Higher efficacy of letrozole in combination with trastuzumab compared to letrozole monotherapy as first-line treatment in patients with HER2-positive, hormone-receptor-positive metastatic breast cancer - results of the eLEcTRA trial.

The eLEcTRA trial compared efficacy and safety of letrozole combined with trastuzumab to letrozole alone in patients with HER2 and hormone receptor (HR) positive metastatic breast cancer (MBC). Patients were randomized to either letrozole alone (arm A, n = 31) or letrozole plus trastuzumab (arm B, n = 26) as first-line treatment. Additional 35 patients with HER2 negative and HR positive tumors received letrozole alone (arm C). Median time to progression in arm A was 3.3 months compared to 14.1 months in arm B (hazard ratio 0.67; p = 0.23) and 15.2 months in arm C (hazard ratio 0.71; p = 0.03). Clinical benefit rate was 39% for arm A compared to 65% in arm B (odds ratio 2.99, 95% CI 1.01-8.84) and 77% in arm C (odds ratio 5.34, 95% CI 1.83-15.58). The eLEcTRA trial showed that the combination of letrozole and trastuzumab is a safe and effective treatment option for patients with HER2 positive and HR positive MBC.

Impairment of the antiproliferative effect of glucocorticosteroids by 11beta-hydroxysteroid dehydrogenase type 2 overexpression in MCF-7 breast-cancer cells.

To verify the relevance of 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2) activity in controlling breast-cancer cell growth, we have evaluated the correlation of 11beta-HSD2 expression and antiproliferative effects of glucocorticosteroids (GCs) on breast cancer cell proliferation. We cloned human 11beta-HSD2 cDNA into the expression vector pBK-CMV. The interspersing lac promoter region was deleted, achieving differential translational efficiency. The constructs were stably transfected into wild-type MCF-7 breast-cancer cells possessing almost no oxidative and no reductive 11beta-HSD activity. Low (times 7) and high (times 718) 11beta-HSD2 overexpression was achieved. We compared growth behavior of transfected cells In the presence of GCs to MCF-7 cells transfected with pBK-CMV alone (internal control). The antiproliferative effects of GCs were reversed and total cell growth boosted by overexpression of 11beta-HSD2; about 50 % of the increase in cell proliferation was attained by low 11beta-HSD2 overexpression, while high enzyme overexpression led to an increase in cell growth of about 120 %. Using direct evidence, this study shows 11beta-HSD2 to impair antiproliferative glucocorticosteroid effects, thus acting as an enzymatic shield aggravating breast-cancer cell growth. These results indicate a possible therapeutic role for 11beta-HSD inhibitors in the treatment of breast cancer.

11beta-hydroxysteroid dehydrogenase type 1: a new regulator of fetal lung maturation.

Glucocorticoids (GCs) induce surfactant synthesis in the late fetal lung. Deficient GC action causes respiratory distress syndrome. 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) converts inert cortisone (11-dehydrocorticosterone in rodents) into active cortisol (corticosterone), thus amplifying intracellular GC action. We investigated 11beta-HSD1 in the late fetal lung using the licorice-derived inhibitor, glycyrrhetinic acid (GE), in pregnant rats (day 13 of gestation until term). Control fetal mice and rats showed high 11beta-HSD activity in the late fetal lung; levels of plasma 11-dehydrocorticosterone were also high. Reduction/loss of pulmonary 11beta-HSD1 activity in GE-treated rats substantially impaired fetal lung maturation. Lungs from GE-exposed rats had lower surfactant protein-A (mRNA and protein) levels and reduced amniotic fluid lecithin/sphingomyelin ratios. There was a marked depletion of lung surfactant before and after birth, as detected by both light and electron microscopy. The data emphasize the importance of 11beta-HSD1 in amplifying key GC-dependent maturational processes in the late fetal lung.

The relevance of placental location at 20-23 gestational weeks for prediction of placenta previa at delivery: evaluation of 8650 cases.

OBJECTIVE: To determine the correlation between placental position at 20-23 weeks and incidence of birth complications caused by placental position. SUBJECTS AND METHODS: In an ongoing prospective study, placental position was determined by transabdominal sonography as part of anomaly scanning at 20-23 gestational weeks, followed by transvaginal sonography in uncertain or suspicious situations. Examination was performed in 9532 cases; feedback was obtained from 8650 patients (90.7%). RESULTS: Transabdominal sonography was followed by transvaginal scan in 363 of 8650 cases (4.2%). In 8551 cases (98.9%), we found normal placental position, with the placenta not reaching the internal os and a Cesarean section rate of 17.1% (1458/8551). The incidence of 'low placental position', with the placenta reaching the internal os was 0.66% (57/8650), with a Cesarean section rate of 21% (12/57). In 0.49% (42/8650) of cases, the placenta overlapped the internal os at 20-23 weeks; Cesarean section because of placenta previa or bleeding was performed in 28 of 8650 cases (0.32%). Vaginal delivery was possible in 43% of cases (13/30), when the overlap did not exceed 25 mm. If the overlap exceeded 25 mm (12 cases), no vaginal delivery was reported. There was no reported case of placenta previa missed at the 20-23-week scan. CONCLUSION: At 20-23 weeks, a combination of routine transabdominal and indication-based transvaginal location of placental position is a powerful tool in predicting placenta previa at delivery. The advantage of determining placental position at this stage of pregnancy is a low false-positive rate compared to at earlier stages of pregnancy. We conclude that an overlapping placenta at 20-23 weeks has the consequence of a high probability of placenta previa at delivery. An overlap of 25 mm or more at 20-23 weeks seems to be incompatible with later vaginal delivery.

Ontogeny of 11beta-hydroxysteroid dehydrogenase: activity in the placenta, kidney, colon of fetal rats and rabbits.

Mechanisms to regulate closely fetal GC exposure are of considerable importance, as certain organs (kidney, brain) are adversely affected by excess GCs. 11beta-Hydroxysteroid dehydrogenase type 2 (11beta-HSD2) reduces transplacental passage of maternal GCs to the fetus. We hypothesized that 11beta-HSD2, if active in fetal kidney and colon, might allow local tissue modulation of GC access during the critical last trimester. We determined the presence, ontogeny and functionality of 11beta-HSD in the placenta and fetal, neonatal and adult kidney and colon in rats and rabbits and the cortisol:cortisone ratio in human amniotic fluid, which represents fetal urine. There was clear a 11beta-HSD2 expression in last trimester fetal colon, kidney and placenta in both rats and rabbits. This appeared of functional importance, since the potency of cortisol on fetal rabbit colonic sodium flux in the Ussing chamber was increased by 11beta-HSD inhibition. In human amniotic fluid, we found a decreasing ratio of cortisol:cortisone across the last trimester, suggesting an analogous onset of renal 11beta-HSD2 activity in the human fetal kidney. Local fetal tissue 11beta-HSD2 may modulate exposure to the deleterious effects of GCs upon target tissue maturation during sensitive periods of late gestation when fetal GC levels rise to prepare other organs (lung) for adaptations at birth.

Could a combined administration of dexamethasone and 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) be a more effective alternative to dexamethasone alone in the prevention of RDS?

OBJECTIVE: To test whether the combined application of dexamethasone (DEXA) and 3,5-dimethyl-3'-isopropyl-L-thyronine (DIMIT) induces the synthesis of surfactant protein A (SP-A) mRNA at a higher rate than both substances given alone? STUDY DESIGN: Organoid culture of fetal rat lungs (Wistar rats; day 19 of gestation) was prepared. After 48h of incubation we added DEXA (10(-5), 10(-7), 10(-8) and 10(-9)mol/l), DIMIT (10(-5), 10(-7) and 10(-9)mol/l) and the combination of DEXA in 10(-8)mol/l with various concentrations of DIMIT. After another 48h of incubation, northern blot and hybridization with a 32P-labeled SP-A cDNA probe was performed. One-way-variance-analysis with a Scheffé-test, Levene-test and one-sample-t-test were used for statistical analysis. RESULTS: DEXA alone above 10(-8)mol/l resulted in a significant increase, DIMIT resulted in a decrease of SP-A mRNA induction. Combined application of DIMIT and DEXA resulted in a significant increase compared to the controls. Compared to DEXA alone in 10(-8)mol/l, we found an increased induction, but the data were not significant. CONCLUSIONS: The combined application of DEXA and DIMIT shows a higher induction of SP-A mRNA than both drugs given alone.

Kinetic studies on rabbit liver glucocorticoid 5alpha-reductase.

The serum concentration of active glucocorticosteroids depends not only on adrenal synthesis but also on enzymatic activation of 11-dehydro-glucocorticoids in the liver by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1). In order to define the respective involvement of other regulative enzymes in the metabolism of 11-dehydro-glucocorticoids in the liver, the objective of this study was to evaluate the kinetic behavior of NADPH:delta 4-3-ketosteroid-5alpha-reductase (5alpha-reductase, EC 1.3.99.5). The interrelations to liver 11beta-HSD1 will be discussed. The kinetic properties of 5alpha-reductase of the rabbit liver were measured by a radioenzymatic assay and characterized with respect to protein-, substrate-, cosubstrate-, and pH-dependence. Michaelis-Menten enzyme kinetic parameters (Km and Vmax) were obtained for the formation of 5alpha-reduced 11-dehydrocorticosterone and corticosterone metabolites. We found that both 11-dehydrocorticosterone (Km 4.2 x 10(-6) mol/l, Vmax 2,600 pmol x min(-1) x mg(-1)) and corticosterone (Km 0.5 x 10(-6) mol/l, Vmax 38 pmol x min(-1) x mg(-1)) exhibit a high affinity to 5alpha-reductase. With respect to cosubstrate-, pH-dependence and finasteride inhibition, it is likely that 11-dehydrocorticosterone metabolism is primarily controlled by isoenzyme 5alpha-reductase type 1. This study shows that the deactivation of GCS especially of 11-dehydro-glucocorticoids via 5alpha-reductase is an important metabolic pathway in the liver. The metabolic activation of GCS by 11beta-HSD could possibly lead to an excess of GCS in the hepatocytes. Due to 5alpha-reductase activity this excess can be limited - on the level of CORT as well as of 11-DHC.

Effect of dexamethasone, triiodothyronine and dimethyl-isopropyl-thyronine on lung maturation of the fetal rat lung.

Our purpose was to elucidate why clinical studies have up to now failed to demonstrate a positive effect of TRH combined with glucocorticosteroids on fetal lung maturity. Morphological and biochemical lung maturation were determined by electron microscopy, choline incorporation, and surfactant-protein-A m-RNA synthesis in rat lung organoid cultures after exposure with a series of concentrations of dexamethasone, triiodothyronine, and dimethyl-isopropyl-thyronine. Thyroid hormones improved morphogenesis of lung histotypic structures but had a negative effect on surfactant synthesis whereas glucocorticosteroids had a positive effect on the surfactant synthesis but a negative effect on morphogenesis. The combination of both substances even had the most negative effect on morphogenesis. Since morphogenesis of lung histotypic structures is prerequisite for surfactant synthesis and secretion, we hypothesize that a sequential treatment of thyroid hormones to improve morphogenesis followed by the application of glucocorticosteroids might be an option to improve neonatal lung function.

Effect of epidermal growth factor on enzymes of phospholipid biosynthesis in lung and liver of fetal rat in vivo and in vitro.

Epidermal growth factor (EGF), a mitogenic polypeptide that binds to cell surface receptors, is an important regulator of cell differentiation and fetal lung surfactant synthesis, and may be used as a potential novel therapeutic agent in prematurity. Nevertheless, the distinct role in lung development and its mechanisms of action are not well understood. We investigated in vivo the systemic effect of intrafetally administered EGF (200 ng/g fetal body weight) and maternally administered dexamethasone (DEXA; 0.2 and 2.0mg/kg maternal body weight) on the activity of important enzymes of the phospholipid synthesis in the fetal rat lung and liver: choline kinase (EC 2.7.1.32), cholinephosphate cytidyltransferase (EC 2.7.7.15), choline phosphotransferase (EC 2.7.8.2), lysolecithin acyltransferase (EC 2.3.1.23) and glycerolphosphate phosphatidyltransferase (EC 2.7.8.5). Additionally, in vivo and in vitro effects of DEXA on EGF receptor synthesis, and the effects of EGF on protein content and morphogenesis of the fetal rat lung organoid culture, were evaluated. Whereas DEXA induced the activity of all investigated enzymes of phospholipid synthesis and increased EGF receptor synthesis, EGF has no effects on the enzymes, either in vivo or in vitro. EGF enhanced protein synthesis and morphogenesis in vitro. With respect to our data and the literature, we hypothesize that DEXA and EGF may act on different cellular sides. Whereas glucocorticoids induce surfactant phospholipid synthesis, EGF should be more involved in cell proliferation and morphogenesis.

Inhibition of 11 beta-hydroxysteroid dehydrogenase activity enhances the antiproliferative effect of glucocorticosteroids on MCF-7 and ZR-75-1 breast cancer cells.

This in vitro study on MCF-7 and ZR-75-1 breast cancer cells showed that the antiproliferative action of glucocorticosteroids (GCS) on breast cancer cells is weakened by a high oxidative activity of 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD; EC 1.1.1.146): both endogenic as well as synthetic GCS (dexamethasone, prednisolone) were metabolised to hormonally inactive 11-dehydro metabolites. This enzymatic shield protected the breast cancer cells from the antiproliferative action of GCS. Continuous exposure of breast cancer cells to GCS resulted in enhanced 11 beta-HSD activity. The intracellular GCS concentration was further reduced by this feedback and thus the antiproliferative effect was additionally weakened. These mechanisms of GCS deactivation could be influenced by inhibiting 11 beta-HSD with the liquorice compound glycyrrhetinic acid (GLY). In MCF-7 and ZR-75-1 cultures the antiproliferative effect of GCS was significantly increased by GLY.

[Effect of maternal age on the course of labor--analysis of women over 40 years of age]. / Einfluss des mütterlichen Alters auf den Geburtsverlauf--Analyse bei Frauen über 40 Jahre.

In order to determine the birth risk for pregnant women in the age group > or = 40, the delivery data of 143 pregnant women in this age group were retrospectively evaluated over a 3-year period. Here, 37 of these 143 women (25.9%) were primiparae. The following was examined: The number of prenatal examinations (including ultrasound examinations), the incidence of genetic examinations, the delivery methods with the percentage of surgical deliveries, complications at the time of delivery as well as the fetal outcome with APGAR values, umbilical artery pH, birth weights, neonatal morbidity and mortality. The delivery results were compared with representative populations of women between 20-29 years (n = 2252) and 30-39 years (n = 1980). Pregnancy in older women still ends significantly more often with cesarean section than in younger women. Here, the rate of cesarean sections was 32.7% compared to 21.9% in 30-39-year-olds and 15.8% in 20-29-year-olds. However, parity has an even greater influence on the mode of delivery than age. Only 30.1% of multi-parae over 40 years underwent surgical delivery (vaginal and abdominal) compared to 77.3% of primiparae. It was also found that multiparae more rarely had surgical delivery than younger primiparae (30-39 years 53.3%, 20-29 years 39.3%). Despite the high surgical delivery rate being in the group of primiparae over 40 years, the fetal outcome was comparatively poor, so that the less restrictive indication for surgical delivery seems justified.

[Accuracy of ultrasound weight assessment--comparison of vertex vs. breech presentation]. / Genauigkeit der sonographischen Gewichtsschätzung--Vergleich Schädellage vs. Beckenendlage.

AIM: To determine the quality of prenatal sonographic weight estimation, comparing breech and vertex presentations. METHOD: In 147 breech presentations (BP) and 149 vertex presentations (VP), the biparietal head diameter (BPD), the fronto-occipital head diameter (FOD) and the transverse abdominal diameter (ATD) were measured. From these data, the weight was estimated, using Shepard's formula before 28 weeks and Hansmann's thereafter, and compared to the delivery weight. Both formula were modified to incorporate the virtual BPD (vBPD), derived from the BPD, FOD and the calculated head circumference. In the BP group, the role of examiner skills was evaluated, comparing the accuracy of experienced (DEGUM II qualifications) and average individuals. RESULTS: The accuracy for BP was nearly identical to that for VP (= 0.915 vs. = 0.929). The examiners' qualifications had a detectable but not significant influence on the results (= 0.942 vs. = 0.892). CONCLUSION: Ultrasound measurements yield comparable results in both BP and VP, if the vBPD is used. In our opinion, ultrasonic weight estimation is a useful adjunct when determining the manner of delivery in BP.

[Notch in the umbilical artery Doppler profile in umbilical cord compression in a twin]. / Der Notch im Nabelarteriendopplerprofil bei Nabelschnurkompression eines Zwillings.

Monoamniotic twins have a mortality rate of up to 50%, mainly due to umbilical cord accidents, e.g. true knots. Because of the rarity of monoamniotic twin gestation, few data are presently available on the optimal management of these gestations. Some authors recommend delivery at 32 weeks of gestation, while others state that the risk of cord accidents declines with advancing gestational age, thus questioning the usefulness of routine delivery at 32 weeks. It is possible nowadays to obtain an impression of the fetal blood supply by Doppler sonography. In our case, Doppler sonographic evaluation showed a notch in the umbilical artery in the twin, who later developed a pathological CTG requiring delivery at 28 weeks of gestation. Both fetuses are liveborn and developed normally. Our case shows that a notch in the umbilical artery could be an indication of umbilical cord compression and that attention should be paid to it in monoamniotic twin gestation.

[Insulin-like-growth-factor-binding-protein 1 (IGFBP-1) and fetal fibronectin in diagnosis of premature rupture of fetal membranes]. / Insulin like growth factor binding protein 1 (IGFBP-1) und fetales Fibronectin in der Diagnostik eines vorzeitigen Blasensprunges.

The diagnosis of a premature rupture of membranes presents no problem in the vast majority of cases. However, a reliable diagnosis is clinically not possible in about 10%. Most methods available lack the necessary sensitivity and specificity. Since the clinical consequences of a false diagnosis are considerable (overtreatment for false-positive and risk of infection for false-negative results), it is essential to clinically establish new, minimally invasive methods with higher predictive powers. In the present study we compared: the AMNI Check for detection of insulin-like growth-factor binding protein 1 (IGFBP-1); a membrane immunoassay for detection of fetal fibronectin (fFn); pH indicator paper; and, to verify a rupture of membranes in unclear cases, amniocentesis with installation of indigo carmine. The examination was performed in a group of 75 patients, 35 with and 40 without rupture of the membranes. The best results were obtained for the AMNI Check (sensitivity and negative correctness 100%, specificity and positive correctness 83%). With the same sensitivity and negative correctness, the membrane immunoassay for fFn achieved a specificity of 70% and a positive correctness of 74%. The pH indicator paper had the lowest predictive value (sensitivity 94%, negative correctness 93%, specificity 63%, positive correctness 69%). Both the AMNI Check and the test for detection of fetal fibronectin can be recommended for reliable exclusion of premature rupture of membranes. Amniocentesis should however be performed in uncertain cases with a positive test result. Nevertheless, considerable reduction of this invasive method is possible.

Indication and results of insulin therapy for gestational diabetes mellitus.

The aim of this study was to determine whether amniotic fluid insulin concentration (AFI) is a better parameter than mean maternal blood glucose values (MBG) for deciding about insulin therapy in patients with gestational diabetes. MBG's were calculated on the base of 9 blood glucose levels during a 24 hour period after one week of diet therapy. In a prospective trial between 1987 and 1989 in Karlsburg, 123 gestational diabetic patients were randomized into two groups. Treatment was either based on the concentration of AFI or MBG levels. In a second series in Berlin, 103 patients were offered amniocentesis. 81 patients agreed and 22 refused. Treatment was then analogous to that in Karlsburg. In both groups of the randomized population, strict metabolic control was achieved. There was no difference regarding pregnancy complications. Earlier labor induction and higher cesarean section rates were seen in the non-invasive group (p < 0.05). The incidence of diabetic fetopathy and neonatal hypoglycemia was significantly lower in the invasive group (p < 0.01), even though the metabolic control parameters did not differ between the two groups. The results in Berlin correspond to these findings. In conclusion, AFI enables the recognition of any hyperinsulinism reaction to the maternal metabolic situation. We recommend the additional measurement of the AFI concentration between 28 and 36 weeks as the direct fetal parameter for deciding about insulin treatment.

[Management of premature rupture of fetal membranes in obstetrical departments in Germany]. / Management des frühen vorzeitigen Blasensprungs an geburtshilflichen Abteilungen in Deutschland.

Since the treatment of premature ruptures of membranes is not only controversial in the German but also in the international literature, we performed a survey of all obstetrics departments in Germany. From a total of 843 hospitals, 444 questionnaires were returned for evaluation (52.7%). The purpose was to determine which diagnostic and therapeutic regimes are used and how these agree with the literature. In addition to questions on the type of hospital, birth rates with a percentage of premature births and applied diagnostic parameters, our special interest focused on therapy, particularly with regard to prophylactic antibiotic application, tocolytic treatment and lung maturity induction. Prophylactic antibiotics are used in 36.7% and prophylactic tocolytic therapy in 41.7% of the departments. Interestingly, lung maturity induction was performed in 93.5%, in part even before the 28th week of pregnancy, although the effect of this therapy has not yet been proven at a very early stage of gestation. Due to the different views in the literature and, in part, a lack of basic scientific data, it seems there is a preference for the procedure, in which the best personal experience has been made. Because premature ruptures of the membranes is responsible for 30-40% of premature births, it is urgently necessary to clarify this controversial problem by large multicenter studies so that the treatment of early premature ruptures of the amnion can be founded on a rational basis.

Correlation of surfactant phosphatidylcholine synthesis and 11 beta-hydroxysteroid dehydrogenase in the fetal lung.

Glucocorticosteroids (GCS) are prerequisite for the induction of surfactant synthesis in the fetal lung. The 11 beta-hydroxysteroid dehydrogenase (11 beta-HSD) regulates the intracellular concentration of biologically active GCS. In this study we demonstrate the correlation of 11 beta-HSD activity and the GCS-induced surfactant phosphatidylcholine synthesis in organoid cultures of fetal rat lung. In the first series of experiments, [3H]corticosterone (CORT) or [3H]11-dehydrocorticosterone (11-DHC) were added to lung organoid cultures to test 11 beta-HSD activity. We found a low oxidative and a high reductive conversion indicating that in intact cells the equilibrium tends to biologically active GCS. However, in homogenized organoid cultures oxidative outweighed reductive activity. Secondly, the phosphatidylcholine synthesis of organoid cultures was enhanced by preincubation with GCS. CORT, as well as the hormonally inactive 11-DHC, increased the incorporation of [14C]choline into phosphatidylcholine. The effect of the latter was completely inhibited by glycyrrhetinic acid (inhibitor of 11 beta-HSD) indicating that it is caused by a previous conversion of 11-DHC into CORT via 11 beta-HSD. Thirdly, preincubation with GCS also altered 11 beta-HSD activity: dexamethasone or CORT both decreased the oxidative and increased the reductive activity in intact cells, indicating that glucocorticoids increase the rate of their own activation by positive feedback.

From biochemical to biophysical placental function tests in fetal surveillance.

Radioimmunoassays of human placental lactogen and estriol levels in the maternal plasma, ultrasound biometry of the abdominal diameter (AD), pulsed Doppler measurements of uteroplacental arteries, the common carotid artery (CCA), and the umbilical artery (UA) and fetal heart rate monitoring were simultaneously performed in 219 risk pregnancies from 26 weeks' onward at regular intervals. The prognostic value of all tests to predict small for gestational age infants (SGA) and fetal distress was evaluated simultaneously. Receiver operator characteristic allowed the simultaneous comparison of all methods: The AD was most predictive for early detection of SGA, even more than uteroplacental blood flow. Fetal blood flow redistribution expressed as a ratio of the resistance index of CCA/UA was the most significant test for detection of fetal distress later in pregnancy, even more than antenatal cardiotocography. Considering cutoff levels used in clinical routine, the sensitivity and specificity of the fetal AD in detecting intrauterine growth retardation more than 28 days before birth, were 71 and 81%, respectively. Pulsed Doppler measurements of CCA/UA less than 7 days before the delivery had a sensitivity and specificity of 83 and 90%, respectively. Our results demonstrate the historical change in fetal surveillance within one study group: If accurate routine ultrasound is available, the use of biochemical placental function tests is not justified, a procedure that is already accepted in nearly all perinatal centers. Fetal cerebral versus umbilical blood flow measurements should be applied as a tool to measure fetal blood flow redistribution in small fetuses to predict most precisely the risk for poor outcome and perinatal hypoxia.

[Prevention of neonatal risk by general screening for diabetes in pregnancy, intensive diagnosis and subsequent therapy]. / Vermeidung kindlicher Risiken durch ein generelles Gestationsdiabetes-Screening, intensivierte Diagnostik und konsequente Therapie.

Only 10% of all gestational diabetic mothers in Germany are diagnosed with the current risk-screening. The elevated perinatal risks in case of an unrecognized or insufficiently treated gestational diabetes remains controversial. The purpose of our study was to determine if the number of recognized cases could be increased by a general screening method, and with intensive medical diagnostics the complication rate reduced. Routine blood glucose samplings during the outpatient care were performed throughout the pregnancy. In case of values over 100 mg/dl a 75 g OGTT was done for an exclusion of gestational diabetes. In case of gestational diabetes the patients were asked to follow a special exercise and diet programme as well as self-blood glucose determinations throughout the day. The amniotic fluid insulin level was of substantial value for the indication of insulin therapy. In 6% of the screened patients a gestational diabetes was diagnosed. There was a significant increase (p < 0.001) of fetal macrosomia and diabetic fetopathy in the group without amniocentesis (n = 22) in comparison to the group with invasive (n = 81). We demand the introduction of a general screening for every pregnant patient. By an intensification of the diagnostic methods as well as by a strictly appropriate therapy it should be possible to reduce the fetal and neonatal complications.