Prenatal diagnosis of the Rhesus D fetal blood type on amniotic fluid in daily practice.

OBJECTIVE: To retrospectively examine the diagnostic accuracy of prenatal RhD blood type genotyping on amniotic fluid, using a combination of two polymerase chain reaction (PCR) methods in daily practice. METHODS: Amniotic fluid was obtained from women undergoing amniocentesis. Two PCR protocols were carried out in two different laboratories. We obtained the postnatal serological RhD status. In cases with differing prenatal and postnatal test results, we investigated the possible error source by different methods. Sensitivity, specificity and the predictive values were calculated. RESULTS: Prenatal RhD genotyping was applied in 1,640 cases, of which the postnatal serologic RhD status was obtained in 927. No discordance between both PCR methods occurred. In nine out of 927 cases differing results between PCR and serologic status were encountered. The sensitivity was 99.5%, the specificity 98.6%, and both positive and negative predictive values 99.1%. CONCLUSION: Prenatal diagnosis of the fetal RhD blood type with PCR from amniotic fluid is highly accurate in daily practice and associated with a minimal sensitivity of 99.5% and a minimal specificity of 98.6%.

Screening for trisomy 21 with maternal age, fetal nuchal translucency and maternal serum biochemistry at 11-14 weeks: a regional experience from Germany.

OBJECTIVE: To examine the efficacy of first trimester screening for trisomy 21 using a combination of maternal age, fetal nuchal translucency (NT), maternal serum free beta-human chorionic gonadotropin (free beta-hCG) and pregnancy-associated plasma protein A (PAPP-A) in a regional setting [maternity unit of the Women's University Hospital, Hannover Medical School (study center); two regional private centers for prenatal diagnosis and human genetics; laboratory for prenatal diagnosis and human genetics]. METHODS: Fetal NT, crown-rump length, maternal serum free beta-hCG and PAPP-A were measured at 11-14 weeks of gestation. Risk calculation was carried out using the FMF computer algorithm. The patients were informed and counseled about possible invasive test options if the risk was 1 in 300 or greater. Fetal outcome was obtained by questionnaires given to the patients or sent to their gynecologists. The detection and false-positive rates for the different screening strategies were calculated. RESULTS: Pregnancy outcome was obtained in 2,497 cases, of which 2,196 cases had completed first trimester screening with NT and maternal serum biochemistry and 301 additional cases had NT measurement only. The median age was 32.5 years. In our population 11 affected fetuses were found. The estimated risk for trisomy 21 was 1 in 300 or greater in 64, 82, 88 and 88% of affected fetuses using maternal age alone, in combination with nuchal translucency, with maternal serum biochemical markers or with both NT and biochemical markers for a false-positive rate of 28.2, 5.1, 15.3 and 4.0%. CONCLUSIONS: First trimester screening using maternal age, NT, free beta-hCG and PAPP-A is highly effective for the detection of trisomy 21 and is associated with a sensitivity of about 90% for 5% false-positive patients.

Fetal serum concentrations of cystatin C and beta2-microglobulin as predictors of postnatal kidney function.

OBJECTIVES: Cystatin C and beta(2)-microglobulin are established serum markers of renal function in children and adults. In contrast to creatinine, diaplacental exchange is minimal. The aim of the study was to establish reference values in fetal serum and to test their efficiency in predicting postnatal kidney function. STUDY DESIGN: This was a prospective noninterventional study measuring cystatin C and beta(2)-microglobulin by particle-enhanced immunoturbidimetry in excess serum from 129 cordocenteses performed in 84 fetuses. Reference intervals (mean +/- 1.96 SD) were calculated in a subgroup of 54 fetuses without evidence of kidney disease, and these reference values were evaluated in 75 sera from 55 fetuses. RESULTS: Mean cystatin C was 1.66 +/- 0.202 mg/L (upper limit 2.06), and mean beta(2)-microglobulin was 4.25 +/- 0.734 mg/L. Unlike cystatin C, beta(2)-microglobulin decreased significantly with gestational age so that the upper reference limit was 7.19-0.052 x gestational age in weeks. beta(2)-Microglobulin had higher sensitivity (90.0% vs 63.6%) and cystatin C a higher specificity (91.8% vs. 85.5%) for the prediction of impaired renal function; diagnostic efficiency was equal (87.6% vs. 86.1%). Fetuses with impaired renal function at birth or who were aborted for renal malformations had higher cystatin C concentrations than those in a control group. beta(2)-Microglobulin was increased only in fetuses who were aborted. CONCLUSION: Fetal serum cystatin C and beta(2)-microglobulin concentrations may be useful predictors of postnatal kidney function.

Patient with trisomy 6 mosaicism.

Trisomy 6 and trisomy 6 mosaicism were found in chorionic villi cell culture and short term incubation in a prenatal diagnosis at 12 weeks of gestation in a pregnancy with a growth retarded fetus showing nuchal translucency. The child was born in the 25th gestational week with a number of malformations including heart defects, deep-set ears, cleft right hand, cutaneous syndactylies, and overlapping toes of irregular shape and length. Trisomy 6 was not found in peripheral blood lymphocytes but was confirmed in umbilical cord fibroblasts. Currently, at the age of 2-3/4 years, the development of the child is relatively normal despite considerable growth delay. At the age of two years, she developed a papular erythema clinically suggestive of epidermal nevi. Cytogenetic analysis of fibroblast cultures derived from skin from a right hand finger and the inguinal area confirmed the presence of a trisomy 6 mosaicism. This is the first observation of a liveborn with trisomy 6 mosaicism.

[Efficacy of ultrasound screening in pregnancy]. / Qualität des Ultraschall-Screenings in der Schwangerenvorsorge.

OBJECTIVE: The purpose of this study was to examine the effectiveness of ultrasound screening in pregnancy. MATERIAL AND METHODS: Therefore, it was registered whether fetal malformations in a study population of 11,172 deliveries were already diagnosed before birth. RESULTS: 341 defects were found in 297 children from mothers who had had prenatal care. Most anomalies were seen in the urogenital tract (n = 98; 28.7%), the heart (n = 67; 19.6%), the connective tissue (n = 39; 11.4%), the gastrointestinal tract (n = 32; 9.4%), and in the central nervous system (n = 33; 9.7%). Chromosomal anomalies (n = 22; 6.5%) and orofacial defects (n = 21; 6.2%) were more rare. 8.8% of all defects were lethal, 37% severe. 237 (69.5%) were classified as "diagnosable by ultrasound prenatally". 125 of them (53%) were identified prenatally, with high rates of 71% in central nervous system, 65.5% in intestinal and 54% in urogenital tract, while the detection rate was only 13.6% in chromosomal and 3.3% in cardiac defects. Only 14.3% were found before 24 weeks of gestation. CONCLUSIONS: Thus, the effectiveness of ultrasound screening has to be improved by adequate measures.

[Experiences with primary fascia closure of the abdomen in gastroschisis--a 16 year review]. / Erfahrungen mit dem primären Faszienverschluss des Abdomens bei Gastroschisis--ein 16-Jahresüberblick.

47 children with gastroschisis were operated at the Hannover Medical School between 1980 and 1995. The average gestation period was the 36th week of pregnancy with an average birthweight of 2370 gr. A primary layered closure of the abdominal wall was performed on 46 children. A multi-sided closure of the abdominal wall defect using Gore-Tex was necessary in only one case. Post-operative intubation lasted for an average of 56 hours. The children were fed by parenteral nutrition for an average of 32 days, with oral feeding starting on the 15th post-operative day. The average weight on discharge was 3035 gr. 18% of the children had post-operative problems such as sepsis, necrotic enterocolitis and ileus. A death rate of only 2% is proof of the progress that has been made in prenatal care of the newborn child suffering from gastroschisis and suggests that primary closure of the abdomen is the operative method to be aimed for.

[Pregnancy follow-up of a twin pregnancy with acardius acephalus]. / Schwangerschaftsverlauf einer Geminigravidität mit Acardius acephalus.

Beginning with the 20th week of gestation a monoamniotic twin pregnancy with acardius acephalus was intensively observed by ultrasound and doppler ultrasound. The acardius only grew until the 24th week of gestation; the fetus underwent a normal development during the entire pregnancy. Doppler ultrasound showed low resistance indices in both umbilical arteries. During the 24th week of gestation the flow in the umbilical artery of the acardius could no longer be registered due to a cessation of development. A normal flow could be registered from the 28th week of gestation until the end of pregnancy in the umbilical artery, aorta fetalis and the art. cerebri med. of the fetus. During the 36th week of gestation the fetus died because of umbilical cord entanglement with the cord of the acardius.

Alpha-Fetoprotein and renal dysfunction of the fetus.

Alpha-fetoprotein (AFP) levels were measured in 25 pregnancies with renal dysfunction of the fetus. Oligohydramnios was found in 14 of 16 patients diagnosed by 20 weeks of gestation and in all of those diagnosed later. AFP levels in maternal serum were normal in 17 (68%), elevated in five (20%), and low in three patients (12%). AFP serum levels up to 24 weeks of gestation were significantly higher than after 24 weeks. AFP levels in amniotic fluid obtained from amniocentesis in six patients were normal or slightly elevated. We suggest that the concentration of AFP in amniotic fluid and maternal serum does not only depend on the physiologic proteinuria of the immature fetal kidneys but also on the permeability of the not yet keratinized fetal skin and the diluting volume of the amniotic fluid.

Antenatal diagnosis of a rare combined fetal malformation: acardius acephalus and single ventricle of the twin.

The development of an acardius in a monozygotic multiple pregnancy has been reported in more than 200 cases. We present the case of an acardius acephalus in a twin pregnancy additionally complicated by a serious cardiac malformation of the donor twin (single ventricle). Antenatal diagnosis and development as well as intrauterine treatment of the donor twin from 26 to 34 weeks of gestation are described.

[Vaginal sonographic follow-up of embryo development]. / Vaginosonographische Kontrolle der Embryonalentwicklung.

The clinical study reports on facilities of transvaginal sonography to demonstrate early embryological structures. A collective of 659 sonographical examinations in 593 women between 4. and 13. week of gestation (wog) is described. The earliest imagery of an intrauterine pregnancy could be performed at 28. day post menstruation (p.m.) and first heard beats could be detected at 36./37. day p.m.. The secondary yolk sac could be discovered at the end of 5. wog and first motions of the embryo in 8. wog. Certain structures as parts of the skull, brain and spine were clearly to be differentiated in 10.-12. wog. Transvaginal sonography renders an very early and comprehensive control of regular embryological growth and development. Striking malformations are early detected.

[Maternal serum AFP determination in the 2d trimester: a suitable screening method for detection of fetuses with Down's syndrome in young females?]. / Mütterliche Serum-AFP Bestimmung im 2. Trimenon: Eine geeignete Screeningmethode zur Erkennung von Feten mit Morbus Down Syndrom bei jungen Frauen?

The frequency distributions of maternal serum alpha-fetoprotein levels in pregnancies with fetal Down syndrome (n = 84) and in unaffected pregnancies (n = 9982) were fitted to extreme value distributions. The risk of an individual woman having a pregnancy associated with Down's syndrome was estimated depending on age and serum AFP level (MOM). A risk of Down's syndrome greater than 1:384 corresponding to the risk of a greater than or equal to 35-year-old woman was chosen to the lowest risk indicating referral for amniocentesis. The retrospective analysis of our data showed an age depending sensitivity of the maternal serum AFP screening. Only five of twenty-one cases in younger women (less than 35-year-old) but all of the thirteen cases in older women (38-40 years old) could have been detected based on low AFP levels. By calculating the sensitivity of the AFP Screening it seems to be impossible to reduce clearly the risk of Down's syndrome in young women.

[Effect of dihydroergotamine (DHE) on fetal hemodynamics]. / Wirkung von Dihydroergotamin (DHE) auf die fetale Hämodynamik.

With this article we have pursued the question if the fetal hemodynamic will change under Dihydroergotamine-treatment (DHE) of the mother during pregnancy. For that purpose, the S/D-ratio in 20 hypotensive pregnant women was determined before and one week after treatment with 2 x 2.5 mg DHE (DETMS retard) daily by Doppler-sonographic measurement in the fetal aorta. The control group consisted of 20 healthy, untreated normotensive pregnant women not differing from the hypotensives as regards age, parity, and gestational age. The results show that in hypotensive pregnant women the S/D-ratio, and therefore the resistance in the fetal periphery respectively in the placenta circulation is increased by 22% (p less than 0.002) on the average compared with the normotensives. A one week's treatment with DHE led to a significant decrease of the S/D-ratio by 20% (p less than 0.001). Herewith, the values after DHE-treatment did not differ from those of the normotensives. Therefore we conclude that the treatment of hypotensive pregnant women with DHE in the above mentioned dosage produces a significant improvement of fetal hemodynamic.

[Acute polyhydramnios in a twin pregnancy--case history of a successful therapy attempt]. / Akutes Polyhydramnion bei Geminigravidität--Kasuistik eines erfolgreichen Therapieversuches.

Acute polyhydramnios is a rare complication in twin pregnancies. The perinatal mortality is about 100% without treatment. We present a case of twin pregnancy with an early acute polyhydramnios which was treated with serial transabdominal amniocentesis. 11 litres of amniotic fluid were removed and we succeeded to prolong the pregnancy by 13 weeks. In the 35th week of gestation, two healthy newborns were delivered by cesarean section. After exclusion of fetal malformations, we recommend the early beginning of serial amniocentesis to normalize the intrauterine pressure and to prevent premature labor or cervical incompetence. Compared to the poor prognosis of an untreated pregnancy, we consider the punction even of large volumes of amniotic fluid as a procedure of an acceptable risk.

[Vaginal sonography as a method of study in the evaluation of cervix insufficiency. A useful complement to vaginal palpation?]. / Vaginalsonographie als Untersuchungsverfahren zur Beurteilung der Zervixinsuffizienz. Eine sinnvolle Ergänzung zum vaginalen Tastbefund?

In a clinical study a group of pregnant women with suspected cervical incompetence was examined by vaginal sonography. Aim of the investigation was to compare results of performed vaginal palpation with results of sonography. 53 pregnant women between 20th und 31st week of gestation were examined by a 5 MHz vaginal sector-scanner probe. After focussing sagittal projection of uterine cervix and lower uterine segment the cervical length and opening of the internal os were assessed prior to cerclage. Postoperative vaginal sonography was performed to ascertain lengthening and stabilization of the incompetent cervix. Comparing results of vaginal palpation and vaginal sonography showed, that the cervical length obtained by sonography was constantly higher in all patients than the results obtained by palpation. This difference became more distinct in the group of patients with extreme cervical incompetence. We are of the opinion that vaginal sonography is an objective method revealing the extent of cervical incompetence. Exact measurement of the cervical length and assessment of the internal os are efficient diagnostic criteria. They complete results of cervical palpation and offer precise information concerning an intended cerclage.

[Transvaginal ultrasound biometry of crown-rump length in the 1st trimester]. / Transvaginale Ultraschallbiometrie der Scheitel-Steiss-Länge im ersten Trimenon.

The embryonary crown-rump-length (CRL) in 225 pregnant women between the 6th and 13th week of gestation was measured by the technique of transvaginal sonography. A curve and a rate of growth was determined. The investigation showed that the CRL can already be measured in the 6th week of gestation when using transvaginal sonography, whereas transabdominal sonography makes a CRL measurement in the 7th week possible. A comparison of results and growth rates revealed a deviation up to 12th week of gestation age in both ultrasound methods. The known tabels with embryonary data, obtained by transabdominal technique, should not be used any longer for CRL determination, when prefering the technique of transvaginal sonography.

[Delayed bone growth as a sonographic sign in the early detection of Smith-Lemli-Opitz syndrome]. / Verzögertes Knochenwachstum als sonographisches Zeichen zur Früherkennung eines Smith-Lemli-Opitz-Syndroms.

The Smith-Lemli-Opitz syndrome was first described in 1964. It is inherited as an autosomal recessive trait. Characteristic manifestations are abnormalities of the facial skull, a delayed growth, lazy feeder, zygodatly and a cryptorchism in males. The case of a girl is presented born with this syndrome likewise her sister. Diagnosis was confirmed in the 30th gestational week by means of ultrasound. A retardation of bony growth and telltale signs of this syndrome were observed. At birth length of diaphysis differed 5 weeks compared with standard.

[Amniocentesis in the 2d trimenon: comparison of 2 technics]. / Amniozentese im zweiten Trimenon: Vergleich zweier Techniken.

The results of 1245 amniocenteses performed by the "free hand needle" technique and ultrasonic control are discussed. The use of ultrasonic control showed a much lower incidence of blood-stained amnionic fluid as well as a decreased number of repeated punctures of the amnion. The abortion rate was almost the same in both groups. According to our experience ultrasonic controlled puncture seems to be more reliable in terms of safety and success.

[Acardius--prenatal diagnosis and pregnancy in 2 twin pregnancies]. / Akardius--pränatale Diagnose und Schwangerschaftsverlauf bei zwei Geminigraviditäten.

The development of acardiac monsters had been observed in less than 200 cases. Antenatal diagnosis can be performed in the 2nd trimenon. We report about two twin pregnancies with acardius acephalus. In one case the beginning of cardiac failure was detected by ultrasound in the 28th week. Transplacental treatment of the fetus with beta-acetyldigoxine was successful during a period of seven weeks. In both cases delivery was performed in the 35. and 36. week of gestation--the twins are still alive.

Enzyme release from the perfused rat heart. The functions of the cytoskeleton under cell-pathological conditions.

The mechanism of enzyme release from Langendorff-perfused rat hearts was studied under the injury conditions of the Ca2+ paradox and 2,4-dinitrophenol poisoning. During perfusion with Krebs-Ringer buffer or in buffered sucrose sarcoplasmic enzymes were massively released when Ca2+ was reintroduced to the perfusion medium (Ca2+ paradox). Mitochondrial matrix enzymes were released to a very small extent. Only the cytoplasmic isoenzyme of the bilocular enzyme malate dehydrogenase was released. The release kinetics of various enzymes with greatly differing molecular weights showed no significant differences. Qualitatively the same results were obtained under 2,4-dinitrophenol poisoned conditions in Ca2+ -free sucrose media. Sarcoplasmic enzymes were massively released, mitochondrial enzymes did not appear in the perfusate. 2,4-Dinitrophenol poisoning alone was not sufficient to cause enzyme release. An additional swelling under these conditions was necessary. ATP from the extracellular space was able to enhance the enzyme release, which was brought about by 2,4-dinitrophenol and cell swelling. A hypothesis is presented that enzyme release is produced by initiating a membrane blebbing process. An elevated intracellular Ca2+ concentration is a necessary prerequisite. In the presence of ATP, active membrane blebbing is caused by contractions of the membrane-anchored cytoskeleton. In the absence of ATP passive membrane blebbing is induced by cell swelling, provided that the cytoskeleton has been crosslinked by Ca2+.