the multiple pregnancy after the death of one foetus until the surviving child is viable. This requires intensive supervision.

[Fetomaternal transfusions in early pregnancy]. / Fetomaternale Transfusionen in der Frühschwangerschaft.

Fetomaternal bleeding is the major cause for rhesus immunization in pregnancy. This study evaluates the amount of fetomaternal bleeding in 345 pregnancies before 28th week of gestation. Fetomaternal bleeding was of clinical relevance (HbF greater than 0.015%) in 2.2% of all uncomplicated pregnancies. In case of abortion or vaginal bleeding in early pregnancy we observed a statistical significant increase of transplacental hemorrhage. The need for anti-D-prophylaxis in this patients is obvious.

Fetal urinary tract obstructions: prenatal diagnosis--prenatal and postnatal therapy.

A retrospective study was conducted comprising 78 cases of fetal urinary tract obstructions diagnosed by ultrasound. Thirteen of the obstructions were subvesical and 65 supravesical. In only one fetus with a subvesical obstruction leading to megacystis was a puncture of the fetal bladder performed--in the 17th week of gestation--resulting in restitution of the bladder to its normal size. In all of the remaining fetuses the kidneys, lungs, and bladder changes had already reached an advanced stage by the time the ultrasound diagnosis was made. In the 65 fetuses with supravesical urinary tract obstructions in utero puncture to relieve a rapidly developing hydronephrosis only seemed advisable in two cases. All of the prenatal diagnoses were confirmed postpartum with the exception of two Potter IIa kidneys, which had been interpreted as being hydronephrosis. The time and method of postnatal management are described. The results of the study indicate that in utero intervention is only indicated in the very rare case. Nearly all of the supravesical obstructions remained unchanged, some even for months. In these cases there was no evidence of cystic-dysplastic renal changes after delivery.

[Fetomaternal transfusion in relation to mode of delivery. Comparison of data from the DFG multicenter study "Rhesus negative" (1965-70) with data from the Freiburg University Gynecologic Clinic (1989)]. / Fetomaternale Transfusionen in Abhängigkeit vom Geburtsmodus. Vergleich der Daten aus der DFG Gemeinschaftsstudie "Rhesus negativ" (1965-70) mit Daten aus der Universitäts-Frauenklinik Freiburg (1989).

Fetomaternal hemorrhage with transfusion of more than 10-25 ml fetal blood into the maternal circulation ("macrotransfusion") is one possible cause of the failure of combined pre- and postpartal anti-D prophylaxis. We analyzed the data from 391 patients who delivered at the UFK Freiburg in 1989. We evaluated the amount of fetomaternal bleeding in different modes of delivery. We observed fetomaternal hemorrhage of clinical relevance in 7.5% of spontaneous delivery, 11.1% of vacuum extraction, 17.7% of cesarean section (p less than 0.05). There was no difference concerning macrotransfusions in the above mentioned modes of delivery. Our data are compared with the data of the DFG multicenter trial "rhesus negative" (1965-79).

[Refractory vomiting with cisplatin therapy. Prospective study with the serotonin receptor antagonist GR 38032F]. / Therapierefraktäre Emesis unter Cisplatin. Prospektive Studie mit dem Serotonin-Rezeptor Antagonist GR 38032F.

Emesis in chemotherapy containing Cisplatinum (DDP) is still a therapeutical dilemma. Emesis and nausea cause the cessation of a potential curative therapy in up to 10% of patients treated with DDP. We studied the antiemetic effectiveness of the selective Serotonin (5HT3)-receptor-antagonist Ondansetron (GR 38032F, Glaxo) in patients receiving high dose platinum chemotherapy. All patients suffered from severe emesis and were refractory to any standard antiemetic regimen (Metoclopramid). We studied the efficacy of the new drug against acute and delayed emesis following platinum chemotherapy. All adverse events are listed. Thirty four courses (n = 17 patients) of a platinum-containing regimen were analyzed so far. A sufficient antiemetic efficacy was observed in 56% of the courses. In 32 of 34 course (94%) the patients preferred the new drug compared with the standard antiemetic regime (Metoclopramid). In most cases only minor adverse events--which do not require any medical therapy--occurred. The most common adverse events were headache, constipation, dry mouth, abdominal discomfort and elevation of liver enzyme level without any clinical symptoms. One patient needed bowel surgery for severe constipation based on widespread intra-abdominal carcinosis.

[Oral contraceptive-induced liver tumors and pregnancy]. / Durch orale Kontrazeptiva induzierte Lebertumoren und Schwangerschaft.

This paper reports on four pregnancies with maternal liver tumors induced by oral contraceptives. No increase in size and no rupture of these liver lesions were observed during the gestational and postpartum period. The toxic potentials of orally active sex steroids and the role of natural sex steroids are discussed. Criteria for differential diagnosis and practical suggestions are presented.

[Systemic lupus erythematosus and pregnancy. Clinical aspects, serology and management]. / Systemischer Lupus Erythematodes und Schwangerschaft. Klinik, Serologie und Management.

Systemic lupus erythematosus (SLE) is an autoimmune disease affecting the connective tissue of the skin and the vascular system. In about 90% of the cases, the first diagnosis is made in women of child-bearing age. We report on 11 pregnancies in 5 patients with SLE. The incidence of SLE was found to be 1:2966 in relation to obstetric cases in our hospital. In one patient, an acute exacerbation of the disease led to preterm delivery in the 31st week of pregnancy. The affected patient died postpartum due to generalised disease and septic complications. In general, perinatal mortality was found to be 25% (excluding early abortion). The number of spontaneous abortions, premature deliveries and small for date babies was elevated in our group of patients, in comparison to the normal group. As a result of our own observations in serological controlled pregnancies and of an extensive review of the literature, we came to the following conclusions: Uncomplicated SLE is no contraindication for pregnancy. However, an SLE nephritis represents a relative or even absolute contraindication, depending on the clinical course. Recent prospective studies permit us to conclude, that a pregnancy will not lead to an aggravation of SLE. On the other hand, SLE can cause complications in pregnancy with a subsequent rise in maternal and foetal morbidity and mortality. Most frequent are preeclampsia, premature labour, foetal maldevelopment and flare-ups of the underlying disease. For monitoring the disease, frequent determinations of complement proteins C3/C4 are helpful. The measurement of the C3 turnover can be used to distinguish between the development of preeclampsia and exacerbation of the disorder.(ABSTRACT TRUNCATED AT 250 WORDS)

[The Arabin cerclage pessary--an alternative to surgical cerclage]. / Das Arabin-Cerclage-Pessar--Eine Alternative zur operativen Cerclage.

During 1986-1988, the Arabin-cerclage pessary was used alternatively to surgical cerclage in 58 patients for prophylactic and in 44 cases of therapeutic indications. In 5 additional patients, the pessary was applied instead of emergency cerclage. The advantages of the cerclage pessary compared to other rigid pessary types, are based on its flexibility and adjustment to the anatomic conditions of vagina and cervix. The bowl-shaped pessary is inserted with the curvature upwards and the cervix is fixed in the central opening of the cerclage pessary. Thus a constriction, reconfiguration, and elongation of the incompetent cervix is obtained as evidenced by ultrasonography. The only side effect of the pessary treatment is an increase in cervical secretion and subsequent vaginal discharge. No infectious complications occurred. In 92% of the treated gravidae the cerclage pessary could be removed after the 36th week of gestation. Cerclage pessary can be recommended as a favourable alternative to surgical procedures as prophylactic or therapeutic approach, reducing surgical treatment significantly to less than 0.5%.

[Late morbidity following cesarean section--a neglected factor]. / Spätmorbidität nach Kaiserschnitt--ein vernachlässigter Faktor?

Based on the data of a questionnaire this study was designed to follow the obstetrical and gynecological history of 269 women who were delivered at our hospital by Caesarean section during 1960-1969. The Caesarean section group was compared with a control group of 229 women who were delivered spontaneously during the same period. Patients with cesarean sections had less children and more often they had been afraid of further deliveries. In patients with vaginal deliveries there was a significant higher incidence of descensus and prolapse uteri and more often a therapy because of premalignant or malignant diseases of the cervix had to be performed. However, there was no significant difference in the frequency of hysterectomies in both groups. The main indication for hysterectomy in the vaginal delivery group was prolapse and descensus, and in the Caesarean section group fibromyoma of the uterus. Except one case of uterine rupture the rate of complications in subsequent pregnancies was similar for both groups. Compared to the control group a higher rate of maternal morbidity due to Caesarean section could not be proved.

The effect of acetylsalicylic acid and indomethacin on the catecholamine- and oxytocin-induced contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha)-production of human pregnant myometrial strips.

The effects of acetylsalicylic acid (ASA) and indomethacin (IND) on the epinephrine and oxytocin stimulated contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha) production of superfused myometrial strips from the pregnant human uterus at term are reported. Without preincubation in ASA or IND epinephrine dose-dependently (10 ng/ml to 1 microgram/ml) stimulated the contractility and significantly increased the PG-release of the myometrial strips. The epinephrine induced increase in contractility was correlated to a higher increase in PGF2a production and a decreased 6-keto-PGF1 alpha/PGF2 alpha ratio (5.4 to 1.8). Superfusion of oxytocin increased myometrial contractions and PGF2 alpha release according to dose (3-12 microU/ml). However, 6-keto-PGF1 alpha production was not affected by oxytocin. Myometrial strips preincubated with ASA (100 micrograms/ml) or IND (10 micrograms/ml) demonstrated little spontaneous activity and the PG production was below the detection limit of the RIA. The stimulating effect of epinephrine and oxytocin on the contractility and PGF2 alpha release of the myometrial strips was inhibited significantly. During continuous superfusion of the ASA and IND preincubated myometrial strips with Tyrode's solution the inhibitory effect on spontaneous, epinephrine-, and oxytocin-stimulated contractility and PGF2 alpha release gradually declined over a period of 2 hours. This decrease of the inhibitory effect was more significant in ASA preincubated specimens. Our results demonstrate that spontaneous, epinephrine-, and oxytocin-stimulated contractility and PG release of human myometrial strips can be inhibited by ASA and IND and that this inhibitory effect is reversible. Furthermore our results suggest that in pregnant human myometrium the inhibition of PGF2 alpha production by ASA and IND is more pronounced than that of 6-keto-PGF1 alpha (PGI2).

[Cervix ripening using drugs before oxytocin labor induction. Clinical study of a new prostaglandin E2 triacetin gel]. / Medikamentöse Zervixreifung vor Oxytocin-Geburtseinleitung. Klinische Studie mit einem neuen Prostaglandin E2-Triacetin-Gel.

In an open randomized clinical study, 50 of 100 gravidae with a low Bishop score (less than or equal to 5) at term were treated with prostaglandin E2 (0.5 mg PGE2 in 2.5 ml Triacetin gel. Prepidil, intracervically) 12 hours before the indicated i.v. oxytocin induction. In 50 patients labor was induced intravenously without any pretreatment. In 46 of 50 pretreated women (92%) there was an increase in the Bishop score of at least three points, and of only two points in the remaining four. In the control group no significant increase in the Bishop score was measurable. Sixteen patients delivered within the first 12 hours after PGE2 gel administration, before oxytocin induction. Three women in the untreated control group also delivered during this pre-observation period. In 14 (64%) of 22 women in whom cervical priming with PGE2 was performed and 26 (57%) of 47 patients in whom it was not the first intravenous oxytocin induction was successful. The frequency of cesarean sections was 10% (n = 5) in the PGE2 gel group and 12% (n = 6) in the oxytocin group. The oxytocin dose needed to induce labor was significantly lower after cervical priming. No severe side effects were observed during and after PGE2 treatment, in either the mothers or the children.

Urinary protein patterns and EPH-gestosis.

In pregnancy a glomerular or mixed glomerular/tubular proteinuria in excess of 0.5 g/day was found in EPH-gestosis or preceding glomerular disease. A pure tubular proteinuria was not found in EPH-gestosis. The severity of the clinical picture was positively correlated with the daily protein loss.

[The course of labor in very young and older pregnant patients]. / Geburtsverlauf bei sehr jungen und älteren Gebärenden.

The course of pregnancy and delivery and the fetal outcome were analyzed in 23 women aged less than 16 years and 151 women aged 42 years or more. Most of the adolescent mothers were delivered spontaneously without any major problems. In patients aged 42 years and more there was a higher rate of pregnancy complications due to predisposing risks and a high incidence of prolonged labour, correlated to an increased frequency of operative deliveries and in general more active obstetrical management. Fetal outcome was good in both groups. The results demonstrate the necessity of intensive prenatal care in both groups. Whereas in young gravidae spontaneous delivery can be expected in most cases, the women with advanced maternal age do need an active obstetrical management including all the abilities of modern perinatal medicine. Intensive antenatal and perinatal care provided, the prognosis for mother and child can be estimated as good in both groups.

[Perinatal medical possibilities and limitations of the obstetrical center--an analysis of the causes of perinatal mortality 1982-1985]. / Perinatalmedizinische Möglichkeiten und Grenzen des geburtshilflichen Zentrums--eine Analyse der Ursachen perinataler Mortalität 1982-1985.

Based on the analysis of 4,881 deliveries during 1982-1985 the perinatal statistical data of a regional perinatal center (level 3) are presented. There is high percentage of pregnancies at risk (57%), preterm deliveries (11%), and increasing incidence of multiple pregnancies (3%). The rate of spontaneous deliveries amounts to more than 70%, the frequency of cesarean sections reached a maximum of 19%. As causes of 82 perinatal deaths (16.8% mortality rate) were found above all fetal malformations (42%), multiple pregnancy (18%), severe intrauterine growth retardation (17%), and premature rupture of membranes with septic complications (10%). Further causes of perinatal death were severe umbilical cord complications (5%), diabetic pregnancy (5%), abruptio placentae and maternal high risks. After detailed analysis 55% of all perinatal deaths proved to be unavoidable, 18% possibly avoidable, and 27% avoidable. The presentation of the avoidable perinatal deaths demonstrates the shortcomings and possible improvements of the obstetrical management and organization. The possibly avoidable cases could be solved in future. According to the purged perinatal mortality rate there are 4 remaining avoidable cases for which the perinatal center proved to be responsible. The perinatal mortality risk in the regional center is therefore less than 1%o.

[Prognosis of pregnancy in diabetes mellitus]. / Zur Prognose der Schwangerschaft bei Diabetes mellitus.

From 1970-1984 116 pregnant diabetic patients were monitored and delivered at the University Hospital of Freiburg, Department of Obstetrics and Gynecology. During these 15 years, a decrease in maternal and fetal complications was observed. Today the risk of some complications in diabetic pregnancy is not greater than that of pregnancy in nondiabetic women. There is, however, still a higher incidence of gestosis and polyhydramnion in diabetics. The main fetal risk is macrosomia. There is an increasing tendency to spontaneous delivery near term. Today incidence rate of caesarean sections is below 30%.

[Monitoring of pregnancy in diabetes mellitus]. / Die Uberwachung der Schwangerschaft bei Diabetes mellitus.

From 1970-1984 116 diabetic pregnant patients were monitored and delivered at the University Hospital of Freiburg, Department of Obstetrics and Gynaecology. The pregnant diabetics were managed and controlled by an interdisciplinary team of internists and obstetricians. For better control of the maternal metabolic status, the diabetic patients were admitted to the hospital three times during their pregnancy. Foetal monitoring was done by ultrasonography, hormone analyses and cardiotocography. In most cases foetal growth retardation and macrosomia were detected early via sonography. Decreased urinary excretion of total oestrogen was measured during late pregnancy in 13% of the diabetic patients. In cardiotocography a loss of foetal reactivity was observed in 11% of all non-stress tests (NST). In more than 50% of these cases, the total oestrogen excretion also decreased. In patients with normal oestrogen values, an abnormal NST was rarely observed. Abnormal oxytocin challenge tests (OCT) were recorded in 19% of the patients. Among these cases most of the patients with a non-reactive NST were found. In 85% of the patients with pathological changes in the OCT a Caesarean section had to be performed, and among these in all patients with a loss of foetal reactivity in the cardiotocogram. In correlation with the foetal outcome, loss of reactivity in the cardiotocogram has greater pathological relevance than deceleration with maintenance of reactivity. For an early recognition of imminent placental insufficiency, OCT proved to be the most sensitive parameter. The increased incidence of acute placental insufficiency in diabetics during delivery underlines the need for repeated stress tests during late pregnancy.

[Interaction of sex steroids, prostaglandins (6-keto-PGF1 alpha, PGF2 alpha) and beta adrenergic agonists (adrenaline, fenoterol-Partusisten) in the human non-pregnant myometrium in vitro]. / Wechselwirkung von Sexualsteroiden, Prostaglandinen (6-keto-PGF1 alpha, PGF2 alpha) und beta-adrenergen Agonisten (Adrenalin, Fenoterol-Partusisten) im menschlichen nicht-schwangeren Myometrium in vitro.

The in vitro effects of epinephrine and fenoterol (Partusisten) on contractility and prostaglandin (6-keto-PGF1 alpha, PGF2 alpha) production of human, non-pregnant myometrial strips dependent on the phase of the menstrual cycle and after pretreatment with estrogens and progesterone are reported. Superfusion of epinephrine (100 ng/ml) stimulated contractility and PG-synthesis of myometrial tissue from the proliferative phase of the cycle, whereas fenoterol (10 ng/ml) had only a little inhibitory effect. After pretreatment with conjugated estrogens (Presomen) the maximal epinephrine-stimulated contractions were correlated to a further increase in PGF2 alpha-synthesis even during fenoterol superfusion. In myometrial tissue obtained during the secretory phase of the cycle, both epinephrine and fenoterol had a significant inhibitory effect on spontaneous contractions associated with an increase in 6-keto-PGF1 alpha-production. After pretreatment with an estrogen-progestin combination (Primosiston) fenoterol superfusion resulted in a complete inhibition of myometrial contractions. These results demonstrate that estrogens increase the myometrial sensitivity to catecholamines leading to increased contractility and increased PGF2 alpha-synthesis, whereas progesterone probably mediates the beta-adrenergic inhibitory effect on myometrial contractions. Thus, the contractions inhibiting effect of the betamimetic drug fenoterol associated with decreased PGF2 alpha- und increased prostacyclin (PGI2) synthesis depends on the effect of progesterone in human, non-pregnant myometrium.

Clinical evaluation of endocervical prostaglandin E2-triacetin-gel for preinduction cervical softening in pregnant women at term.

In an open randomized clinical trial 100 pregnant women with low Bishop Scores at term were treated either with intracervical Prostaglandin (PG) E2 (0.5 mg in 2.5 ml triacetin-gel) 12 hours before labor induction with intravenous oxytocin or with oxytocin infusion alone. In 46 of the 50 pretreated patients (92%) the Bishop Score progressed at least 3 points, in four cases only 2 points. The mean Bishop score in the untreated patients increased insignificantly. After PGE2-gel administration 16 patients delivered during the 12 hour interval compared to 3 in the group without pretreatment. The first induction attempt was successful in 14 (64%) of the 22 patients that were left to be induced after cervical softening and in 26 (57%) of the 47 women without cervical priming. The Cesarean section rate was 10% (n = 5) in the PGE2-gel group and 12% (n = 6) in the control group. Dosage of oxytocin required for labor induction was significantly lower after cervical softening. No serious fetal or maternal side effects were observed after PGE2 pretreatment.