The twin-twin transfusion syndrome - an unsolved problem.

AIM: We analysed the data of pregnancies with twin-twin transfusion syndrome (TTTS) in order to identify clinical factors present at the time of diagnosis which can be used to predict the outcome of the pregnancy. METHOD: We report prenatal sonographic findings, interventions and outcomes of 28 TTTS pregnancies over a three-year period. Patients were classified into stages of TTTS as follows: Stage I: bladder of donor visible, normal Doppler studies; Stage II: bladder of donor not visible, normal Doppler studies; Stage III: abnormal Doppler studies; Stage IV: hydrops. RESULTS: In nine pregnancies the infants did not survive the perinatal period (the first 28 days after delivery): the median gestational age at delivery was 24 (range 21 - 29) weeks; six of these nine pregnancies (66 %) were classified as stages III or IV. In five pregnancies one infant survived the perinatal period: the median gestational age at delivery was 28 (range 27 - 32) weeks; four of these five pregnancies (80 %) were classified as stages III or IV. In 14 pregnancies both infants survived the perinatal period: the median gestational age at delivery was 30.5 (range 28 - 39) weeks; two of these 14 pregnancies (14 %) were classified as stages III or IV. CONCLUSION: In pregnancies complicated by TTTS, the results of Doppler studies at the time of diagnosis represent the most important clinical factor predicting the outcome of the pregnancy. At the time of delivery, however, the predicted outcome is most directly linked to the gestational age.

Dandy-Walker malformation as sonographic marker for fetal triploidy.

Fetal triploidy is a frequent reason for early abortion, and only few fetuses survive into the second trimester of pregnancy. Common sonographic markers for triploidy in the second trimester are severe asymmetric growth restriction (triploidy of maternal origin) and partial molar changes of the placenta (triploidy of paternal origin), together with structural fetal malformations. We report prenatal sonographic findings of thirteen triploid fetuses between 18 and 34 weeks' gestational age (eleven fetuses with 69, XXX, and two fetuses with 69, XXY). Intrauterine growth restriction (11/13 fetuses), oligohydramnios (8/13), bilateral cerebral ventriculomegaly (6/13), structural heart defects (4/13), and Dandy-Walker malformation or Dandy-Walker variant (4/13) were the most frequent findings. We conclude that the Dandy-Walker malformation and Dandy-Walker variant should be considered as additional sonographic markers for fetal triploidy.

Human papillomavirus in the cervix and placenta.

OBJECTIVE: To determine the prevalence and association of human papillomavirus (HPV) infection in the cervices and placentas of pregnant women. METHODS: Cervical samples were taken from 179 of 226 women who had placental biopsies because of abnormal ultrasound findings or were older than 35 years, to detect HPV infections with hybrid capture II tests. Polymerase chain reaction (PCR) was done on placental tissue of 147 of the 226 women to detect HPV DNA. RESULTS: We found 44 of 179 women (24.6%, 95% confidence interval 18.3, 31.0) to test positive for HPV in their cervices. Logistic regression analyses showed decreased prevalence of HPV infection with increased maternal age (P =.039). The HPV DNA E6 PCR from the villus tissue was negative in the 147 cases examined. However, a significant contingency coefficient between low-risk HPV infection and elevated risk of chromosome aberration was found (φ = V = 0.15, P =.050). CONCLUSION: The infection rate of 24.6% in women without clinical symptoms of HPV infection was high, but there seemed to be no virus transmission to the placenta in women with subclinical infections. Low-risk cervical HPV infection might be associated with a slightly higher risk of abnormal fetal karyotype.

[Testicular feminization--sequelae of chronic neglect of a neoplastic process]. / Zur testikulären Feminisierung--Folgen langdauernder Verschleppung eines neoplastischen Geschehens.

This paper reports on a 56-year-old patient with a history of "testicular feminization syndrome" who was admitted to hospital because of a rapid gain in her abdominal girth (106 cm). A benign cyst was removed laparotomically which, histologically, was equivalent to a cystadenofibroma. Based on this case report, the clinical significance of testicular feminization syndrome and the necessity for gonadectomy due to the risk of growth of a possibly malignant tumor are discussed.

Twenty-four cordocenteses in one woman.

We report on 2 consecutive pregnancies in a woman with a history of neonatal death secondary to Rhesus alloimmunization. Her first subsequent pregnancy was complicated by fetal hydrops at 20 weeks of gestation. The fetus received a total of 11 intrauterine transfusions, and was delivered at 38 weeks. In the patient's next pregnancy, the fetus developed hydrops at 18 weeks of gestation. Thirteen intrauterine transfusions were given to correct fetal anemia, and a healthy baby was delivered at 38 weeks of gestational age. Continuation of intravascular transfusion therapy may represent a reasonable alternative to selective premature delivery even in cases with highly aggressive maternal Rhesus alloimmunization.

Maternal cigarette smoking increases F2-isoprostanes and reduces prostacyclin and nitric oxide in umbilical vessels.

The objective of this study was to evaluate the influence of smoking on F2-isoprostanes, prostacylin and nitric oxide in human umbilical vessels. Umbilical cords from 13 babies of smoking mothers and from 28 babies of non-smoking mothers were examined for levels of F2-isoprostanes, prostacyclin, L-arginine, and L-citrulline. Forty-one umbilical arteries and eleven umbilical veins were analyzed. Statistical analysis of data was done using modified t-test. Cigarette smoking increased F2-isoprostane levels and reduced the generation of prostacyclin, L-arginine and L-citrulline comparably in umbilical arteries and veins. Notably, in umbilical cords of babies of non-smoking mothers the F2-isoprostane level was significantly higher in arteries. Cigarette smoking correlates with a direct vasoconstrictive effect. We suggest that smoking might enhance the vasoconstrictory capacity in umbilical arteries by increased F2-isoprostanes and by a simultaneous decrease in the production of the vasodilatory compounds, prostacyclin, and nitric oxide.

Unfused amnion and chorion after 14 weeks of gestation: associated fetal structural and chromosomal abnormalities.

OBJECTIVE: To assess possible associations between delayed chorioamniotic fusion after the end of the first trimester and fetal structural and/or chromosomal abnormalities. DESIGN: We prospectively studied 492 fetuses from high-risk pregnancies between 14 and 18 weeks of gestation by transabdominal ultrasonography. Of these, 60 (12%) had unfused amnion and chorion. RESULTS: No additional abnormalities were detected in 28/60 fetuses (47%). Karyotyping was performed in 27/28 cases, and one fetus had trisomy 13 (4%). Ten of 24 fetuses (42%) of this group attending a second mid-trimester scan after 18 weeks of gestation had abnormal sonographic findings not noted at the initial scan. Thirty-two of 60 (53%) fetuses had additional abnormalities at the initial scan: cystic hygroma (n = 12), increased nuchal translucency (n = 10) and other abnormalities (n = 10). Karyotyping revealed aneuploidy in 13 of 28 fetuses (46%) tested: trisomy 21 (n = 5), Turner's syndrome (n = 3), trisomy 18 (n = 3) and trisomy 13 (n = 2). Additional fetal abnormalities were detected only at the second scan after 18 weeks of gestation in three of eight fetuses (38%). CONCLUSIONS: These preliminary data suggest that the sonographic finding of unfused amnion and chorion after 14 weeks of gestation may be associated with fetal structural and/or chromosomal abnormalities.

Ultrasound evaluation of fetal spine length between 14 and 24 weeks of gestation.

The objective of our study was to establish a nomogram of fetal spine length in the second trimester of pregnancy by using two and three-dimensional ultrasound. Fetal spine length was measured prospectively by means of transabdominal ultrasonography in 114 normal singleton pregnancies between 14 and 24 weeks of gestation. Regression analyses were performed on spine length, gestational age, biparietal diameter and femur length. Supplementary three-dimensional ultrasound to assess fetal spine length was performed in 75 cases. Fetal spine length, as a function of gestational age, was expressed by the following regression equation: spine length (mm) = -47.2 + 7.16 x gestational age (weeks), with a Pearson correlation coefficient of R(2)=0.956. The results of the measurements revealed no difference between two and three-dimensional ultrasound. Our study defines the normal limits of fetal spinal length in the second trimester of pregnancy and demonstrates a high correlation between spinal length, gestational age, biparietal diameter and femur length. However, there are still too few prenatal research data to say whether and to what extent an assessment of fetal spine length at this stage of pregnancy can be used for prenatal diagnosis of congenital syndromes, which, among other manifestations, are marked by fetal spine lengthening or shortening.

Isolated Dandy-Walker malformation: prenatal diagnosis in two consecutive pregnancies.

We report a family with recurrent Dandy-Walker malformation (DWM). The first offspring was found prenatally to have isolated DWM at 30 weeks' gestation. Ultrasonography at 19 weeks' gestation in the subsequent pregnancy revealed isolated DWM in both dizygotic twins. Chromosome analysis was normal in all three infants, and autopsy confirmed that no other congenital abnormalities were present. Evidence suggests that rare families transmit the disorder in an autosomal or X-linked recessive pattern, with a high recurrence risk.

Three-dimensional ultrasonographic imaging of fetal tooth buds for characterization of facial clefts.

The purpose of this prospective study was to investigate whether the antenatal characterization of fetal facial clefts can be improved by three-dimensional ultrasonographic visualization of fetal tooth buds. Between January 1996 and June 1998, seventeen consecutive fetuses with facial clefts were examined for fetal maxillary tooth buds in the cleft area using three-dimensional multiplanar reconstruction. It was possible in all cases to classify the clefts either as cleft lip alone or unilateral cleft lip and palate or bilateral cleft lip and palate. Three-dimensional computed tomography and histological jaw sections of three stillborn infants were produced in order to examine the correlation between the sonographic, radiographical and histological findings. The prenatal characterization of the facial clefts by means of a visualization of the tooth buds showed to be accurate postnatally in all cases. The sonographic proof of tooth buds might gain increasing importance as this technique seems to facilitate and improve the prenatal classification of suspected facial clefts.

[Echogenic intracardiac structures (golf ball phenomenon) as predictors of chromosome anomalies]. / Zur Wertigkeit der echodichten intrakardialen Strukturen beim Fetus (= "Golfballphänomen") als Hinweiszeichen für chromosomale Anomalien.

UNLABELLED: Small echogenic areas in the fetal heart are known as the golf ball phenomenon. These structures are considered by some to be a marker for chromosomal anomalies. AIM: To prospectively study the relationship of echogenic intracardiac structures and chromosomal aberrations. METHODS: Over a 15 month period (6/96-9/97) 4500 unselected fetuses between 16-31 weeks were screened for malformations; in each case echogenic intracardiac structures were sought. RESULTS: In 77 cases (1.17%) single or multiple echogenic punctate intracardiac structures could be diagnosed. In 60 fetuses (78%) chromosome analysis was performed. Two (3.3%) had chromosomal abnormalities--trisomy 21 and 45.XO/46.XX. CONCLUSION: The golf ball phenomenon appears to be a normal variation in the development of the papillary muscle. This sign is usually easily to identify and if present, should lead to a more detailed screening for anomalies. In the case of other sonographic abnormalities, with advanced maternal age or with a positive triple test, a chromosomal analysis should be performed.

Male fetuses are particularly affected by maternal alloimmunization to D antigen.

BACKGROUND: It is hypothesized that male fetuses are more severely affected by fetomaternal alloimmunization to D antigen than female fetuses. STUDY DESIGN AND METHODS: One hundred four consecutive pregnancies with single D+ fetuses (51 males, 53 females) and maternal anti-D titers >16 were analyzed retrospectively. RESULT: Sixty fetuses (58%) received intrauterine transfusions. Male fetuses required more transfusions than females (5.0 vs. 2.0, p = 0.0001). At the initial transfusion, male fetuses had a lower gestational age (24.5 vs. 31.0 weeks, p = 0.0007), cord blood hemoglobin content (6.45 vs. 8.75 g/dL, p = 0.01), and hematocrit (19.8 vs. 26.8%, p = 0.004) than female fetuses. After adjustment for maternal gravidity, parity, and history of affected offspring, the odds ratio for development of hydrops by male fetuses was 13.1 (95% CI 2.69-63.6, p = 0.001). Perinatal mortality was higher in male (18%) fetuses than in female (6%) (adjusted odds ratio for males 3.38; 95% CI 0.59-19.46, p = 0.17). CONCLUSION: Male fetuses are particularly affected by maternal alloimmunization to D and require more intense antepartum surveillance than female fetuses.

Three-dimensional ultrasound evaluation of fetal tooth germs.

OBJECTIVE: A total of 126 genetic syndromes are associated with oligodontia or anodontia. The most frequent of these are ectodermal dysplasias, all types of facial cleft and Down's syndrome. With the advent of three-dimensional ultrasonography, accurate assessment of many fetal abnormalities has become possible. The objective of this study was to determine the effectiveness of three-dimensional ultrasonography in the visualization of fetal tooth germs. DESIGN: We examined 45 women with singleton pregnancies between 16 and 36 gestational weeks who were undergoing routine ultrasound check-ups for fetal tooth germs with conventional two-dimensional ultrasonography, followed by three-dimensional ultrasonography using multiplanar reconstruction. RESULTS: In the 45 fetuses studied, fetal tooth germs were visualized at the first attempt in 36 cases (80%). In the group of fetuses aged between 19 and 36 weeks of gestation, the overall detection rate in both jaws was at least 86% for three-dimensional ultrasonography, compared to at least 56% for two-dimensional ultrasonography. CONCLUSIONS: Three-dimensional ultrasonography was clearly superior to conventional ultrasonography in the visualization and evaluation of fetal tooth germs. Three-dimensional ultrasonography therefore has a potential for enhanced visualization of fetal tooth germs and may aid in the antenatal detection of syndromes associated with oligodontia or anodontia.

An undetected reason for severe fetal growth retardation.

In a severely growth-retarded fetus, repeated Doppler ultrasound examinations from the 23rd week of gestation on, showed normal and highly pathological blood flow velocities in the umbilical artery. A caesarean section performed in the 39th week of gestation revealed two true umbilical cord knots. Sonographic screening for umbilical cord knots may be valuable in similar cases. The use of color Doppler could help to visualize the entire course of the umbilical cord.

Fetal bradycardia following cordocentesis.

Several clinical investigations on the course and outcome of pregnancies following cordocentesis have mentioned the occurrence of fetal bradycardia at the time of umbilical cord puncture. The prognostic impact of this common complication has remained controversial. Our purpose was to investigate the prevalence and the short-term and long-term consequences of fetal bradycardia associated with cordocentesis. This study included all 339 cordocenteses performed in 290 fetuses at the Division of Prenatal Diagnosis and Therapy, University of Vienna, between 1991 and 1994. Clinically significant bradycardia was defined as a drop in the heart rate to less than 100 beats/min for a period of > or = 60 s. Bradycardia during or immediately after cordocentesis was observed in 13 cases (3.8 per cent). The fetal/neonatal loss rate per procedure was 61.5 per cent (8/13) in cases with bradycardia and 3.1 per cent (10/326) in those without bradycardia (P < 0.001). Early gestational age and hydrops fetalis correlated significantly with the development of bradycardia at cordocentesis. The other risk groups, including fetuses with intrauterine growth retardation, the puncture site, and the number of puncture attempts did not correlate with fetal bradycardia. Our results indicate that prolonged fetal bradycardia during or after cordocentesis is characteristic of a group of fetuses with an especially unfavourable prognosis.

Pronounced insulin resistance and inadequate beta-cell secretion characterize lean gestational diabetes during and after pregnancy.

OBJECTIVE: To evaluate beta-cell secretion and glucose metabolism in lean subjects with gestational diabetes mellitus (GDM) compared with that in subjects with normal pregnancy and obesity. RESEARCH DESIGN AND METHODS: Insulin secretion, insulin sensitivity (S1), and hepatic insulin extraction were assessed in pregnant women with GDM before and after delivery and in those with normal glucose tolerance (NGT) in comparison to healthy nonpregnant lean and obese women. Kinetic analysis of glucose, insulin, and C-peptide plasma concentrations during oral and intravenous glucose tolerance tests was performed by mathematical modeling. RESULTS: S1 was blunted in pregnant women with GDM by 84% and in those with NGT by 66% compared with lean nonpregnant women (P < 0.005 vs. healthy nonpregnant lean control subjects; P < 0.05, GDM vs. pregnant women with NGT), whereas glucose effectiveness was decreased by 33% in both pregnant groups (P < 0.05 vs. healthy nonpregnant lean control subjects). Insulin secretion was 30% higher (P < 0.05) in subjects with GDM than in pregnant women with NGT or in nonpregnant lean women, but decreased (P < 0.005) when compared with obese women with a comparable degree of insulin resistance. Fractional hepatic insulin extraction was similar in both pregnant groups, being lower (P < 0.0001) by 30% versus nonpregnant females. beta-cell sensitivity to glucose for insulin release was decreased in subjects with GDM versus pregnant women with NGT as well as nonpregnant women by 40-50% (P < 0.01). Twelve weeks after delivery, GDM returned to normal glucose tolerance, but S1 remained 50% lower than that in lean nonpregnant women, while beta-cell sensitivity to glucose did not change (P < 0.01 vs. healthy nonpregnant lean control subjects). CONCLUSIONS: Pregnancy is characterized by insulin resistance, diminished hepatic insulin extraction, and glucose effectiveness. Lean subjects with GDM are additionally characterized by having more pronounced insulin resistance and inadequate insulin secretion, which persist after delivery. Compared with other insulin-resistant prediabetic states like impaired glucose tolerance (IGT), defective insulin secretion seems to be a predominant defect in lean GDM subjects, indicating that it might represent a specific prediabetic condition.

Dandy-Walker malformation diagnosed before 21 weeks of gestation: associated malformations and chromosomal abnormalities.

This study examined rates of concomitant structural and chromosomal abnormalities in 14 fetuses with a diagnosis of Dandy-Walker malformation or Dandy-Walker variant before 21 weeks' gestational age, compared to 14 fetuses with a diagnosis of Dandy-Walker malformation or variant between 21 weeks' gestation and delivery. A total of 24 fetuses had Dandy-Walker malformation and four had Dandy-Walker variant. Eight of the fetuses with the malformation had ventriculomegaly: one of the fetuses with early diagnosis and seven with later diagnosis (p = 0.027). None of the fetuses with Dandy-Walker variant had ventriculomegaly. The overall prevalence of concomitant structural abnormalities was 13/28; 8/14 for fetuses with early prenatal diagnosis and 5/14 for fetuses with late prenatal diagnosis of the malformation or the variant. Chromosomal abnormality rates were significantly higher among fetuses with early prenatal diagnosis (7/14) than among those with later prenatal diagnosis (1/14; p = 0.032). Abnormal karyotypes were more prevalent among fetuses without ventriculomegaly (7/20), compared to fetuses with ventriculomegaly (1/8). We conclude that fetuses with an antenatal diagnosis of Dandy-Walker malformation or Dandy-Walker variant before 21 weeks' gestational age have worse prognosis than fetuses with a later prenatal diagnosis of the same defect.

Umbilical artery Doppler velocimetry in fetuses with a single umbilical artery.

OBJECTIVE: Doppler waveform analysis of the umbilical artery is an important tool for the evaluation of high-risk pregnancies. Yet, available data are based on normal values from three-vessel umbilical cords. Our purpose was to evaluate the value of umbilical artery Doppler velocimetry in fetuses with a single umbilical artery. METHODS: One hundred thirteen consecutive singleton fetuses with a single umbilical artery between 16 and 40 weeks' gestational age were studied prospectively at a tertiary referral center for prenatal diagnosis and therapy. Complete follow-up was obtained from 103 cases. RESULTS: The systolic-diastolic ratio in the umbilical artery was abnormal in 31 fetuses (30%) and normal in 72 fetuses (70%). Fetuses with abnormal Doppler waveform analysis in the umbilical artery were significantly more likely to be growth restricted (55 compared with 15%), to have complex malformations (58 compared with 1%) or an abnormal karyotype (29 compared with 0%), or not to survive the fetal/perinatal period (42 compared with 0%) than those with normal Doppler waveform analysis. CONCLUSION: Fetuses with a single umbilical artery and abnormal umbilical Doppler velocimetry had a significantly increased risk of adverse fetal and neonatal outcome compared with those with a single umbilical artery but normal Doppler studies.