[The ultrasound markers of the aneuploid fetus in the first and second trimesters of pregnancy].
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Aneuploidy↗
Biomedical subjects
S Yagel
Publications and source records attributed to S Yagel.
Noonan syndrome: a cryptic condition in early gestation.
Noonan syndrome is one of the most common of genetic syndromes and manifests at birth, yet it is usually diagnosed during childhood. Although prenatal diagnosis of Noonan syndrome is usually not possible, in a few cases the ultrasonographic findings suggested the diagnosis in utero. Reported sonographic clues include septated cystic hygroma, hydrothorax, polyhydramnios, and cardiac defects, such as pulmonic stenosis and hypertrophic cardiomyopathy. During a 6-year period, 46,224 live-born infants were delivered at the Chaim Sheba Medical Center. Seven newborn infants and four fetuses were found to have Noonan syndrome. One fetus showed transient nuchal translucency of 4 mm and bilateral neck cysts at the 13th gestational week. Both findings resolved spontaneously by the 18th gestational week, but during the third trimester this fetus developed hydrothorax, skin edema, and polyhydramnios. In the three other fetuses, first- and second-trimester ultrasonographic findings were normal, and the diagnosis of Noonan syndrome was suggested only during the third trimester. All three fetuses had polyhydramnios and skin edema. A cardiac malformation, hydrothorax, and a large head were present in one fetus. Sonographic facial findings were investigated. In all four fetuses posteriorly angulated, apparently low-set ears and depressed nasal bridge were identified. Wide nasal base was seen in two fetuses. In two fetuses, persistent opening of the fetal mouth was interpreted as fetal hypotonia. One fetus developed progressive postnatal hypertrophic cardiomyopathy and in one case, pulmonic stenosis became apparent at age 6 months. This small series suggests that Noonan syndrome has an evolving phenotype during in utero and postnatal life. Amelioration of early nuchal region findings and late onset of the more "typical" ultrasonographic changes may limit early prenatal detectability.
Adult↗
Re: The clinical significance of fetal isolated cerebral borderline ventriculomegaly: report of 31 cases and review of the literature. Ultrasound Obstet Gynecol 1999; 14(5):320-6.
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Cerebral Ventricles↗
Abnormalities of the fetal central veins and umbilico-portal system: prenatal ultrasonographic diagnosis and proposed classification.
OBJECTIVES: Anomalies of the fetal venous system are poorly documented and their pathogenesis is not well understood. The present study was undertaken to review the spectrum of fetal central veins and umbilico-portal system anomalies, and to propose a classification system. METHODS: A 7-year restrospective survey was conducted. RESULTS: Nineteen fetuses showed abnormal connection between central veins and the fetal heart. Three fetuses showed abnormal connections of the cardinal veins, two of which had interruption of the inferior vena cava, and one had isolated persistent left superior vena cava. Anomalies of pulmonary veins were seen in four fetuses: in two with asplenia syndrome, a vertical confluent pulmonary artery was observed. In a further two cases total anomalous pulmonary venous connections were found. Abnormalities of the umbilical vein (UV) were seen in 10 cases; seven had persistent right UV, and three had a spectrum of anomalies: One had abnormal connections of the UV to the left iliac vein associated with agenesis of the ductus venosus (DV) and hydrops fetalis. One case showed in utero occlusion of the DV by echogenic foci that resulted in a persistent left proximal UV and porto-systemic shunt. One case had obliteration of the DV secondary to in utero fetal hepatic fibrosis. Abnormalities of the vitelline veins or portal system were demonstrated in two cases. One had a left porto-systemic shunt which resolved spontaneously at 3 months of age, and one had secondary partial occlusion of the left portal system with liver echogenicities and direct communication of the UV with the right atrium. None of the 19 cases had an abnormal karyotype or evidence of in utero infection. CONCLUSIONS: Detection of various fetal vein anomalies in utero is feasible. The anomalies vary according to embryologic precursors or etiology. Two major mechanisms seem to be involved in the genesis of fetal vein anomalies: in most cases primary maldevelopment of the venous system occurs, while in the minority secondary anomalies from possible thromboembolic events or systemic disease may play a role.
Abnormalities, Multiple↗
Tie-2 and angiopoietin-2 expression at the fetal-maternal interface: a receptor ligand model for vascular remodelling.
The blood vessels at the fetal-maternal interface widen dramatically during pregnancy in order to increase blood flow to nourish the developing fetus. This vessel remodelling destroys normal vessel integrity and encompasses the dissolution of vessel muscle and elastic tissue. It also includes the displacement of endothelial cells by fetal trophoblasts that invade the maternal arteries of the uterus. Interaction between the endothelial cell receptor, Tie-2, and its recently discovered antagonist ligand, angiopoietin-2 (Ang-2), has been implicated in the loosening of vessel structure. Using Northern blot hybridization and RNA in-situ hybridization analysis the expression pattern of Tie-2, and Ang-2 in the placenta throughout pregnancy, was investigated. We found Ang-2 expressed in the syncytiotrophoblast during the first trimester. In addition to the expected expression of the Tie-2 receptor in both fetal and maternal endothelial cells, we observed Tie-2 expression in endovascular invasive trophoblasts. These cells of epithelial origin invade the uterine spiral arteries and acquire endothelial cell properties. The temporal- and lineage-specific pattern of expression of Tie-2 and Ang-2 suggests that this receptor-ligand pair functions during the critical phase of development of the fetal vasculature and reworking of the maternal vessels during normal placentation.
Angiopoietin-2↗
Lack of human leukocyte antigen-G expression in extravillous trophoblasts is associated with pre-eclampsia.
Pre-eclampsia, a common complication of first pregnancies, is thought to result from a poorly perfused placenta and may reflect an abnormal maternal immune reaction to the hemiallogenic fetus. Human leukocyte antigen (HLA)-G, a major histocompatibility tissue-specific antigen expressed in extravillous trophoblast cells (fetal-derived), may protect trophoblasts from maternal-fetal immune intolerance and allow these cells to invade the uterus. Through RNA in-situ hybridization analysis, we studied the expression pattern of HLA-G in normal placentae and placentae from pregnancies complicated by severe pre-eclampsia. In normal placenta we found HLA-G expression in the anchoring extravillous trophoblasts with an increasing gradient of expression in the more invasive cells. However, in nine out of 10 pre-eclamptic placentae HLA-G expression was absent or reduced. We conclude that HLA-G is normally expressed in invasive trophoblasts and HLA-G expression is defective in most pre-eclamptic placentae. We propose that trophoblasts lacking HLA-G are vulnerable to attack by the maternal immune system. These defective trophoblasts will be unable to invade the maternal spiral arteries effectively, thereby developing vessels which cannot adequately nourish the developing placenta. This poorly perfused placenta may initiate the systemic cascade of events associated with pre-eclampsia.
Female↗
HLA-G expression in extravillous trophoblasts is an intrinsic property of cell differentiation: a lesson learned from ectopic pregnancies.
Human leukocyte antigen (HLA)-G is a major histocompatibility gene expressed almost exclusively in extravillous trophoblasts at the fetal-maternal interface. HLA-G may play a role in protecting the fetus from attack by the maternal natural killer cells. The extravillous trophoblasts invade the decidua and maternal spiral arteries. The factors which regulate the cell-specific expression of HLA-G are unknown. In this study we asked if HLA-G is expressed in extravillous trophoblasts that develop outside of their normal cellular environment, as in the case of ectopic pregnancies. Since all ectopic pregnancies implant in the absence of underlying decidua we also used a placenta accreta as an experimental control. We found that HLA-G mRNA and protein were expressed in the extravillous trophoblasts in the 13 ectopic specimens studied. In a case of placenta accreta (which develops without decidua basalis and is therefore adherent to the underlying myometrium), HLA-G mRNA and protein were also expressed. These results suggest that HLA-G expression is induced in a cell autonomous manner rather than determined by appropriate environmental cues.
Adult↗
Puerperal and intrapartum group A streptococcal infection.
OBJECTIVE: To determine the demographic and clinical variables characteristic of non-epidemic intrapartum or puerperal group A streptococcal (GAS) infection. METHODS: The records of 47 patients diagnosed with intrapartum or puerperal GAS infection over a 6 1/2 year period at Hadassah-University Hospital-Mt. Scopus, Jerusalem were reviewed. Data regarding 25,811 women, the general population of women that delivered during that period, were obtained from their computerized medical records. Frequency distributions, t-test, chi-square, and Spearman's Rank Correlation were used, as appropriate, to analyze and compare demographic and clinical variables associated with development of GAS infection, its clinical course and subsequent development of septic shock. RESULTS: Mean age of mothers with GAS infection was higher than that of our general pregnant population (30.4 versus 27.4 years, P = 0.0019), and a higher proportion of GAS infected patients (30% versus 12%, P < 0.005) experienced PROM. Thirty-one (66%) women had fever as their sole presenting symptom, eight (17%) had fever and abdominal pain, seven (15%) had fever and abnormal vaginal bleeding, and one patient (2%) presented with a rash. Three patients (6%) developed a septic shock. Two of these patients presented with symptoms more than 14 days after delivery. CONCLUSIONS: We describe the characteristics of non-epidemic intrapartum or puerperal GAS infection. Data from our study and review of the literature suggest that some patients who develop septic shock may present later in the puerperium than patients with an uncomplicated GAS infection.
Abdominal Pain↗
Simultaneous multigate spectral Doppler imaging of the umbilical artery and placental vessels: novel ultrasound technology.
OBJECTIVE: To establish gestational age-specific nomograms of pulsatility indices in the umbilical artery and chorionic and intraplacental vessels, using novel ultrasound technology. STUDY DESIGN: A prospective, cross-sectional study of 160 healthy singleton pregnancies between 18 and 33 weeks of gestation. MEASUREMENTS: Using simultaneous multigate spectral Doppler imaging specialized hardware and software, we measured the flow velocity waveforms of the umbilical artery, chorionic and intraplacental vessels. Computerized automatic mapping calculated the pulsatility indices in regions of interest. RESULTS: Data were adequately obtained for 160 fetuses. The pulsatility index values in the three sites measured decreased with advancing gestational age; the correlation coefficients r = -0.74, r = -0.67 and r = -0.68 for the umbilical artery, chorionic and intraplacental vessels, respectively, were found to be highly statistically significant (p < 0.0001). CONCLUSION: Simultaneous multigate spectral Doppler imaging provides simultaneous measurements of the velocity waveforms in the umbilical artery, chorionic and intraplacental vessels, and is a feasible and reproducible method of obtaining these data. The normal data presented may facilitate early detection of flow disturbances in the fetoplacental circulation.
Adult↗
Placental blood flow measured by simultaneous multigate spectral Doppler imaging in pregnancies complicated by placental vascular abnormalities.
OBJECTIVE: To evaluate the role of placental blood flow measurements by simultaneous multigate spectral Doppler imaging in pregnancies complicated by intrauterine growth restriction (IUGR), and for early detection of placental vascular abnormalities in high- and low-risk pregnancies. METHODS: To assess the sensitivity and specificity of abnormal placental blood flow in detecting IUGR, we followed 22 women whose pregnancies were complicated by IUGR at 28-34 weeks' gestation, and compared the findings with those obtained in 22 matched controls. We defined placental blood flow impedance as abnormal when 10% of placental pulsatility index (PI) measurements were greater than, or equal to, the mean umbilical artery PI (placental PI/umbilical PI > or = 1). To determine the predictive value of abnormal placental blood flow measurement for identifying developing uteroplacental insufficiency, we examined an unselected group of 100 low- and high-risk patients at 20-22 weeks' gestation. We correlated the Doppler findings with the development of pre-eclampsia, IUGR, placental abruption, oligohydramnios and the presence of persistent late decelerations during labor. RESULTS: Placental blood flow determination was more sensitive than umbilical artery blood flow in detecting abnormal umbilical-placental flow impedances as manifested by the presence of IUGR. Of the 100 mixed high- and low-risk patients examined at 20-22 weeks, 32 had abnormal placental blood flow. Of these, 19 (59.4%) subsequently developed pathologies associated with placental vascular disease. Of the 68 patients with normal placental blood flow, only six (8.8%) developed such pathologies. The sensitivity was 76% (19/25), with positive predictive value 59.4% (19/32); the specificity was 82.7% (62/75), with negative predictive value 91.2% (62/68). CONCLUSIONS: Abnormal intraplacental blood flow at 28-34 weeks' gestation is strongly associated with IUGR. In addition, it has moderate positive and negative predictive values for identifying subsequent development of uteroplacental vascular abnormalities.
Adult↗
Defective induction of the transcription factor interferon-stimulated gene factor-3 and interferon alpha insensitivity in human trophoblast cells.
During pregnancy, trophoblast cells of the placenta contact maternal immune cells and yet are protected from attack. One mechanism that may account for this is that trophoblasts show altered expression of major histocompatibility complex (MHC) antigens. The gene for human leukocyte antigen G (HLA-G), a nonclassical gene, is expressed at high levels in trophoblast. Unlike other MHC class I genes, the HLA-G gene lacks an interferon (IFN) response element. Moreover, we demonstrate here that IFN, which regulates classical MHC class I genes in other cell types, does not affect these genes in trophoblast, owing to inactivation of an IFNalpha signaling pathway. Trophoblast cells (JEG-3 and JAR) were found to be selectively refractory to IFN. Specifically, although IFNalpha induced the transcription factors STAT1, STAT2, and IFN regulatory factor-1, and a protective response against encephalomyocarditis virus, it failed to protect the cells from vesicular stomatitis virus, activate a transfected MHC class I gene promoter, and induce the transcription factor IFN-stimulated gene factor (ISGF)-3. The lack of ISGF3 DNA-binding activity apparently was due to diminished p48/ISGF3gamma subunit activity since ISGF3 DNA-binding activity and IFNalpha induction of MHC class I promoter activity were reconstituted by p48/ISGF3gamma supplementation. These data indicate that a specific IFN signaling pathway is inactive in JEG-3 trophoblast cells because of altered activity of p48/ISGF3gamma, and they suggest IFN insensitivity as a mechanism that may help promote feto-placental survival.
Choriocarcinoma↗
Prenatal sonographic appearance of congenital fibrosarcoma.
Congenital fibrosarcoma is a rare soft tissue sarcoma. A 22-year-old woman in the 22nd week of her first pregnancy underwent sonographic examination, which revealed a soft tissue swelling of the fetus's left thigh. The pregnancy was terminated, and congenital fibrosarcoma was diagnosed by pathologic examination. To our knowledge, this is the first published report of the intrauterine sonographic observation of this tumor in a fetal extremity.
Adult↗
Expression of gelatinase B by trophoblast cells: down-regulation by progesterone.
OBJECTIVE: It is now accepted that gelatinase B (92 kd type IV collagenase) is involved in blastocyst implantation and trophoblast invasion. However, little is known about the regulation of this enzyme at the fetomaternal interface. Progesterone has been demonstrated to inhibit gelatinase B secretion from endometrial cells, myometrium, and cervical fibroblasts. Interestingly, the promotor of gelatinase B contains a progesterone-responsive element that may explain transcriptional activation of this metalloproteinase by progesterone. It may be hypothesized that progesterone secreted from trophoblast cells, representing the fetal part of the fetomaternal interface, may have a role in the regulation of gelatinase secretion and blastocyst implantation. STUDY DESIGN: To this end, use was made of first-trimester trophoblast cells obtained from first-trimester pregnancy terminations. The trophoblast cells were separated by trypsin degradation and fractionation on Percoll gradients. Metalloproteinase activity was measured by zymography, and the expression of the gelatinase B messenger ribonucleic acid was determined by the solution hybridization/ribonuclease protection assay. RESULTS: Primary cell cultures of trophoblasts from first trimesters of pregnancy constitutively elaborated two species of type IV collagenases (gelatinase A and B) as assessed on a gelatin matrix. Treatment with progesterone decreased the accumulation of a gelatinase B species in a dose-dependent fashion. Administration of a progesterone receptor antagonist onapristone (ZK-98.299) neutralized the progesterone inhibitory effect on the gelatinase B in a dose-dependent fashion, thus supporting the presumption that the progesterone effect is receptor mediated. Progesterone significantly attenuated the expression of gelatinase B by trophoblast cells, an effect that was neutralized by ZK-98.299. CONCLUSION: These observations provide strong indirect support for the participation of progesterone in the regulation of gelatinase B in trophoblast cells. It may be an important regulator of gelatinase production at the fetomaternal interface.
Cells, Cultured↗
The role of midtrimester targeted fetal organ screening combined with the "triple test" and maternal age in the diagnosis of trisomy 21: a retrospective study.
OBJECTIVE: Our purpose was to evaluate the role of fetal ultrasonography in prenatal detection of trisomy 21. STUDY DESIGN: A retrospective study was performed on all cases of trisomy 21 diagnosed prenatally or postnatally between January 1990 and December 1993 in the Jerusalem metropolitan area. Our program of prenatal detection of trisomy 21 is a three-tiered, chronologically progressive screening that includes maternal age, biochemical serum markers, and targeted fetal organ survey. Sixty-seven thousand ninety-two babies were born during the study period; 17,084 maternal biochemistry analyses (triple test) were performed; and 6315 fetuses were karyotyped. RESULTS: One hundred eight cases of trisomy 21 were diagnosed prenatally and postnatally. The overall rate of detection of trisomy 21 was 92.2% when our recommendations were followed. Among those cases diagnosed prenatally, 66.6% of trisomy 21 cases had been referred for fetal karyotyping because of maternal age > or = 35 years, 18.5% because of abnormal triple test results, and 11.1% because of fetal ultrasonographic findings associated with trisomy 21. Among women < 35 years old, 80% of trisomy 21 cases were detected prenatally. Of these, 50% had been referred for karyotyping because of triple test results and 30% because of abnormal ultrasonographic findings. CONCLUSION: Midtrimester ultrasonographic targeted fetal organ screening plays a critical role in prenatal diagnosis of trisomy 21 among women under the age of 35 years.
Adult↗
Developmental fetal malformations: time to change terminology.
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Female↗
Assessment of first-trimester nuchal translucency by daily reference intervals.
Increased fetal nuchal translucency measured in the first trimester is associated with an elevated frequency of chromosomal abnormalities, yet no reference intervals for transvaginal sonographic measurements of fetal nuchal translucency in that period of development have been established. The aim of the present cross-sectional study was to construct appropriate gestational age-specific reference intervals for nuchal translucency. Transvaginal ultrasound was used in 180 normal pregnant women between 9 and 14 weeks of gestation. Reference intervals were constructed by the parametric method. These reference intervals were then compared to the traditional threshold value of 3 mm, when applied to 287 women scheduled for amniocentesis or chorionic villus sampling (CVS). Both methods had the same sensitivity, 85.7%, and negative predictive value, 99.6%, in predicting fetal chromosomal abnormalities. However, the specificity of the gestational age-related reference intervals tended to be higher than that of the 3-mm threshold: 94.6% vs. 87.9%. The positive predictive value of the former method was higher than that of the 3-mm threshold: 28.6% vs. 15%. The increased specificity and positive predictive value of these reference intervals are of particular importance when applied to women under the age of 35 years. In those women, the finding of an abnormally thick nuchal translucency can lead to the performance of amniocentesis or CVS. Therefore, using these reference intervals instead of the traditional 3-mm threshold may save a significant number of unnecessary invasive procedures.
Adult↗
Outcome of fetuses with isolated borderline unilateral ventriculomegaly diagnosed at mid-gestation.
OBJECTIVE: To evaluate the outcome of fetuses with isolated borderline, unilateral ventriculomegaly. DESIGN: A retrospective survey was conducted at four perinatal centers in Israel. SUBJECTS AND METHODS: Only fetuses with one ventricular width of > or = 11 mm and the other < 10 mm were included in the study. In all cases, the difference of the ventricular width between the two ventricles was > 2.4 mm (two standard deviations). Fetuses with other malformations, chromosomal abnormalities, or those with evidence of in utero infection, were not included in the study. RESULTS: Unilateral ventriculomegaly was found in 27 subjects (after excluding one case with unilateral ventriculomegaly and Down's syndrome). The mean width of the enlarged ventricle was 11.7 +/- 0.9 mm, while the other normal ventricle was 7.2 +/- 0.9 mm. The mean gestational age at diagnosis of the unilateral ventriculomegaly was 23.6 +/- 2.7 weeks. In one case, pregnancy was terminated, and pathological examination of the fetal brain failed to detect any structural abnormality. Twenty-five patients delivered at term and only one at 34 weeks' gestation. The neurological development in all 25 fetuses was normal, and one fetus had petit mal seizures. CONCLUSION: Fetuses with isolated, borderline unilateral ventriculomegaly, but without other abnormalities, have a good neurological outcome.
Cerebral Ventricles↗
A rational approach to prenatal screening and intervention.
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Abortion, Induced↗