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Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in -1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.

The finding of absent or reverse end-diastolic flow velocities (AREDV) in the umbilical artery already prior to viability corresponds to the most severe end of the clinical spectrum of placental insufficiency. However, there is little or no experience or published literature with regard to perinatal outcome. We report 2 cases in which structurally and chromosomally normal foetuses showed severe early onset retardation but were continuing to grow. These gestations could be prolonged by 62 and 64 days, respectively. Perinatal outcome was good in both following Caesarean section at 32+3 and 31+5 gestational weeks respectively.

Significant placental insufficiency, indicated by Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV), is associated with increased morbidity and mortality. Analysis of blood flow in the ductus venosus should assist in early intrauterine recognition of threatened foetuses. 58 high-risk pregnancies with umbilical AREDV were repeatedly examined (n=364). Doppler findings were correlated with neonatal signs of deterioration (ratio of normoblasts to leukocytes, pH, base excess, Apgar score), as well as short-term morbidity [need for intubation, duration of assisted respiration, evidence of respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), necrotising enterocolitis (NEC), intraventricular haemorrhage (IVH grade III+IV)] against the analysis of the blood flow findings (normal or increased pulsitility, absence or reverse end-diastolic flow) in the umbilical arteries (AU), the middle cerebral arteries (ACM) and ductus venosus (DV) relating these to birth weight and the duration of the pregnancy. The median period of observation was 12.8 days, 48% of the foetuses showed an abnormal ductus venosus flow and 26% an absent venous or reverse end-diastolic flow. The median date of delivery was 30 weeks, with a mean birth weight of 816 g. 93% were live births with 12% dying postnatally. Although the criteria for postnatal morbidity (BPD, NEC, IVH III+IV) and mortality did not correlate with changes in arterial and venous Doppler parameters in our group, there was a significant relationship between the normoblast count, known to be a marker of chronic hypoxia. The Apgar 10 minte score, umbilical arterial pH and base excess were correlated with changes in the DV flow curves. Healthy survival started, irrespective of arterial or venous blood flow criteria, from 27+0 weeks of pregnancy. If born between 27.0 and 30+6 weeks, the infants were more likely to be healthy the less the blood flow had been compromised. A birth weight of 590 g (sensitivity 62.5%; specificity 93.5%) and gestational age of 28+5 weeks (sensitivity 87.5%; specificity 90.3%) were shown to be cut-off points between healthy survival and survival with serious neonatal complications.

Significant placental insufficiency with Doppler ultrasound findings of absent or reverse end-diastolic flow velocities (AREDV) is associated with increased morbidity and mortality. An analysis of blood flow in the ductus venosus assists in the early recognition of threatened foetuses. However, the prognostic value of multivessel Doppler assessment for the timing of delivery is being questioned. Four high-risk pregnancies with umbilical AREDV were repeatedly examined prior to intrauterine foetal demise. Our results demonstrate that ductus venosus Doppler flow velocimetry can be normal prior to intrauterine foetal death.

Intrauterine growth restriction (IGUR) can have different etiologies, but placental insufficiency is the clinically most relevant. Fetuses with IUGR have a significantly higher morbidity and mortality than normally grown fetuses of the same gestational age. It is important to distinguish a growth restricted fetus from a normal, small fetus and from a fetus being small because of a disease, e.g., an aneuploidy. This differentiation requires the knowledge of the gestational age and the use of multiple imaging modalities. Serial assessments of fetal growth by ultrasound are necessary to recognize declining growth. Doppler sonography can detect changes in the uteroplacentar and the fetal perfusion. Blood vessels of clinical relevance are the uterine arteries, the umbilical artery, the middle cerebral artery and the ductus venosus. When no fetal anomalies can be detected, fetal growth is parallel to the percentiles and Doppler sonography measurements are normal, IUGR is unlikely. In most IUGR fetuses, a typical sequence of circulatory changes and ultrasound findings can be observed. As there is no evidence-based treatment option for IUGR until now, obstetric management consists in defining the optimal time of delivery. This means weighing the risks of prematurity against the risks of a potentially hostile intrauterine environment.

Aim of the prospective study was to investigate perinatal parameters and outcome of term SGA neonates. 100 term neonates were enrolled into 2 groups: group 1: 50 SGA neonates with birth weight below tenth percentile, group 2: 50 appropriate-for-gestational-age neonates. Both groups were compared concerning parental anamnesis, perinatal parameters, postnatal adaptation and development during the first days of life. After discharge from the hospital all children were observed during the first 15 weeks. In all infants the gain of weight, length, head circumference and the amount and type of nutrition were recorded. It was observed that only 13% of the SGA neonates were small children of small parents. Most of the SGA neonates had a normal target high. We found a significantly increased number of mothers with disturbed uterine or placental perfusion in the SGA group as well as increased problems in postnatal adaptation. SGA children had a significantly faster increase of gaining weight and a higher amount of nutrition during the first 15 weeks of life. This could be an early sign of catch-up-growth in SGA neonates, which could be regard as a part of the complex risk for developing a metabolic syndrome in formerly SGA children.

Fetuses with a reversed enddiastolic flow in the umbilical artery and/or aorta are at risk pregnancies and show a higher incidence of perinatal morbidity and mortality. The aim of this study was to evaluate the pathological changes in the terminal villous tree in fetuses with a reverse flow in the fetal aorta or umbilical artery.In this retrospective study, 16 cases with a reverse flow in the fetal aorta or umbilical artery (Gr. 1) were compared with gestational age matched 16 healthy pregnant women (Gr. 2). The following morphometric parameters were evaluated in 50 sections in each placenta (1600 measurements): mean vessel diameter, volume density of the villous tissue, stem villi and terminal villi. Measurements were performed using a computerized Video Image Analysis system.The mean gestational age at birth was similar in both groups (30 + 4 weeks gestation vs. 30 + 6 weeks gestation, respectively, for Gr. 1 and Gr. 2). The birth weights (985 g vs. 1780 g) and the placental weights (216 g vs. 385 g) were significantly lower in the reverse flow group. There was a significant reduction in the proportion of total villous tissue (19 % versus 45 %) and in the diameter of tissue at the terminal villi (2.1 % versus 7.6 %) in the reverse flow group. Although the mean number of vessels at the terminal villi was lower than the control group (4.1 versus 5.6), the mean and total areas of the vessels were not different.Our observations showed a significant association between the placental morphometric parameters and reversed enddiastolic flow in the umbilical artery or fetal aorta. The reduced number of functional placental units is responsible for the diminished exchange function of the placental vessels in "reverse flow" cases. This could partially explain the adverse outcome in this clinical situation.

Chorangioma is a benign angiomatous tumor of the placenta occurring with a frequency of approximately 1 % of all examined placentas. Pregnancies especially with large chorangiomas are frequently complicated by abruptio placentae, premature labour, fetal anaemia, hydrops, cardiomegaly and polyhydramnios. We here report a case of an extremely rare chorangiomatosis. Multiple chorangiomas measuring up to 1.5 cm comprised approximately one third of the placenta. A caesarean section had to be performed at 36 weeks of gestation because of uteroplacental insufficiency with oligohydramnios. Displacement of normal placental parenchyma by chorangiomatosis as a cause of uteroplacental insufficiency is very likely. Colour doppler imaging allows early diagnosis and management of chorangiomas. Thus, in our case early diagnosis of uteroplacental insufficiency was rendered. Principally, early diagnosis of fetal hazard due to myocardial insufficiency of the fetus is feasible. In-utero-endoscopy permits prenatal laser devascularisation of large chorangiomas. In the reported case the pregnancy was closely monitored with colour flow imaging. The diagnosis of uteroplacental insufficiency was established because of abnormal blood flow of the uterine arteries and abnormal fetal heart rate (FHR). At the same time fetal cardiomegaly and pathologic blood flow of the ductus venosus in terms of beginning fetal myocardial insufficiency was recognized. Consequently, caesarean section could be performed opportune.

Hypertensive disorders complicating pregnancy are the most common medical complications of pregnancy and are a major cause of maternal and perinatal morbidity and mortality. Thorough ambulatory obstetric care is likely to achieve a risk reduction. The main topics of ambulatory obstetric care are early identification of typical signs of preeclampsia, detection of uteroplacental insufficiency, and their consequences, detailed information of the patient, and early admission to a specialised obstetric care unit or perinatal center. Early diagnosis, close medical supervision, and timely delivery are the keys of the treatment of preeclampsia.

High AFP level (386.9 ng/ml) at the 16th gestational week in a 23-year old pregnant woman was observed. Fetal malformations or maternal causes could not be detected. Monitoring of fetal development and that of the fetal heart rate showed a worsening intrauterine growth retardation (IUGR). Due to the chronic hypoxia and IUGR cesarean section was performed in the 32nd gestational week and a 960 g female newborn was delivered. Histological examination of the placenta showed signs of maternal floor infarct (MFI): intervillous fibrin netlike deposition with the increase of extravillous trophoblast (X cells) and septal cystic formation. High unexplained AFP level and IUGR can draw attention to the possibility of intrauterine fetal demise, which indicates intensive intrauterine fetal monitoring.

The cases of two patients, in whom conspicuous CTGs with restricted oscillation and late decelerations were registered in the final trimester of pregnancy, are presented. Following immediate hospitalisation and the rapid execution of a caesarean section, two depressed, severely acidotic neonates were born. Whilst the course of the pregnancy in the first case had been completely inconspicuous up to that point, and the acute occurrence of placental insufficiency must be assumed, the second patient was subject to pregnancy-induced hypertension with discrete foetal growth retardation. It is shown that two almost identical pathological CTG registrations may have different causes but that one must assume a high degree of sub partu risk to the child on the occurrence of a terminal CTG witch is characterised by line-shaped oscillation, possibly in combination with late decelerations.

Respiratory distress syndrome (RDS) due to surfactant deficiency remains a cause of considerable mortality in the neonatal period.In a retrospective study we analysed the records of 1109 premature newborns with a birth weight below 1500 g that were treated on our unit. RDS was assumed if the infants needed mechanical ventilation with oxygen supplementation and the typical radiological signs were present on chest x-ray.No changes in the incidence of RDS were found during the period of observation. Below 29 weeks gestational age 90% of infants suffered from RDS (55% severe RDS grade III or IV). The incidence was 75% (grade III or IV: 32%) for infants born at 29 and 30 weeks, 48% (grade III or IV: 15%) at 31 and 32 weeks and 33% (grade III or IV: 6%) for neonates born at 33 weeks of gestation. Using a logistic regression analysis model the following parameters were found to increase the risk for RDS significantly (p0.05): no prenatal steroid treatment, Cesarean section, male gender, APGAR at 5 min7, metabolic acidosis (base excessor = -6 mval) and rectal temperature36 degrees C on admission. Following gestosis, insufficiency of the placenta and premature rupture of membranes a decrease in the incidence of RDS was observed.We conclude that although some risk factors for RDS will be difficult to exclude (e.g. maternal disease, gender) the incidence and severity of RDS can be reduced by measures like maternal antenatal steroid treatment. Perinatal asphyxia (low APGAR values and/or acidosis) and hypothermia should be avoided, as these conditions increase the relative risk for developing RDS.

The genetic risk for the offspring of patients treated with high doses of radioiodine was to be assessed with special regard to the gonadal dose caused by diagnostic and therapeutic procedures.41 young females (aged between 19 and 39 years) and four young males (aged 26 to 36 years) treated with radioiodine because of a thyroid carcinoma were interviewed by use of a questionnaire. The course of pregnancy and birth history could be documented as well as the congenital and developmental conditions of 56 children.The amount of radioactivity applied for therapy and whole body scans ranged over 4.144 and 35.15 GBq 1-131; the individual gonadal dose was calculated based on the MIRD model and ranged over 0.2 and 2.2 Sv (0.51 Sv at a mean). The period of time between the last radioiodine application and confinement was at least 9 months, not exceeding 14 years. As to the course of pregnancy and birth two early abortions, one extrauterine gravidity and one premature birth due to an insufficiency of the placenta were stated. In one case a chromosomal translocation 7/14 occurred as a genetic defect which lead to an interruption. The children's development was unconspicuous except of two cases of neurodermatitis as well as multiple allergies and an early closure of the anterior fontanelle in one child each.Although the genetic risk is supposed to increase with the gonadal dose achieved (doubling dose 1 Sv) and the increased risk of any congenital anomaly was calculated as about 13% at a mean in our patients, the rate of genetic determined diseases was not elevated (1.8% or 1/57). Thus, no increase of genetic defects or congenital malformations was reported in a total of 408 children described in the literature and in our group.

In order to determine the diagnostic value of various methods for placental insufficiency, the following parameters were obtained from 108 patients with intrauterine growth retardation (IUGR) as the only risk factor: A/B-ratio, resistence index (RI), pulsatility index (PI) of the umbilical artery (UA) and descending fetal aorta (FA), maternal serum estriol, grading of the placental maturity according to Grannum, amount of amniotic fluid, and fetal heart rate tracings. All Doppler indices showed the same efficacy as regards prediction of neonatal growth retardation. With a value of 8.0 for the A/B ratio of the FA and 4.5 for the UA neonatal dystrophy may be recognized with a precision of 72.2% (sensitivity 65.2%, specificity 77.4%). Maternal serum estriol has an accuracy of 64% (sensitivity 50%, specificity 74%), fetal heart rate tracings are able to predict neonatal growth retardation with a precision of 63% (sensitivity 43.5%, specificity 77.4%) determination of the amount of amniotic fluid has an accuracy of 58% (sensitivity 69%, specificity 50%) and grading of placental maturity 61% (sensitivity 17%, specificity 95%). The parameters combined yield in an accuracy of 75% (sensitivity 72%, specificity 74%). The fetal outcome of neonates with preceeding pathologic Doppler indices differed significantly from those with normal Doppler indices as regards indication for cesarean section, necessity of therapy in the intensive care unit, and preterm labor rate (chi square test, p0.05). This result could be improved to 2-4% by obtaining additional parameters. Pulsed Doppler sonography of fetal vessels is an additional tool in diagnosing intrauterine growth retardation.

The sonographic diagnosis can be expanded by Color Doppler. Nevertheless something is missing, especially concerning the demonstration of the very slow velocities as it can be found in neovascularized malignant tumors. A recently developed new color technique--the Angio-Color of the Diasonics Corporation, Sonotron (other companies have prototypes of this color)--promises to improve the detection of very low flow velocities. Due to a method very different to the conventional Doppler technique the registered signal is coded in the color image of the blood flow: that means that the amplitude and not the frequency shift is coded in color. Therefore there is less noise in the color mode with the possibility of showing the lower flow in comparison to the conventional Doppler. In Gynaecology and Obstetrics the advantages in the demonstration of the placental blood flow were obvious. In eutrophic fetuses the blood flow could be registered over the whole breadth of placenta, while in dystrophic fetuses this was possible only at the margin of the placenta with some color pixels in the middle of the organ. The conventional Color Doppler was not able to show the flow in the placenta even in eutrophic fetuses. Also the flow in fetal organs produced different results using both methods. So the angio-technique showed more color pixels in the periphery. In 8 malignant breast tumors both methods were able to show blood flow, but the Angio-Color showed more color pixels as the conventional color did.(ABSTRACT TRUNCATED AT 250 WORDS)

Early diagnosis of intrauterine growth retardation is important to ensure optimal obstetric monitoring. Current methods of diagnosing and assessing the growth retardation include clinical evaluation, various ultrasonic parameters and Doppler ultrasound. In this study Dopplersonographic measurements of the umbilical artery, fetal aorta and the middle cerebral artery were performed on 19 patients having been diagnosed with a placental insufficiency and maternal haemoconcentration. The patients were treated 10 days by a daily hypervolemic haemodilution with 500 ml 10% hydroxyethylstarch and 1000 ml ringersolution. The blood flow velocimetry showed changes in the fetal circulation characterized by a redistribution of the fetal blood flow. The aortic and umbilical resistance indices decreased. The resistance index of the middle cerebral artery demonstrated a significant rise during the haemodilution. The fetal circulatory changes represents a better oxygenation during the therapy with hydroxyethylstarch. The intravenous haemodilution can be seen as an effective and easy treatment of fetal growth retardation by increasing the placenta perfusion.

Based on 132 histomorphological placental investigations and their related Doppler test results, the question was asked, whether a strong correlation exists between Doppler test results and histomorphological placenta results, and whether these are uniform with respect to histomorphological changes. The results showed that all histomorphologically inconspicuous placenta findings were also inconspicuous doppler-sonographically. The viewing resulted in no histomorphologically unifying aspect of change. However, the investigation was able to demonstrate, that a distinction must be made between acutely developing changes and chronically developing changes. Along these lines, the last groups produced not only changes which compensate each other, but also changes, which are harmful to organic functioning and thus may diminish foetal supply without being detected by pulsed Doppler ultrasound.

1. Fibronectin does not correlate with the grade of proteinuria. 2. Fibronectin does not correlate with birth weight. 3. Fibronectin level is not elevated in pregnancy-induced hypertension and preeclampsia. 4. Fibronectin level is elevated in cases of preeclampsia, combined with chronic placental insufficiency respectively intrauterine growth retardation. 5. There is a statistic significant difference between pregnancy-induced hypertension/preeclampsia with or with out placental insufficiency. 6. Extremely problematic pregnancies ended in all pregnancies with values of fibronectin above 0.4 g/l in caesarean section without knowledge of the elevated fibronectin level at the time of operation. 7. In the group of pregnancy-induced hypertension the fibronectin level is elevated in relation to control group. This increase is particularly evident, if a placental insufficiency is concontinant with preeclampsia.

An account is given of morphological issues relating to placental insufficiency. Variable manifestations of placental insufficiency in foetuses and newborns are described in some detail. Reference is made to morphological clues useful in diagnosing causes of placental insufficiency. It proved to be particularly difficult to find quantitatively recordable parameters for such diagnosis, comparable to morphological indicators resulting from various placental measurements or from determination of exchange area and thickness measurement of placental basal membranes. Most of these quantitative methods, after all, would not even be applicable to routine examination. All the other diagnostic criteria of placental insufficiency are part of obstetrics (placental hormone production, measurement of uterus circulation and of intervillous space). In a more specialized section of this paper, reference is made to various pathologico-anatomic patterns of placental disorders and their specific relevance to placental insufficiency. Circulatory disorders (maternal side), placental inflammation, impaired maturation and obliterative endarteriitis were the most common findings in this order.

In a double-blind study, 12 patients with an Hb13 g/dl in the second trimester, a pretherapeutic hematocrit38%, and a fetal aortal resistance index0.75 underwent hemodilution. The patients were given either 500 ml hydroxyethyl starch (HAES) or 500 ml NaCl 0.9%. In addition, all patients received 500 ml NaCl 0.9% by infusion. HAES therapy caused a lowering of the fetal aortal and uterine artery resistance indices. This was not the case with NaCl. The causes for this lie in the specific anti-aggregation and viscosity-reducing effect of hydroxyethyl starch with an identical lowering of hematocrit.

To evaluate the frequency of abnormal doppler results in pregnancies complicated by placental insufficiency, flow waveforms of 100 patients with documented intrauterine growth retardation--birthweight below the 10th percentile--were analysed. Uterine, arcuate and umbilical artery velocimetry were performed by means of a continuous wave Doppler ultrasound. Neither the range of serial examination nor the interval between last prepartal doppler test und delivery showed influence on the doppler results. Compared to normal pregnancy, a significant increase of diastolic notching and incomplete registration of maternal vessels were found. Using 90th percentile as cut-off limit last doppler examination before delivery showed pathological results in 76% of all cases with growth retardation and 90% of pregnancies with an additional risk of pregnancy induced hypertension. As pathological waveforms in the maternal compartment contribute a major part to abnormal velocity waveforms, doppler study of utero-placental vessels plays an important role in the diagnose of impaired persuasion of the placenta.

Pregnancy is a state of natural insulin resistance, which is due to placental production of human placental lactogen (HPL), an insulin antagonising hormone, leading to a remarkable increase of insulin requirement in pregnant diabetics in the 2nd and 3rd trimester. Aim of the prospective study was the quantification of daily insulin requirement during the last 28 days before delivery in pregnant women suffering from insulin-dependent diabetes mellitus (n = 20) with and without evidence of "placental insufficiency syndrome" employing peripheral rheography as indirect parameter for placental haemoperfusion. All diabetic women included controlled carbohydrate metabolism by means of a functional insulin therapy (FIT; HbA1c in normal range5.8%), a multiple injection regime with frequent blood glucose self-control at least from the 2nd trimester of pregnancy. According to the results of peripheral rheography in the 34th gestational week, an impedanceplethysmographic method for quantifying peripheral haemoperfusion, patients were subdivided in a group with (B: n = 8) and without (A: n = 12) indirect evidence of placental dysfunction. Groups did not differ in maternal age, duration of diabetes, maternal weight and week of delivery (A: 39.08 +/- 1.44; B: 39.12 +/- 1.46). Mean weight of neonates was lower in group B (3319 +/- 619 g) compared to group A (3613 +/- 437 g). During a comparable state of near-normoglycaemia in both groups, 7 out of 8 women in group B, but only 1 out of 12 women in group A displayed a significant decrease in daily insulin requirement from day -28 to day -3 before delivery (linear regression; p0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Doppler ultrasound measurement of blood flow velocity represents a non-invasive method of studying uteroplacental and feto-placental haemodynamics. Using a continuous-wave Doppler device, the blood flow velocity was examined in the uterine and arcuate arteries, as well as in the umbilical artery in 81 patients demonstrating fetal growth retardation. An increase in vessel resistance was found in the uterine and arcuate arteries in most of the patients. In addition, patients with fetal retardation showed a significantly higher rate of diastolic notching and incomplete registration of uterine and arcuate wave forms, especially in pregnancies complicated by hypertension. The implementation of the continuous-wave technique as a simple Doppler system allows differential evaluation of placental function and provides information on the nutritional supply to the fetus.

Using a 4 MHz continuous wave Doppler device reference values for resistance index (RI) and pulsatility index (PI) of uterine and arcuate arteries as well as umbilical artery were established based on 510 patients with uneventful pregnancies and deliveries. Percentiles are more suitable localisation gauge than are standard deviations. Neither RI nor PI of maternal arteries proved to be dependent on gestational age in the observation period. If the heart rate are in physiological ranges no clinically relevant effect on the results were observed in either the maternal of the foetal copartment. By contrast umbilical artery shows a definite linear relation between the indices measured and gestational age. A significant effect of placental site on the measurement was found in both, uterine and arcurate arteries, but only the differences found in arcuates were of clinical value. An increase of diastolic notching was observed in both, uterine and arcuate arteries during pregnancy. Mostly only one vessel showed diastolic notching when observed in normal pregnancy. With a lateralized placenta the condition was more probable on the contralateral site.

Cardiotocography (CTG) is to be considered today's most sensitive monitoring tool for the functional surveillance of placental performance during parturition. 351 cardiotocographically monitored singleton pregnancies were used as patient material for fine tissue examination of the state of maturity of the villi of the relevant placentas. In histological assessment, placental diagnoses are allocated to defined CTG changes; in particular, however, the identification of reserves, capable of maturing (immature intermediate villi in the centres of the placental subdivisions or placentones), is subject to separate scrutiny. The following results emerge clearly: terminal placentas without maturing potentials, prematurely matured placentas and placentas with deficiency of terminal villi, as well as the absence of immature intermediate villi in the centers of the placentones, are connected with a suspected prepathological or pathological CTG assessment. The histological groups have the lowest incidence of the normal oscillatory type and normal oscillatory frequency and have the highest proportion of abnormal CTG assessments according to the Hammacher score. The absence of the identification of potential maturing reserves (immature intermediate villi) is associated with the highest incidence of Caesarean sections (29.8%). These results show, that the physiological maturing potentials (immature intermediate villi) which can be identified up to term are a histological indication towards regular placental performance, even in labour.

Previous perinatal trials using Doppler ultrasound have demonstrated a favorable correlation between abnormal blood flow spectra and feto-maternal problems. 33 patients with manifest placental unsufficiency were subject to daily transcutaneous nerve stimulation in a 2-week therapeutic course. 23 patients of the control group were treated by bed rest over 2 weeks. The patient group with transcutaneous nerve stimulation (TNS) showed significant improvement of the investigated blood flow parameters (A/B ratio) of the umbilical artery and fetal aorta (p less than 0.01). In the placebo group there were no significant alterations of blood flow parameters. The clinical findings (improved flow parameters and perinatal outcome) are not expected to yield any significant improvement when placental insufficiency is treated with bed rest alone.

"Reverse Flow" as a Doppler sonographic finding indicates the appearance of retrograde blood flow in the diastolic part of the cardiac cycle. It has so far not been observed in uncomplicated pregnancies and seems to be an indicator of severe deterioration of the foetal condition. Several pathophysiological hypotheses are discussed in this paper on the basis of own results and the findings of other investigators.

In a group of 810 singleton pregnancies without malformations or chromosomal abnormalities blood flow velocity wave forms of the umbilical artery were recorded in the third trimester by means of a pulsed duplex Doppler system. We calculated the pulsatility index (PI). 133 newborn with a birthweight below the 10th centile were classified as small-for-gestational-age (SGA) (prevalence: 16%). The sensitivity of the test (elevated PI) for these neonates is 52% and the specificity 97%, the positive predictive value is 78% and the negative predictive value 91%. Therefore, Doppler Sonography of the umbilical artery is not an appropriate screening test to identify SGA babies prenatally. The results for jeopardized SGA babies (caesarean section because of pathological CTG traces, transfer to the neonatal intensive care unit) are much better. 31 out of 133 belonged to that group. For these foetuses, the sensitivity of the test is 94% and the negative predictive value 97%. Hence, Doppler Sonography of the umbilical artery allows very well to identify the endangered SGA foetuses on the one hand and to exclude foetal jeopardy with a normal PI on the other.

The respiratory pathophysiology of placental insufficiency is well understood, whereas the metabolic effects of chronical or acute malnutrition still need further evaluation. In a comprehensive study of 20 deliveries respiratory parameters and substrates of carbohydrate- and lipid-metabolism were analysed simultaneously from maternal blood at 4 cm dilatation, at cord clamping immediately delivery and 2 hours post partum as well as from arterial and venous umbical blood samples. Normal deliveries were compared with cases of fetal retardation and moderate acute fetal acidosis. For glucose, insulin, c-peptide and pyruvate a strong rise in maternal blood during labour was observed as well as for the non-esterified fatty acids (NEFA), which have a high materno-fetal gradient. Arterio-venous differences of concentrations were found in the umbilical cord blood for glucose, pyruvate and NEFA. In cases of chronical insufficiency of the placenta especially elevated lactate levels were measured, whereas a moderate fetal acidosis obviously leads to an additional feto-maternal pyruvate transfer. The results lead to the conclusion that the fetal metabolism has considerable means of adaptation during delivery even under chronical or moderate acute stress conditions.

Deafness following complications of pregnancy and obstetrics occurs frequently. The temporal bones of stillborn or neonates who died several days after delivery have often been examined, and haemorrhage and serous labyrinthitis have been found in infections, diabetes and trauma. In this study, pathological findings in the temporal bones of foetuses who died of chronic asphyxia in utero are described. 7 out of 15 cases had no labyrinthine pathology. Four had haemorrhage into the tissue or into perilymphatic or endolymphatic spaces. Likewise, four had developed eosinophilic precipitates in the liquid spaces of the inner ear. If the foetus survives such phases of hypoxia in utero, this might be the morphological correlate of developing deafness. Similar findings in infections such as rubella or cytomegalovirus infection are discussed.

40 fetuses with diastolic zero flow or diastolic reverse flow of the umbilical arteries were examined in a longitudinal analysis. While 35 fetuses had to be delivered by cesarean section, three fetuses showed intrauterine death which seemed to be inevitable, and two fetuses were delivered vaginally without signs of fetal distress. In one third of our study group the cesarean section was necessary immediately after admittance to the obstetrical ward. The remaining two thirds were clinically observed up to one or up to four weeks respectively. The shorter the interval between diagnosis of the zero flow and delivery the larger was the gestational age, the amount of severe fetal acidosis, and the number of emergency cesarean section. The clinically observed groups were delivered significantly earlier and fetal blood gases were normal. Only one case of emergency cesarean section was observed. The bad fetal outcome of fetuses with diastolic zero flow of the umbilical arteries is therefore caused by the hypoxia and asphyxia of the not hospitalized and clinically observed high risk pregnancies. The early diagnosis of this flow pattern and the immediate clinical admittance and surveillance with doppler flow measurements and CTG-monitoring including the oxytocin challenge test allows to reduce the amount of fetal acidosis by adequate timing of the delivery. Acute placental insufficiency in cases with diastolic zero or reverse flow commonly occurs before the 33. week of pregnancy.

In the course of normal pregnancy the selenium concentration in serum decreases significantly. The selenium concentration is enhanced in pregnant women with intrauterine growth retardation or hepatosis and unchanged in those with pregnancy-induced hypertension in comparison with healthy pregnant women. In our investigations no changes of the intracellular selenium concentrations in erythrocytes were measured in normal as well as in pathological pregnancy.